putting the horse before the cart: the ethical case for animal patient values in ebvm david mills ma, vetmb, certavp(vc), mrcvs1 1rspca, putney animal hospital, 6 clarendon dr, london, sw15 1aa *corresponding author (dmills@rvc.ac.uk) vol 2, issue 2 (2017) published: 08 may 2017 doi: 10.18849/ve.v2i2.112 this talk will argue that patient values should be the central, primary and overriding consideration in both its practice and research if ebvm is to be an ethically acceptable pursuit. find out more about david. view presentation slides comments: clinical audit experiences of veterinary surgeons undertaking farm animal work in the uk katie waine bvsc, mrcvs1* 1school of veterinary medicine and science, university of nottingham, nottingham, ng7 2rd *corresponding author (svxkw@exmail.nottingham.ac.uk) vol 2, issue 3 (2017) published: 21 jul 2017 doi: 10.18849/ve.v2i3.137 clinical audit can play an important part in improving the services offered by farm animal veterinary practices. its current use however is very varied. understanding experiences, considering concerns and taking into account the thoughts of veterinary surgeons is vital when creating guidance for the profession, or when choosing a single topic to audit in a practice setting. find out more about katie. view presentation slides comments: evidenced based approach for a definition of defined daily dosages of antibiotics used in german pig production lothar kreienbrock 1* 1university of veterinary medicine hanover, bünteweg 2, 30559 hannover, germany *corresponding author (lothar.kreienbrock@tiho-hannover.de) vol 3, issue 1 (2018) published: 08 feb 2018 doi: 10.18849/ve.v3i1.170 the use of antibiotics in veterinary medicine and a resulting development of antimicrobial resistance is a topic of major concern. especially for primary care, evidence is needed to guarantee the efficacy of anti­biotic drugs in future. for this, the correct dosage is an essential measure to prevent antibiotic resistance. because veterinarians used practice differs from the manufacturer’s recommendations, data is needed to describe evidence-based defined daily doses for animals (ddda). view presentation slides comments: efficacy of non-steroidal anti-inflammatory drugs for the treatment of acute puerperal metritis in dairy cows alina pohl 1* 1freie universität berlin, kaiserswerther str. 16-18, 14195 berlin, germany *corresponding author (alina.pohl@fu-berlin.de) vol 2, issue 3 (2017) published: 10 aug 2017 doi: 10.18849/ve.v2i3.143 acute puerperal metritis (apm) is a potentially life threatening, painful disease and is often treated with third-generation cephalosporins. due to increasing antibiotic resistance, alina discusses the need to evaluate alternative therapies to antibiotics. find out more about alina. view presentation slides comments: how to critically appraise a paper & run a journal club dr tim mair bvsc phd deim dipeceim dests mrcvs bell equine veterinary clinic (bevc) vol 1, issue 1 (2016) published: 12 feb 2016 a slide-cast of dr mair's presentation from rcvs skills day 2015, london. are blood lactate levels better than a crystal ball – the veterinary evidence base amanda boag ma, vetmb, dipacvim, dacvecc, fhea, mrcvs1* 1vets now, 1 george square, castle brae, dunfermline, fife, ky11 8qf *corresponding author (amanda.boag@vets-now.com) vol 2, issue 2 (2017) published: 16 jun 2017 doi: 10.18849/ve.v2i2.127 in this talk amanda will briefly review lactate physiology and then focus on the small animal veterinary evidence base – how has it evolved, what do we now know and where are the gaps in knowledge and potential misinterpretations that could affect our use of this clinical tool. find out more about amanda. comments: clinical decision making and treatment patterns in canine prolapsed nictitans and feline herpetic keratitis constance white dvm, phd1* 1fremont veterinary clinic, 5055 ne fremont street, portland, or 97213 *corresponding author (doctornev2000@yahoo.com) vol 2, issue 1 (2017) published: 28 mar 2017 doi: 10.18849/ve.v2i1.106 no evidence-based treatment guidelines exist for any ophthalmic conditions of dogs and there is limited published evidence supporting treatments of feline herpes viral keratitis (fhvk). the aim of this study was to document current treatment patterns of canine prolapsed nictitans (pn) and fhvk through the use of a vignette-based survey administered to general practitioner (gp) and ophthalmic specialist (sp) veterinarians. find out more about constance.  view presentation slides comments: is the simplicity of the evidence pyramid actually detrimental for understanding evidence? annette o'connorbvsc, mvsc, dvsc, fanzcvs1 1iowa state university, college of veterinary medicine, iowa city, ia 52242, usa *corresponding author (oconnor@iastate.edu) vol 2, issue 1 (2017) published: 16 feb 2019 doi: 10.18849/ve.v2i1.100 the evidence pyramid for assessing the efficacy of interventions under real world conditions has been used in various forms for many years, and to a lesser extent the pyramid has been used for assessing evidence for disease risk factors. while acknowledging minor differences, many pyramids list the following information sources for interventions in decreasing order of “validity”: systematic review and meta-analysis of randomised control trials, randomised controlled trials, cohort studies, case control studies, case series and case reports. in this presentation annette discusses the validity of the evidence pyramid on the interpretation of evidence from primary research. she proposes a new way to think about evidence from primary studies using the framework for classifying epidemiologic studies proposed by pearce (2012) based on incident and prevalent cases. this would also result in a rethinking of the current evidence pyramid. find out more about annette. comments: the global resource for online evidence-based veterinary medicine learning kristen reyher bsc(florida), dvm(cornell), phd(upei), mrcvs1* 1university of bristol, school of veterinary sciences, senate house, tyndall ave, bristol bs8 1th *corresponding author (kristen.reyher@bristol.ac.uk) to help make ebvm accessible to the veterinary profession worldwide, we assembled an extensive international team (the ebvm learning consortium) with a collective passion for delivering high-quality teaching of ebvm and developed an open access, online resource: ebvmlearning.org. it is hoped that the development of this resource will increase awareness of ebvm in the veterinary profession and allow practitioners the opportunity to develop the skills needed to utilise ebvm in everyday clinical practice. find out more about kristen. vol 2, issue 1 (2017) published: 13 march 2017 doi: 10.18849/ve.v2i1.103 comments: evidence aid: using systematic reviews to improve access to evidence for humanitarian emergencies mike clarke 1* 1centre for public health, queen’s university belfast *corresponding author (m.clarke@qub.ac.uk) vol 2, issue 4 (2017) published: 27 oct 2017 doi: 10.18849/ve.v2i4.156 evidence aid is an international initiative to improve access to reliable evidence that will help people and organisations make well-informed decisions about interventions, actions and strategies in the disaster setting. it focuses on systematic reviews as the most reliable source of research evidence, maximising the power of existing research, avoiding undue emphasis on single studies and reducing the waste associated with research that is ignored or not accessible to decision makers. evidence aid is knowledge champion for influencers of the humanitarian sector, including funders, policy makers, ngos, and humanitarian professionals. evidence aid was established by members of the cochrane collaboration after the indian ocean tsunami of december 2004. it provides access to information relevant to disaster risk reduction, planning, response, recovery, resilience and rehabilitation. this presentation will discuss the need for evidence aid, and describes its activities. find out more about mike. view presentation slides comments: thank you to our reviewers peter cockcroft ba, ma, vet. mb, msc, dip. dat., dvm&s, dchp, fhea, dip. ecbhm, mba editor-in-chief vol 2, issue 4 (2017) published: 20 dec 2017 doi: 10.18849/ve.v2i4.167 the work of a reviewer is a challenging commitment. there are no monetary rewards and their time and dedication often go unrecognised although no journal could exist without them. all scientific journals have an enormous responsibility in ensuring the papers that it publishers reflect the accepted principles and methods of scientific research. their impact as gate keepers of scientific validity and good communication is immense and critical to ensure misleading information is not propagated, whether it be either in ignorance or in error. the bridge between science and clinical practice is hastened and shortened by the practice of evidence-based veterinary medicine. an important aim of this journal is to provide knowledge summaries for important questions that support decision making in clinical practice. these papers provide an important conduit of knowledge from science into practice. the immediacy of the adoption and propagation of new knowledge into practice increases the responsibility both of the authors and the reviewers. as editor-in-chief i would like to thank all the reviewers listed below for their support of the new journal and their diligence in meeting demanding timelines. their knowledge, expertise and insights are duly acknowledged and highly valued.    nicola ackerman jane alexander konstantinos antonopoulos victoria arbona sebastian arlt sue badger david barrett simon bate nicola bates nick bell jackie belle bruce bladon clare boulton tim brazil james breen louise buckley sarah caney james carmalt william chandler john chitty peter clegg peter cockcroft jacqueline cole polly compston jonathan cracknell richard evans virginia fajt erik fausak myra forster-van hijfte mary fraser lisa freeman laura garrett simon girling wanda gordon-evans kelly hall (wilke) elizabeth jackson shailen jasani stephen jones nicolette joosting kristina kiefer nina kieves matti kiupel shauna krkalo matyas liptovszky alycen lundberg tim mair kate mcgovern cathy mcgowan wayne mcilwraith gillian monsell stewart morgan morag moseley stephanie noel russell parker christopher parratt hannah perrin brian pound claire robinson pete rodgers bruce smith eva spada mike steele matthew stewart kit sturgess meghan sullivan adam swallow rachel tucker laura urdes nieky van veggel becky whay constance white richard white roger wilkinson john williams jim willshire thank you to our reviewers peter cockcroft ma vetmb msc dchp dvm&s dipecbhm mba mrcvs1* 1university of surrey, school of veterinary medicine, daphne jackson rd, guildford gu2 7al *corresponding author (p.cockcroft@surrey.ac.uk) vol 4, issue 1 (2019) published: 07 jan 2019 doi: 10.18849/ve.v4i1.236 as editor-in-chief i would like to thank all of our editors and reviewers for their continued support of the veterinary evidence journal and their diligence in meeting demanding timelines. their knowledge, expertise and insights are duly acknowledged and highly valued. all reviewers who have taken the time to review for veterinary evidence are listed in the full text. in the coming year we hope to develop a new approach and construct for the recognition and delivery of important information needs. this will take the form of a condition specific decision support algorithm with links to knowledge summaries providing the best current evidence. we also intend to publish a series of papers from targeted invited authors to highlight important areas of evidence-based practice including patient safety, quality improvement, business and workplace learning. we have also launched a knowledge summary competition for students studying veterinary medicine, veterinary nursing and veterinary bio-science, so that we may engage with the next generation of practice professionals. i look forward to a challenging and innovative new year with your continued support. thank you to all who have contributed.   nicola ackerman jane alexander david allman konstantinos antonopoulos victoria arbona sue badger david barrett nicola bates nick bell jackie belle hasan bilgili tiffany blackett bruce bladon filip blent tim brazil marnie brennan katherine briscoe andrew brown marta brscic christopher bruce riley louise buckley sarah caney james carmalt thomas chambers marge chandler william chandler scott christopher david church jacqueline cole polly compston elena contreras giulio cozzi jonathan cracknell linda dahlgren julie de lasalle laura dixon dario d'ovidio ken drobatz anna dunlap sushmitha durgam sue dyson rebecca elliott amanda-jane erne virginia fajt erik fausak mireia fernandez john fishwick geoffry fordyce myra forster-van hijfte mary fraser lisa freeman jennifer garcia mark garneau laura garrett paula giaretta toby gimmel laurie goodrich wanda gordon-evans cecilia gorrel kelly hall (wilke) annick hamaide anna hammond jeanette hanson frances harcourt-brown anke hendricks katleen hermans jo hockenhull mark holmes shailen jasani norman johnston stephen jones philip kass nina kieves stanley kim simone kirby matti kiupel barbara kohn sheila laverty daniel lewis matyas liptovszky jason lombard leo londono david maggs denis marcellin-little stanley marks cathy mcgowan maureen mcmichael anna meredith gillian monsell stewart morgan andy morris philippa morrison pam mosedale morag moseley hans nauwynck stéphanie noël ingo nolte marianna norring nicole northrup kazuya oikawa mateus paranhos da costa russell parker andrew parry bob partridge rachel perry federica pirrone simon platt siegfried platz brian pound antonio pozzi nicola robinson pete rodgers jeffrey runge silke salavati richard saunders michael schaer silke schmitz stefan schwarz phil scott gonçalo serrano bradley simon lisa smart bruce smith eva spada kit sturgess meghan sullivan jo suthers sienna taylor david thomas mickey tivers mandy wallace lisa weeth becky whay constance white richard white roger wilkinson john williams cenk yardimci there is no evidence that the addition of antimicrobials reduce the risk of sepsis after intra-articular corticosteroids in horses with arthritis a knowledge summary by elena gogua dvm 1* 1moscow state academy of veterinary medicine and biotechnology named k.i. skryabin, moscow, russia *corresponding author (goguaveter@gmail.com) vol 5, issue 1 (2020) published: 14 jan 2020 reviewed by: nick parkinson (ma, ms, vetmb, certem(int.med.), dacvim, mrcvs)and matthieu cousty (dvm, ecvs) next review date: 04 may 2021 doi: 10.18849/ve.v5i1.220 pico question in horses with arthritis, does the treatment with intra-articular antimicrobials concurrently with intra-articular corticosteroids reduce the risk of sepsis compared to intra-articular corticosteroids alone? clinical bottom line the three studies identified did not demonstrate a reduction of risk when antimicrobials were used. however, the strength of evidence provided by the studies was weak. the power of the studies to detect an effect of antimicrobials was low due to the small number of sepsis cases recorded. further studies are therefore required to draw conclusions. the evidence despite appearing to be common practice, there is no convincing evidence that the use of intra-articular antimicrobials concurrently with intra-articular corticosteroids reduces the risk of sepsis. literature searches uncovered three papers that partially addressed the pico question. in these papers the authors among other things considered the result of the addition of antimicrobials to corticosteroids for intra-articular injection, therefore it were included in the evidence. one of these works is a cross-sectional study (gillespie et al., 2016), two other works (smith et al., 2018 and steel et al., 2013) are retrospective cohort studies, one of which (steel et al., 2013) includes a case-control design. the authors of all three publications detected no effect of the addition of antimicrobials on the risk of sepsis after intra-articular corticosteroids. however, due to low numbers of adverse outcomes and consequent low power, conclusions should be interpreted with caution. summary of the evidence smith et al. (2018) population: data from clinical records of all horses undergoing intrasynovial medication by 10 ambulatory clinicians in the uk 2006–2011 sample size: 9456 intrasynovial injections in 4331 sessions in 1732 horses intervention details: a similar protocol of aseptic technique was used for each joint injection. the concurrent use of medications was dependent on clinician preference. corticosteroids were used in 3869 of 4331 (89.3%) sessions, including triamcinolone acetonide in 3592 of 4331 sessions (82.9%). amikacin sulphate was used in 4044 of 4331 (93.4%) sessions information on dosages is not reported. study design: retrospective cohort study outcome studied: objective assessment. frequency of sepsis after joint injection. the intrasynovial medications studied: triamcinolone acetonide dexamethasone phosphate methylprednisolone acetate autologous conditioned serum stanazolol platelet rich plasma polysulphated glucosaminoglycans (psgag) hyaluronate amikacin sulphate main findings (relevant to pico question): 4/9456 horses developed post medication synovial sepsis (0.04%) of all medications. in one of the sepsis cases there was a combination of triamcinolone acetonide with amikacin, one sepsis case was triamcinolone without amikacin, and two sepsis cases was polysulphated glycosaminoglycan. hyaluronate was used in all four of the sepsis cases. limitations: due to the low incidence of cases statistical analysis was not performed. non-random treatment allocation. gillespie et al. (2016) population: equine veterinarians sample size: 241 surveys intervention details: online cross‐sectional survey of veterinarians – members of the american association of equine practitioners (aaep) study design: cross‐sectional survey outcome studied: objective assessment. data from medical records for a period of up to 10 years prior to the survey for the number of intra‐articular injections performed and the number of joints that developed septic arthritis. variables studied: number of years in practice duration of skin preparation at injection site (and details) use of sterile gloves (and details) use of individual medication vials one‐time use of each needle antibiotic added to other medication main findings (relevant to pico question): the number of septic joints following intra‐articular injection was 67 joints out of 319,760 intra‐articular injections, giving an incidence of 2.1 septic joints per 10,000 intra‐articular injections. intra‐articular antimicrobial usage as an adjunct for all intra‐articular injections was used by 46.5% of veterinarians (112/241) and additional 39.4% of veterinarians (95/241) used antimicrobials some of the time. the data from the 64 veterinarians providing data from medical records did not show a reduction in joint sepsis associated with the use of antimicrobial administration. limitations: there is no way of determining validity. data obtained from surveys may be inexact. steel et al. (2013) population: horses having intra‐articular medication at the singapore turf club 2002–2005 excluded: injection of local anaesthesia alone sample size: 16,624 joints injected in 1103 horses study population included septic arthritis in 13 joints from 13 horses intervention details: 15,934 intra-articular injection of corticosteroid. 824 intra-articular injections of amikacin sulphate. the combination of drugs, doses, frequency determined by the clinical situation. any information on dosages is not reported. joints were prepared using a standardised procedure. control group – 224 horses study design: retrospective and prospective descriptive cohort study, and case-control study outcome studied: objective assessment. septic arthritis was diagnosed if bacterial culture of synovial fluid was positive or if synovial fluid analysis was consistent with sepsis. assessment potential risk factors septic arthritis following intra‐articular medication: using corticosteroids repeated joint injections using amikacin sulphate with the intra‐articular medication main findings (relevant to pico question): septic arthritis was diagnosed following intra‐articular medication in 13 joints from 13 horses of the 16,624 injections – a risk of 7.8 per 10,000 joints injected. statistically significant risk factors: veterinarian type of corticosteroid none of the 824 joints in which amikacin sulphate was injected developed septic arthritis (risk of 0.0 per 10,000 injections, 95% ci 0.0–44.7), but 13 of the 15,800 joints injected without amikacin sulphate or any antimicrobial did develop sepsis (risk of 8.2 per 10,000 injections, 95% ci 4.4–14.1). however, this was not statistically significant. limitations: 13 cases is a small number and statistical analysis of risk factors is difficult. non-random treatment allocation. appraisal, application and reflection intra-articular injections of corticosteroids are employed in horse practice for the treatment of non-inflammatory synovitis and osteoarthritis. the risk of developing iatrogenic septic arthritis after intra-articular injections is well known. the aim of this knowledge summary was to critically appraise published evidence where the addition of intra-articular antimicrobials is to reduce the risk of sepsis. the search strategy did not include the terms corticosteroid, antibiotic, and their derivatives, since specific drug names may have been used in publications. the search gave a lot of results, as it was not very specific, but it makes sure that relevant publications were not missed. however, only two publications related to the pico question were found and one publication (smith et al. 2018) was mentioned by a reviewer but was not picked up in the searches due to search query restrictions. one paper was a cross-sectional study and the other two were retrospective cohort studies, one of which includes a case-control design. none of these publications respond directly to the pico question, but the authors looked at the result of using antimicrobials in addition to intra-articular injections of corticosteroids. in general, the risk of sepsis after intra-articular injections is very low – 7.8 cases per 10,000 injections (steel et al. 2013) or 2.1 cases per 10,000 injections (gillespie et al. 2016) or 4.2 cases per 10,000 injections (smith et al. 2018). the veterinarian and type of corticosteroid were identified as risk factors (steel et al. 2013). while the use of intra-articular amikacin sulphate or gentamicin was not a statistically significant factor (gillespie et al. 2016 and steel et al. 2013) or did not prevent the development of synovial sepsis (smith et al. 2018). these observations should be interpreted with caution – due to the low incidence of sepsis after intra-articular injections, the statistical power of the studies may not be sufficient to reflect true results. thus, the use of antimicrobials is a very common practice – 46% (gillespie et al. 2016) to 93% (smith et al. 2018) of veterinarians combine intra-articular corticosteroids with intra-articular antimicrobials to reduce the risk of septic inflammation of the joint, but there is no evidence of efficiency of this approach and this treatment is pure empirical. prospective randomised controlled trials using standardised treatment protocols could answer this clinical question. smith at al. (2018) estimated that approximately 12,500 medication sessions would be needed to provide a power of 80% for relative risk estimation. but such clinical trials are unlikely to be of practical value given the low incidence of sepsis. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform; 1973 to week 13 2019 pubmed via the ncbi website; 1910 to week 13 2019 search strategy: cab abstracts: (equine* or horse* or mare* or equus or equid*).mp. or exp equidae/ or exp equus/ or exp horses/ or exp mares/ (arthrit* or osteoarthrit* or arthros* or osteoathros* or 'joint disease*' or djd or oa).mp. or exp osteoarthritis/ or exp arthritis/ or exp joint diseases/ ('joint injection*' or 'synovial injection*' or intraarticular or intrasynovial) ('synovial sepsis' or 'joint sepsis' or 'septic arthritis' or sepsis or 'septic infection').mp. or exp sepsis/ 1 and 2 and (3 or 4) pubmed: equine or horse or mare or equus or equid arthritis or osteoarthritis or djd or oa or degenerative joint disease joint injection or synovial injection or intra-articular or intraarticular or intrasynovial synovial sepsis or joint sepsis or septic arthritis or sepsis or septic infection 1 and 2 and (3 or 4) dates searches performed: cab abstracts: 25/4/18 pubmed: 4/5/18 exclusion / inclusion criteria exclusion: non-english language publications conference paper or thesis articles not relevant to the pico book chapters inclusion: articles available in english which were relevant to the pico search outcome database number of results excluded – non-english language excluded – conference paper or thesis excluded – not relevant to pico excluded – book chapters total relevant papers cab abstracts 458 81 50 316 9 2 pubmed 466 10 0 454 0 2 hand search 1 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflicts of interest. i would like to acknowledge clare boulton for her help with the search strategy and finding full-text papers, bridget sheppard for her support throughout the process, the reviewers for their helpful and detailed comments, and jennifer morris for her thorough copyediting. references gillespie, c. c., adams, s. b. & moore, g. e. (2016). methods and variables associated with the risk of septic arthritis following intra-articular injections in horses: a survey of veterinarians. veterinary surgery. 45(8):1071–1076. doi: https://doi.org/10.1111/vsu.12563 smith, l.c.r., wylie, c.e., palmer, l. & ramzan, p.h.l (2018). synovial sepsis is rare following intrasynovial medication in equine ambulatory practice. equine veterinary journal. doi: https://doi.org/10.1111/evj.13063 steel, c. m., pannirselvam, r. r. & anderson, g. a. (2013). risk of septic arthritis after intra-articular medication: a study of 16,624 injections in thoroughbred racehorses. australian veterinary journal. 91(7):268–273. doi: https://doi.org/10.1111/avj.12073 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. can iodine-restricted diets normalise serum total thyroxine (tt4) and subsequently improve clinical signs in cats with hyperthyroidism? a knowledge summary by oliver gilman bvsc mrcvs 1* 1university of bristol, langford vets, langford, somerset, bs40 5du united kingdom *corresponding author (o.gilman.mrcvs@gmail.com) vol 4, issue 1 (2019) published: 19 feb 2019 reviewed by: nicola ackerman (bsc(hons) rvn certsan certvnecc vts(nutr) a1 v1 mbvna) and sarah caney (bvsc phd dsam(feline) mrcvs) next review date: 19 feb 2021 doi: 10.18849/ve.v4i1.176 pico question in cats with hyperthyroidism, does an iodine-restricted diet normalise the serum tt4 (total thyroxine) levels and reduce the severity of the clinical signs when compared to cats on a normal diet? clinical bottom line whilst there is some evidence that iodine-restricted diets can help to renormalise serum tt4 in cats with hyperthyroidism, this is not always effective and there is a lack of compelling evidence to suggest this is associated with a resolution of clinical signs in the long-term. clinical scenario often, a diagnosis of feline hyperthyroidism raises more questions than it solves; with owners striving for a noninvasive and simple treatment for their usually geriatric cat. for the clinician, this has traditionally involved a choice between surgery, lifelong medical management or radioactive iodine treatment. surgery is invasive, irreversible and carries the risks of anaesthetising a geriatric patient with a strong possibility of concurrent disease. whereas traditional medical management is lacking in options, often resulting in owners being left with the task of daily/twice-daily tableting of a potentially noncompliant cat. this is often difficult for owners to achieve, and radioactive iodine treatment is only available at limited centres, with owners being required to leave their beloved pet for long periods. what if something as simple as a dietary change could help manage the disease? summary of the evidence hui et al., (2015) population: client-owned cats with hyperthyroidism sample size: 49 intervention details: cats with hyperthyroidism were fed solely on an iodine-restricted diet. study design: retrospective case series outcome studied: objective assessment of: heart rate serum tt4 blood urea nitrogen (bun) creatinine subjective assessment of: weight – body condition score (bcs) main findings (relevant to pico question): serum tt4 was normalised in 83% of cats by 180 days. normalisation of tt4 did not lead to any improvement of weight or heart rate. however, weights did stabilise and clinical signs did not worsen. limitations: retrospective case studies are relatively low down the evidence hierarchy. multiple laboratories used for blood analysis. serum tt4 and physical parameters were monitored only for a limited time period of 8 weeks. nine cats had already been treated using methimazole. van der kooij et al., (2014) population: group 1: hyperthyroid cats previously medicated with antithyroid medications. group 2: recently diagnosed and untreated hyperthyroid cats. sample size: 225 intervention details: hyperthyroid cats were fed solely on an iodine-restricted diet. study design: prospective, multi-centre study. outcome studied: subjective assessment: body condition score (1–5) clinical signs were scored by owners and vets at day 0, week 4 and week 8.  objective assessment: tt4 urea creatinine main findings (relevant to pico question): serum tt4 was normalised in 75% of cats by 56 days. in the remaining 25%, serum tt4 was lower but still above the reference range. clinical signs were perceived to have improved by both the owners and veterinarians. bcs stabilised during the course of the study. limitations: weight was monitored with subjective body condition scores, rather than using scales, and by multiple different assessors. multiple laboratories were used, with different reference ranges. missing data due to voluntary participants. not documented if wet or dry food was used – the two contain differing levels of iodine. fritsch et al., (2014) population: client-owned cats over 10-years-old, with suspected hyperthyroidism and with a serum tt4 > 4.0 ug/dl sample size: 22 cats completed the study. intervention details: 12 cats were fed a prototype restricted iodine diet and ten were fed a control diet. study design: randomised control trial. outcome studied: cats were assessed at 0, 3, 6 and 12 weeks. subjective assessment: physical examination objective assessment: urine specific gravity tt4, ft4 and t3 bun creatinine alkaline phosphatase (alp), alanine transaminase (alt) and aspartate aminotransferase (ast) main findings (relevant to pico question): all cats fed the iodine-restricted diet had decreased tt4 concentrations by the end of the study, with half attaining euthyroid status. in the control group, tt4 was increased in four cats, was reduced in four cats and stable in two. no cats in the control group achieved euthyroid status. serum creatinine, bun, ast, alt and urine specific gravity (usg) remained stable or decreased in cats fed the iodine-restricted diet. limitations: funded and designed by hill’s pet nutrition, producer of the iodine-restricted diet. relatively small sample sizes. whether or not there was a resolution of clinical signs was not mentioned in the discussion. vaske et al., (2016) population: client-owned cats with hyperthyroidism. sample size: 15 intervention details: cats were fed an iodine-restricted diet (hills y/d, the proprietary diet produced by hill’s pet nutrition) dry or canned version) and assessed at 0, 1, 2, 3 & 6 months study design: prospective study outcome studied: subjective: physical examination objective: tt4 haematology biochemistry symmetric dimethylarginine assay (sdma) urinalysis, urine protein to creatinine ratio (upc), gamma-glutamyl transferase (ggt) and creatinine systolic bp   main findings (relevant to pico question): tt4 was reduced in 100% of the cats after 6 months. 9–10 cats remained persistently hyperthyroid after 6 months. limitations: funded and designed by hill’s pet nutrition, producer of the iodine-restricted diet. very small sample size. whether or not there was a resolution of clinical signs was not mentioned in the discussion. scott-moncrieff (2015) population: client-owned hyperthyroid cats. sample size: 8 intervention details: cats were fed an iodine-restricted diet for 6 months. study design: prospective study outcome studied: subjective: physical examination objective: tt4 ft4 haematology biochemistry urinalysis 123i (a radioactive iodine isotope) uptake by thyroid glands scintigraphically main findings (relevant to pico question): clinical signs reportedly resolved. both tt4 and ft4 were significantly improved, with 7/8 cats achieving euthyroid status by week 8. no significant change in body weight. limitations: very small sample size. whilst it is stated that clinical signs resolved, there is no standardised assessment described. appraisal, application and reflection during the literature search, it soon became apparent that there were only limited studies investigating the efficacy of the relatively recently introduced iodine-restricted diets for successful control of feline hyperthyroidism. a second point of note was that a substantial proportion of the studies into iodine-restricted diets were undertaken in conjunction with hill’s pet nutrition, a key developer and producer of the commercially available diet, and unfortunately this introduces a suspicion of potential bias in those studies. both the papers from van der kooij et al., (2014) and hui et al., (2015) used a large sample population, but unfortunately the studies by fritsch et al., (2014), scott-moncrieff et al., (2015) and vaske et al., (2016) had more limited sample sizes of 22, 8 and 15 respectively, reducing the reliability of their findings. a limitation of all the studies into this subject is the difficulty in maintaining and proving 100% compliance, as all the patients enrolled in the studies were client-owned and potentially allowed outdoor access. as well as this, documenting an improvement in clinical signs is difficult, given the subjective nature of the task, and made more complicated by the fact that the cats were only assessed by veterinarians at set intervals (it is also unclear whether or not these assessments were made by the same veterinarian). van der kooij et al., (2014) used an online questionnaire, allowing owners to submit data regarding the clinical signs, however details of the questionnaire are not included in the paper, so its suitability cannot be assessed. finally, the limited follow-up undertaken during any of the studies reduces the value of any conclusions that can be made. hui et al., (2015) included nine cats which had already been taking methimazole as treatment, prior to starting the iodine-restricted diet. whilst it was ensured methimazole treatment had been halted, and tt4 was over the reference range before starting the iodine-restricted diet and including these cats in the study, there was no information regarding how long the methimazole had been stopped for, or whether tt4 had returned to pre-methimazole treatment levels. all of the studies found that by the end of their follow-up period 100% of the cats had lower serum tt4 values than when they were started on the iodine restricted diet. hui et al., (2015) found that by 61–180 days into treatment serum tt4 had normalised in 83% of the cats in the study. van der kooij et al., (2014) had similar findings, with 75% of those cats having normal serum tt4 by week 8. similarly, scott-moncrieff et al., (2015) found serum tt4 normalised in seven out of eight cats by week 8. fritsch et al., (2014) reported 50% of the enrolled cats becoming euthyroid by week 12 and vaske et al., (2016) had 33% of the cats become euthyroid by 6 months into treatment. neither of the studies by fritsch et al., (2014) or vaske et al., (2016) monitored clinical signs during the iodine-restricted diet trial, so it is impossible to draw any conclusions regarding improvement of clinical signs from these studies. hui et al., (2015) documented a cessation of the progression of clinical signs, whilst both scott-moncrieff et al., (2015) and van der kooij et al., (2014) showed an improvement, perceived by both owners and veterinarians. no cats were removed from any of the studies due to concerns about the safety of the diet, or as a result of any side effects, so it can be concluded at least that the diet is safe. so whilst there is limited literature investigating the efficacy of iodine-restricted diets as a treatment for feline hyperthyroidism, all the studies so far have documented a 100% improvement in serum tt4 when cats have been started on an iodine restricted diet, though this did not always guarantee a return to euthyroid status. there is, however, a lack of consensus regarding the resolution of clinical signs. further to this disparity amongst the literature, the limited number of studies and the limitations of those studies mean a prospective study with large sample size and– lifelong follow-up would improve the evidence base greatly. methodology section search strategy databases searched and dates covered: ovid medline on ovid sp 1946 – week 4 2019 web of science core collection on web of science 1946 – week 4 2019 ovid cab abstracts 1973 – week 4 2019 search terms: ‘animal feed’ or ‘diet’ and ‘cats’ or ‘feline’ and ‘hyperthyroidism’ dates searches performed: 22/01/19 exclusion / inclusion criteria exclusion: articles not in english, unrelated to the pico, single case reports, book chapters and conference proceedings. inclusion: articles in english, related to the pico. search outcome database number of results excluded – relevance excluded – language excluded – duplicates total relevant papers ovid medline 228 225 0 0 3 cab abstracts 485 480 0 3 2 web of science 24 19 0 5 0 total relevant papers when duplicates removed 5 conflict of interest the author declares no conflicts of interest. references fritsch, d., allen, t., dodd, c., wedekind, k. & sixby, k. 2014. a restricted iodine food reduces circulating thyroxine concentrations in cats with hyperthyroidism. international journal of applied research in veterinary medicine, 12(1), pp.24–32. hui, t., bruyette, d., moore, g. & scott-moncrieff, j. 2015. effect of feeding an iodine-restricted diet in cats with spontaneous hyperthyroidism. journal of veterinary internal medicine, 29(4), pp.1063–1068. http://dx.doi.org/10.1111/jvim.13368 van der kooij, m., becvarova, i., meyer, h., teske, e. & kooistra, 2014. effects of an iodine-restricted food on client-owned cats with hyperthyroidism. journal of feline medicine and surgery, 16(6), pp.491–498. http://dx.doi.org/10.1177/1098612x13512627 vaske, h., armbrust, l., zicker, s., jewell, d. & grauer, g. assessment of renal function in hyperthyroid cats managed with a controlled iodine diet. international journal of applied research in veterinary medicine, 14(1), pp.38–48. scott-moncrieff, j., heng, h., weng, h., diemo, d. & jones, m. effect of a limited iodine diet on iodine uptake by thyroid glands in hyperthyroid cats. journal of veterinary internal medicine, 29, pp.1322–1326. http://dx.doi.org/10.1111/jvim.13577 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. outcome of electrosurgery versus scalpel blade for intestinal incisions in dogs a knowledge summary by emmanouil tzimtzimis dvm, msc (sas), mrcvs 1* 1university of glasgow small animal hospital, school of veterinary medicine, college of medical veterinary and life sciences, garscube estate, switchback rd, bearsden, glasgow, g61 1bd, scotland, uk *corresponding author (manolis.dvm@gmail.com) vol 4, issue 3 (2019) published: 14 aug 2019 reviewed by: nausikaa devriendt (dvm, ecvs) and hilde de rooster (phd, ebvs) next review date: 23 aug 2020 doi: 10.18849/ve.v4i3.243 pico question in dogs that undergo intestinal surgery, does the use of monopolar electrosurgery for intestinal incisions increase the risk of dehiscence when compared to a scalpel blade? clinical bottom line currently there are two experimental in vivo studies comparing electrosurgery with scalpel blade intestinal incisions in dogs, one in cats and one in pigs. in dogs and cats, there is data regarding incisions on the large intestine but not the small intestine. colotomy and colectomy performed with monopolar electrosurgery has resulted in significant mortality (up to 60%) during the short-term postoperative period in dogs. although the studies reviewed have several limitations, the outcome using scalpel blades was significantly better, therefore colonic surgery using electrosurgery is contraindicated. it is likely that small intestinal surgery has the same contraindication but more definite conclusions cannot be made until higher quality evidence is available. the evidence all of the studies reviewed here are randomised controlled trials, therefore they provide strong evidence regarding the use of electrosurgery in intestinal surgery in dogs. two studies in dogs, one study in cats and one study in pigs are available. the canine trials were precisely designed but there were several limitations arising from the fact that these studies were conducted by human surgeons as experimental models. the studies in cats and pigs were included because they address the clinical question fulfilling most of the criteria of an accurate design, despite the different animal species. summary of the evidence hottenrott et al. (1983) population: cross-breed dogs sample size: 12 dogs intervention details: group 1 (six dogs): left partial colectomy (2 cm length from descending colon) with a scalpel blade and scissors under local relative ischaemia conditions (ligation of the caudal mesenteric artery and maintenance of mean arterial blood pressure of 40 mmhg for 15 min). functional end-to-end single-layer anastomosis with polyglactin 910. two 0.5 × 2 cm sized colonic biopsies collected proximally to the anastomotic site with scalpel blade – scissors and defect closed with single-layer polyglactin 910 sutures. group 2 (six dogs): same procedure as above but the colectomy and colonic biopsies were performed with monopolar electrosurgery. hospitalisation and monitoring for 4 days. the descending colon was harvested after euthanasia on day 4 postoperative. study design: randomised, controlled in vivo experimental trial outcome studied: postoperative assessment of clinical abnormalities during 4 days necropsy assessment of colonic wounds healing histopathology of colonic wounds healing postoperative measurement of hydroxyproline concentration in colonic wounds main findings (relevant to pico question): group 1: 1/6 dogs died before day 4 postoperative because of anastomotic failure and septic peritonitis. the rest of the animals showed sufficient healing on necropsy. group 2: 3/6 dogs died before day 4 postoperative because of anastomotic failure and septic peritonitis. the rest of the animals showed small areas of insufficient healing covered with omentum and major adhesions on necropsy. evidence of enhanced colonic wound healing in group 1 compared to group 2 (production of granulation tissue, epithelialisation, numbers of fibroblasts, degree of collagen deposition and width of wound) significant (p<0.05) decrease in concentration of hydroxyproline in colonic wounds of the group 2 compared to group 1. limitations: a partial colectomy was performed in dogs, as a human model, in this study, which is not a commonly performed procedure in dogs in clinical practice. small study population the authors have deliberately simulated conditions of relative ischaemia at the anastomotic site which is a major risk factor for colonic wound healing. no electrosurgery settings (generator brand, cutting/coagulation, voltage, time) are reported. the histopathological assessment of the wounds healing is subjective. animals were euthanised in 4 days, therefore the longer-term complications and outcome is unknown. regadas et al. (2005) population: cross-breed dogs sample size: 40 dogs intervention details: mechanical preparation of the large intestine with an enema of 120 ml 10% glycerine solution 12 h and 2 h pre-operative. group ia (10 dogs): midline laparotomy and transverse colotomy with electrosurgery. group ib (10 dogs): four-port laparoscopy and transverse colotomy with electrosurgery. group iia (10 dogs): midline laparotomy and transverse colotomy with scissors. group iib (10 dogs): four-port laparoscopy and transverse colotomy with scissors. closure of the colotomy with single-layer, interrupted, polydioxanone 0 sutures, not incorporating the mucosa. hospitalisation and monitoring for 7 days. laparotomy and euthanasia at day 7. study design: randomised, controlled in vivo experimental trial outcome studied: postoperative assessment of clinical abnormalities during 7 days necropsy assessment of colonic wounds healing postoperative measurement of colonic wounds resistance to increased intraluminal pressure with a sphygmomanometer histopathology of colonic wounds healing main findings (relevant to pico question): groups iia and iib: all animals (20/20) had good postoperative clinical outcome and survived to day 7. groups iia and iib: all animals (20/20) showed uneventful macroscopic colonic wound healing. groups ia and ib: anorexia, vomiting, diarrhoea and death on day 4–7 postoperative in 5/10 and 6/10 animals respectively. group ia: 3/10 animals showed normal healing, 2/10 had omental adhesions to colonic wounds and 5/10 had dehiscence and peritonitis. group ib: 2/10 animals showed normal healing, 2/10 had omental adhesions to colonic wounds and 6/10 had dehiscence and peritonitis. statistically significant (p<0.005) difference between groups i and ii but not between groups ia and ib with regards to clinical outcome. statistically significant (p<0.005) difference between groups i and ii with regards to macroscopic wound healing. groups iia and iib: none of the animals had colonic wound dehiscence after application of a mean intraluminal pressure of 222.1 mmhg. groups ia and ib: 3/10 and 2/10 colonic wounds resisted a mean 222.1 mmhg of pressure respectively. 2/10 colonic wounds from each groups failed under mean pressure of 94 mmhg. histopathology of colonic wounds at day 7 postoperative revealed an inflammatory process in all groups. limitations: a human model colotomy was performed in dogs in this study, which is not a commonly performed procedure in dogs in clinical practice. mechanical preparation of the large intestine was performed which is largely controversial in colonic surgery, both in humans and small animals due to increased risk of intraoperative contamination with liquid feces. no electrosurgery settings (generator brand, cutting/coagulation, voltage, time) are reported. a polydioxanone 0 suture material was used for colotomy closure which is significantly over-sized. generally polydioxanone 3-0 or 4-0 is recommended. no detailed and/or quantified histopathology results are provided. animals were euthanised in 7 days, therefore the long-term complications and outcome is unknown. kott & lurie (1973) population: cross-breed cats sample size: 40 cats intervention details: preparation of the large intestine with only water per os for 48 h pre-operatively. group i (20 cats): partial colectomy of a 2 cm segment from the descending colon with a stainless steel scalpel blade. group ii (20 cats): partial colectomy of a 2 cm segment from the descending colon but using electrosurgery. end-to-end anastomosis in two layers: appositional pattern in the mucosa and inverting pattern in the seromuscular layer using 5-0 silk interrupted sutures. hospitalisation and monitoring for 1 day (8 cats), 2 days (8 cats), 4 days (8 cats), 6 days (8 cats) and 11 days (8 cats). specimens with the colectomy wounds were randomly harvested on necropsy after euthanasia on postoperative days 1 (8 cats), 2 (8 cats), 4 (8 cats), 6 (8 cats) and 11 (8 cats). study design: randomised, controlled, in vivo experimental trial outcome studied: intraoperative findings were recorded. necropsy assessment of colonic wounds healing histopathology of colonic wounds healing (40 specimens, 8 specimens for each of the days 1, 2, 4, 6 and 11 [20 specimens from group i and 20 from group ii]) main findings (relevant to pico question): haemostasis during colectomy with electrosurgery was superior to stainless steel scalpel blade. no macroscopic compromise of the vascular supply or the viability of the colonic wall was observed in any of the animals. no dehiscence was found on necropsy assessment in any of the animals. group ii anastomotic sites were oedematous and friable. there were adhesions and local peritonitis. the overall wound healing process was delayed by 48 h in group ii compared to group i, mostly evident in day 4 and 6 postoperative (necrotic tissue, exudates of fibrin and leucocytes, incomplete fusion of the muscular layer). no quantitative data are provided. limitations: no electrosurgery settings (generator brand, cutting/coagulation, voltage, time) are reported. colectomy closure was performed in a double-layer pattern, no submucosal apposition is mentioned and the superficial layer was closed in an inverting pattern. this technique is generally regarded as inappropriate for colonic closure in companion animals (williams 2017). a 5-0 silk suture material was used for colectomy closure which is generally considered an inappropriate material (increased capillarity, tissue drag, predisposing to infection, non-absorbable) [williams 2017]. animals were euthanised on days 1, 2, 4, 6 and 11, therefore the longer-term complications and outcome is unknown. the findings from the histopathology of the colonic wounds’ healing were presented and compared in detail but no quantitative data are provided. pollinger et al. (2003) population: pigs, domestic-cross, female sample size: 18 pigs intervention details: full thickness transverse enterotomies using two different feedback circuit electrosurgical generators at 20 w cutting mode and no. 10 scalpel blade. two enterotomies with each modality. a total of 108 enterotomies. all enterotomies closed on a single-layer, interrupted pattern with 3-0 braided polyglactin 910. specimens with the enterotomy wounds were randomly harvested on necropsy after euthanasia on postoperative days 3, 7 and 14. study design: randomised, controlled, in vivo experimental trial outcome studied: histopathology of intestinal wound healing (54 specimens, 18/modality and 6/each time point/modality): inflammatory response (cells/high power field [hpf]), predominant cell species, thermal injury (mm), degree of epithelialisation, density of collagen deposition, stage of healing measurement of wound tensile strength (54 specimens, 18/modality and 6/each time point/modality): unit-o-matic fm-20® universal testing machine, within 60 min from necropsy main findings (relevant to pico question): evidence of thermal injury in all specimens incised with electrosurgical devices. mean width of thermal injury 5.57 mm (range 3–10 mm) with the first generator and 5.28 mm (range 2–9 mm) with the second one. no significant difference in inflammatory response, predominant cell species, degree of epithelialisation and density of collagen deposition at any time point for the three modalities tested. significant difference in the stage of healing between enterotomy sites created via electrosurgery (earlier stage) when compared to scalpel blade (later stage) [p<0.0001]. no significant difference in intestinal wound tensile strength at any time point for the three modalities tested. limitations: no limitations detected appraisal, application and reflection the use of electrosurgery (diathermy or radiofrequency) to perform intestinal incisions in dogs has never been reported in clinical cases according to the author’s research of current veterinary literature. the canine studies reviewed here have investigated the use of monopolar electrosurgery in oncologic colectomy or colotomy as experimental model for humans (hottenrott et al., 1983 and regadas et al., 2005). colectomy and colotomy are not very frequently performed in dogs in clinical practice, particularly in comparison with enterotomy or enterectomy. the anatomy of the intestinal wall is similar in the small and large intestine but the healing process of these two structures differs in a few aspects. bacterial population is larger in the colon (1010–1011 bacteria per gram of faeces) which could be predisposed to infection. return of wound-bursting strength is slower in the colon than in the small intestine with 75% of the normal strength being reached at 4 months postoperative (williams, 2017). collagenolysis 48 h after surgery has been shown to be much more activated in the colon compared to the small intestine (thornton et al., 1997). the colonic intraluminal pressures may be higher than the small intestinal ones as faecal masses pass through. also, in one of the studies (hottenrott at al., 1983) tissue hypoperfusion was evoked. both infection and hypoperfusion are factors that can negatively affect the colonic wound healing regardless of the modality used for the incision. however, the same factors were present in the control groups in both studies. there was a significant difference in complications rate, mortality rate, macroscopic and microscopic healing progress (hottenrott et al., 1983 and regadas et al., 2005) and colonic wounds bursting strength (regadas et al., 2005). it can be concluded that the use of electrosurgery in colonic surgery in dogs is contraindicated. in a feline study (kott and lurie, 1973) a fair number of colectomies (40 colectomies) was performed using electrosurgery. subtotal/total colectomy (but not partial colectomy as in this study) is more frequently performed in cats than in dogs, to treat idiopathic megacolon. although there were no reported postoperative complications and mortality, these clinical aspects were not the main objective of the study and they were briefly mentioned in the materials and methods section. in addition, most of the animals were euthanised by day 4 postoperative (24/40) which can obscure the true complications and mortality rate. histopathology of the wound healing revealed an overall delayed healing when the wounds were created via electrosurgery. in those wounds, there was necrosis at the wound edges up to 4 days postoperative, the fibroblastic proliferation was delayed at all time points, maturation of the granulation tissue had not occurred at day 11 postoperative and fusion of the individual layers was not observed up to day 11 postoperative. although these results are not quantified, they can be considered strong evidence against the use of diathermy in colonic surgery in cats. contrarily to the previous data, a large number of enterotomies (72 enterotomies) using electrosurgery was performed in pigs with no complications or mortality reported until the day 14 postoperative (pollinger et al., 2003). histopathology of the wound healing revealed an overall delayed healing when the wounds were created via electrosurgery but no significant differences in specific histologic parameters or tensile wound strength were found. pigs have an unusual distribution of mesenteric arterial blood supply with approximately 500 bundles of arteries consisting of up to 30 anastomosing arteries each (spalding, 1987). although these results do not show a clear clinical disadvantage of feedback circuit electrosurgery in comparison to “cold instrument” intestinal surgery, an experimental or clinical study in dogs would be necessary for safe conclusions to be drawn. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform covering from 1973 to 2018 week 32. pubmed via the ncbi website covering from 1910 to august 2018. google scholar covering from 1982 to 2016. search terms: cab abstracts (dog or dogs or canine or canines or canis or bitch or bitches or puppy or puppies or pup or pups).mp. or exp dogs/ or exp bitches/ or exp puppies/ or exp canidae/ or exp canis/ (222717) (enterotomy or enterectomy or intestinal or intestines or intestine or bowel or bowels).mp. or exp intestines/ (189759) (diathermy or diathermic or electrosurgery or electro-surgery or electrosurgical or electro-surgical).mp. (247) (scalpel or blade or bladed or "conventional surgery" or "cold instruments" or "cold instrument").mp. (11131) 1 and 2 and (3 or 4) (20)   pubmed (dog or dogs or canine or canines or canis or bitch or bitches or puppy or puppies or pup or pups) (enterotomy or enterectomy or intestinal or intestines or intestine or bowel or bowels) (diathermy or diathermic or electrosurgery or electro-surgery or electrosurgical or electro-surgical) (scalpel or blade or bladed or "conventional surgery" or "cold instruments" or "cold instrument") 1 and 2 and (3 or 4) (20)   google scholar (intestine or intestinal or enterotomy) (electrosurgery or electrosurgical or diathermy) (scalpel and blade) (wound healing or dehiscence) 1 and 2 and 3 and 4 (4,020)   the reference list for the studies that were identified has also been searched. dates searches performed: 23/08/2018 exclusion / inclusion criteria exclusion: opinion pieces, articles on intestinal surgery and diathermy but not for creation of incisions, articles on intestinal surgery and different cutting modalities (laser, harmonic scalpel) and articles that were not relevant to the pico question. inclusion: articles that were relevant to the pico question. the articles did not have to be from the veterinary literature. case reports were considered but none was retrieved. the reference list for the studies that were identified has also been searched. search outcome database number of results excluded – opinion pieces excluded – diathermy not used for incisions excluded – different cutting modalities (laser, harmonic scalpel) excluded – not relevant to pico question excluded – not accessible total relevant papers cab abstracts 20 0 1 5 14 0 0 pubmed 20 0 3 4 9 2 2 google scholar 4,020 0 0 0 4,019 0 1 reference list checking 4 0 0 0 3 0 1 total relevant papers when duplicates removed 4 conflict of interest the author declares no conflicts of interest. the author would like to thank ana ferreira and lukas huber from the university of glasgow small animal hospital for their valuable help in translation of two articles that were not in english. references hottenrott, v.c., et al. (1983) anastomotic problems in colonic surgery. zentralblatt fur chirurgie. 108: 1263–1271. kott, i., and lurie, m. (1973) the effects of electrosurgery and the surgical knife on the healing of intestinal anastomoses. diseases of the colon & rectum. 16: 33–38. doi: http://dx.doi.org/10.1007/bf02589907 pollinger, h.s., et al. (2003) comparison of wound-healing characteristics with feedback circuit electrosurgical generators in a porcine model. the american surgeon. 69: 1054–1060. regadas, s.m.m., et al. (2005) experimental model of laparoscopic handsewn suture in colon of dogs. acta cirúrgica brasileira 20: 323–328. http://dx.doi.org/10.1590/s0102-86502005000400011 spalding, h., and heath, t. (1987) arterial supply to the pig intestine: an unusual pattern in the mesentery. anatomical record. 218: 27–29. doi: http://dx.doi.org/10.1002/ar.1092180106 thornton, f.j., and barbul, a. (1997) healing in the gastrointestinal tract. surgical clinics of north america. 77: 549–573. doi: https://doi.org/10.1016/s0039-6109(05)70568-5 williams, j.m. (2017) colon. in: veterinary surgery: small animal, 2nd, eds k.m. tobias, s.a. johnston, elsevier, st. louis, mo, usa, pp. 1767–1771. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. which sternotomy closure method (orthopaedic wire or suture) is recommended in large breed dogs undergoing a median sternotomy? a knowledge summary by charlotte howes bvsc pgcert pgdip mrcvs 1* guillaume chanoit dedv msc phd dipecvs dipacvs mrcvs 1 1university of bristol, senate house, tyndall ave, bristol bs8 1th *corresponding author (ch8067.2008@my.bristol.ac.uk) vol 3, issue 2 (2018) published: 14 may 2018 reviewed by: gillian monsell (ma, vetmb, phd, mrcvs) and bruce smith (bvsc ms fanzcvs dacvs) next review date: 14 may 2020 doi: 10.18849/ve.v3i2.159 pico question which sternotomy closure method (orthopaedic wire or suture) is recommended in large breed dogs undergoing a median sternotomy? clinical bottom line the literature search revealed no clinical studies on large breed dogs comparing the clinical outcomes following either orthopaedic wire or suture sternotomy closure methods. post-mortem studies on large breed dogs suggest that sutures are as suitable as orthopaedic wires for sternal closure with regards to their biomechanical properties. there is insufficient clinical evidence to make a recommendation that sutures be used in large breeds of dog. clinical scenario a 5-year-old, male neutered labrador, weighing 27kg presents with a spontaneous pneumothorax. following initial stabilisation and advanced imaging there is a high suspicion of pulmonary bullae. a median sternotomy is performed to examine both sides of the thorax. at surgery, a ruptured bulla is identified and a partial lung lobectomy is performed. on closure of the median sternotomy, the surgeon must decide on the best method of closure based on the evidence available. summary of the evidence pelsue (2002) population: research dogs with a mean weight of 29±3kg, undergoing a median sternotomy sample size: 20 intervention details: prior to surgery all dogs had a pre-anaesthetic complete blood count, serum biochemistry and heartworm serology. baseline heart and respiratory rates and sternal pain threshold measurements were obtained daily for one week prior to surgery. a median sternotomy was performed using a sagittal saw. the sternum was halved from the second sternebra through the xiphoid (which was cut), leaving only the manubrium intact. as part of the concurrent research, dogs underwent coronary arterial bypass grafting. the dogs were randomised into one of the two following treatment groups for median sternotomy closure: sternotomy closure using an overlapping figure-of-eight pattern and no. 2 polybutester suture (10 dogs) sternotomy closure using an overlapping figure-of-eight pattern and 20g orthopaedic wire (10 dogs) at day 7 post-operatively, six dogs were euthanised (three from each group) and gross assessment of sternal stability was performed. at day 28 post-operatively, the remaining fourteen dogs were euthanised (7 from each group) and the sterna were split transversely between the 5th and 6th sternebrae. the cranial portions were radiographed and caudal portions were fixed for histopathology. study design: randomised controlled trial outcome studied: duration of median sternotomy closure pain assessments at 1, 2, 4 and 12 hours post-operatively by a blinded observer, using a multiple-category numerical rating system pain threshold measurements were obtained using a spring action load device. maximum tolerable force was recorded as the pressure applied to the mid sternum that resulted in a negative patient reaction or when a maximum force of 50 newtons was obtained. wound healing complications gross sternal stability at 7 days deemed unstable if >2cm of dorsoventral displacement was manually obtained radiographic and histopathologic evidence of osteolysis and  fracture healing at 28 days main findings (relevant to pico question): suture closure of the median sternotomy was significantly faster than wire closure (7±1.8 minutes versus 9.1±1.9 minutes) there was no significant difference in post-operative pain between the two closure groups wound complications were observed in both treatment groups, including skin dehiscence, incisional drainage and seroma formation there was no significant difference in complication rates between groups all dogs had stable sternal fixations at day 7 all dogs in the wire group had stable sternal fixations at day 28 3/7 dogs in the suture group had unstable sterna at day 28 radiographically, none of the sterna showed complete osseous healing at day 28. radiographically, wire closure resulted in a significantly smaller fracture gap than suture closure at day 28 histologically, osteochondral/chondral bridging seen in the wire group (3 sterna) and only fibrous tissue and inflammation seen in the suture group (3 sterna) at day 28 limitations: small sample sizes – post-hoc power calculations were performed for pain and haemodynamic variables and the authors concluded that the sample sizes were sufficiently large; however no power calculations were performed for assessment of sternal stability or bone healing. pain assessment is subjective and was only assessed for the first 24 hours post-operatively not all sterna are accounted for in reported radiographic and histopathological findings short duration of study (28 days) with no long-term follow-up, does not allow assessment of complete sternal healing mccready (2015) population: canine cadaveric sterna from skeletally mature dogs, weighing 14.6kg to 36.8kg and euthanised for reasons unrelated to the study. sample size: 14 intervention details: for each cadaveric sternum, a median sternotomy was performed using an oscillating saw. the sterna were halved from the second to the eighth sternebrae, leaving the manubrium intact. there was no specific mention as to whether the xiphoid process was cut or not. each sternum was randomly assigned to one of the two following sternotomy closure method groups: closure using 20g orthopaedic stainless-steel wire (ssw) in a figure of 8 pattern, leaving the wire unbent (7 dogs) closure using 80lb monofilament nylon leader (mnl) sutures in a figure of 8 pattern, secured with a crimp (7 dogs) following sternotomy closure, the sterna were loaded in a mechanical testing machine and underwent constant axial displacement. load and displacement were recorded continuously until failure. mechanical testing of each sternum was recorded with a digital video camera and radiographs were obtained before and after testing to determine the mode of failure. study design: ex-vivo randomised controlled trial outcome studied: load at yield maximum load stiffness displacement mode of failure main findings (relevant to pico question): there was no significant difference for load at yield, maximum load at failure, stiffness or mean displacement for ssw and mnl closure. mode of failure for ssw constructs was fracture of the sterno-costal junction (5/6) and fracture of the costal cartilage (1/6). mode of failure for mnl constructs was pulling of the suture through the crimp (4/6) and fracture of the sterno-costal junction (2/6).  limitations: ex vivo experimental study – may not reflect in vivo conditions sterna subjected to abnormal/non-physiological forces provides information on mechanical properties of sutures/wires only, unable to draw conclusions regarding post-operative complications and sternal healing two constructs eliminated from final results small sample size – is the lack of significant difference between closure methods is true or type ii error (incorrectly accepting the null hypothesis). no post-hoc power calculations performed. gines (2011) population: canine cadaveric sterna from mature greyhounds, weighing 25kg to 37kg, euthanised for reasons unrelated to the study. sample size: 12 intervention details: for each cadaveric sternum, a median sternotomy was performed using a sagittal saw, cutting from the second sternebra and through the xiphoid whilst leaving the manubrium intact. each sternum was randomly assigned to one of the two following sternotomy closure groups, with six sterna in each group: closure using four metric polydioxanone (pds) sutures in a figure of 8 pattern, secured with a sliding knot and a total of five throws. closure using 20g stainless-steel wire (ssw) in a figure of 8 pattern, leaving the wire unbent. following sternotomy closure, the specimens were loaded into a mechanical testing machine and tested under displacement control mode, pulling them apart at a constant rate until failure.  radiographs were obtained before and after testing to determine the mode of failure. study design: ex-vivo randomised controlled trial outcome studied: displacement at different loads stiffness mode of failure failure was defined as a fracture of sternebrae or sternocostal junction, or rupture of wire or suture maximal load at failure radiographic findings main findings (relevant to pico question): there was no significant difference in displacement at loads up to 400n or sternal stiffness between the pds and ssw groups the load at failure for the ssw group was significantly higher than for pds group mode of failure for the ssw group was fracture of the sterno-costal junctions (6/6) mode of failure for the pds group was suture failure (5/6) and manubrium fracture (1/6) radiographic analysis of ssw specimens showed no evidence of implant failure limitations: ex vivo experimental study abnormal forces only single distractive forces until failure does not replicate in vivo conditions only provides information on mechanical properties of sutures/wires, unable to draw conclusions regarding post-operative complications and sternal healing small sample sizes a power analysis was performed for a specific setting (2-mm gap for a load of 125 n) and it was concluded that the sample size was ample to show clinical differences.  bright (1983) population: dogs weighing 20kg to 30kg sample size: 9 intervention details: a median sternotomy was performed for all nine dogs. all sterna were closed with parasternal and transsternal orthopaedic wires . for the first five dogs non-swaged wire was used. swaged wire was used for the final four dogs. the dogs were assessed daily for 30 days post-operatively and were then euthanised.   study design: descriptive/non-comparative case series outcome studied: daily records of pain, pleural drainage, gross wound characteristics and pyrexia were taken for 30 days. post-mortem assessment of wound healing was made at day 30 and included: gross assessment of wound healing manual assessment of sternal stability radiographic evidence of healing  main findings (relevant to pico question): post-operative pain was noted in 4/9 dogs, with one dog requiring additional analgesia. wound complications were recorded in 5/9 dogs (56%) fewer complications noted following change from use of non-swaged to swaged wire. all dogs had a clinically stable sternum at 30 days radiographs at 30 days showed: displacement in 8/9 dogs no signs of osseous healing in 6/9 dogs partial osseous healing in 2/9 dogs complete osseous bridging in one dog radiographs showed the following complications: cranio-caudal shift of sternebrae boney lysis reabsorption of sternebrae wire breakage the authors concluded that fibrous union provided sufficient stability to the sternum para-sternal wiring technique shown to be effective in preventing cortical destruction in human studies not supported by the findings of this paper. limitations: small sample sizes no control groups – unable to draw comparisons with other methods of wire or suture closure. more than one surgeon performed the surgeries unable to state whether reduced complication rate following change in surgical technique was the result of use of swaged wire or improved technique/experience/surgeon variability. pain assessment subjective davis (2006) population: sternal segments from dogs weighing 22.8kg to 43.3kg, euthanised for reasons unrelated to the study. sample size: 40 intervention details: the sternal segments were clamped into a custom-made platform and a complete median sternotomy was performed using a sagittal saw. all sternal segments were closed using 18g orthopaedic wire and were randomly assigned to one of the following five sternotomy closure groups with a total of eight specimens per group: two single twist cerclage centered on the sternebrae single twist figure of 8 pattern centered on the sternal synchondrosis double twist figure of 8 pattern centered on the sternal synchondrosis two double looped cerclage centered on the sternebrae double loop cerclage centered over the sternal synchondrosis each segment was radiographed and then loaded into a custom-made jig. each specimen was loaded to failure in tension and the process was recorded with a digital video camera. displacement at each load was measured. the specimens were then radiographed to determine the mode of failure.  study design: ex-vivo randomised controlled trial outcome studied: displacement load at failure radiographic findings main findings (relevant to pico question): there were no significant differences in displacement between fixation methods for loads ≤ 125n sternal wiring techniques centred on the sternal synchondroses (groups 2, 3 and 5) had the least displacement at higher loads (150, 175, and 200n) when compared with techniques centered on the sternebrae. both figure of 8 patterns (groups 2 and 3) had the least displacement at higher loads (150, 175, and 200n) sternal body fracture was the most common method of failure for all groups. limitations: ex-vivo experimental study sternal segments consisted of two sternebrae and therefore have different mechanical properties to an entire sternum sternal segments subjected to abnormal forces tested with single pull to failure – different to in vivo conditions provides no information on post-operative outcome no comparison with suture closure methods appraisal, application and reflection five articles were reviewed, four of which were randomised controlled trials (including two experimental ex-vivo studies), with the remaining article being a non-comparative case series. the clinical bottom line can be summarised as: “the literature search revealed no clinical studies on large breed dogs comparing the clinical outcomes following either orthopaedic wire or suture sternotomy closure methods. post-mortem studies on large breed dogs suggest that sutures are as suitable as orthopaedic wires for sternal closure with regards to their biomechanical properties. there is insufficient clinical evidence to make a recommendation that sutures be used in large breeds of dog.” median sternotomy in dogs is associated with a high rate of post-operative complications. common complications include; seroma formation, skin dehiscence, discharging sinus tracts, osteomyelitis and post-operative pain. there are several different sternotomy closure techniques discussed in the human and veterinary literature, however there are few studies that directly compare the use of suture versus wire for median sternotomy closure in large breed dogs.    of the articles reviewed, pelsue et al (2002) directly compares wire and suture median sternotomy closure in large breed dogs in a randomised controlled trial. interestingly, no significant difference in complication rates was found between the two closure methods over a 28 day period. in addition, there was no significant difference in post-operative pain in the first 24 hours following surgery between the wire and suture group.  randomised controlled trials provide a good level of evidence, however the small sample sizes used in this study must be considered when interpreting the significance of these results. post-hoc power calculations were performed for pain and haemodynamic variables, for which the authors concluded that the sample sizes were sufficiently large to discount type ii error. however, no power calculations were performed for assessment of sternal stability or bone healing, for which the sample sizes were the smallest. pelsue et al (2002), conclude that wire sternotomy closure is superior to suture sternotomy closure and recommend its use in large breed dogs. however, no direct correlation between the findings of this study and clinical outcome has been drawn. furthermore, the conclusions are based on results that indicate that sterna closed with wires had a significantly smaller fracture gap and histological evidence of superior sternal healing when compared with sterna closed using sutures. however, study duration is a limitation of this study, as at 28 days none of the sterna showed complete osseous healing, indicating that the study duration was not long enough to assess complete sternal healing. this result is echoed by a non-comparative case series by bright et al (1983), in which nine dogs underwent median sternotomy with wire closure; eight of which had either no radiographic signs of osseous healing or only partial healing at 30 days post-operatively. it is therefore difficult to draw meaningful conclusions on sternal healing from data collected in such a short time frame. it also appears from our search that there are no available studies that correlate the apparent weakness of sternotomy suture closure in large dogs with clinical outcome. two experimental ex-vivo studies compare the mechanical properties of suture versus wire closure of median sternotomy (gines et al, 2011 & mccready et al, 2015). both found sutures and wires to be mechanically comparable when exposed to forces deemed as physiological (<400n). gines et al (2011) demonstrated that wire has a superior loading force to failure when compared with sutures. however, neither of these studies provide information on post-operative outcome and therefore the clinical significance of these ex-vivo studies remains undetermined. in summary, it is evident that there is a requirement for more large-scale clinical studies directly comparing the use of wires and sutures for median sternotomy closure in large breed dogs. retrospective studies reviewing the clinical outcome of large breed dogs undergoing suture sternotomy closure would also provide useful information and enable more informed clinical decision making in the future. methodology section search strategy databases searched and dates covered: cab abstracts on ovid 1973 to 2017 week 20 medline on ovid 1946 to may 2017 search terms: dogs/ or (dog* or canine*).mp and sternotomy/ or sternotom*.mp and wire*.mp or sutures/ or polydioxanone/ or nylons/ or (suture* or polydioxanone or nylon).mp dates searches performed: 31/05/2017 exclusion / inclusion criteria exclusion: case reports, articles not relevant to the pico question and duplicated articles inclusion: all accessible articles relevant to the pico question search outcome database number of results excluded – case report excluded – not relevant to pico question excluded – not available excluded – duplicated total relevant papers cab abstracts 12 1 5 1 0 5 medline 24 2 18 0 4 0 total relevant papers when duplicates removed 5 conflict of interest the authors declare no conflicts of interest. references bright, r., mcintosh bright, j., richardson, d. et al (1983) clinical and radiographic evaluation of a median sternotomy technique in the dog. journal of veterinary surgery. 12 (1) pp.13-19. doi: http://dx.doi.org/10.1111/j.1532-950x.1983.tb00695.x davis, k., roe, s., mathews, k. et al. (2006) median sternotomy closure in dogs: a mechanical comparison of technique stability. journal of veterinary surgery. 35 pp. 271-277. doi: http://dx.doi.org/10.1111/j.1532-950x.2006.00143.x gines, j., friend, e., vives, m. et al. (2011) mechanical comparison of median sternotomy closure in dogs using polydioxanone and wire sutures. journal of small animal practice. 52 pp. 582-586. doi: http://dx.doi.org/10.1111/j.1748-5827.2011.01106.x mccready, d., bell, j., ness, m. et al. (2015) mechanical comparison of monofilament nylon leader and orthopaedic wire for median sternotomy closure. journal of small animal practice. 56 (8) pp. 510-515. doi: http://dx.doi.org/10.1111/jsap.12378 pelsue, d., monnet, e., gaynor, j. et al. (2002) closure of median sternotomy in dogs: suture versus wire. journal of the american animal hospital association. 38 pp. 569-576. doi: http://dx.doi.org/10.5326/0380569 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. evaluation of cosmetic results of surgical wound closure in dogs rachel williams dvm1* wanda gordon-evans dvm, phd, dacvs, dacvsmr2 jeffery biskup dvm, dacvs3 dominique griffon dmv, ms, phd, dacvs, decvs1 1western university of health sciences college of veterinary medicine, east 2nd street pomona ca, ca 91766, united states 2university of minnesota college of veterinary medicine, 1365 gortner ave, st paul, mn 55108, usa 3university of tennessee college of veterinary medicine, 2407 river dr, knoxville, tn 37996, usa *corresponding author (rchlwilliams9@gmail.com) vol 3, issue 1 (2018) published: 15 feb 2018 reviewed by: kristina kiefer (dvm, phd) and victoria arbona (dvm, ms) doi: 10.18849/ve.v3i1.123 section index:    abstract | introduction | methods | results | discussion | conflict of interest | references | supplementary files abstract objective: to evaluate the correlation between wound cosmesis and pet owner satisfaction, to determine the agreement among vet surgeons, and pet owners evaluating a surgical wound with a visual assessment score (vas), and to determine the agreement between the vas, a semi-quantitative score of wound inflammation, and wound width. background: perception of post-surgical cosmesis by human patients has been found to influence their satisfaction and perceived adequacy of vet surgeons. due to the trend of owners anthropomorphising pets, this logic can be extended to veterinary patients. also, there is a lack of consistent, reliable methods to evaluate cosmesis have been developed, creating the need for a scoring system that is accurate and reproducible. evidentiary value: this was a prospective cohort study with one hundred and seven patients. this study may not change day-to-day practices, but it will bring to light for practitioners the discordance between pet owners and vet surgeons concerning attractiveness of an incision as well as overall satisfaction with a procedure. methods: photographs of surgical wounds were taken immediately, 2 weeks, and 8 weeks after surgery in dogs. owners were asked to evaluate satisfaction with the procedure and attractiveness of the incision using the vas. photos were evaluated for cosmetic outcome by pet owner and vet surgeon evaluators with different scoring systems. the reliability of the scoring systems was evaluated using intraclass correlations and kappa statistics as appropriate. results:  owners’ evaluation of cosmetic outcome correlated with their overall satisfaction. (r2=0.37, where r2 is the coefficient of determination, and can be used to determine what proportion of variance in one variable is predictable from the other variablethere was generally poor reliability of the subjective scoring between both vet surgeons and pet owners, and the less subjective scoring systems. conclusion: the cosmetic outcome as judged by the owner accounted for 37% of the variability in satisfaction, that is to say that 37% of the total variation in satisfaction could be explained by the cosmetic outcome as evaluated by the owner. this suggests that wound cosmesis significantly influences clients’ satisfaction. however, the other methods of rating cosmesis evaluated in this study were unreliable. application: the results of this study are relevant to all veterinarians in clinical practice, from general practice to tertiary referral centers. this study should be kept in mind when speaking with owners to establish pre-surgical expectations as well as mediating conflict due to a difference in opinion with regards to a surgical outcome. introduction in human surgery, patient’s perception of outcome is affected by the cosmetic appearance of the scar. there can be marked psychosocial changes related to the appearance of the surgical site over multiple surgical disciplines (duncan et al 2006; exner et al 2012; flanagan 2009; kim et al 2015). in addition, it has been shown that cosmetic outcomes can affect patient-perceived adequacy of their surgeon in human medicine (boulding et al 2011).   although it is unlikely that animals are psychologically affected by appearance as humans are, owners may anthropomorphise especially as pets become increasingly treated like family members and thus leaving owners less satisfied with less cosmetic incisions (boni 2008). owners may also use the incisional appearance to judge the quality of the surgery or the ability of the surgeon. cosmesis of the incision is an obvious outcome that owners are able to easily see and understand at home, as compared to other factors such as hemostasis and the ability to acquire margins such as in the case of a mass removal. although this is logical, it has not been evaluated scientifically in veterinary medicine. a variety of validated scoring systems have been developed for use in humans with different types of surgery, ranging from deformity correction to cancer reconstruction. these scoring systems range from a simple, self-reported visual analog score to a complicated psychological screening test evaluating the effect of cosmetic results on quality of life (duncan et al 2006; holland et al 2001; kim et al 2015). evaluators in these studies included pet owners (duncan et al 2006); vet surgeons (holland et al 2001); and psychologists (kim et al 2015). in spite of the multitude of scoring systems designed for multiple types of cosmetic outcomes, the authors were unable to find scoring systems that could be extrapolated to veterinary surgery.  no scoring system for surgical wounds has been validated in animals. in recent publications dealing with cosmesis, scoring systems were either absent, or were substituted by parameters like inflammation (gallegos 2007; maninchedda 2015). additionally, no evidence of validity or reproducibility was disclosed in these reports (etter et al 2013; peeters 2011; sylvestre 2002). in this study, the authors chose to use the visual analog score that had been previously described (duncan et al 2006) due to its demonstrated validity, consistency, and reliability. the objectives of this study were to evaluate the correlation between wound cosmesis and owner’s satisfaction with the surgery, to determine the inter-rater agreement, among vet surgeons, and pet owners evaluating a surgical wound with a visual assessment score (vas), and to determine the agreement between the vas, a composite score of wound inflammation and wound width. we hypothesised that cosmesis would influence owner satisfaction and that the agreement in wound assessment would be fair between owners and vet surgeons, and good between vet surgeons. we hypothesised that the vas would correlate with the composite scores. finally, we hypothesised that the scar width and the less subjective scores would have the highest inter-rater reliability and correlation with owner opinion. methods animals dogs were recruited from wisconsin veterinary referral center or banfield pet hospital of oviedo with owners’ consent.  animals were included if they underwent soft tissue or orthopaedic surgery between may 2014-july 2014. surgery was performed by vet surgeons as well as general practitioners. fractious patients and those subjected to radiation therapy were excluded. signalment, location, and type of surgery were recorded. owners were asked at 2 and/or 8 weeks to evaluate the incision and satisfaction with the surgery. photographs were taken post-operatively, at 2 weeks, and at 8 weeks if possible for evaluation by the pet owners and vet surgeons. vas score owners used a visual analog score to rate the appearance of the surgical wound. a 10cm line was marked where the level of cosmetic outcome fell. the 0cm point was defined as the most unacceptable cosmetic outcome, whereas the 10cm point represented the cosmetically pleasing outcome. a similar line and instructions were provided to rate owner’ satisfaction with the surgery. digital image analyses digital photographs were taken immediately, 2 weeks and 8 weeks after surgery. the photographs were taken with a camera placed perpendicular to the incision. a ruler was placed on the skin adjacent to, but not interfering with the incision.  the photos were assigned a numerical identifier and provided to masked evaluators. each image was provided to each evaluator in a random order, without any identification or indication of timing relative to surgery. composite score three of the pet owners were recruited, 3 vet surgeons (jb,wge, dg) independently evaluated all photographs using the vas used by pet owners. additionally, the vet surgeons evaluated each image with a numerical rating scale (sylvestre et al 2002) to assess 4 aspects of the wounds: swelling, erythema, discharge, and dehiscence. these factors were adopted from a publication comparing different suture patterns to close celiotomies after canine ovariohysterectomies (sylvestre et al 2002). these 4 scores were added together and the mean was found to calculate a composite score for each wound, at each time point, and for each surgeon. quantitative image analysis: after completion of the subjective and semi-quantitative scorings, the same 3 board certified vet surgeons (jb, wge, dg) evaluated each image with image processing software (image j, nih, usa). each image was calibrated with the ruler placed next to the incision. the width of abnormal tissue surrounding the beginning, the middle, and the end of the wound was measured (table 1) and the 3 values were averaged. data analysis correlation of owner cosmetic and satisfaction vas scores were performed using a regression analysis. the inter-rater reliability of the pet owner and vet surgeon vas scores, composite score, and average width of incisions were evaluated using intraclass correlations (icc). each individual category within the composite score was evaluated with a kappa statistic. significance was set at p<0.05. if the inter-rater reliability was significant, a regression was used to determine the correlation with owner opinion and satisfaction. iccs were considered poor for values less than 0.40, fair for values between 0.40 and 0.59, good for values between 0.60 and 0.74, and excellent for values between 0.75 and 1 (hallgren 2012). kappa values 0-0.20 indicated slight agreement, 0.21-0.40 fair agreement, 0.41-0.60 moderate agreement, 0.61-0.80 substantial agreement, and 0.81-1 almost perfect agreement (landis 1977). table 1: mean ± standard deviations of the vas, composite score, and wound width results one hundred and seven patients were included in this study. the average age of patients included in this study was 5.88 years ranging from 0.4 to 14.7 years. of those 119 patients, 64 of them underwent soft tissue surgery while the remaining 55 were orthopaedic procedures. of the orthopaedic procedures, 26 of them were tibial plateau leveling osteotomies (tplo) which accounted for 24% of all procedures. owner satisfaction and owner cosmetic score was correlated significantly, with an r2-value of 37% (p<0.0001).  in general, the majority of the incisions were rated above the 5cm mark with only a few raters assigning vas scores below 5cm. at the first recheck, 56 of the reported vas scores by owners were rated above the 5cm mark, while only two were scored below that, indicating that most owners evaluated the incision as having an appearance closer to excellent. this could demonstrate a limitation in the study by which there was not a wide enough spread with regard to the appearance of incisions. the intraclass correlation of the pet owners and vet surgeon groups, composite score, and average scar width are presented in table 2. overall, only the 2 week composite score and the average scar width at 8 weeks were moderately reliable. when evaluating the individual components of the composite score (table 3), reliability was generally poor. the kappa statistic could not be calculated at 8 weeks because of low numbers of cases evaluated. table 2: intraclass coefficients of vas, composite score, and average width to evaluate inter-rater reliability table 3: kappa statistic for the components of the composite score to evaluate inter-rater reliability between vet surgeons. this statistic is used to demonstrate the reliability of non-parametric data and compares only 2 observers at a time. therefore, 1x2 signifies observer 1 compared to observer 2 and 2x3 signifies observer 2 compared to observer 3 etc. if p<0.05, no significant finding (nsf) was listed. discussion owners’ opinion of cosmesis accounted for 37% of the variation in satisfaction. although this is not a high correlation, it is a clinically significant portion of overall satisfaction. over 1/3 of the owners’ satisfaction was due to the cosmetic appearance of the surgery site. other factors affecting satisfaction, such as resolution of disease, interactions with staff, or prior expectations for outcome were not evaluated in this study. however, some types of surgery may be more or less dependent on cosmesis in terms of owners’ satisfaction. for example, almost half of the procedures were orthopaedic and within that group tplos were overrepresented. it is possible that factors such as return to function, or lameness could have influenced the satisfaction response provided by owners. additionally tplo incisions may be more noticeable on a day-to-day basis than an abdominal incision. alternatively, owner satisfaction may have been higher in patients that underwent oncologic surgery. in such cases, the owner may give higher priority to the success of disease than appearance of the wound, than owners of pets undergoing elective procedures. for example, cases where large malignancies were removed may be found very satisfactory in spite of unsightly scars because the disease has been addressed successfully. our inability to assess these variables could be considered limitations of this study, and further investigation is warranted to determine that relationship. the reliability of the vas, composite score, and scar width measurements was generally disappointing. in general, the intraclass coefficient is an indicator of inter-rater agreement with 1 indicating perfect agreement. the highest intraclass coefficient (icc) in this study was equal to 0.74 and characterised the composite scores assigned 2 weeks after surgery. the higher level of agreement likely reflects the fairly uniform levels of inflammation between wounds at this stage. the relative uniformity facilitates the evaluation compared to that at the time of surgery. in general, most of the characteristic signs of inflammation take at least a day to appear (flanagan 2009). the subsequent decrease in icc at 8 weeks may have been influenced by the decrease in number of follow-ups available at this stage. many owners did not follow up at referring veterinary hospitals or were not medically required to return after suture removal. the second highest agreement between observers consisted of the scar width measured at 8 weeks, with an icc equal to 0.73. this level of agreement is not surprising, since incisions should be more uniform by this time. in addition, subjective factors, such as swelling and inflammation likely affected early postoperative measurements but would have likely been less of a factor by 8 weeks, as they should have resolved by that point in time. moving forward, this would indicate that use of the composite score would facilitate evaluation by multiple veterinarians, such as in the situation where a patient is seen by a specialist but follow-ups are conducted  by the primary veterinarian, as compared to using the vas, or something similar, that has not demonstrated reproducibility. this data also suggests a use for the composite score in further studies evaluating wound healing. the poor agreement amongst evaluators using the vas may reflect interindividual variations in assessing different aspects of the incision. a small misalignment between skin edges may be perceived acceptable by a surgeon, but may be considered as a poor outcome by another.  additionally, the majority of the incisions in our study were cosmetically acceptable, and tended to score favorably via vas. the agreement between observers would have likely been improved if our study included more cases with poor cosmesis. wounds would have been better distributed along the entire spectrum of possible cosmetic results.  the poor agreement between pet owners and vet surgeons when using the vas emphasises the importance of direct follow-up, as opposed to follow-up via phone. the kappa statistic reflects the difference between how much agreement is observed and how much should be present based on random chance. based on this test, we found some agreement amongst the observers for the components of the composite score. when looking at the traditional kappa statistic, 0 indicates no agreement above what would be expected by random chance, while 0.01-0.20 is slight chance, 0.21-0.40 is fair, 0.41-0.60 is moderate, 0.61-0.8 is substantial, and 0.81-1.00 is almost perfect agreement. the kappa statistics calculated here ranged from fair to moderate with no scores reported above 0.53. the best scores were reported for erythema and dehiscence.  unlike the icc which took all three evaluators into consideration, the kappa statistic only evaluates 2 evaluators at a time. although some of the evaluators were in high agreement, this finding was not consistent among all of them.  interobserver agreement was best when evaluating dehiscence, but the level of agreement between all evaluators remained fair to moderate regardless. the ideal scoring system for cosmesis would be objective, accurate, and highly reliable. in general, evidence is stronger when objective methods are used because of the reduction in variation and bias introduced by subjectivity. for example, gait analysis is an accepted objective proxy for joint pain and is considered the gold standard for lameness evaluation whereas subjective lameness scoring is less reliable (donnell 2015 waxman et al 2008). developing objective measures to characterise inherently subjective traits is difficult. cosmesis is much like pain in that it is subjective by definition, and therefore hard to reliably quantify. in a study comparing the subjective assessment of colic, there was a high degree of interobserver variance, leading to the conclusion that it was inaccurate (keppie et al 2008). it is not surprising that a subjective method of determining cosmetic outcomes of surgery, as used in this study, would perform similarly to other subjective assessments such as those mentioned earlier. there are multiple ways to improve the reliability of scoring systems devised in this study. image capture of the incisions may be improved with standardised lighting and focus. digital imagery and analysis also improves rapidly and it is possible that 3-dimensional analysis would improve results. swelling and scars that are raised were difficult to discern from flat scars in this study. training can also improve agreement amongst evaluators. however, cosmesis is an inherently subjective evaluation that is influenced by multiple factors and scoring systems will likely always need refinement and improvement. limitations that were noted in this study were the lack of spread when it came to the reported scores by owners. as mentioned earlier in this paper, the majority of the owner-reported scores of the appearance of their incisions were above the 5 cm mark. a wider spread in the data could have strengthened the significance of the findings addressed here. another limitation that was encountered was the lack of follow up at 8 weeks, which likely affected the icc for the composite scores at that time frame. given the severe reduction in cases at the 8 week time frame, this would have allowed for outliers to shift calculations far more than if there had been a greater number or wider variety in cases. the final limitation that was noted in this study was the use of 2-dimensional images for this study. images were analyzed from a uniplanar approach, which may not have been sufficient at the 8 week time from when scar tissue may protrude from the surface of the patient and be unable to be visualized using the methods detailed here. future studies may consider the use of photographs from multiple angles or a standardized video platform. conflict of interest acknowledgments: the authors thank banfield pet hospital of oviedo for their technical assistance. funding: supported in part by the steve henriksen extramural grant. competing interests: no competing interests. references boni, s. (2008). anthropomorphism: how it affects the human-canine bond. journal of applied companion animal behavior, 2(1), 16-21. boulding, w. glickman s. manary m. et al. (2011). relationship between patient satisfaction with inpatient care and hospital readmission within 30 days. american journal of managed care, 17(1), 41-48. donnell, j. frisbie, d. king, m. et al. (2015). comparison of subjective lameness evaluation, force platforms and an inertial-sensor system to identify mild lameness in an equine osteoarthritis model the veterinary journal, 206(2), 136-142. http://dx.doi.org/10.1016/j.tvjl.2015.08.004 duncan, j. bond, j. mason, t. et al. (2006). visual analogue scale scoring and ranking: a suitable and sensitive method for assessing scar quality? plastic and reconstructive surgery, 118(4), 909-918. http://dx.doi.org/10.1097/01.prs.0000232378.88776.b0 etter, s. ragetly, g. bennett, r. et al. 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(1977). the measurement of observer agreement for categorical data. biometrics, 33(1), 159-174. http://dx.doi.org/10.2307/2529310 maninchedda, u. nottrott, k. gangl, m. (2015). enucleation in equids with and without the use of an orbital suture meshwork implant: a retrospective study of 37 cases. veterinary record, 177(14), 367. http://dx.doi.org/10.1136/vr.103305 peeters, m. kirpensteijn, j. (2011). comparison of surgical variables and short-term postoperative complications in healthy dogs undergoing ovariohysterectomy or ovariectomy. journal of the american veterinary medical association, 238(2), 189-194. http://dx.doi.org/10.2460/javma.238.2.189 sylvestre, a. wilson, j. hare, j. (2002). a comparison of 2 different suture patterns for skin closure of canine ovariohysterectomy. canadian veterinary journal, 43(9), 699-702. waxman, a. robinson, d. evans, r. et al. (2008). relationship between objective and subjective assessment of limb function in normal dogs with an experimentally induced lameness. veterinary surgery, 37(3), 241-246. http://dx.doi.org/10.1111/j.1532-950x.2008.00372.x supplementary files, images & tables all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. the use of canine stifle orthotics for cranial cruciate ligament insufficiency b.j. carr dvm, ccrt1 s.o. canapp jr. dvm, ms, ccrt, dacvs, dacvsmr1* s. meilleur dvm, ccrp1 s.a. christopher vmd, ccrp1 j. collins co2 c. cox ms1 1veterinary orthopedic and sports medicine, annapolis junction, md, usa 2k-9 orthotics & prosthetics inc., nova scotia, canada *corresponding author (scanapp@vosm.com) vol 1, issue 1 (2016) published: 22 jan 2016 reviewed by: wanda gordon-evans dvm, phd, dacvs, dacvsmr and adam swallow bvsc mrcvs doi: 10.18849/ve.v1i1.10 section index:    abstract | introduction | results | discussion | methods & materials | footnotes | references | supplementary figures & tables abstract objective: to assess weight bearing of dogs treated for unilateral cranial cruciate ligament insufficiency with a custom stifle orthotic. background: cranial cruciate ligament (ccl) insufficiency is the most common cause of hind limb lameness in dogs. while there are numerous options for surgical management, surgery is not always an option. recently, the use of canine stifle orthotics has also emerged as a means to non-surgically manage patients with cranial cruciate ligament insufficiency. evidentiary value: this is a retrospective study of ten dogs treated for unilateral cranial cruciate ligament rupture with a stifle orthotic. methods: medical records (january 2005december 2012) of ten dogs treated for unilateral cranial cruciate ligament rupture with a stifle orthotic were reviewed. temporospatial gait analysis was performed using a pressure sensing walkway at baseline and 90 days or greater post orthotic placement to identify weight bearing with total pressure index % (tpi%). results: tpi% improved significantly by 5.1% in the affected limb when compared to baseline (p = 0.0020). at final gait analysis, tpi% significantly improved by 3% in the affected limb with the orthotic off when compared to the unaffected limb (p = 0.0020). conclusion: custom canine stifle orthotics allow for improved weight bearing in the affected limb. application: custom canine stifle orthotics should be considered for cases with concurrent medical conditions or financial constraints that do not allow for surgical intervention. abbreviations: tpi%: total pressure index percentage introduction cranial cruciate ligament (ccl) insufficiency is the most common cause of hind limb lameness in dogs (1). many recent studies have shown surgical stabilization to be effective in managing cranial cruciate ligament insufficiency (2-12). while there are numerous options for surgical management, surgery is not always an option.  concurrent medical problems, financial concerns, or staging procedures for bilateral ccl insufficiency are all reasons for either forgoing or delaying surgical treatment.  one recent study reported that dogs treated surgically and with non-surgical methods (weight loss, administration of nsaids, and rehabilitation therapy) had better overall outcomes compared with dogs that were treated via non-surgical methods alone (6). recently, the use of canine stifle orthotics has also emerged as a means to non-surgically manage patients with cranial cruciate ligament insufficiency.  in human medicine, knee braces are commonly used for multiple conditions (13-19). bracing of the human knee has been shown to enhance proprioception/joint position sense, permit the injured limb to relax, reduce fatigue in injured limb, provide some mechanical protection against impact, and slow movement down to allow muscles time to react and control motion (14,17-22). recently there has been debate over the efficacy of functional knee braces in neutralizing excessive anteroposterior translation in the acl deficient knee.  functional knee braces are designed to reduce knee instability by neutralizing forces to support the affected ligament (i.e. neutralizing cranial tibial thrust in the acl deficient knee).  one recent review reported that biomechanical evaluations of functional braces have been mixed and concluded further functional brace studies designed to apply forces to the knee joint similar in magnitude to the native acl should be performed (16). in spite of this, functional knee braces are still thought to be effective in controlling anteroposterior translation in acl-deficient knees under low loading conditions (17-22). however, knee braces are not believed to be effective under high loading conditions, such as those that occur during athletic activity (16,17,20,21). functional knee braces are utilized in veterinary medicine with the most common indication being cranial cruciate ligament insufficiency (23). to the author’s knowledge, no objective data is available to support the use of stifle orthotics in dogs. the goal of this study is to evaluate weight bearing of patients diagnosed with a unilateral cranial cruciate ligament insufficiency while wearing a stifle orthotic using a pressure sensing walkway. the hypothesis is that the use of a custom stifle orthotic would allow for increased weight bearing as demonstrated by temporospatial gait analysis using a pressure sensing walkway. results patient demographics of the 160 patients that have been treated at vosm with stifle orthotics for ccl insufficiency, 10 fit the inclusion criteria for this study. all 10 patients were assessed at baseline and presented 90 days or greater post orthotic placement for re-evaluation (mean, 180 days; range 90 – 540 days). there were 9 breeds represented, the labrador retriever was the most common (n= 2, 20%), followed by one each of beagle, bernese mountain dog, doberman, german shorthaired pointer, mastiff, newfoundland, pit bull terrier and west highland white terrier. the average age was 10.4 years old (range 3-15.7 years, median 10.4 years). the average weight was 29.8 kg (range 6.8-52.7kg, median 31.8kg). males accounted for 1 patient (10%) who was altered. females accounted for 9 patients (90%) with 8 being altered and 1 being intact (table 1-2). (table 1 and table 2). medications seven of the ten patients were on medications when they presented at 90 days or greater post orthotic placement. three of the seven were taking gabapentin and tramadol for pain. five of the ten patients were taking a non-steroidal anti-inflammatory medication (carprofen). two patients were on joint supplements, including adequan(1), dasuquin with msm(1). one patient with concurrent hepatic insufficiency was on denamarin and meclizine. many patients were on a multimodal drug therapy plan (table 3). orthopedic examination findings of the ten study patients identified, the right stifle was affected in 50% of the cases and the left stifle affected in 50% cases. patients with bilaterally affected stifles were excluded from the study. at diagnosis cranial drawer in both flexion and extension was identified in 8 patients (80%) and 2 patients (20%) had cranial drawer in flexion only. the meniscus was evaluated in all cases with only 1 (10%) having a suspect meniscal injury as identified by a meniscal click, pain on deep flexion, and positive mcmurray test for meniscal injury (table 2). no examination findings had changed at the 90 days or greater post orthotic placement evaluation. no evidence of neoplasia or progression of osteoarthritis was noted on radiographs of the affected stifle. total pressure index baseline data showed an average total pressure index (tpi%) of 21.6% (range 14.6%-25.7%) in the unaffected limb and 13.4% (range 7.3% -18.8%) in the affected limb. at 90 days or greater post orthotic placement, when dogs were walked over the pressure mat without their orthotic in place, an average tpi% of 22.1% (range 19%-25.3%) in the unaffected limb and 15.5% (range 11.7%-18.9%) in the affected limb was found (fig 1; p = 0.0020). there was also a statistically significant increase in affected limb tpi% without the orthotic when compared to baseline data (fig 2; p = 0.0195). when dogs were walked over the pressure mat with their orthotic in place, an average tpi% of 21.3% (range 17.7%-24.9%) in the unaffected limb and 18.5% (range 13.9%-22.1%) in the affected limb was found (fig 3; p = 0.0098). when comparing the patient using their orthotic to their initial consultation, we found a statistically significant average increase in tpi % of 5.1% in the affected limb (fig 2 and fig 4; p = 0.0020). when comparing the difference of wearing the orthotic versus not wearing the orthotic on the patients final recheck analysis, we found a statistically significant average increase of 3% in the affected limb (fig 2 and fig 4; p = 0.0020). validated client survey on 90 days or greater post orthotic placement, owners were asked to complete the helsinki chronic pain index. only five of the ten owners completed the survey. owners were asked to assess the patient’s mood, pain level, willingness to play, and ability to walk, trot, gallop, jump, rise, move after periods of long rest, and move after heavy exercise. client follow-up (mean, 180 days; range 90 – 540 days) revealed overall improvement in terms of function in all cases, indicating that patients were able to return to near normal (prior to stifle instability) activity levels. while only five of the ten owners completed the survey, all owners expressed satisfaction with the orthotic. only two of the owners stated the orthotic required minor adjustments after the initial placement and fitting appointment. discussion the present study demonstrates that custom canine stifle orthotics allow for improved weight bearing in patients with unilateral cranial cruciate ligament insufficiency. validated client survey also revealed overall improvement in terms of function.  thus, canine stifle orthotics should be considered for those cases with concurrent medical conditions or financial constraints that do not allow for or require a delay of surgical intervention.  while surgery is the gold standard treatment for treating cranial cruciate ligament insufficiency, this study showed that custom stifle orthotics can still help improve overall function. in the one case where a meniscal click, pain on deep flexion, and positive mcmurray test for meniscal injury was identified, this patient also had improved weight bearing while wearing the stifle orthotic.  further study would be needed to fully assess the outcome of custom stifle orthotics in dogs with concurrent meniscal injury.  whether surgery is declined for medical or financial reason, custom stifle orthotics can be offered to help improve function.  however, in the authors’ experience, prior to recommending a custom stifle orthotic, it is important to consider patient and owner factors as complications can include rub sores, persistent instability, and secondary soft tissue injuries if the orthotics are not casted for, fitted, worn and monitored correctly and consistently. the effect of custom stifle orthotics combined with rehabilitation therapy remains unknown as all patients in this study declined enrollment in a dedicated rehabilitation therapy program. it is possible that rehabilitation therapy could further improve function as previous studies have shown that rehabilitation therapy alone can improve patient outcome (6). future study should assess the outcome and level of return to function of patients with cranial cruciate ligament insufficiency treated with rehabilitation therapy and a custom stifle orthotic. it is also important to note that custom stifle orthotics have been used for a variety of conditions, including collateral ligament injuries, deranged stifles, post stem cell therapy, and post patellar ligament repair (23). while assessing these outcomes is beyond the scope of this study, future studies should also assess outcomes of patients treated with a custom stifle orthotic for such conditions.  limitations of this study are predominantly due to the small sample size and retrospective nature of the study. many of the initial 160 patients identified were either deceased or lost to follow up at the time the study was performed.  also, all patients were not reassessed at 90 days following stifle orthotic placement (range 90 – 540 days), and there was no control group.  seven of the ten patients were also on medications over the course of the study, and this could also affect outcomes.  further study is still needed to assess the efficacy of canine stifle orthotics.  also, while improved weight bearing may suggest improved comfort, this study does not assess the kinetic or kinematic effect of custom stifle orthotics on the stifle or gait.  while stifle orthotics are believed to limit anterior tibial translation and excessive internal rotation, further study is indicated to assess this.  while further study is still needed to assess the kinetic and kinematic effect of custom stifle orthotics, this study demonstrates that custom canine stifle orthotics allow for improved weight bearing on objective gait analysis and satisfaction in terms of function by validated client survey. thus, custom stifle braces should be considered for those cases with concurrent medical conditions or financial constraints that do not allow for or require a delay of surgical intervention. methods & materials patient selection medical records (january 2005december 2012) of veterinary orthopedic and sports medicine (vosm) of dogs treated for cranial cruciate ligament rupture with a stifle orthotic were reviewed. inclusion criteria were a diagnosis of a unilateral cranial cruciate ligament rupture on the basis of positive cranial drawer and cranial tibial thrust, a baseline temporospatial gait analysis at the time of diagnosis, radiographs of the affected stifle at the time of diagnosis, and stabilization with a custom stifle orthotic with a polycentric mechanical joint and harness system for suspension.a all patients included in the study were fitted for the stifle orthotic with their owner present.  at the time of the stifle orthotic fitting, all owners were shown how to correctly apply the orthotic and instructed to apply the orthotic when the patient was active.  initially dogs were placed in the brace for 2 to 4 hours per day during periods of activity with the owner checking the orthotic every 30 to 60 minutes to ensure proper fit.  this time was gradually increased over 2 weeks until the patient was wearing the orthotic all day during periods of activity.  owners were allowed to remove the orthotic at night while the patient was sleeping. dogs with concurrent orthopedic disease, bilateral cranial cruciate ligament rupture, or concurrent neurologic disease were excluded from the study. dogs who went on to have surgical repair for the cranial cruciate ligament instability, were deceased, or lost to follow up were also excluded from the study. finally, if the recommendations for orthotic usage were not complied with, the dog was excluded from the study.  owners of dogs who met the study inclusion criteria were contacted and invited to bring their dog back for a 90 days or greater post orthotic placement re-evaluation that included an orthopedic evaluation, objective gait analysis, and validated client survey. orthopedic evaluation patients were asked to return to vosm for an evaluation 90 days or greater post orthotic placement. a complete orthopedic and neurological examination was completed by the primary investigator. routine craniocaudal and mediolateral radiographs of the affected stifle were also performed and evaluated by the primary investigator for progression of osteoarthritis and to rule out neoplasia. objective gait analysis objective gait analysis was performed in a quiet room using a temporospatial pressure sensing walkway at the time of diagnosis and at 90 days or greater post orthotic placement. the walkway system was equipped with an 8.23 x 0.85-m portable mat that had 29,952 encapsulated sensors.b the active dimensions of the mat were 8.04 x 0.61-m. a 1.25 x 0.85-m section of inactive mat was placed at each end of the walkway system to provide transition surfaces when entering and exiting the system. the mat was calibrated by the manufacturer. the walkway system interfaced with a computer and software program for processing and storage of raw data recorded from quadruped gait analysis.c one camera was positioned at a height of 50 cm at the end of the walkway system to record movement.d digital video files of each pass across the walkway system were automatically linked to the data files for footfall verification. owners and other dogs were not permitted to be present during gait analysis. every dog was handled by the same examiner and allowed to acclimate to the room prior to data collection. dogs were walked on the mat until they appeared relaxed (approximately 4 to 6 passes/dog). at 90 days or greater post orthotic placement patients were walked down the pressure sensing walkway with the orthotic on and off to collect the total pressure index percentage (tpi%). each patient performed three satisfactory passages at a walk with the orthotic on and then the orthotic off. a walk is defined as a 4-beat gait in which all legs step sequentially. a passage down the walkway was considered satisfactory if the patient was walking in a straight line over the center of the mat, looking straight ahead and with less than two standard deviations in variation of the velocity with walk velocity of 0.9 to 1.2 m/s. a successful passage must consist of at least three full gait cycles consecutively without a change in footfall pattern. the gait analysis data with the orthotic off and with the orthotic on were completed at 90 days or greater post orthotic placement and was compared to baseline gait analysis performed at the time of diagnosis. validated client survey patient owners completed the helsinki chronic pain index (hcpi) at 90 days or greater post orthotic placement or were contacted by phone if their dog was no longer an active patient at vosm. the helsinki chronic pain index (hcpi) is a validated, reliability tested and responsiveness tested pain questionnaire that was completed by the dog owner. statistical analysis wilcoxon matched-pairs signed rank test (non-parametric, paired t-test) was performed for all data.e significance was established at p footnotes k-9 orthotics and prosthetics inc., nova scotia, canada gaitfour pressure sensing walkway, platinum version, cir systems inc, harvertown, pa gaitfour, platinum version, cir systems inc, harvertown, pa logitech mega pixel web camera, logitech, freemont, ca graphpad prism version 6.00, graphpad software, la jolla, california usa references witsberger,t. h. et al (2008) prevalence of and risk factors for hip dysplasia and cranial cruciate ligament deficiency in dogs. journal of the american veterinary medical association. 232(12) pp 1818-1824 http://dx.doi.org/10.2460/javma.232.12.1818 kim, s.e. , lewis, d.d. and pozzi, a. 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(2013) functional bracing of acl injuries: current state and future directions. knee surgery sports traumatology arthroscopy. 22(5) pp 1131–1141  http://dx.doi.org/10.1007/s00167-013-2514-z chew, k.t.l et al, (2007) current evidence and clinical applications of therapeutic knee braces. american journal of physical medicine & rehabilitation. 86(8) pp:678–686 http://dx.doi.org/10.1097/phm.0b013e318114e416 birmingham, t.b. et al, (2001)  knee bracing for medial compartment osteoarthritis: effects on proprioception and postural control. rheumatology. 40(3) pp 285-289 http://dx.doi.org/10.1093/rheumatology/40.3.285 birmingham, t.b. et al, (2001) knee bracing after acl reconstruction: effects on postural control and proprioception. medicine & science in sports & exercise. 33(8) pp 1253-1258 http://dx.doi.org/10.1097/00005768-200108000-00002 giotis, g et al (2013). effects of knee bracing on tibial rotation during high loading activities in anterior cruciate ligament–reconstructed knees. arthroscopy. 29(10) pp 1644–1652  http://dx.doi.org/10.1016/j.arthro.2013.07.258 giotis, g et al (2011), knee braces can decrease tibial rotation during pivoting that occurs in high demanding activities. knee surgery sports traumatology arthroscopy. 1998) pp 1347–1354  http://dx.doi.org/10.1007/s00167-011-1454-8 palm, h.g. et al. (2012) effects of knee bracing on postural control after anterior cruciate ligament rupture. the knee. 19(5) pp 664–671 http://dx.doi.org/10.1016/j.knee.2011.07.011 canapp, s.o., campana, d.m and fair, l.m. (2012) orthopedic coaptation devices and small-animal prosthetics, in tobias km, johnston sa: veterinary surgery small animal. st. louis, missouri, elsevier, pp  628-646. supplementary figures & tables all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form,and will in return retain certain rights as detailed on the form. collaboration as a key feature of equine evidence-based research: a laminitis case study claire wylie bvm&s, msc, phd, mrcvs1 1rossdales equine hospital, beaufort cottage stables, high street, newmarket, suffolk, cb8 8js *corresponding author (claire.wylie@rossdales.com) vol 2, issue 1 (2017) published: 16 march 2017 doi: 10.18849/ve.v2i1.104 it is widely believed that laminitis poses a threat to the health and welfare of all equidae; however, there is a paucity of evidence-based research on fundamental aspects of the disease, including how commonly it occurs, its clinical presentation and those animals at greatest risk. following generous funding from world horse welfare, we have produced a programme of work over the last eight years to improve the evidence base regarding the epidemiology of laminitis. this talk will outline the methods we used to gather evidence-based data in the equine field, highlight the challenges and lessons we have learnt, and emphasise the crucial role the veterinary practitioner can play in both providing and using such evidence-based data. find out more about claire. view presentation slides comments: the use of an evidence based practice approach to promote active student engagement and life long learning in an online graduate certificate emma o'neill bsc, bvsc, phd1* 1university college dublin, school of agriculture, food science and veterinary medicine, belfield, dublin *corresponding author (emma.oneill@ucd.ie) vol 2, issue 2 (2017) published: 11 apr 2017 doi: 10.18849/ve.v2i2.108 educational research has realigned away from the delivery of information towards the enhancement of learning and construction of knowledge (edmondson, 2001). the availability of information is no longer the limiting factor; the ability to process and rationalise the vast amount of information available is now far more important. as suggested by alvin toffler, “the illiterate of the 21st century will not be those who cannot read and write, but those who cannot learn, unlearn and re-learn.” hence, it is important to consider ways to equip students with the skills for critical appraisal and life-long learning. teaching strategies that engender a deep approach to learning by promoting active student engagement are key to these aims. find out more about emma.  view presentation slides comments: effective dissemination building an 'evidence to impact' strategy dan o'neill mvb bsc(hons) gpcert(sap) gpcert(felp) gpcert(derm) gpcert(b&ps) msc(vetepi) phd mrcvs1 1veterinary epidemiology, economics and public health, the royal veterinary college, hertfordshire, al9 7ta, united kingdom *corresponding author (doneill@rvc.ac.uk) vol 2, issue 1 (2017) published: 22 feb 2017 doi: 10.18849/ve.v2i1.101 when a piece of ‘evidence’ is generated in the research environment and almost nobody hears about it, then can we really still call it a piece of ‘evidence’? does evidence only become evidence once it is used; and until then, is it just a piece of insignificant information? as we inexorably travel through the ebvm era, we must increasingly prioritise effective dissemination of evidence. this paper will use the vetcompass programme at the royal veterinary college as a case study to explore a strategic dissemination plan and examine routes for effective dissemination. this podcast is from dan's talk at the veterinary evidence today conference, edinburgh november 2, 2016. find out more about dan. view presentation slides comments: diagnostic accuracy: the wellspring of ebvm success, and how we can improve it david mills ma, vetmb, certavp(vc), mrcvs1* 1rspca, putney animal hospital, 6 clarendon dr, london, sw15 1aa *corresponding author (dmills@rvc.ac.uk) vol 2, issue 3 (2017) published: 04 aug 2017 doi: 10.18849/ve.v2i3.147 therapy and prognosis are entailed by the diagnosis: the holistic success of the ebvm approach therefore firmly and critically rests on diagnostic accuracy. unfortunately, medical professionals do not appear to be very accurate with diagnoses. in human medicine, there is 30-50% discordance reported between doctors’ ante(presumptive) and post-mortem (definitive) diagnoses, with no significant change in the last 100 years (goldberg et al 2002). veterinary surgeons do not perform much better, although it is a chronically under-researched area. this talk looks at how vets and vet nurses can maximise their impact on clinical performance. find out more about david. view presentation slides comments: finding the evidence clare boulton rcvs knowledge | head of library and information service vol 1, issue 1 (2016) published: 22 jan 2016 a slide-cast of clare boulton’s presentation from skills day 2015, london. which is more effective in altering the intra-gastric ph in dogs, omeprazole or ranitidine? a knowledge summary by adam swallow bvsc mrcvs 1* 1university of bristol, senate house, tyndall ave, bristol, bs8 1th *corresponding author (adam.swallow@bristol.ac.uk) vol 1, issue 2 (2016) published: 5 may 2016 reviewed by: nieky van veggel (msc) next review date: 5 may 2018 doi: 10.18849/ve.v1i2.14 clinical bottom line based on the current available evidence, omeprazole is the superior choice for raising intra-gastric ph. question in canine patients requiring suppression of gastric acid production, is ranitidine as effective as omeprazole in raising the intra-gastric ph? clinical scenario you are presented with a 7 year old male neutered labrador who has acute onset vomiting. the dog has previously been diagnosed with severe hip dysplasia with secondary osteoarthritis and is on long term oral meloxicam therapy. however, two weeks ago he began vomiting intermittently which has now progressed to haematemesis. you have provisionally diagnosed gastric ulceration whilst histopathology on your mucosal biopsies is pending. you wish to start the dog on a gastro-protectant. your practice has both ranitidine and omeprazole available but you are wondering which one would be best to use. the evidence the available evidence studied was generally well planned and consists of well-controlled studies. it is disappointing that no trials in a clinical setting were available, although it is appreciated that the phrasing of the pico could have affected this outcome. a repeat literature search looking for evidence of efficacy in terms of managing gastric lesions would be beneficial in this regard. whilst there is more evidence available evaluating the efficacy of omeprazole compared to ranitidine, in the majority of studies omeprazole emerged as the superior choice compared to ranitidine; the effect was more reliable and persisted for longer. whilst specific criteria for treating acid-related diseases are not published for the dog, unlike in human medicine, it would seem that omeprazole is the most likely candidate to achieve these requirements. summary of the evidence bersenas et al (2005) population: healthy intact beagles, bred for the purpose of the study. sample size: 12 intervention details: intra-gastric ph was measured continuously in 24hr periods, in both a fed and fasted state. they were then treated for 7 days with a gastric-acid suppressant (1 of 4 for a week, ultimately received all of the treatments) or saline control and gastric ph recorded on days 0, 2, 6. then the effect of omeprazole and famotidine combined was assessed. study design: randomised controlled trial outcome studied: aimed to determine the normal gastric secretion pattern of dogs and the degree of gastric acid suppression that could be achieved with 4 different agents. main findings (relevant to pico question): feeding resulted in a decreased gastric ph. omeprazole (1mg/kg) was given once a day orally, and ranitidine every 12 hours intravenously (2mg/kg). omeprazole did significantly suppress gastric acid secretion compared to saline, whereas ranitidine did not (mean gastric ph on day 2 2.53 for ranitidine, vs 3.86 for omeprazole and day 6 2.05 versus 4.09). omeprazole managed to maintain a gastric ph of >3 for 70.2% of the time on day 6, (66.9% on day 2) versus 37.2% of the time for ranitidine (44.6% for day2). drug carry-over effects were noted; these were reportedly adjusted for in the statistical analysis. omeprazole sodium bicarbonate suspension did cause vomiting and diarrhoea in 4/6 dogs (done separately to omeprazole tablet dosing). twice daily omeprazole was the only product that met criteria for permitting acid-relating injuries to heal as assessed using human criteria (ph >3-4 for >75% of the day). limitations: injectable drugs were blinded whereas omeprazole was not. omeprazole given orally, other agents were given iv. large age range in dogs existed. dose of omeprazole varied between dogs from 0.8-1.3mg/kg. other medicines were dosed accurately per kg bodyweight. no referenced compatibility studies used to adding saline to injectable solutions to make them 3ml in volume. only beagles used in the study; unknown if breed variations exist? discussed but did not test the theory of using ranitidine at a dosing frequency of q8hrs; in humans it has been shown to have a linear relationship between dosing and gastric acid suppression.  multiple confounding factors limit the usability of the obtained data. katz et al (1987) population: female mongrel dogs with either a chronic gastric fistula or a heidenhain pouch of the greater curvature of the stomach. sample size: n=5-7 intervention details: dogs had a single piece, plastic cannula inserted into a chronic gastric fistula along the greater curvature of the stomach. the fistula or the heidenhain pouch was created at least 4 weeks prior to any of the experiments. dogs were fasted overnight prior to any experiments but allowed free access to water. water was withheld on the day of the experiment. for the gastric fistula dogs: on the day of the experiment, the gastric content was drained and then basal secretions were collected for around 30 minutes. oral medications were given via the gastric cannula at a volume of 0.2ml/kg. intra-venous medications (compound dissolved in 0.1n hydrochloric acid) were given via a foreleg vein. after “oral” dosing, 30 minutes was allowed before gastric stimulation. however, following intra-venous injection gastric stimulation occurred straight away. gastric stimulation involved either: betazole hydrochloride (8mg/kg), tetragastrin (0.5mg/kg) or 2-deoxy-glucose (100mg/kg) were provided sub-cutaneously. these doses were designed to cause maximal gastric secretory activity. gastric secretions were collected via passive drainage every 30 minutes for 3 hours. volume of secretion, acid concentration and total acid output were calculated. prior to the experiment, control values for total acid output was determined for each dog. dogs were used no more than once a week for experiments. for the heidenhain pouch dogs: dogs were again fasted overnight before being placed in a sling on a pavlov stand and an intra-venous catheter was placed in the cephalic vein. maximal gastric secretion was stimulated with bethanecol (120ug/kg/hr) or histamine (50ug/kg/hr) in a volume of 30ml/hr. orf 17583 or its vehicle (0.5% carboxymethylcellulose for all compounds) was provided orally via gavage 30 minutes before the bethanecol or 75 minutes after the histamine infusion started. gastric content was collected via passive drainage every 15 or 30 minutes and secretion volume, acid concentration and total acid output was calculated. dogs with heidenhain pouch were also stimulated by means of a meal following an 18 hour fast, but only orf 17583 was assessed here. a total acid output of 450µeq was used to denote a 50% of maximal response in this study, based on previously published work. students t-test was used to compare the results with significance set at p <0.05. dose-response curves were created following gastric stimulation. study design: non-randomised controlled trial. outcome studied: to examine the gastric anti-secretory effect of orf 17583 in dogs and rats. in dogs, this effect was characterized against histaminergic and non-histaminergic stimulation. to compare the potency of orf 17583 to ranitidine, cimetidine, famotidine and omeprazole. to investigate the duration of the anti-secretory effect of orf 17583 in comparison to ranitidine. main findings (relevant to pico question): orf 17583 yielded marked gastric acid suppression against all secretagogues, nearing 100%. each of the other compounds markedly suppressed acid production in a dose-related manner. each compound was able to achieve marked acid suppression. the overall potency was famotidine= orf 17583= omeprazole > ranitidine > cimetidine. ranitidine was found to have a relatively good oral bioavailability of 2.4 (or 42%); determined by comparing the oral to the intra-venous potency ratio. a value of 1 indicated excellent bio-availability. after a supra-maximal dose of ranitidine (4mg/kg orally), marked acid suppression (>80% of supramaximal secretion) was noted 4 hours later. however, no effect was seen at 24 or 48 hours. ranitidine showed evidence of around 25% suppression of gastric acid output after 16 hours following betazole stimulation, down from >80% at 0.5 hours. limitations: this paper primarily looked at the effect of orf 17583 and not necessarily the effect of ranitidine compared to omeprazole. not all details of the results are presented here as they were not relevant to the pico. not all results were presented in written form, only in graphical form so understanding the exact effects is difficult. the exact number of dogs used in each experiment was not stated, merely a range of 57dogs. this is still a small number though. it would have been useful had the authors looked at the effect of a meal on all of the different compounds, not just orf 17583 as this method of stimulation is physiological and therefore more applicable to practice. again, this is not a clinical study and so the clinical relevance of these results is unclear. p-values are not presented in this paper for the dog results and so it is not known if the difference between the gastro-protectants used was significant or not. it is interesting that omeprazole was dissolved in a low concentration of acid as omeprazole is known to be unstable at low ph. however a marked effect on acid output would imply that this did not affect the omeprazole in this study. kromer et al (2000) population: male beagle dogs aged 2-8yrs sample size: unknown intervention details: gastric ph was monitored after being stimulated using either histamine or carbachol. the dogs received either pumaprazole iv, ranitidine iv or omeprazole per os (po). study design: controlled trial outcome studied: whether or not the medications had any effect on the intra-gastric ph. main findings (relevant to pico question): study found that whilst pumaprazole was the most effective, ranitidine resulted in mild elevations in gastric ph although there was marked variation in the effect seen. omeprazole was not really discussed, more it mentioned that the effects seen would likely be additive over a periods of 2-3days. limitations: numbers used were unknown. no blinding or randomisation was performed. no advanced statistical analysis was performed. only graphical results were shown, it was difficult to observe what the mean ph values were. discussion was not easy to follow. method of delivery of the drugs was not consistent. okabe et al (2001) population: male and female beagles with denervated gastric pouches (heidenhain pouch) sample size: n=10 intervention details: intra-gastric ph was measured in response to stimulation of acid production using either histamine, pentagastrin or carbachol. then various preparations of ant-acids were given and the intra-gastric ph was measured by serial cannula samples. study design: controlled laboratory trial. outcome studied: whether or not the intra-gastric ph could be affected, and therefore basal gastric acid secretion, by various pharmaceutical interventions. main findings (relevant to pico question): omeprazole was effective in reducing gastric acid secretion when applied locally to the heidenhain pouch, and also when given intra-venously. this effect seemed slightly improved with application prior to histamine infusion. ranitidine appeared to have no effect on histamine-stimulated gastric acid secretion when applied into the heidenhain pouches. higher doses appeared to be needed to be effective when using locally applied omeprazole vs. systemic therapy using omeprazole, the role of a topical effect of omeprazole on the apical cell border was proposed.  limitations: small numbers used, no study calculations performed. measurements made were not continuous, but intermittent sampling performed. did not take into account the time potentially needed for the agents to be effective. the time for which the effect persisted for however was measured. high doses of omeprazole were infused into the gastric pouch, beyond normal clinical doses. did not describe an effect of ranitidine given systemically. the published reports does not go into detail about the effect of ranitidine on intra-gastric ph when given systemically, it merely notes that it was effective in elevating the gastric ph. polentarutti et al (2010) population: male labrador/ labrador crosses 25-35kg in weight. sample size: n=4 intervention details: intra-gastric ph was monitored and chyme collected to monitor gastric emptying after either oral buffers or intra-venous pharmaceutical agents. study design: prospective experimental trial outcome studied: whether or not the agents of interest where able to consistently alter the gastric ph in fasted dogs. main findings (relevant to pico question): ranitidine was successful in raising the gastric ph to target level (>4) in all 8 experiments performed. average time to onset was 46 minutes (although each dog was quite variable) and lasted, on average, 86minutes. in the ranitidine experiments, the ph was >4 in 4/8 experiments at the start. for omeprazole, the target ph was <4 in 3/7 experiments. in 2/3 experiments a target of >4 was achieved, whilst in 1 the ph fell. the average duration of ph modification was 103mins, with an average time to onset of 50mins.  starting ph did not affect efficacy. authors concluded that omeprazole was more reliable and produced a better effect over ranitidine. limitations: very few dogs used in the study, authors did acknowledge this. no control agents were used, no advanced statistics were used to analyse the data. ph was not measured before administration of intra-venous agents, measurements began just after it was given. a set dose or ranitidine was used, whereas omeprazole was dosed according to body weight (50mg versus 1mg/kg).  stachura et al (1983) population: mongrel dogs weighing 1418kg with a gastric fistula and a denervated fundic pouch (heidenhain pouch). sample size: n= 4 intervention details: the gastric fistula was placed 6 months prior to the experiments. animals were fasted but had ad libitum water for at least 18 hours prior to each experiment (four experiment in total per dog). gastric fluid and mucosal samples were all collected via the gastric fistula. gastric acid stimulation was achieved using histamine, infused at 40ug/kg/hr to achieve 50% of maximal stimulation. omeprazole was given intra-venously at 1mg/kg either 30 minutes before or 60 minutes after starting the histamine stimulation. the omeprazole was dissolved in 5ml of 10mmol sodium bicarbonate, and then in saline. ranitidine was dissolved in 50ml of saline and provided intra-venously at 0.5mg/kg either 30 minutes before or 60 minutes after the start of the histamine infusion. multiple mucosal samples were obtained using biopsy forceps via the gastric fistula 30 and 60 minutes after the administration of either omeprazole or ranitidine. these were obtained from the fundic gland area. during histamine infusion, mucosal samples were collected 60minutes after the start of the infusion of histamine alone or histamine combined with either omeprazole or ranitidine. samples were then washed of all mucous in saline before being fixed for histological and ultra-structural examination with electron microscopy. for the ultra-structural assessment, a semi-quantitative assessment using the previously published scale by fallenius et al (1981, 1982). data was represented as mean ±sd of 1525 measurements. this scale was: 0= resting, 1= half-stimulated, 2= fully stimulated cells. gastric secretions were collected continuously via the gastric fistula and heidenhain pouch. these were vided into aliquots every 15 minutes. gastric secretory volume and acid output were calculated and presented as 30 minute outputs as a mean± sem. a t-test was used to compare the mean responses to histamine alone and to pre-treatment or to combination of histamine with omeprazole/ ranitidine. significance was regarded as p <0.05. study design: non-randomised, controlled trial. outcome studied: to compare the anti-secretory effects on the stomach of omeprazole and ranitidine. also, to compare the effect on the morphological appearance of the parietal cells of the stomach following histamine stimulation before and during treatment with either omeprazole or ranitidine. main findings (relevant to pico question): the gastric fistula was placed 6 months prior to the experiments. animals were fasted but had ad libitum water for at least 18 hours prior to each experiment (four experiment in total per dog). gastric fluid and mucosal samples were all collected via the gastric fistula. gastric acid stimulation was achieved using histamine, infused at 40ug/kg/hr to achieve 50% of maximal stimulation. omeprazole was given intra-venously at 1mg/kg either 30 minutes before or 60 minutes after starting the histamine stimulation. the omeprazole was dissolved in 5ml of 10mmol sodium bicarbonate, and then in saline. ranitidine was dissolved in 50ml of saline and provided intra-venously at 0.5mg/kg either 30 minutes before or 60 minutes after the start of the histamine infusion. multiple mucosal samples were obtained using biopsy forceps via the gastric fistula 30 and 60 minutes after the administration of either omeprazole or ranitidine. these were obtained from the fundic gland area. during histamine infusion, mucosal samples were collected 60minutes after the start of the infusion of histamine alone or histamine combined with either omeprazole or ranitidine. samples were then washed of all mucous in saline before being fixed for histological and ultra-structural examination with electron microscopy. for the ultra-structural assessment, a semi-quantitative assessment using the previously published scale by fallenius et al (1981, 1982). data was represented as mean ±sd of 1525 measurements. this scale was: 0= resting, 1= half-stimulated, 2= fully stimulated cells. gastric secretions were collected continuously via the gastric fistula and heidenhain pouch. these were vided into aliquots every 15 minutes. gastric secretory volume and acid output were calculated and presented as 30 minute outputs as a mean± sem. a t-test was used to compare the mean responses to histamine alone and to pre-treatment or to combination of histamine with omeprazole/ ranitidine. significance was regarded as p <0.05. limitations: this is not a physiological study and used only 1 type of secretagogue. therefore the clinical applicability should be interpreted with caution. statistical analysis was not performed and so it is difficult to know whether or not the difference between omeprazole and ranitidine was significant. only a small number of dogs were used in this study and the breed used was not stated. baseline data was not presented, even though it is stated to be negligible the actual values would be useful. whether any of the dogs required sedation was not clarified; this might have affected the results. the authors state they aimed for 50% of maximal secretion, but how this value was arrived at was not discussed. appraisal, application and reflection the trials were all very specific in their objectives and the measurement of gastric ph often used similar methods. however, not many of the studies evaluated the response to stimulation with food material, so whilst the effects on acid secretion following chemical stimulation are clear, it has not completely proven that these effects are the same when stimulated with a food material. for clarity, the full reference for the scale (fallenius et al, 1981, 1982) referred to by stachura et al (1983) is included in the reference list despite the actual paper not being reviewed for the knowledge summary should any readers wish to investigate this further. finally, in this summary only papers in which the effects of both ranitidine and omeprazole were compared were investigated. there are several other papers which investigated the efficacy of these compounds in various settings, either in isolation or in combination with alternative gastro-protectants. however, to investigate these further is deemed to be outside the scope of the current pico although there is definitely the potential for either a systematic review or a meta-analysis which would likely enhance our current understanding of gastro-protectants in the dog. methodology section search strategy databases searched and dates covered: the search string was applied to the cab abstracts and pub med databases searching from january 1973 to january 2016. search terms: (dog or dogs or canine or bitch or bitches or puppy or puppies) and (omeprazole or gastroguard or losec or zantac or ranitidine) and (ph or acid). dates searches performed: monday 18th january 2016 exclusion / inclusion criteria exclusion: single-case reports, or articles in which the effect of both omeprazole and ranitidine in the intra-gastric ph (either directly or indirectly) in dogs was not evaluated, or articles where the full text could not be located, or were not available in english. inclusion: journal articles published between 1973 and the present, which specifically investigated and compared the effect of both omeprazole and ranitidine on the intra-gastric ph in dogs (either directly or indirectly). both clinical and laboratory studies were considered. search outcome database number of results excluded – nonenglish language publication excluded – single case report/ book chapter/ conference proceedings/ review articles etc. excluded – not relevant to the pico total relevant papers ncbi pubmed 266 0 08 252 6 cab abstracts 33 0 3 30 0 total relevant papers when duplicates removed 6 conflict of interest the author declares no conflict of interest. references bersenas, a.m.e. et al. (2005) effects of ranitidine, famotidine, pantoprazole, and omeprazole on intragastric ph in dogs. american journal of veterinary research, 66 (3), pp. 425-431 http://dx.doi.org/10.2460/ajvr.2005.66.425     fallenius, e. et al. (1981) substituted benzimidazoles inhibit gastric secretion by blocking h+/ k+atpase. nature 29:159161 http://dx.doi.org/10.1038/290159a0  fallenius, e. et al. (1982) inhibition of acid secretion in isolated gastric glands by substituted benzimidazoles. american journal of physiology 243: g505g510.  katz, l.b.tobia, a.j. and shriver, d.a. (1987) effects of orf 17583, other histamine h2-receptor antagonists and omeprazole on gastric acid secretory states in rats and dogs. journal of pharmacology and experimental therapeutics, 242 (2), pp. 437-42. kromer, w. postius, s. and riedel, r. (2000) animal pharmacology of reversible antagonism of the gastric acid pump, compared to standard antisecretory principles. pharmacology, 60 (4), pp. 170-187 http://dx.doi.org/10.1159/000028367  okabe, s. shimosako, k. and amagase, k. (2001) pharmacological regulation of gastric acid secretion in the apical membrane of parietal cells; a new target for antisecretory drugs. journal of physiology and pharmacology, 52 (4 pt 1) pp. 639-56. polentarutti, b. et al. (2010) modification of gastric ph in the fasted dog. journal of pharmacy and pharmacology, 62 (4), 462-469 http://dx.doi.org/10.1211/jpp.62.04.0008  stachura, j. et al. (1983) comparison of the effect of omeprazole--a substituted benzimidazole--and ranitidine--a potent h2-receptor antagonist--on histamine-induced gastric acid secretion and the ultrastructure of canine parietal cells. hepatogastroenterology, 30 (5), pp. 205-10. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. distal tarsal joints osteoarthritis: evidence behind bisphosphonates and nsaids to improve lameness a knowledge summary by julia dubuc dmv, dés, dacvs-la, m.sc, mrcvs 1* 1university of nottingham, sutton bonnington campus, sutton bonnington, leicestershire, le12 5rd *corresponding author (julia.dubuc@nottingham.ac.uk) vol 5, issue 1 (2020) published: 28 feb 2020 reviewed by: michael schoonover (dvm, ms, dacvs-la, dacvsmr) and elisabeth swann (bsc, pgcert, ma) next review date: 25 july 2020 doi: 10.18849/ve.v5i1.204 pico question in lame horses affected by osteoarthritis of the distal tarsal joints (bone spavin), are bisphosphonates more effective than nsaids in long-term alleviation of lameness?   clinical bottom line category of research question treatment the number and type of study designs reviewed two papers were critically reviewed. there was one field study and a multicentric randomised double-blind placebo control study strength of evidence weak outcomes reported each study looked at the effect of either tiludronate or firocoxib on alleviation of tarsal lameness. both tiludronate and firocoxib, while administered independently, provided some degree of relief (for up to 120 days) and improved the lameness related to tarsal osteoarthritis conclusion since no study was found to directly compare the use of non-steroidal anti-inflammatory drugs and bisphosphonates and that none evaluate the long-term effects of these treatment options on lameness, it is not possible to recommend one treatment option over the other to alleviate lameness caused by tarsal osteoarthritis in horses   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are presented with an 18-year-old retired 3 star eventer, predominantly used now for low level work in the manège. the owner reports the horse lacks impulsion prior to jumping and that he now engages both hindlimbs much less under saddle. on lameness exam, no proper lameness is observed, but the full flexion of both hindlimbs is clearly positive. you elect to perform bilateral tarsal radiographs, which highlight periarticular osteophytes over the dorsomedial aspect of both the distal intertarsal and tarsometatarsal joints. on the dorsoplantar view, some lysis of these joint spaces is observed and is surrounded by sclerosis. you diagnose the horse with bilateral osteoarthritis (oa) of the distal tarsal joints. the evidence only two relevant studies were identified, one of which is a field study with no mandatory radiographs required to enter the study, indicating the horses included were not necessarily diagnosed with distal tarsal joints oa. the second study is a randomised double-blind placebo control study, but it was not entirely blinded. the level of evidence of the studies summarised below is low regarding the use of bisphosphonates as a treatment for distal tarsal joint oa. there is a more substantial body of literature focusing on the use of bisphosphonates as a treatment of navicular syndrome in horses. there is no study in the literature providing a direct comparison of non-steroidal anti-inflammatory drugs (nsaids) and bisphosphonates for the long-term alleviation of lameness related to distal tarsal joints oa and for navicular syndrome. summary of the evidence orsini et al. (2012) population: horses from 25 states in the usa. age: mean 13.3 years old (yo) (range 18 months–32 yo) breeds: quarter horse (qh) and thoroughbred (tb) = > 50% of population others: standardbred (stb), appaloosa, tennessee walking horse, crossbreeds inclusion criteria: > 1 yo lameness and signs of pain attributed to oa lameness at least moderate (grades 2–4/5 american association of equine practitioners (aaep) lameness scale) lameness duration of at least 4 weeks sample size: initial n=467 enrolled final n=390 were included for analyses intervention details: for each horse: firocoxib paste, 0.1 mg/kg, per os (po), once a day (sid) for 14 consecutive days (day 1 to 14 included). three scheduled examinations (including lameness) by attending veterinarian: day 0 day 7 day 14 caregivers daily interpretation of the horse’s lameness status (as well as palatability and convenience of administration) was recorded on a lameness form (for each of the 14 days) study design: field study outcome studied: subjective assessment of the lameness by a veterinarian on day 7 and 14, using the aaep lameness scale scoring guide. main findings (relevant to pico question): initial diagnosis of oa: lameness at day 0 (starting lameness): 155/390 (39.7%) had grade 2/5 lameness 160/390 (41%) had grade 3/5 lameness 75/390 (19.2%) had grade 4/5 lameness no horses with a grade 5/5 lameness oa related radiographic findings: 193/390 (49.5%) = multiple joints involved 197/390 (50.5%) = single joint involved of these, 79/197 (40%) had distal tarsal joints (tarsometatarsal and distal intertarsal joints involved) lameness at day 7: vets noted 275/390 (70.5%) improved ³ 1 grade caregivers noted that 297/390 (76.2%) improved lameness at day 14: vets noted 316/390 (81%) improved 6% of caregivers that responded noted an improvement in gait complete resolution of lameness at day 14: 28/78 (36%) of horses which started with a grade 2/5 21/155 (13.5%) of horses which started with a grade 3/5 9/157 (5.7%) of horses which started with a grade 4/5 limitations: no details on lameness examinations (particularly response to hindlimb flexions or response to diagnostic anaesthesia) radiographic confirmation of primary diagnosis oa was advised but not mandatory no numbers confirming how many horses were explicitly diagnosed with oa no placebo paste group the medication dose was based on an estimated weight only and therefore imprecise no categorisation detailing the effect of firocoxib between oa joints do not know if firocoxib is more effective in carpi compared to tarsi or fetlocks for example many biases are present in that study (namely, no control group and not blinded) no information on level of activity of the horses, neither prior nor during the study period no subsequent follow-up of lameness after 14 days incongruity between number of horses with grade 2-3-4 lameness between publication sections as a result, percentages regarding complete resolution of lameness are misleading unclear if horses with a grade 1/5 lameness were included not mentioned as a starting lameness but is mentioned in results somehow gough et al. (2010) population: adult horses from 13 centres and multiple countries age: mean 11 yo (range 5–20 yo) weight: mean 540.2 kg (range 304–748) inclusion criteria: 6 weeks to 1 year spontaneous lameness horses with walking + ³ 30 minute of trot per day lameness score of lamest limb ³ 3 after intra-articular (ia) analgesia of tarsometatarsal or centrodistal joints positive intra-articular ia analgesia (³ 50 % improvement) for centrodistal or tarsometatarsal joints radiographic signs of oa on 1 or more of the 4 standard tarsal views of lamest hindlimb: joint space narrowing, lytic lesions, sclerosis, thickening of subchondral bone and new bone proliferation sample size: initial n=108 enrolled final n=87 were included for analyses intervention details: horses divided in to two groups: tiludronate (t), n=42, 1 mg/kg placebo (p), n=45 treatment/placebo administered intravenously (iv) in 1l bag of saline over 30 minutes three scheduled examination by veterinarian: day 0 day 60: ia analgesia of least lame limb repeated + scoring of lamest limb* day 120: ia analgesia of least lame limb repeated + scoring of lamest limb* *if lamer than before, distal tarsal ia block repeated + tarsus radiographs nsaids use was allowed for lameness or other concurrent disease, but a 15 day wash out period was mandatory prior to next examination by the veterinarian no rest during the study period as owners were advised to gradually increase their horses’ level of exercise study design: randomised double-blind placebo control study multicentric (13 centers) and multinational outcome studied: lameness scores at day 60 and 120 compared to day 0 0–10 wyn-jones lameness grading scale main findings (relevant to pico question): significant treatment effect in favour of tiludronate the higher the lameness score at day 0, the higher the score at day 60 (covariate baseline significant) at day 60, lameness scores of group t < p group t: 4.5 ±1 (day 0) vs 2.6 ± 1.7 (day 60) group p: 4.5 ±0 (day 0) vs 3.3 ± 2.0 (day 60) at day 60, no difference in lameness between groups associated to nsaids use at day 120, significant improvement in lameness for group t in horses with peri-articular osteophytes, mean lameness score was lower in group t vs p significant difference in mean body weight between groups (tiludronate: 521 kg; placebo: 568 kg) limitations: no subsequent follow-up of lameness after 4 months lameness evaluations are extremely subjective and was evaluated by multiple different individuals use of nsaids was permitted during the clinical trial not a fully double-blind placebo control study at day 60, horses with inadequate response could be treated with tiludronate unclear if this includes placebo only cases or if tiludronate horses had a second dose then no exercise protocol established for the study period and left at the attending clinicians discretion despite this, statistical analyses and conclusions are drawn about improvement of exercise during the study no objective measure of tiludronate effect: unclear if tarsal radiographs were repeated at day 60/120 no subsequent follow-up of lameness after 4 months appraisal, application and reflection there is no prospective clinical study comparing the effects of nsaids versus bisphosphonates on improvement of lameness related to bone spavin in horses. there are two generations of biosphosphonates. the early generation, contains nitrogen and includes tiludronate and clodronate, which are considered less potent. the latest generation comprises pamidronate and zoledronate and are highly potent. there are more publications looking into bisphosphonates as a treatment for navicular disease (denoix, j. m. et al., 2003; dyson, s. j. et al., 2005; mitchell, a. et al., 2019; and whitfield, c.t. et al., 2016), but the work of gough et al. (2010) appears to be the only publication found by the author on the use of bisphosphonates as a treatment for bone spavin in horses. a review of the efficacy of tiludronate in horses (kamm, l. et al., 2008) mentions several smaller studies, namely a case series (riccio, b. et al., 2002) and clinical observations (dyson, s. j. et al., 2004) that were never officially published. none of these provide sufficient evidence that bisphosphonates are truly beneficial in cases of distal tarsal joints oa. in both of the publications presented here, lameness is used as the principal outcome evaluated to determine if either firocoxib or tiludronate are effective in improving the lameness of the horses with distal tarsal joints oa. as lameness evaluation is a very subjective process and taken together with the fact both studies are “multicentric”, the accuracy of the outcome evaluation is questionable. unlike more recent studies on the topic (mitchell, a. et al. 2019 and whitfield, c.t. et al. 2016), no inertial sensor system nor ground-mounted stationary force plate system was employed. further publications with more objective lameness evaluations and other measured outcomes are needed. for example, in a similar study comparing the efficacy of phenylbutazone versus firocoxib in horses with naturally occurring osteoarthritis (doucet, m. y. et al., 2008), lameness was used as the outcome evaluated, as well as other more objective measures: reaction to manipulation/joint flexion, joint swelling, joint circumference and range of motion. in the study by orsini et al. (2012), the lamenesses were graded on the aaep lameness scale (grade 0–5) by a veterinary surgeon on days 0, 7 and 14, but were also graded by the horses’ caregivers on days 7 and 14. as there was no placebo or control group in this study, none of these individuals were blinded and all were aware the horse was under treatment with firocoxib. in the study by gough et al. (2010), the lameness was graded on a scale of 0-10 by a veterinary surgeon on days 0, 60 and 120 in a randomised double-blind placebo control study. however, the authors state that horses not responsive to treatment at day 60 could receive the standard dose of tiludronate at that time, voiding the double-blind aspect of the study design. these breaches in study designs introduce biases, namely in the assessment of the lameness and this greatly impacts on the reliability of the results. interestingly, the author only found the study from orsini et al. (2012) looking at firocoxib as an nsaid medication for distal tarsal joints oa and “none” using phenylbutazone. the study from orsini et al. (2012) is in fact a clinical trial investigating the efficacy of firocoxib in management of musculoskeletal pain and lameness associated with osteoarthritis. while 197/390 (50.5%) of the horses had signs of musculoskeletal pain or lameness associated with one joint, 79/197 (40.1%) of these were thought to involve the tarsus (radiographs were not mandatory to confirm the diagnosis). the results are presented in such a way that it is not possible to determine how many of these horses affected with tarsal oa really improved because of firocoxib administration. the authors report 80% improvement of lameness overall after 14 days. in a very similar study (doucet, m. y. et al., 2008), published prior to the above mentioned, there was no difference in lameness scores between the firocoxib group (0.1 mg/kg, po, sid for 14 days) and the phenylbutazone group (4.4 mg/kg, po, sid for 14 days) for pain related to naturally occurring osteoarthritis (which was confirmed radiographically prior to entering the study). in the latter as in the former, there is no clear groups separating the effect of each nsaids on horses affected by tarsal oa compared to any other degenerative joint disease. however, the author chose not to present the work of doucet here as all horses fell under one large category: naturally occurring oa. based on the current literature, there is insufficient evidence to advocate for the use of nsaids more than bisphosphonates or the contrary for the treatment of distal tarsal joints oa in horses. the longest follow-up period was 4 months in the study from gough et al. (2010) and 2 weeks for orsini et al. (2012). there is a need for a prospective double-blind clinical trial including one bisphosphonates group, one nsaid group and one control group with long-term follow-up of the horses lameness as well as other more objective outcomes. for an overview of the efficacy and effects of bisphosphonates in horses with navicular disease, the reader can consult recent publications, including different administration routes: im (mitchell, a. et al. 2019), iv or intravenous regional limb perfusion (iv-rlp) (whitfield, c.t. et al. 2016; schoonover, m.j. et al. 2019). methodology section search strategy databases searched and dates covered: cab abstracts 1973 to week 28 2018 pubmed ncbi 1910 to week 28 2018 search strategy: cab abstracts equine or equines or horse or horses or equus or equid or equids or mare or mares or broodmare or broodmares or pony or ponies or filly or fillies or colt or colts or yearling or yearlings or stallion or stallions or thoroughbred or thoroughbreds or standardbred or standardbreds or racehorse or racehorses or "race horse" or "race horses" or exp horses/ or exp equus/ or exp equidae/ or exp mares/ or exp colts/ or exp foals/ or exp stallions/ or exp thoroughbred/ or exp racehorses/ arthritis or arthritic or arthritogenic or arthritical or osteoarthritis or osteoarthritic or osteo-arthritis or osteo-arthritic or synovitis or "joint disease" or "joint diseases" or oa or djd or osteoarthrosis or osteo-arthrosis or lame or lameness or spavin or gait or exp osteoarthritis/ or exp arthritis/ or exp joint diseases/ tarsal or tarsals or tarsale or tarsometatarsal or tarsometatarsus or tarsometatarsals or tarso-metatarsal or tarso-metatarsals or carpus or carpuses or carpometacarpal or carpometacarpals or carpo-metacarpal or carpo-metacarpals or hock or hocks or carpal or carpals or exp tarsus/ or exp carpus/ bisphosphonate or bisphosphonates or biphosphonate or biphosphonates or bisphosponate or bisphosponates or biphosponate or biphosponates or disphosponate or disphosponates or diphosphonate or diphosphonates or diphosponate or diphosponates or disphosphonate or disphosphonates or osphosreg or tiludronate or tiludronic or tildren or tildrenreg or clodronate or clodronic nsaid or nsaids or "non steroidal anti inflammatory" or "non steroidal anti inflammatories" or "non steroidal antiinflammatory" or "non steroidal antiinflammatories" or "nonsteroidal anti inflammatory" or "nonsteroidal anti inflammatories" or "nonsteroidal antiinflammatory" or "nonsteroidal antiinflammatories" or phenylbutazone or phenylbutazones or pbz or firocoxib or firocoxibs or firo or cox-2-selectives or cox-2-selective or exp antiinflammatory agents/ or exp non-steroidal antiinflammatory agents/ 1 and 2 and 3 and (4 or 5)   pubmed equine or equines or horse or horses or equus or equid or equids or mare or mares or broodmare or broodmares or pony or ponies or filly or fillies or colt or colts or yearling or yearlings or stallion or stallions or thoroughbred or thoroughbreds or standardbred or standardbreds or racehorse or raceshorses arthritis or arthritic or arthritogenic or arthritical or osteoarthritis or osteoarthritic or osteo-arthritis or osteo-arthritic or synovitis or "joint disease" or "joint diseases" or oa or djd or osteoarthrosis or osteo-arthrosis or lame or lameness or spavin or gait tarsal or tarsals or tarsale or tarsometatarsal or tarsometatarsus or tarsometatarsals or tarso-metatarsal or tarso-metatarsals or carpus or carpuses or carpometacarpal or carpometacarpals or carpo-metacarpal or carpo-metacarpals or hock or hocks or carpal or carpals bisphosphonate or bisphosphonates or biphosphonate or biphosphonates or bisphosponate or bisphosponates or biphosponate or biphosponates or disphosponate or disphosponates or diphosphonate or diphosphonates or diphosponate or diphosponates or disphosphonate or disphosphonates or osphosreg or tiludronate or tiludronic or tildren or tildrenreg or clodronate or clodronic nsaid or nsaids or "non steroidal anti inflammatory" or "non steroidal anti inflammatories" or "non steroidal antiinflammatory" or "non steroidal antiinflammatories" or "nonsteroidal anti inflammatory" or "nonsteroidal anti inflammatories" or "nonsteroidal antiinflammatory" or "nonsteroidal antiinflammatories" or phenylbutazone or phenylbutazones or pbz or firocoxib or firocoxibs or firo or cox-2-selectives or cox-2-selective 1 and 2 and 3 and (4 or 5) dates searches performed: 25/7/2018 and 27/7/2018 exclusion / inclusion criteria exclusion: articles not relevant to pico question carpal joints induced arthritis ex vivo research conference papers/proceedings not published/review paper publications in other languages than french or english inclusion: relevant to pico question tarsal joints/hocks oa bisphosphonates/tildren/tiludronate/clodronate/ nsaids search outcome database number of results excluded – other languages excluded – not relevant to pico excluded – duplicates excluded – conference papers or proceedings not published, book chapters total relevant papers cab abstracts 72 10 50 0 10 2 pubmed 45 1 23 21 0 0 total relevant papers 2 conflict of interest the author declares no conflicts of interest. references denoix, j.m., thibaud, d. & riccio, b. tiludronate as a new therapeutic agent in the treatment of navicular disease: a double‐blind placebo‐controlled clinical trial. equine veterinary journal. 2003; 35(4): 407–13. doi: https://doi.org/10.2746/042516403776014226 dyson, s. are there any advances in the treatment of distal hock joint pain? proceedings international symposium on diseases of the icelandic horse, 2004. dyson s.j., murray r. & schramme m.c. lameness associated wth foot pain: results of magnetic resonance imaging in 199 horses (january 2001–december 2003) and response to treatment. equine veterinary journal. 2005; 37: 113–121. doi:  https://doi.org/10.2746/0425164054223804 gough, m.r., thibaud, d. & smith, r.k. tiludronate infusion in the treatment of bone spavin: a double blind placebo-controlled trial. equine veterinary journal. 2010; 42(5): 381–7. doi: https://doi.org/10.1111/j.2042-3306.2010.00120.x kamm, l., mcilwraith, w. & kawcak, c. a review of the efficacy of tiludronate in the horse. journal of equine veterinary science. 2008; 28(4): 209–14. doi: https://doi.org/10.1016/j.jevs.2008.02.007 riccio, b., thibaud, d. & denoix, j.m. a double-blind placebo-controlled trial of tiludronate in the treatment of bone spavin. beva congress; 2002. doucet, m.y., bertone, a.l., hendrickson, d., hughes, f., macallister, c., mcclure, s., reinemeyer, c., rossier, y., sifferman, r., vrins, andre a., white, g., kunkle, b., alva, r., romano, d. & hanson, p.d. comparison of efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis. journal of the american veterinary medical association. 2008; 232(1): 91–7. doi: https://doi.org/10.2460/javma.232.1.91 orsini, j.a., ryan, w.g., carithers, d.s. & boston, r.c. evaluation of oral administration of firocoxib for the management of musculoskeletal pain and lameness associated with osteoarthritis in horses. american journal of veterinary research. 2012; 73(5): 664–71. doi: https://doi.org/10.2460/ajvr.73.5.664 mitchell, a., wright, g., sampson, s.n., martin, m., cummings, k., gaddy, d. & watts, a.e. clodronate improves lameness in horses without changing bone turnover markers. equine veterinary journal. 2019; 51: 356–63. doi: https://doi.org/10.1111/evj.13011  whitield, c.t., schoonover, m.j., holbrook, t.c., payton, m.e. & sippel, k.m. quantitative assessment of two methods of tiludronate administration for the treatment of lameness caused by navicular syndrome in horses. american journal of veterinary research. 2016; 77(2): 167–73. doi: https://doi.org/10.2460/ajvr.77.2.167  schoonover, m.j., whitield, c.t., young, j.m., sippel, k.m. & payton, m.e. quantitative assessment of intravenous regional limb perfusion of tiludronate as an adjunctive treatment for lameness caused by navicular syndrome in horses. american journal of veterinary research. 2018; 79(12): 1313–1320. doi: https://doi.org/10.2460/ajvr.79.12.1313  acknowledgement rcvs knowledge was supported in producing this knowledge summary by an educational grant from petplan charitable trust. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. erratum to: does adding transdermal nitroglycerine to other therapies used for management of left-sided congestive heart failure in dogs speed the resolution of clinical signs? jenefer r stillion dvm, dacvecc1 søren r boysen dvm, davecc2* 1western veterinary specialist and emergency centre, calgary, canada 2department of veterinary clinical and diagnostic sciences, faculty of veterinary medicine, university of calgary, calgary, canada *corresponding author (srboysen@ucalgary.ca) vol 3, issue 1 (2018) erratum published: 01 feb 2018 original paper published: 12 dec 2017 the original article was published in veterinary evidence vol 2, issue 4 (2017): http://dx.doi.org/10.18849/ve.v2i4.115 doi: 10.18849/ve.v3i1.168 erratum unfortunately the original version of the article had the following two errors. within the exclusion/inclusion criteria table the inclusion section was changed from: transdermal, or cutaneous, or ointment, and dog or dogs or canine or bitch* or canis or bitches and heart or cardiac or chf or cardio* or left ventricular or left ventricle* or lv or heart diseases or cardiovascular diseases and glyceryl trinitrat* or glyceryltrinitrat* or trinity glycerin* or nitro glycerin* or nitroglycerin* to: any relevant primary veterinary research or systematic review which compared transdermal nitroglycerine to other therapies to answer the following question; “does adding transdermal nitroglycerine to other therapies used for management of left-sided congestive heart failure in dogs speed the resolution of clinical signs?”  this error was in both the html and pdf versions. this has now been updated in both the html and pdf versions.   within the search outcome table for ncbi pubmed the number of results under ‘excluded did not address the pico’ was incorrectly inputted as 10. the number should have been 6. this error was in the html version only. this has now been updated in the html version. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. are old dogs who undergo total hip replacement more predisposed to perioperative femoral fractures than young dogs? a knowledge summary by valentine jacot dvm1* 1vetsuisse faculty university of zurich rämistrasse 71, 8006 zürich, switzerland *corresponding author (vjacot@vetclinics.uzh.ch) vol 1, issue 2 (2016) published: 22 june 2016 reviewed by: nina kieves (dvm, dacvs-sa, dacvsmr) next review date: 20 jan 2018 doi: 10.18849/ve.v1i2.28 clinical bottom line there is currently insufficient evidence that old dogs undergoing total hip replacement are more predisposed to perioperative femoral fractures in comparison to young dogs. question are old dogs undergoing total hip replacement more predisposed to perioperative femoral fracture in comparison to young dogs? the evidence by reviewing the veterinary literature relative to the general complications and outcomes of total hip arthroplasty, a variation in the prevalence of femoral fractures was noticed. regarding the design of these studies, the level of evidence provided is weak. currently, there are insufficient strongly convincing studies in the veterinary literature. summary of the evidence liska (2004) population: client-owned dogs. sample size: 22 dogs (n=22) with 24 femoral fractures (n=24) intervention details: two surgeons at different hospitals performed the same technique of modular hip replacement with cemented total hip replacement (thr) (biomedtrix). one surgeon performed 20 of the thrs. for two dogs, thr was performed at other hospitals using the same technique and system. 1) fracture groups 2) non-fracture groups medical records evaluated: radiographs ventrolateral and mediolateral of the affected femur. preand postop during follow-up visits, fracture healing, and periodically after fractures were healed until either the patient died or the study ended. evaluated/identified interval between thr and femur fracture, orientation of fracture lines, events that occurred at fracture and treatment methods. patient information fixation method, joint alignment, bone healing implant integrity, bone-cement interface, implant-cement interface. limb function evaluated by examination and client interview and classified as either normal or good. mean, median and range of numerical values were calculated for variables such as age, body weight, body score, bone healing and follow-up intervals. t-tests to compare fracture group and non-fracture group. study design: retrospective observational case-control study. outcome studied: objective: to report femur fracture as a complication of thr and to report the incidence, predisposing factors, treatment options and outcome. main findings (relevant to pico question): overall incidence of femur fracture after thr: 2.9%. age at thr dogs that had femur fractures were significantly older (7.4 years) at thr than dogs that did not sustain femur fractures (4.9 years) (p=0.0063). predisposing factors osteopathy (n=5) iatrogenic fissures created during reaming (n=9) and previous hip surgery. fracture characteristics fracture occurrence 22 after original thr, 1 after revision, 1 after explanation: traumatic events in 17 dogs osteopathy present at thr in 5 dogs cortical thinning secondary to aseptic loosening in 3 dogs fracture treatment: plate and screw fixation (10 with and 7 without cerclage wires) resulted in the most favourable outcome healing occurred in 6-10 weeks full cerclages wires in 3 dogs strict confinement in 3 dogs euthanasia in 1 dog outcome: 22 fractures healed and there were no non-unions two fractures that did not heal: 1 dog died 16 days after surgery of an unrelated illness and 1 dog was euthanised without treatment 20 clients with a dog with a healed fracture were interviewed > 65 days after surgery: 12 dogs were alive at the end of the study 15 clients (75%) reported normal limb function and 5 (25%) reported good limb function old dogs with osteopathies, dogs that have had previous hip surgery, and dogs that have intraoperative fissures should be recognised as potentially being at greater risk of femoral fracture. limitations: retrospective study different surgeons, different hospitals surgeon experience was not evaluated as a risk factor different follow-up 10 dogs (45.5%) with fractures were followed until death client interview ganz et al (2010) population: client-owned dogs. sample size: 74 dogs (n=74), 84 total hip arthroplasty (tha) (n=84) intervention details: two different surgeons performed the same technique and modular hip replacement using bfx (biomedtrix) from two referral hospitals. 1) fracture group (n=11) 2) non-fracture group (n=73) inclusion criteria cases with preoperative, immediate postoperative and initial follow-up radiographs. exclusion criteria dogs without complete surgery reports, dogs in the non-fracture group without documentation of absence of femoral fracture on recheck radiographs at least 4 weeks postoperatively. dog factors analysed age, breed, sex, weight, canal flare index (cfi), indication for arthroplasty, intraoperative fissure, cerclage usage, implant size. statistical analysis: preliminary univariate tests were performed and any factors with p>.30 were excluded for further consideration continuous variables: non parametric wilcoxon’s rank sum test binary variables: fisher’s exact test factors included for multicollinearity were entered in to the logistic equation previously deleted factors were singly added to the final model to reassess significance study design: retrospective observational cases cohort study. outcome studied: to evaluate risk factors for femoral fracture after porous-coated cementless tha. main findings (relevant to pico question): incidence femoral fracture: documented postoperatively 13.1% (11 of 84) with complete statistical analysis 13.5% (7 of 52) this is higher than previously reported. it may partially represent a selection bias (dogs with complications are more likely to be seen for follow-up) and patients operated during the earlier part of the period were more likely to have incomplete medical records, this resulted in the exclusion of 12 dogs in the non-fracture group. dog factors: age was positively associated with femoral fracture. mean dog age was 7.3±0.69 years for fracture group and 4.77±0.37 years for non-fracture group (p=0.022). cfi was negatively associated with fracture. mean cfi was 1.80±0.09 for the fracture group and 1.98±0.04 for the non-fracture group (p=0.045). body weight, intraoperative fissure, cerclage use, implant size, position and canal fill did not influence the occurrence of femoral fracture. operative factors indications for tha: coxofemoral osteoarthritis (oa) secondary to canine hip dysplasia (chd) (n=78) traumatic craniodorsal coxofemoral luxation (n=4) coxofemoral oa secondary to capital physeal fracture (n=1) femoral neck fracture malunion (n=1) intraoperative fissures reported in 3 cases. none of these dogs had femoral fractures. all fissures were addressed with cerclage wires. radiographic evaluation none of the measures of implant positioning or canal fill were associated with risk of femoral fractures. limitations: retrospective study small number of dogs in the fracture group (may have led to type ii error) different surgeons with 2 slightly different methods, 2 different hospitals and surgeon experience was not evaluated as a risk factor partial selection bias possible quality of radiographic positioning varied among patients radiographs not evaluated from a board diplomate in radiology canal flare index (cfi) not always available length of radiographic and clinical follow-up varied body score missing hummel et al (2010) population: client-owned dogs that underwent zurich cementless thr. sample size: 163 dogs (n=163) intervention details: inclusion criteria at least 8 weeks of documented postoperative radiographic and orthopaedic evaluations. exclusion criteria thr performed as the second procedure in dogs operated bilaterally, previous ipsilateral coxofemoral surgery, cases without sufficient client communication. medical records of dogs sex, breed, age, body weight, body condition score, side of arthroplasty, date of surgery, history of previous contralateral coxofemoral surgery, urinalysis results, intraoperative surgical site culture results, lameness score at presentation (0=no lameness, 1=slight lameness, 2=obvious weight-bearing lameness, 3=intermittent non-weight bearing lameness, 4=continuous non-weight-bearing lameness) size of prostheses implanted, duration of surgery. complications were separated into: intraoperative (ioc) short-term (stc) long-term (ltc) bivariate and multivariate statistical analysis was used to compare complications. procedures were performed by 10 different surgeons. study design: retrospective cohort study. outcome studied: to determine the prevalence of complications and identify prognostic indicators of success or failure for the zurich cementless thr. main findings (relevant to pico question): increased body weight prior femoral head and neck ostectomy (fho) or cemented-thr in the contralateral joint was identified as a negative prognostic indicator for successful outcome (p<0.05). ioc overall ioc rate = 11% fracture of the femoral diaphysis (n=12)=7.4% fracture of the greater trochanter (n=3) lost screw in soft tissue (n=1) excessive haemorrhage (n=1) immediate revision of acetabular cup placement (n=1) stc overall stc rate=6.75% coxofemoral luxation (n=6) transient neuraprexia (n=2) fracture of the femoral diaphysis (n=2)(1.2%) fracture of the acetabulum (n=1) ltc overall ltc rate=10.4% septic loosening (n=6) coxofemoral luxation (n=6) implant failure (n=4) fracture of the femoral diaphysis (n=1)(0.6%) limitations: retrospective surgery performed by 10 different surgeons follow-up performed in different ways and by different persons relatively short scheduled radiographic follow-up (8 weeks) 50 cases in which the 8 week follow-up was not performed by board certified specialists (surgery and radiology), body score not evaluated in all dogs increased rate of complications higher than previous studies. likely influenced in part by varying degrees of z-thr experience (technical error) surgeon’s experience not evaluated as prognostic factor no evaluation of technical errors immediately post operatively bergh et al (2006) population: client-owned dogs that underwent cthr at the university of pennsylvania school of veterinary medicine. sample size: 97 dogs (n=97) intervention details: medical records signalement, body weight, body condition score, diagnosis at the time of surgery, history of previous or subsequent hip surgery. complications intraoperative (ioc) short term (stc) long term (ltc) evaluation of radiographs 2-view radiographic hip studies pre-operatively, immediately post-operatively and at the longest follow-up were evaluated by one investigator. pre-operatively severity of osteoarthritis (oa) was graded (0=normal, 1=subtle, 2=grade 0 or 1 with severe subluxation or luxation, 3=mild oa, 4=moderate oa, 5=severe oa). immediately post-operatively surgical technique (implant size, implant position, cement quality) and technical errors. radiographs at the longest available follow-up and at least at 8 weeks post-operatively evaluated and compared to the immediate post-operative films (fracture of cement, medullary infection, loosening of the acetabular component, prosthetic luxation, fracture of the femoral diaphysis or greater trochanter and infection). statistical analysis: categorical data: chi-square or fisher’s exact test logistic regression analysis to access the independent contribution of possible risk factors surgery performed by various board certified surgeons study design: retrospective cohort study. outcome studied: to identify the prevalence of complications and changes following cthr and to identify factors that may predispose to a need for revision surgery. main findings (relevant to pico question): prevalence of complications: 12.1% after primary cthr pre-operative radiographs: available for 79 dogs majority had severe oa post-operative radiographs (primary cthr) (n=97): available for 87 dogs 69 dogs had appropriately sized femoral implants 60 dogs had eccentrically placed implants angle of lateral opening of acetabular component was appropriate in 40 dogs post-operative radiographs (secondary cthr) (n=8): available for 8 dogs 7 dogs had appropriately sized femoral implants 5 dogs had eccentrically placed implants angle of lateral opening of acetabular component was appropriate in 3 dogs technical errors: primary cthr ≥1 technical errors in 43 dogs secondary cthr technical errors in 50% of the dogs stc primary cthr available in 77 dogs ≥1 stc in 7 dogs secondary cthr (n=8) stc in 2 dogs. luxation (n=1) and infection (n=1) ltc primary cthr available for 63 dogs 59 dogs with radiographic changes in the bone, cement or prosthesis secondary cthr available for 5 dogs, all had radiographic changes revision surgery: primary cthr 12.1% (11/90) six had the implant removed, five had a revision (one femoral fracture) secondary cthr two dogs had a revision risk and protective factors: after primary cthr dogs were more likely to have a revision surgery if the femoral implant was eccentrically placed (p=0.01) presence of radiolucent lines at the femoral cement-bone interface in the long-term period was positively associated with revision surgery (p=0.02) male dogs were more likely to have revision surgery on the primary cthr (p=0.05) limitations: retrospective (medical records incomplete, limited follow-up) different surgeons with different experience surgeon’s experience not evaluated as risk factor complications that were treated elsewhere or left untreated would not have been detected variable radiographic technique and patient positioning (may have affected implant assessment) some radiographic films with inadequate quality for evaluation some body condition scores (bcs) were missing guerrero (2009) population: client-owned dogs that had zurich cementless total hip replacement (zcthr). inclusion criteria: medical records of the first 100 consecutives cases with 2nd generation zcthr were reviewed. only those dogs that had clinical and radiographic evaluation with ≥ 6 months follow-up. sample size: 60 dogs (n=60) 65 zcthr (n= 65) intervention details: all surgery was performed by the same surgeon. signalement data: age, breed, body weight, gender indication for thr hip dysplasia and secondary coxarthrosis (n=59), failure of conservative and/or surgical management of traumatic coxofemoral luxation (n=5), old salter-harris fracture of the proximal femoral physis (n=1) date of surgery and operated size cup position (angle lateral opening alo, angle of inclination ai) longest clinical and radiographic follow-up (presence of pain on manipulation of the hip joint, range of motion (rom), muscle mass compared with the contralateral size, lameness). evaluated using a score: excellent, good, fair, poor or failed. complications: intraoperative (n=1) femoral fissure during reaming post-operative (n=11) femoral fracture (1), prosthesis luxation (7), cup loosening (2), implant failure (1) management of complications and outcome  nine cases were successfully revised. explanation of implants was performed in one case because of infection, one dog was euthanised after a new luxation. study design: retrospective descriptive case series. outcome studied: to evaluate the use of, and to identify complications of the zcthr. main findings (relevant to pico question): mean follow-up: 22.68+/16.75 months clinical outcome: of 65 zcthr, 60 were considered to have an excellent outcome, 3 a good outcome, and 2 as failed 97% good or excellent outcome at an average of 2 years post-operatively (similar to previous reported rates of 91-96%) 17% needed one or more revision radiographic findings: findings compatible with bone ingrowth fixation were observed for all acetabular and femoral implants. focal radiolucent zones were observed in the acetabular component of 23 cases and none of the thr had a complete radiolucent zone around the cup or the stem. complications: (n=11, 17%) previous complication rates 6.3%-20.3%. luxation in cemented and cementless systems is the most frequently reported complication 1.1-11.8%, in this study: 11% (n=7). femoral fracture (n=1) well-reported complication after thr in dogs, and appears to be more common in old animals because of nonuse of the leg or other pathologic conditions. this single femoral fracture compares similarly with fractures occurring with cemented thr systems. increased femoral cortical thickening was observed along the medial cortex and distal to the stem in most cases. this bone remodeling and apposition may prevent occurrence of femoral fractures in the long-term that occur with cemented thr because of cortical thinning. component loosening (acetabular component n=1) implant stresses are higher in the zcthr stem compared with cemented stems, reaching a maximum in the neck region of the implant, with a second peak at the level of the most proximal screw. limitations: retrospective descriptive case series study, no control groups, variable follow-up two zcthr were not evaluated radiographically forster et al (2012) population: client-owned dogs that underwent thr. sample size: 170 dogs (n=170) intervention details: entries into the british veterinary orthopaedic association-canine hip registry (bvoa-chr) were reviewed. variables evaluated: age, body weight, breed, indication for thr and prosthesis statistical analysis: association between each variable and the incidence of complications were assessed using logistic regression mann-whitney u-test was performed to assess the significance of total lameness scores before and after thr owner outcomes assessment questionnaire was used additionally to collect data from owners. divided in 4 sections: section a assessed information regarding length of ongoing mobility problem, medications received, and other concurrent medical history unrelated to hip dysplasia (hd). section b assessed activity and willingness to exercise before thr. section c assessed date of surgery, overall owner satisfaction and complications. section d assessed activity and willingness to exercise after thr. surgical implants cfx (biomedtrix), bfx, helica, kyon study design: prospective case series. outcome studied: to assess the variables associated with the complications of thr and report owner-assessed outcomes, through surgeon-based registration of cases via an online database, informed owner consent and prospective outcomes assessment using a client-administered clinical metrology instrument. main findings (relevant to pico question): complications incidence: 9.4%: luxation (n=5) femoral fractures (n=3) minor wound dehiscence (n=1) wound sepsis, (n=1) protrusion acetabuli, (n=1) acetabular cup displacement, (n=1) suspected pulmonary thromboembolism and death at the end of surgery (n=1) femoral pain, (n=1) femoral subsidence, (n=1) siatic paresis and luxation (n=5), femoral fracture (n=3), minor wound dehiscence (n=1) no statistical significance was identified between weight, age, gender, breed, indication for thr, surgical technique and prosthesis and incidence of complications. client questionnaire: a total of 51% response rate to the online owner assessment questionnaire was achieved. 82% described their satisfaction with the outcome of thr as “very good”, 12% “good”, 7%”fair”, 0% “poor”, 0% “very poor”. a total of 20% complication rate was reported statistically significant difference in owner-assessed lameness scores before and after thr (p<0.001). limitations: participating surgeons were requested to submit all of their operated cases to the bvoa-chr (authors unable to control it). in theory it is possible that participating surgeons may have chosen not to submit data from a case with a less successful outcome (selection bias). the complication rate in this study would therefore be higher than documented. client assessment subjective, no controls with force platform peak vertical force for example 51% response rate to the online owner assessment questionnaire different complications rate between owners and surgeons thr was most frequently performed on dogs ≤ 1year (39%) limited ability to fully evaluate the risk factors for thr complications to date, probably because most studies are single-center and have limited power bvoa-chr does not currently include imaging data appraisal, application and reflection the aim of this knowledge summary was to review, summarise and critically appraise the literature regarding the question: are old dogs undergoing total hip replacement predisposed for perioperative femoral fractures in comparison to young dogs? this reflection was investigated in two observational retrospective studies: liska (2004) and ganz et al. (2010). both studies reported that elderly dogs undergoing thr may be at an increased risk of femoral fractures.  according to liska (2004) old dogs with osteopathies, previous hip surgery and iatrogenic fissures created during reaming are predisposing factors for femur fracture after thr. the overall incidence of femur fracture after thr was 2.9%. the author describes an excellent prognosis when the fractures were treated correctly. due to the design of the study (observational and retrospective) and the limitations (retrospective, different surgeons, surgical method/surgical experience not evaluated as a risk factor, different follow-up) the results have to be interpreted with caution. ganz et al. (2010) evaluated the risk factors for femoral fracture after canine press-fit cementless total hip arthroplasty. the conclusions were that older dogs and dogs with lower cfi may be at increased risk of femoral fracture and the incidence of femoral fracture of cases with complete statistical analysis was 13.5%. regarding the design of this study (observational and retrospective) and its limitations (retrospective, different surgeons, surgical method/surgical experience not evaluated as a risk factor, different follow-up) the level of evidence provided by this type of study is weak. however, the results of these studies can be used to counsel clients before performing thr in old dogs. by reviewing the veterinary literature relative to the general complications and outcomes of total hip arthroplasty, a variation in the prevalence of femoral fractures was noticed. none of the studies listed above mentioned that the age of the patient may be a potential risk factor for general complications. again, due to the design of all of these studies the level of evidence is weak. in the study of hummel et al. (2010) the prevalence of femoral fractures occurring intraoperatively was 7.4%, the prevalence of femoral fractures occurring as short-term complications was 1.2% and the prevalence of femoral fractures occurring as long-term complications was 0.6%. increased body weight and prior cemented thr or femoral head and neck ostectomy of the contralateral hip were identified as negative prognostic factors. berg et al. (2006) described a 1.3% prevalence of femoral fracture occurring during the primary thr as short term complications, and fracture of femur diaphysis represented 3.2% of the long term complications. eccentric positioning of the femoral stem and the presence of radiolucent lines at the femoral cement-bone interface were positively associated with the occurrence of revision surgery. the prevalence of femoral fracture post-operatively in the study of guerrero and montavon (2009) was 1.5%.  forster et al. (2012) identified no significant association between weight, age, sex, breed, indication for thr, surgical technique and prosthesis and the incidence of complications of total hip arthroplasty. the incidence of surgeon-reported surgical complications was 9.4%. the femoral fractures represented 18.75% of the complications. in conclusion, there is insufficient evidence that elderly dogs undergoing thr are predisposed to femoral fractures in comparison to young dogs. currently, there are insufficient strongly convincing studies in the veterinary literature to support the results of liska (2004) and ganz et al. (2010). methodology section search strategy databases searched and dates covered: cab abstracts (1973-2015) accessed on the ovid platform vetmed resource (1973-2015) search terms: dogs or dogs or canine and femoral fractures or femur or femoral or fracture and total hip replacement or total hip arthroplasty or cemented total hip replacement or cementless total hip replacement or uncemented total hip replacement or cemented total hip arthroplasty dates searches performed: december 2015 exclusion / inclusion criteria exclusion: non english language, conference papers, summary updates, case reports, reviews. inclusion: studies which were looking for risk factors and outcomes in total hip replacement, studies which described femoral fractures as complications. experimental studies and observational studies. search outcome database number of results number of duplicates excluded – not english language excluded – due to study design excluded – did not answer pico question total relevant papers cab abstracts 194 14 19 34 127 6 vetmed resource 7 0 3 1 3 1 total relevant papers when duplicates removed 7 conflict of interest the author declares no conflict of interest. references bergh, m.s. et al. (2006) complications and radiographic findings following cemented total hip replacement a retrospective evaluation of 97 dogs. veterinary and comparative orthopaedics and traumatology, 19 (3), pp. 172-9. forster, k. e. et al. (2012) complications and owner assessment of canine total hip replacement: a multicenter internet based survey. veterinary surgery, 41 (5), pp. 545-550. http://dx.doi.org/10.1111/j.1532-950x.2012.01015.x    ganz, s.m. jackson, j. and vanenkevort, b. (2010) risk factors for femoral fracture after canine press-fit cementless total hip arthroplasty. veterinary surgery, 39, pp. 688-695.http://dx.doi.org/10.1111/j.1532-950x.2010.00694.x guerrero, t.g. and montavon, p.m. (2009) zurich cementless total hip replacement: retrospective evaluation of 2nd generation implants in 60 dogs. veterinary surgery, 38 (1), pp. 70-80.http://dx.doi.org/10.1111/j.1532-950x.2008.00466.x hummel, d.w. lanz, o.i. and werre, s.r. (2010) complications of cementless total hip replacement a retrospective study of 163 cases. veterinary and comparative orthopaedics and traumatology, 23 (6), pp. 424-432. http://dx.doi.org/10.3415/vcot-09-07-0071    liska, d.w. (2004) femur fractures associated with canine total hip replacement. veterinary surgery, 33 (2), pp. 164-172. http://dx.doi.org/10.1111/j.1532-950x.2004.04024.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. emergency conditions in horses: opinions and decision making of livery yard owners a. bowden bvmedsci, bvm, bvs, mrcvs, phd, afhea 1* j.h. burford ma, vetmb, phd, certva, certes, sfhea, frcvs 1 m.l. brennan bsc(vb), bvms, phd, pgche, dipecvph(pm), mrcvs, fhea1 g.c.w. england bvetmed, phd, dvetmed, dvr, dvrep, dipecar, dipact, pfhea, frcvs, 1 s.l. freeman bvetmed, phd, certva, certvr, certes, dipecvs, fhea, frcvs1 1school of veterinary medicine and science, university of nottingham, college road, sutton bonington, leicestershire, le125rd *corresponding author (adelle.bowden@nottingham.ac.uk) vol 4, issue 2 (2019) published: 03 may 2019 reviewed by: anna hammond (cert em (int med), bvm&s) and jo suthers (bvm&s mphil certes(soft tissue) dipecvs mrcvs) doi: 10.18849/ve.v4i2.199 section index:    abstract | introduction | methods | results | discussion | conflict of interest | references | supplementary files abstract objective: the aim of this study was to evaluate equine livery yard owners’ opinions of emergency conditions, and to identify factors influencing emergency decision making in the horse. background: there is limited data on horse owners’ opinions and decision making in emergency conditions. evidentiary value: an online questionnaire was distributed to uk livery yard owners accredited with the british horse society. there were 104 survey participants, who represented experienced owners with responsibility for care of a number of horses. methods: the questionnaire consisted of open and closed questions on participants’ demographics, their experiences and opinions of the most common equine emergency conditions, and emergency decision making. descriptive data analysis included frequency ranking and categorisation of free text responses. results: the majority of respondents had kept horses for more than 10 years (97%), and reported previous experience of emergency conditions (99%), predominantly colic (96%) and wounds (92%). participants considered that the most common emergency conditions were colic (98%), wounds (49%) and fractures (22%), and the most concerning conditions were colic (94%), lameness (36%) and wounds (21%). factors believed to be important in emergency decision making were: degree of pain, likelihood of condition resolving, and severity of disease. conclusion: this study highlights the importance of colic and wounds as emergency conditions in the horse, and describes factors considered important in emergency decision making. application: the outcomes identify where research and clinical resources should be targeted to improve emergency care for horses. the results were used to inform a survey of the wider horse population. introduction the horse owner plays a crucial role in the maintenance of their animals’ health and welfare, however there are limited studies published about owners’ opinions or experiences of equine disease conditions (ireland et al., 2011; ireland et al., 2013). the majority of studies focus on common conditions in horses, and data for emergency conditions are lacking. there is a single study of veterinary practitioners’ opinions of commonly encountered emergency conditions, conducted in the us in 1991 (traub-dargatz et al., 1991). this study was a survey of veterinary practitioners’ opinions of common medical problems, conducted by the american association of equine practitioners. it provides a useful snapshot of veterinary practitioners experiences and opinions, but there is currently no data from horse owners about the types of emergencies they experience. the owner’s opinion of the importance of a disease will depend both on how common it is, and the impact it has. both these factors may affect owners’ approach to diseases and their decision-making around cases. identifying conditions which are common and concerning to livery yard owners will help recognise which areas or conditions may require further investigation to ascertain where education and resources may be most beneficial. this is particularly important for emergency conditions where horse owners may have limited access to resources to inform decision-making, and may have to make major decisions under financial, time and emotional pressures. the aim of this study was to survey the opinions of experienced horse owners on the most common diseases and emergency conditions in the horse, and identify factors that influence their decision making in emergency situations. the objectives of the study were: to conduct an online survey of livery yard owners’ opinions on the most common and concerning disease conditions in horses to assess livery yard owners’ experiences of emergency conditions and their opinion on the most common emergency diseases to identify factors that influence livery yard owners’ decisions in emergency situations. methods ethics the study was reviewed and approved by the school of veterinary medicine and science ethics committee, university of nottingham. study design a cross-sectional study design was employed via an online survey, which was developed and distributed to livery yard owners. the target population was experienced horse owners. the rationale for this selection was to negate the differences in ability, knowledge and experience in the general horse owner population with the aim of getting a better understanding of the common and important conditions. the sampling frame used was owners of livery yards approved by the british horse society (bhs) as this was an accessible population that was easily contactable within the limits of data protection.  bhs approved yards are yards within the uk, ireland and worldwide which have applied for and met predefined approval criteria (http://www.bhs.org.uk/professionals/become-bhs-approved/approved-livery-yards). there were 503 bhs approved livery yard owners listed with contact details on the bhs website at the time of the study (accessed 05/12/2013).  livery yard owners were emailed a cover letter and link to the online survey on 01/01/2014. a reminder email was sent to all those who had not completed the questionnaire 2 weeks later, at which time non-participants were asked if they would provide a reason for not wishing to participate. survey design the survey consisted of open and closed questions on livery yard owners’ opinions of the veterinary conditions in four main sections: participants’ opinion of conditions requiring veterinary attention and emergency decision making, participants’ experiences of emergency situations, participants’ demographics and equine experience, and where participants sought advice on equine health. the individual questions and their specific formats are listed in table 1. table 1: content and format of questions used in an online survey of uk livery yard owners’ opinions and experiences of common and emergency conditions in horses. the first section related to participants’ opinions of common veterinary conditions, common critical/life threatening conditions and which conditions they were most concerned about  the survey included one ranking question about factors influencing decision making in emergency situations. the closed response options were formulated using the results of a study that investigated horse owner decision making in horses suffering from abdominal pain (scantlebury et al., 2014). the second section related to emergency situations, and asked participants about their experience of different emergency conditions in the horse, their confidence in their decision to call a veterinary surgeon in an emergency, and their experiences of decision making in these situations. the third section contained questions on the owners’ demographics, whilst the final section related to owners’ advice seeking behavior. free text boxes were provided at the end of each section for any further comments, and there was a feedback section at the end of the questionnaire. the questionnaire was initially drafted in a microsoft word (2013) document, and then transferred into the cloud based internet survey tool survey monkey, california.  the survey was pretested by three equine researchers and piloted with 15 horse owners, before the final amended version was distributed. the survey remained open for a total of 23 days (01/01/2014 to 24/01/2014). data analysis data from the online survey tool was transferred to a microsoft excel (2013) spreadsheet for data handling and analysis. data were checked and cleaned with incomplete questionnaires (where only the consent section were completed) removed prior to analysis. a standardised weighting was calculated to quantify factors affecting decision making with a higher weighting attributed to a higher ranking. this enabled identification of the factors that most affected decision making in the study population. data were subject to descriptive analysis, including calculation of the mean, median and range for continuous variables, and percentage frequencies for categorical variables. free text responses were categorised and the frequency of different themes was identified. as not all respondents answered all questions, denominators for each question are given where required. results participants of the 503 possible contacts identified, there were 450 valid email addresses available. there were 133 livery yard owners who consented to participate; 104 participants fully completed the survey, giving a response rate of 30% and a completion rate of 23% (figure 1). figure 1: recruitment of yard owners to participate in a questionnaire about common conditions in horses using a list of british horse society (bhs) approved livery yards. there were 32% of participants aged between 45 to 54 years old, 25% were 55 to 64 years old, 24% were 35 to 44 years old, 11% were 25 to 34 years old and 8% were 65 years old or over whilst no participants were under 24 years old.  females accounted for 89% (n=91/102) of participants. the majority (97%; n=97/100) of respondents had kept horses for more than 10 years, whilst 58% (n=58/100), had kept horses for more than 30 years.  the number of horses that yard owners had responsibility of care for varied considerably, although the majority had more than 20 horses in their care. 33% of respondents (n=33/101) had more than 40 horses, 19% (19/101) had 30–39, 16% (16/101) had 25–29, and 12% (12/101) had 20–24 horses in their care. most of the livery yard owners’ had mixed management strategies on their premises. full livery (yard staff delivering the daily care) was provided by 46% (n=46/99) of yards, whilst ‘do-it-yourself’ livery (owner centred daily care of the horses) was offered by 39% (n=39/99). the majority of horses kept on livery yard owners premises’ (reported by 74% of yard owners; n=64/87) were used for general purpose activities. qualifications held by livery yard owners’ varied from none (16%; n=17/104) to equine undergraduate degrees (8%; n=8/104). the majority of participants (65%; n=68/104) held formal equine qualifications from the british horse society (bhs). the vast majority of participants (95%; n=97/102) felt they were experienced in horse care. livery yard owners’ experiences and decision making with equine veterinary problems the most commonly identified conditions that required veterinary visits were reported in free text format. these were reviewed and retrospectively categorised into main disease types. the most common problems were colic (84%; n=87/104), lameness (75%; n=78/104), wounds (54%; n=56/104) and ‘injury’ (16%; n=17/104). a further 28 common conditions were identified, but these were each mentioned by less than 5% of participants (supplementary item 2). the most commonly identified critical conditions requiring emergency attention were categorised as colic (98%; n=101/103), wounds (49%; n=50/103), fractures (22%; n=23/103), ‘serious injury’ (15%; n=15/103), choke (12%; n=12/103), laminitis (12%; n=12/103) and grass sickness (10%; n=10/103). there were a further 21 critical conditions mentioned, all of which were mentioned by less than 10% of participants (supplementary item 2).  the conditions of most concern to respondents were categorised into colic (93%; n=92/99), lameness (35%; n=35/99), wounds (21%; n=21/99), ‘serious injuries’ (17%; n=17/99), laminitis (16%; n=16/99), fractures (15%; n=15/99), strangles (15%; n=15/99) and infectious diseases (12%; n=12/99). a further 23 conditions were mentioned by less than 10% of participants (supplementary item 2). yard owners were asked to rank the factors that would most influence their decision making with regards to choosing treatment or euthanasia when a horse was critically ill. the factors most commonly nominated were: the amount of pain and suffering the horse was experiencing, the likelihood that the condition would resolve with treatment, how sick the horse was, financial cost of treatment, and age of the horse (figure 2). in addition, 43% of participants chose to use the free text box associated with this question. the main themes identified from the comments were: multifactorial decision making, veterinary advice, sentimentality and length of ownership of the horse, and whether the horse would have to travel for treatment. additionally, concerns were raised about length of recovery and whether the horse’s temperament would lend itself to the recovery process. other influencing factors mentioned were how “useful” the horse was to the business and, previous experience including outcomes of a condition. figure 2: standardised weightings of different factors affecting livery yard owner decision making (n=104) in critical situations as reported in an online survey of livery yard owners about common conditions in horses. *the factor affecting decision making was ranked by participants from a closed list. factors ranked as more important were given a higher weighting, therefore a higher standardised weighting is equivalent to a greater influence on decision making. livery yard owners experience and decision making with equine emergency conditions 103 participants (99%) responded that they had previous experience of emergency conditions (a veterinary surgeon had visited their horse as a result of a condition that they considered to be an emergency). those without personal experience were not required to complete the emergency experiences section. there were 38 separate conditions that had been experienced by participants (table 2). the most frequently experienced conditions were colic (96%; n=99/103), wounds (92%; n=95/103), laminitis (66%; n=68/103), choke (59%; n=61/103) and foot abscesses (57%; n=59/103). table 2: livery yard owners’ experiences of emergency conditions in the horse (n=103 respondents) as reported in an online survey. the majority (96%; n=99/103) of respondents believed that during their experiences, the veterinary surgeon had always been called out to see an emergency soon enough. those participants who had experienced a delay in veterinary treatment (n=4/103) described this as either due to themselves (the yard owner) or the veterinary surgeon. yard owner factors included: waiting to observe a horse, not realising the extent of injury, an inability to contact the individual horse owners, and not having permission to act on their behalf. the circumstances of delays in veterinary surgeons attending were due to attendance at other emergencies at the time of the call, or a large distance to travel. most livery yard owners (95%; n=98/103) considered that they did not find it difficult knowing the correct time to call a veterinary surgeon. whilst 37% (n=38/103) of the study population felt emergency visits were traumatic in nature, 44% (n=45/103) had no strong opinion on whether the experience(s) were traumatic or not. there were 24 participants (23%) who made free text comments regarding the traumatic nature of emergencies. these were grouped into three main categories which related to the veterinary surgeon, the horse and the yard owner. factors that increased the trauma related to the veterinary surgeon, were delays in attendance, unfamiliar veterinary surgeons, and a delay in performing euthanasia of the horse.  factors that increased the trauma related to the horse were when the horse was distressed, when the horse had suffered a fracture, or when euthanasia was required. factors relating to the yard owner were the financial implication of referral, more specifically having/finding a deposit for immediate treatment. other comments included: yard owners experiencing a delayed reaction, emergencies becoming less traumatic with experience, and coping with emergencies being part of a yard owners’ occupation. advice seeking behaviour the most frequent sources of advice were respondents’ veterinary surgeons (99%; n=100/101), farriers (77%; n=78/101) and physiotherapists (42%; n=42/101). other sources of advice were friends and family, trainers, paraprofessionals, yard staff and the internet. when asked who they would seek advice from first, 24% (n=23/94) of participants would always go to a veterinary surgeon, whilst a further 67% (n=63/94) stated they would seek advice from a farrier for foot related problems, and a veterinary surgeon for any other condition. discussion this is the first study to investigate common and important conditions for livery yard owners, and evaluate their experience of equine emergencies.  the survey highlighted the importance of colic amongst the livery yard owner population. it was considered to be the most common reason for veterinary attendance (excluding vaccination and routine dental care), as well as being a cause of concern for 94% of the study population. furthermore, it was the condition that was reportedly experienced by the greatest number of survey participants, reflecting the perception that it was also the most common emergency condition. the survey was developed to capture opinions about common and emergency conditions from an experienced population of horse owners. this introduced a selection bias to the results and thus they are not likely to be representative of the general horse owner population as many demographics of horse owner were excluded from the study.  the number of premises’ appearing on the british horse society’s approved yards list at the time of distribution was 503, but some did not have valid contact details. the response rate was 30%. this response rate is consistent with other online surveys. the results of the survey may not be representative of the horse owning population, however, a specific sampling frame was used to evaluate responses from experienced horse owners/carers with responsibility for a number of different types of horse, and therefore was appropriate to the aim of the study. the target population were assumed likely to be computer literate, given that email addresses were available in the public domain, and therefore the use of an online platform was considered appropriate. the main drop out from the survey was immediately after the consent slide (22%) making it possible that potential participants were deterred by the type of questions, the length of the survey, or the requirement for consent. the demographics questions were placed later in the survey structure to try to engage participants in the study topic early and reduce drop out. the demographics of the study population were similar to other owner focused studies in the literature (scantlebury et al., 2011; scantlebury et al., 2014; murray et al., 2015; slater, 2017) with an even spread of ages and a strong female bias to the study population. the findings of the questions about common, non-emergency conditions in this study were in contrast to other studies reporting on common conditions in horses. other studies of common conditions have identified musculoskeletal conditions, specifically lameness, as the most frequent reason for veterinary attendance (loomans et al., 2007; ireland et al., 2013; nielsen et al., 2014; slater, 2017). the differences are possibly due to the different data collection methods, including whether the studies looked at incidence or prevalence, the categorisation of diseases (whether they are grouped into systems or individual conditions) and whether the data was captured from veterinary practitioners or horse owners. the national equine health survey and the study by ireland et al. (2013), aimed to gain a snapshot of the conditions horses were experiencing at a particular time point, which would be more likely to identify chronic conditions. colic tends to be a short duration disease whereas episodes of lameness can be prolonged or permanently present in some horses.  this current survey may also be subject to recall bias, as colic and other emergency conditions may be more memorable and traumatic for owners, therefore they believe they are generally more common. when considering emergency conditions specifically, colic was identified as the most common in previous studies, although these have focused on referral hospital populations (traub-dargatz et al., 1991; southwood et al., 2009; viljoen et al., 2009). in the united kingdom, there is only one study, which reported on veterinary opinions of common conditions seen in first opinion practice. this did not relate to emergency conditions specifically, but gastrointestinal disease was the second most common complaint nominated by veterinary surgeons after musculoskeletal disease (nielsen et al., 2014). there are very few studies that look at decision making in equine critical cases, and most of these relate to veterinary decision making (archer, 2004; freeman and issaoui, 2013). scantlebury et al. (2014) focused on owner decision making in equine colic specifically. it reported that different typologies of horse owner made different decisions; the results from the current study of livery yard owners therefore may not be applicable to the general horse owning population. furthermore, their decision making was not referenced to their own horse or ‘horses in their care’ (which was undefined and therefore open to participant interpretation). some livery yard owners may have given responses relating to their own horses, and others about clients’ horses which they cared for; these factors should be considered as a potential source of bias in the responses as the two standpoints represent different typologies of horse owner. the majority of participants had sought veterinary attention for emergency situations, and therefore it was surprising that over 50% of the study population had only experienced five different conditions (colic, wounds, laminitis, choke and foot abscesses), and recall bias may again be a factor influencing this. nearly a third of participants found emergency situations traumatic. most participants felt they knew when they required attendance of a veterinary surgeon in emergency situations, but this survey reflects opinion and is not necessarily what actually happens. the majority of participants’ had formal equine qualifications and therefore had received some formal training on equine health and disease. it is reassuring that the majority of participants stated that they would phone a veterinary surgeon directly for advice, and would readily use this source if they were concerned. it would be interesting to explore further the knowledge and understanding of certain emergency conditions of the general horse owning population, and how this potentially impacts on the horses in these yard situations. this study clearly identified the importance of colic to livery yard owners, both in terms of frequency and impact: it was identified as both the most common emergency and nonroutine condition, and as the disease that was most concerning for participants. there were a number of factors involved in emergency decision making, including the severity of the disease, the prognosis, financial considerations, and individual horse factors (including age, use of the animal and any concurrent conditions). this study highlighted concerns and opinions of experienced equine livery yard owners’; future work should focus on the wider horse owning populations’ in knowledge and experience of colic. conflict of interest the authors declare no conflicts of interest. funding: adelle bowden’s phd was supported by funding from the university of nottingham references archer, d. c. 2004. decision making in the management of the colicky horse. in practice, 26, 378–385. doi http://dx.doi.org/10.1136/inpract.26.7.378 freeman, s. & issaoui, l. 2013. code red for colic: decision-making for acute abdominal pain in the horse. equine veterinary education, 25, 245–246. doi https://doi.org/10.1111/eve.12025 ireland, j. l., clegg, p. d., mcgowan, c. m., duncan, j. s., mccall, s., platt, l. & pinchbeck, g. l. 2011. owners' perceptions of quality of life in geriatric horses: a cross-sectional study. animal welfare, 20, 483–495. doi https://doi.org/10.1111/j.2042-3306.2010.00142.x ireland, j. l., wylie, c. e., collins, s. n., verheyen, k. l. p. & newton, j. r. 2013. preventive health care and owner-reported disease prevalence of horses and ponies in great britain. research in veterinary science, 95, 418–424. doi https://doi.org/10.1016/j.rvsc.2013.05.007 loomans, j. b. a., stolk, p. w. t., van weeren, p. r., vaarkamp, h. & barneveld, a. 2007. a survey of the workload and clinical skills in current equine practices in the netherlands. equine veterinary education, 19, 162–168. doi https://doi.org/10.2746/095777307x186875 murray, j.-a. m. d., bloxham, c., kulifay, j., stevenson, a. & roberts, j. 2015. equine nutrition: a survey of perceptions and practices of horse owners undertaking a massive open online course in equine nutrition. journal of equine veterinary science, 35, 510–517. doi https://doi.org/10.1016/j.jevs.2015.02.005 nielsen, t. d., dean, r. s., robinson, n. j., massey, a. & brennan, m. l. 2014. survey of the uk veterinary profession: common species and conditions nominated by veterinarians in practice. veterinary record, 174(13), 324. doi http://dx.doi.org/10.1136/vr.101745 scantlebury, c. e., archer, d. c., proudman, c. j. & pinchbeck, g. l. 2011. recurrent colic in the horse: incidence and risk factors for recurrence in the general practice population. equine veterinary journal, 43, 81–88. doi https://doi.org/10.1111/j.2042-3306.2011.00383.x scantlebury, c. e., perkins, e., pinchbeck, g. l., archer, d. c. & christley, r. m. 2014. could it be colic? horse-owner decision making and practices in response to equine colic. bmc veterinary research, 10. doi https://doi.org/10.1186/1746-6148-10-s1-s1 slater, j. 2017. national equine health survey (nehs). available: https://www.bluecross.org.uk/sites/default/files/downloads/nehs%202017%20results.pdf [accessed: 21/11/2017] southwood, l. l., dolente, b. a., lindborg, s., russell, g. & boston, r. 2009. short-term outcome of equine emergency admissions at a university referral hospital. equine veterinary journal, 41, 459–464. doi https://doi.org/10.2746/042516409x385823 traub-dargatz, j. l., salman, m. d. & voss, j. l. 1991. medical problems of adult horses, as ranked by equine practitioners. journal of the american veterinary medical association, 198, 1745–7. viljoen, a., saulez, m. n., donnellan, c. m., bester, l. & gummow, b. 2009. after-hours equine emergency admissions at a university referral hospital (1998-2007): causes and interventions. journal of the south african veterinary association, 80, 169–173. supplementary files, images & tables all of the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. the staircase of evidence – a new metaphor displaying the core principles of evidence-based veterinary medicine sebastian arlt1* wolfgang heuwieser1 1clinic for animal reproduction, faculty of veterinary medicine, freie universität berlin, königsweg 65, 14163 berlin, germany. *corresponding author (sebastian.arlt@fu-berlin.de) vol 1, issue 1 (2016) published: 20 jan 2016 doi: 10.18849/ve.v1i1.18 competing interests the authors declare that they have no competing interests author contributions both authors developed the staircase metaphor, conducted the survey, analysed the results and drafted and approved the manuscript. list of abbreviations ebm               evidence-based medicine ebvm             evidence-based veterinary medicine rct                randomized controlled trial acknowledgements the authors gratefully thank the students who took part in the survey.       section index:    abstract | introduction | results | discussion | methods & materials | references | supplementary figures & tables abstract background: veterinary practitioners and clinicians should base their clinical decisions on the best evidence obtainable to provide best patient care. the evidence of information concerning diagnostic or therapeutic procedures and disease prevention can be ranked from weak to strong based on the methodology the information is generated by. teaching the concepts and strategies of evidence-based veterinary medicine, however, can be challenging. students and practitioners should become competent in defining a clinical problem, retrieving of information from the literature and independent critical thinking. several authors illustrated the levels of evidence ranked from strongest to weakest using a pyramid metaphor. the basis reflects information of the lowest evidence and towards the tip the evidence increases. the metaphorical concept of the pyramid, i.e. solid foundation and a narrow tip, however, does not adequately represent the hierarchy of evidence as the high evidence levels are represented by narrow fields and vice versa results: we propose an alternative schematic which may be used in order to display the respective evidence levels as a staircase. a reading pictogram character illustrates that the search for information should start at the highest step. to assess which metaphor can be more easily interpreted and is intuitively accessible a survey among 5th semester veterinary students was performed which was completed by 100 respondents. according to the results both metaphors adequately display the hierarchy of evidence. the staircase better represents the fact that high evidence information is more likely to be true and that one should start to look for high evidence when searching information. in contrast more students found that the pyramid represents distracting information i. e. that opinions and information from the internet provide a solid knowledge base. conclusions: the staircase of evidence displays better the evidentiary value of information and how to perform a search for information of high evidence compared to the pyramid of evidence. it therefore can help to teach information search and interpretation strategies in order to answer specific clinical questions. introduction background evidence based medicine (ebm) has become broadly accepted as an appropriate basis for decisions around patient care (ilic et al., 2011; sargeant et al., 2014b). hence, courses teaching ebm to students and postgraduates are held at several universities all over the world to various degrees (miles et al., 2010; petrisor et al., 2006). veterinary medicine has also adopted the principles of ebm leading to the field of evidence-based veterinary medicine (ebvm) (vandeweerd et al., 2012b). the aim of ebm and ebvm is to base decisions concerning treatments in practice on valid, clinically relevant research data (evans et al., 2007). sackett et al. (1996) defined ebm as the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients. hence, practicing ebm requires clinical expertise, and expertise in retrieving, critically appraising, interpreting, and applying the results of scientific studies. in addition, competence in communicating the risks and benefits of different treatments to patients or patient’s owners is necessary. (greenhalgh et al. 2014) stated that usable evidence must be combined with context and professional expertise to achieve an optimal treatment for individual patients. the hierarchy of evidence information concerning diagnostic or therapeutic procedures and disease prevention can be generated using different methods. these methods vary in regard of the certainty that the information is free from bias (gugiu et al., 2010). scientific evidence is the product of appropriately designed and carefully controlled research studies (sargeant et al., 2014a). hence, levels of evidence were defined and ranked from strongest to weakest. the levels of evidence that apply to interventions are presented in table 1. slight modifications exist of the description of the level of evidence depending on the organisation or author (harris et al., 2001); ocebm levels of evidence working group, 2011; petrisor et al., 2006b; rubin, 2008; salmond, 2007; sargeant et al., 2014a). the hierarchy of evidence is a categorisation of sources with the aim to highlight those that are most likely to avoid a biased outcomes (cockcroft et al., 2003). level 1 evidence is obtained from systematic reviews and metaanalyses of randomized controlled clinical trials (rct) or single rct with narrow confidence intervals (gugiu et al., 2010; holmes et al., 2007). ideally, evidence should be derived from multiple studies investigating the same research question (sargeant et al., 2014a). metaanalyses summarize and combine information, weight and analyse the results of independent studies relating to a specific topic. hence by increasing the sample size and statistical power the precision of an estimated outcome can be increased (lean et al., 2009). level 2 evidence is provided by controlled trials without randomisation and cohort studies. level 3 evidence results from case reports and case series. opinions and consensus reports are categorized as level 4 evidence, the weakest category (bassler et al., 2000; harris et al., 2001). within each level of evidence, however, individual information may be evaluated as stronger or weaker after a thorough appraisal (gugiu et al., 2010). this appraisal should address aspects like enrolment criteria, the allocation in experimental designs, blinding, the sample size, statistical methodologies and the objectiveness in the discussion of the results. the pyramid of evidence the hierarchy of evidence has been illustrated by several authors using a pyramid (figure 1) with varying details (arlt et al., 2010; cardwell, 2008; daly et al., 2007; holmes, 2007; kochevar et al., 2006; sargeant et al., 2014a). the common component of all variations of the pyramid is that the basis reflects information of the lowest evidence. results of low evidence are generally prone to bias (petrisor et al., 2006b). towards the tip of the pyramid the evidence increases. hence, on the top randomised, controlled trials and metaanalyses (i.e. level 1 evidence) are located (cockcroft et al., 2003). these study types have lower potential for bias and are more reliable in reproducibly demonstrating causes and effects. clinical decision making should be based on the best evidence obtainable (sackett et al., 1996). hence, the search for information should start at the top of the pyramid. if no sufficient information of the highest levels is available, we must rely on sources of more doubtful evidence and move towards the basis of the pyramid (balshem et al., 2011). the pyramid of evidence may result in disorientation of the reader what was articulated by several students in our courses on ebvm in the last years. one reason is that other pyramid metaphors usually present the best or most important categories at the broad basis. furthermore, several students had the impression, that expert opinions and consensus reports represent a basis of knowledge supporting a superstructure of rct and metaanalyses. considering the historical evolvement of medical knowledge this context might be true for several areas. nevertheless, decision strategies should avoid unduly considering low evidence levels. the staircase of evidence an alternative schematic is the staircase of evidence (figure 2). the lowest step reflects the lowest level of evidence. with every step upwards, higher evidence is reached and represented at a higher level. the highest step implies the maximum overlap with the truth, although the metaphor indicates, that the truth is never reached to one hundred percent as no step fully overlaps with the truth. every step up on the staircase potentially leads to less potential bias and thus to a higher certainty of correctness of the information presented. the fact, that information of different steps can be combined to achieve even higher evidence (donner-banzhoff, 2009; straus et al., 1998) is illustrated as a combination of the overlapping areas of different evidence levels covers a bigger proportion of the truth. every evidence level in the staircase has the same width. hence, the width of the steps does not represent the certainty with which the information is correct. a limitation of the metaphor may be that a reader not familiar with ebm might conclude that he or she has to start at the first step during information search or clinical reasoning. similar to the pyramid, it could also be misinterpreted that the first steps of the staircase are a basis of the higher levels. clinical decisions should be based on information of high evidence. hence, the search for information should start at the highest step. this is illustrated by the reading pictogram character. only if usable high level evidence is not available the reader should go down step by step and search for usable evidence at the respective level. this should be done in consciousness that with every step down the overlap with the truth declines. aim of this project was to develop the staircase and to assess if it can be more easily interpreted and is more intuitively accessible to students compared to the pyramid of evidence.   results a total of 144 students attended the lectures whereas 100 students (69.4%) completed the survey (48 on wednesday, 52 on friday). median (and interquartile range) age of the participating students was 23.0 (21.3 to 25.0) years, 4 respondents were males. in total 9 students stated that they already have heard about ebvm. interestingly 11 participants stated that they would be able to explain ebvm and its aims. further results of the survey are presented in table 2. according to the students both metaphors represent that quality of information is better when displayed at the top. to the statement referring to the staircase “that the metaphor adequately represents that information is more likely to be true if it is of high evidence” significantly more students agreed compared to the same statement referring to the pyramid metaphor (p<0.01, df = 2). in contrary, more students agreed that the pyramid adequately represents that opinions and information from the internet provide a solid knowledge base (p<0.01, df = 2). the statement when searching information one should start to look for high evidence information was more often supported when referring to the staircase metaphor (p<0.01, df = 2). finally, students agreed more often to the statement more information of low evidence is available* referring to the pyramid (p<0.01, df = 2). gender and age of the respondents or the statements that they had heard already about ebvm or could explain the aims of ebvm had no influences on the outcomes. the presentation order of the metaphors had no influence on the outcomes except on the statement that the staircase represents that opinions and internet information provide a solid knowledge base (p<0.01, df = 2). in the wednesday group 25 students (52.1%) disagreed with this statement whereas in the friday group 42 (80.0%) disagreed. some students (7.0%) provided comments within the free text comment section. three students commented that the pyramid provides little or no information about the validity of the respective levels. two students commented that the staircase better represents that opinions and information from the internet are less likely to be true. two other students suggested that the pictogram character should walk upstairs. discussion veterinary practitioners have to use optimal diagnostics, interventions and medications to examine and to treat their patients (arlt et al., 2014). additionally, an inherent responsibility of veterinary medicine is the protection of human health via caring for livestock and its reproduction. major aspects are to ensure sufficient food production, to prevent infectious animal diseases including zoonoses and food borne diseases, and high quality and safety of foods and other products derived from animals. in that regard, ebvm prompts the search for and utilization of information that are valid. evidence levels are indicators of the strength of study designs to be not prone to bias (cockcroft et al., 2003). the hierarchy of evidence aims not to completely disregard data from low evidence sources but alerts the clinician to the critical appraisal of the available information (lohr, 2004). veterinary professional education has historically relied more on establishing solid foundations in physiology and pathophysiology and providing venues for experiential learning than it has on rigorous analytic training (arlt et al., 2014). to be able to practice ebvm students and practitioners should become competent in defining a clinical problem, retrieving of information from the literature and independent critical thinking (steele et al., 2013). the body of published evidence on how to teach ebvm is small. some papers of good quality are available but further research is required to determine the effects of timing, content and length of ebm and ebvm courses and teaching methods (ilic et al., 2014). our survey reveals a dearth of ebvm knowledge of 5th semester veterinary students because only 9% stated that they had heard about ebvm. in addition, 2 participants seem to have engaged in evidence based medicine resulting in 11 people that stated to be able to explain ebvm and its aims. due to the fact that only 5th semester veterinary students of the freie universität berlin were included, one might question the representativeness of our survey. by choosing only 5th semester students we tried to ensure that most students did not know ebvm and the pyramid metaphor in advance to avoid bias based on previous knowledge. as stated above, the graphic representation of a pyramid is well known and supposed to be intuitively to comprehend for the reader. its concept consists of a solid foundation and a sharp tip. one of the probably most popular pyramid schematics is the food guide pyramid (achterberg et al., 1994). it was introduced in 1992 and displays how a diet for humans should be designed (davis et al., 2001). the basis of nutrition should be bread, cereals, rice and pasta, illustrated by the foundation of the pyramid. above this, vegetables and fruits are pictured, followed by milk-products, meat, eggs and nuts, meaning that these components are important but should be less consumed than items of the bread group. at the top a group containing fat, oils and sweets is represented. these products should be consumed sparingly. according to achterberg et al. (1994) the pyramid also illustrates that the consumer can choose foods from a variety within a group but should rely on the illustrated proportions. another example is the learning pyramid (bale, 2006) presenting the success of learning obtained via different techniques and media. the lowest retention rate is obtained by visiting lectures, presented at the top of the pyramid. the most successful methods are presented at the basis. these examples show that the metaphorical concept of the pyramid is usually used presenting the best or most important categories at the broad basis. according to our results both metaphors adequately display the hierarchy of evidence, i. e. that the quality of information is better when displayed at the top. the staircase better represents the fact that high evidence information is more likely to be true and that one should start to look for high evidence when searching information. these core principles are of high relevance in the context of teaching the principles of ebvm. in contrary, we presented statements indicating a disorientation of the reader. more students found that the pyramid represents that opinions and information from the internet provide a solid knowledge base. even if the internet and opinions of colleagues play important roles in the search for veterinary information (haimerl et al., 2013) they provide weak evidence as stated above. the foundation of a building represents a sound and solid basis for the superstructure. in regard to evidence levels one may argue that high evidence is indeed placed on a basis of less good evidence since rcts are often based on findings of uncontrolled studies or case reports. nevertheless, the pyramid of evidence may lead to an overestimation of the scientific value of publications of low evidence. in fact, this kind of information should be integrated in systematic reviews and critically appraised topics (vandeweerd et al., 2012a). however, as soon as high quality research results from randomised, controlled clinical trials are available, not too much importance should be attached to data of low evidence. integration of low quality results, however, may help to enhance the number of probands, to judge practical applicability of interventions or to identify sources of heterogeneity between different results (lean et al., 2009). an option would be to display the pyramid upside down, so that level 1 evidence is illustrated as the broadest. however, this may misleadingly be interpreted that a high number of level 1 evidence resources is available. finally, more students found that the pyramid better represents that more information of low evidence is available. many authors who evaluated literature in human (lohr, 2004) and veterinary medicine (arlt et al., 2010; simoneit et al., 2011) demonstrated that in the majority of topics numerous case reports, several clinical trials with or without a control group and only few metaanalyses could be found. this means, that in progressing from the bottom towards the top of the pyramid, the number of information available tends to decrease (sargeant et al., 2014a). this frequency distribution is to a certain extend represented by the pyramid. nevertheless, it can be assumed that the percentage of high quality publications will increase during the next years. in addition, this characteristic might distract the reader from the actual aims of consideration of the hierarchy of evidence. based on our findings, we suggest using the staircase metaphor in teaching contexts. in addition, using animated slides in a presentation the reading pictogram character could go down the staircase step by step while the lecturer explains the characteristics of every evidence level. two students suggested that the character should walk upstairs. however, when we discussed this issue with 4th year students attending the clinical rotation (n = 17) all were of the opinion that the literature search process is better represented by a character walking downstairs. when teaching evidence levels additional limitations should be taken into account and be discussed with the students. a special issue is the opinion, usually categorized as evidence level four. opinions, results from consensus meetings or information based on pathophysiological principles that are not supported by information of higher evidence are in general prone to bias. if an opinion or a consensus report is based on valid research data it may be regarded belonging to a higher evidence level. this categorisation does not want to completely disregard the advice of experts with a high expertise in their field. nevertheless, also recommendations of experts may be outdated or incomplete (antman et al., 1992). hence, it should always be questioned what the expert´s advice is based on and if he or she is aware of possible limitations of the underlying information. furthermore, important issues related to the rating of evidence have been discussed controversially (balshem et al., 2011). there is overlap between the different levels in the hierarchy since well-designed cohort studies may provide better evidence than poorly designed rct (cockcroft et al., 2003). it is challenging for example to evaluate the strength of evidence based on flawed rct compared to well-conducted non–rct (gugiu et al., 2010). science-based information regarding the repeatability of assessments of evidence levels is scarce (simoneit et al., 2012). therefore, it has to be emphasized again that all quality aspects of every individual study or information have to be appraised (arlt et al., 2005; schmidt, 2007). methods & materials on wednesday 10th and friday 12th of december 2014, we conducted a survey among veterinary medical students in their 5th semester (3rd year) attending a lecture about clinical propaedeutics in animal reproduction. at the beginning of the lecture held by a lecturer of the clinic for animal reproduction, students were asked to voluntarily and anonymously participate in a survey (convenience sample). completion of the survey indicated informed consent and took approximately 10 minutes. the survey contained questions concerning age, semester, and gender and existing knowledge about ebvm. in a short text limited information was provided to enable understanding of the context of the survey but avoiding bias caused by specific information: “veterinary practitioners have to use optimal diagnostics, interventions and medications to examine and to treat their patients. therefore, it is important to base clinical decisions on recent and valid information. high evidence in this context means that information e. g. on the outcomes of a certain therapy can be generalized to other cases. when searching for information sources of high evidence should always be preferred compared to low level evidence information.” on the rear page, the pyramid and the staircase metaphors were presented. to avoid a bias based on the order of the metaphors the wednesday group found the pyramid metaphor on the left and the friday group on the right, respectively. below the figures statements were presented as pairs referring to the respective metaphor above. participants responded to the statements using a three-point likert scale (see below). a free text comment section was provided at the end of the survey. the descriptive statistical analysis was performed using the statistical program spss for windows (version 22.0; spss inc., munich, germany). we hypothesized that the responses to the specific statements did not differ. the data were considered to be quantitative. the data were analyzed using the qi square test, expected frequencies and standardized residuals. the significance level was set as α = 0.05. the free text comment section was considered qualitative data. conclusions several authors have pointed out the need to train students and physicians in evidence-based medicine (arlt et al., 2014; hardin et al., 2006; nault et al., 2011; weiner et al., 2011). this need was confirmed by our survey among 5th semester students. especially for introducing the concepts and levels of evidence an easily interpreted and intuitively accessible schematic would be helpful. the staircase of evidence better represents the evidentiary value of information and displays better how to perform a search for information of high evidence compared to the pyramid of evidence. references achterberg, c.; mcdonnell, e. and  bagby, r. 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(2013): online tools for teaching evidence-based veterinary medicine. journal of veterinary medical education 40(3). pp 272-277 http://dx.doi.org/10.3138/jvme.0113-010r1 straus, s. e.and  sackett, d. l. (1998):using research findings in clinical practice. british medical journal 317(339). pp 339-342 http://dx.doi.org/10.1136/bmj.317.7154.339 vandeweerd, j. m. et al. (2012a):using systematic reviews to critically appraise the scientific information for the bovine veterinarian. veterinary clinics of  north america: food animal practice 28(1).pp 13-21 http://dx.doi.org/10.1016/j.cvfa.2011.12.002 vandeweerd, j. m. et al. (2012b): is evidence-based medicine so evident in veterinary research and practice? history, obstacles and perspectives. veterinary journal 191(1) pp 28–34 http://dx.doi.org/10.1016/j.tvjl.2011.04.013 weiner, s. a.; stephens, g.and  nour, a. y. m. (2011): information-seeking behaviours of first-semester veterinary students: a preliminary report. journal of veterinary medical education 38(1) pp 21-32 http://dx.doi.org/10.3138/jvme.38.1.21 supplementary figures & tables all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form,and will in return retain certain rights as detailed on the form. the use of antibiotics in broodmares with post-service endometritis a knowledge summary by elizabeth barter bvsc, mrcvs 1* annalisa barrelet bvetmed, msc, certesm, mrcvs 1 1rossdales and partners, beaufort cottage laboratories, high street newmarket, suffolk cb8 8js *corresponding author (ebarter@bigpond.net.au) vol 3, issue 1 (2017) published: 19 jan 2018 reviewed by: polly compston (bsc (hons), bvm&s, msc) and adam swallow (bvsc, afhea, mrcvs) next review date: 20 mar 2019 doi: 10.18849/ve.v3i1.132 clinical bottom line there is currently a lack of evidence to suggest that antibiotics delivered into the uterus post-service improves pregnancy rates. the evidence does support that post-service treatment with or without antibiotics improves pregnancy rates in mares with endometritis compared to no treatment (pregnancy rates between 40-90% compared to 0-56% respectively). the studies further identify the need to recognise mares at risk of post-service endometritis to target appropriate therapy. question in broodmares with post-service endometritis after natural cover, is antibiotic intervention superior to other routine therapies without antibiotic intervention in increasing pregnancy rates? clinical scenario it is well recognised that endometritis decreases pregnancy rates (le blanc and cause 2009). however, there is no clear definition of post-service endometritis (le blanc and cause 2009). when mares are presented post-service, and suspected to have endometritis a decision is required by the clinician to use or not use antibiotics in combination with other routine therapies such as uterine flushing and ecbolic agents. it is often unknown when the clinician is making an assessment if the endometritis is infectious or sterile in origin and mares are currently recommended to be treated with antibiotics regardless of cause (morel 2003; blanchard et.al., 2000). the use of antibiotics should be evidence-based to minimise the risk of microbial resistance and opportunist fungal infections (assad et.al. 2015). the evidence seven publications were identified in the literature searches. these comprised 2 descriptive studies, 1 observational study, 2 randomised non-blinded controlled trials and 2 non-randomised non-blinded controlled trials. included publications were of level 3 (randomised control trials) or level 4 (lower quality controlled trial) (ocebm levels of evidence working group). the outcomes studied varied between the studies including pregnancy rates at 15 days (pycock and newcombe 1996; gores-lindholm et.al. 2013; sharma et.al. 2011), 45 days (el-roos 2004), 60 days (noseir 2002; taha 2007), or unknown (pascoe 1990). further, there was no standard population treated, antibiotic prescribed or method of administration between the studies. in the three studies with no case selection any treatment was seen to benefit pregnancy rates over no treatment at all (pycock and newcombe 1996; pascoe 1990; el-roos 2004). this is similar to mares with a previous history of endometritis with a significantly higher pregnancy rate in mares treated with antibiotics and ecbolic agents compared to no treatment at all (noseir 2002; taha 2007). in the two studies which compared mares with and without signs of endometritis and treatment with antibiotics, higher pregnancy rates were achieved in mares that were not treated and had no signs of endometritis (sharma et al., 2011; gores-lindholm et.al., 2013). the findings support the need for case selection in treating mares with post-service induced endometritis. summary of the evidence pycock (1996) population: 574 thoroughbreds, 647 hunters (crossbreds) and 46 pony types with ages ranging from 3-22 years and mixed reproductive status (maiden, barren, post-parturient) sample size: n = 1267 intervention details: mares were assigned in rotation to one of four treatment groups. group 1: no treatment (n=322) group 2: intrauterine antibiotic treatment within 72 hours of mating (1200mg procaine penicillin combined with 1500mg dihydrostreptomycin and 900mgs framycetin made to a volume of 12 mls or neomycin (1g) polymyxin b (40,000 iu) and furaltadone (600mg) with crystalline benzylpenicillin (3g). (n=317) group 3: oxytocin (25 iu) administered by iv injection within 72 hours of mating (n=316) group 4: oxytocin (25 iu) administered iv followed 30mins later by intrauterine antibiotics as described for group 2 within 72 hours after mating (n=314) study design: prospective non-blinded, non-randomised controlledtrial outcome studied: ultrasound pregnancy detection on day 13, 14, or 15 post ovulation and repeat examination between 27-30 days after ovulation. early embryonic death rate determined by the presence of a vesicle at first scan and absence at second scan main findings (relevant to pico question): any treatment (oxytocin alone or in combination with intrauterine antibiotics) significantly increased pregnancy rates over untreated control mare (control pregnancy rate 56%) no difference in pregnancy rates between group 2 (intrauterine antibiotics) (64%) and group 3 (oxytocin) mares (63%) mares in group 4 (intrauterine antibiotics and oxytocin) had higher pregnancy rates than mares in group 2 and group 3 (group 4 pregnancy rate 72%) no difference in early embryonic loss between treatment groups limitations: mares were not subject to any diagnostic procedure to confirm the presence or absence of infection prior to antibiotic treatment there was no data pertaining to presence of clinical or subclinical signs of endometritis such as intraluminal fluid within the groups prior to treatment unknown spread of ages and reproductive status (barren, maiden, post-parturient) within groups unknown if mares were selected at foal heat or recruited to the study after multiple mating attempts during the season pascoe (1990) population: unknown population of foaling mares bred on foal heat, short cycled and bred at 18 days or bred after 30 days sample size: n = 1090 intervention details: mares were treated post ovulation with plasma and intrauterine antibiotic (n=420 composed of foal heat n=240; short cycled n=100; and bred after 30 days n=80), intrauterine antibiotic alone (n= 450 composed of foal heat n=240; short cycled n=100; and bred after 30 days n=110) or control no treatment (n= 220 composed of foal heat n=120; short cycled n=50; and bred after 30 days n=50). (antibiotic used was 6 million iu procaine penicillin and 4gm neomycin sulphate) study design: observational study outcome studied: conception rate (unknown determination) main findings (relevant to pico question): in mares that were short cycled plasma and antibiotic infusion increased conception rates by 30% compared to mares that had no treatment. mares bred on foal heat had higher conception rates when treated with plasma and antibiotic infusion (74%) or antibiotic infusion (64%) alone, than no treatment (52%) limitations: the population of mares within groups regarding age, reproductive status, previous endometritis and breed is unknown. no statistical analysis was performed to determine the significance of the findings no data regarding signs of clinical or subclinical endometritis within the groups taya (2007) population: arabian maiden mares ranging from 4 to 8 years with a diagnosis of persistent mating induced endometritis. mares were determined to have persistent mating induced endometritis if they met one of 3 criteria: a history of repeat breeding (more than 3 natural services and no signs of pregnancy) intrauterine fluid present one/two days after breeding or endometrial cytology showing >5% pmn cells sample size: n = 42 intervention details: mares 6 hours after breeding received a uterine lavage with antibiotics (n=36). 8 hours after breeding mares were divided into 3 groups (n=12 in each group) and received either prostaglandin (250ug cloprostenol sc), or oxytocin (20 i.u im), or no treatment. control mares (n=6) received no treatment. uterine lavage was performed with 500ml n-saline containing 4 million iu of crystalline penicillin and 4g streptomycin sulphate. study design: prospective, randomised, non-blinded controlled trial outcome studied: pregnancy rate after 2 months of treatment main findings (relevant to pico question): there was a significantly higher pregnancy rate in mares that had a uterine lavage containing antibiotics and an injection of prostaglandin (83.3%) compared to other treatment groups there was no difference in pregnancy rates between mares receiving antibiotic lavage alone (50%) or combined with oxytocin (66.6%) all treatments significantly increased pregnancy rates over control (untreated) mares (0%) limitations: no comparison was made to treatment without antibiotics such as oxytocin alone no description of how randomisation was performed and if mares were randomised based on criteria for selection into the study between treatment groups unusual antibiotic delivery through lavage system and unusual cytology performed from antibiotic flush no cytology or culture performed prior to antibiotic lavage no evidence of other complicating factors such as presence of fluid or uterine oedema gores-lindholm (2013) population: mares aged 4-24 years majority thoroughbred (3 standard bred and 1 quarter horse) sample size: n = 154 intervention details: mares were client owned and divided into groups based on endometrial swab and culture results obtained pre-breeding. group 1 (n=44): repeat breeders that had clinical findings suggestive of mucus over-secretion with no evidence of bacterial infection from culture of uterine lavage fluids. mares were treated with n-acetylcysteine (nac) 24-36 hours prior to cover followed by oxytocin (20 iu im) 4-8 hours after infusion group 2 (n=85): control group of reproductively normal mares presented on their first cycle showing no evidence of infection or inflammation on swab and cytology and intra-uterine fluid <5mm group 3 (n=25): mares that had previous positive uterine cultures treated with lavage and antibiotics on previous cycle and no evidence of mucus over-secretion, intrauterine fluid >1cm mares within these groups were additionally treated with intrauterine antibiotics (1g ceftiofur) dependent on previous history and farm management preferences. study design: descriptive study outcome studied: first cycle pregnancy rate between 13 and 15 days main findings (relevant to pico question): in mares that were suggestive to have mucous over secretion (group 1) there was no significant difference in first cycle pregnancy rates between mares receiving antibiotics and nac and those not receiving antibiotics (80% and 71% respectively) similarly, in mares that had previously been treated for endometritis (group 3) there was no significant difference in pregnancy rates between mares treated with lavage and oxytocin, and lavage, oxytocin and antibiotics (50% and 62% respectively) in mares with no history of endometritis (group 2) the pregnancy rate was higher for mares that were lavaged with lrs and given oxytocin (89%) than those additionally treated with antibiotics (60%) limitations: the study was aimed at assessing the potential for nac to be used to clear mucous and was not comparing antibiotics as post-service treatment the study was not blinded and it is not possible to tell why antibiotics were used or not used mares that previously swabbed clean may have been better identified with a low-volume lavage than uterine swab no separation of mare age or status in group 2 mares that had no evidence of infection, 80% of those treated with antibiotics had greater than 1cm of fluid or marked oedema 18-24 hours post-mating. there was only 18% of mares with greater than >1cm of fluid in mares treated with lrs and oxytocin alone noseir (2002) population: thoroughbred mares aged 10-15 years with a history of recurrent and persistent endometritis sample size: n = 36 intervention details: mares were assigned into 4 treatment groups post-mating (9 horses in each) group 1: untreated control group 2: intrauterine infusion of antibiotics (1200mg procaine penicillin with 1500 mg dihydrostreptomycin, and 1500mg gentamicin made up to 20mls) group 3: single intravenous injection 4-12 hours post-mating of oxytocin (20iu) group 4: intrauterine infusion of antibiotics and subsequently injected with oxytocin intravenously 30mins later study design: prospective, non-blinded, non-randomised, controlled trial outcome studied: pregnancy rates at 60 days post mating either by palpation or rectal ultrasound main findings (relevant to pico question): there was no significant difference in pregnancy rates between mares receiving intrauterine antibiotics alone (57.3%)or oxytocin administration alone (52.5%). there was, however, a significantly higher pregnancy rate between mares receiving antibiotics combined with oxytocin (67.8%) compared to other treatment groups. there was a significantly higher pregnancy rate in all treatment groups compared to the control (22.5%). limitations: small sample size and low power no definition given of recurrent and persistent endometritis no evaluation of contributing factors such as mare status barren or rested no available data on changes to early embryonic loss with late pregnancy diagnosis a higher proportion of mares that received no treatment had between 6mm and20mm of fluid (7 mares) compared to mares that were treated with antibiotics and oxytocin (3 mares) no evidence of assessment of underlying bacterial endometritis from swab or culture results prior to cover el-roos (2003) population: native bred mares both barren and lactating sample size: n = 115 (60 barren and 55 lactating) intervention details: post-breeding mares were randomly assigned into 9 treatment groups. group 1: no treatment (control) (n=13, 7 barren, 6 lactating) group 2: intrauterine infusion of 120mls of homologues plasma (n=15, 7 barren, 8 lactating) group 3: intrauterine infusion of leukocyte enriched plasma (n=14, 7 barren, 7 lactating) group 4: intrauterine infusion of antibiotics (5x106 iu procaine penicillin and 2g streptomycin sulphate) (n=11, 6 barren, 5 lactating) group 5: intrauterine infusion of plasma and antibiotics (n=12, 6 barren, 6 lactating) group 6: intrauterine infusion of antibiotics and leukocyte enriched homologous plasma (n=13, 7 barren, 6 lactating) group 7: intravenous injection with oxytocin at 0, 12, and 16 hours post breeding (n=11, 6 barren, 5 lactating) group 8: intrauterine infusion with homologous plasma and intravenous oxytocin given at breeding. (n=12, 6 barren, 6 lactating) group 9: intrauterine infusion of leukocyte enriched homologous plasma and intravenous oxytocin given at breeding (n=14, 8 barren, 6 lactating). breeding and treatment was repeated every 48 hours until ovulation was detected study design: prospective, non-blinded, randomised controlled trial outcome studied: pregnancy confirmed by ultrasound at 45 days main findings (relevant to pico question): higher pregnancy rates were achieved with the combination of leukocyte enriched plasma and oxytocin (72%), compared to leukocyte enriched plasma and antibiotics (61%) limitations: unknown randomisation method, low statistical power, and lack of statistical tests performed mares received double guarded swabs for culture prior to cover; however a mare with a positive culture (current endometritis) was not excluded from the trial. the distribution of mares with endometritis prior to cover was unknown between the groups unknown presence of clinical or subclinical signs of endometritis between groups unknown age distribution of mares and inclusion of maiden, barren and foal heat mares sharma (2011) population: thoroughbred mares in india aged from 3 years to greater than 18 years sample size: n = 253 mares, (n= 1976 oestrous cycles) intervention details: untreated oestrous cycles (n=1619) (control) with treated oestrous cycles (n=357) receiving either: intrauterine antibiotics (n=57) uterine lavage (n=30) oxytocin (n=55) intrauterine antibiotics with oxytocin (n=90) uterine lavage plus oxytocin (n=50) intrauterine lavage plus antibiotics (n=39) intrauterine lavage, intrauterine antibiotics, and oxytocin (n=36) study design: descriptive study outcome studied: day 16 and day 39 pregnancy rates main findings (relevant to pico question): significantly higher (p<0.05) day 39 pregnancy rates and foaling rates observed in untreated oestrous cycles (46.39%) than treated cycles (40.62%). no difference in pregnancy rates between treated oestrous cycle and untreated oestrous cycle at day 16 of pregnancy (46% and 51% respectively) the incidence of uterine therapies increased with increasing age limitations: there were no criteria defined to determine which treatment option was chosen and the duration of treatment antibiotic choice and method of administration not discussed unclear at what time antibiotics were used post ovulation and if other methods were used prior to cover no prior history of mares to determine spread of barren, maiden or foaling mares and if endometritis was present prior to cover appraisal, application and reflection post-service endometritis is a common condition and can be challenging for the clinician to diagnose and treat. current treatment options for endometritis include intrauterine antibiotics, lavages (lrs or antibiotic infused), other uterine infusions such as mucolytics (nac, edta), immune modulation treatments (plasma), and ecbolic agents (oxytocin and / or prostaglandin). the purpose of this knowledge summary was to evaluate the evidence comparing the use of intrauterine antibiotics in the treatment of endometritis to other routine therapies. the diagnosis of post-service endometritis can be challenging for the clinician and varied between the studies. 4/7 studies compared treatments in mares affected by endometritis whilst the remaining studies compared treatment in all mares. two studies gave descriptions of how they diagnosed endometritis. sharma et.al., (2011) and noseir (2002) treated mares with endometritis with no definition stated. taha (2007) defined persistent mating induced endometritis as a history of repeat breeding of more than 3 natural services without a pregnancy, intrauterine fluid one to two days after breeding, or endometrial cytology showing >5% pmn’s. gores-lindholm et.al., (2013) diagnosed endometritis based on previous cycle uterine lavage fluid with a positive culture, repeat breeding of at least 2 cycles or 2 unsuccessful embryo transfer attempts. the lack of a consistent definition of endometritis makes comparison of treatment options challenging. the use of controls that did not receive antibiotics was highly variable amongst the studies. the most consistent comparisons used between the studies were either no treatment or ecbolic agents alone. 6/7 studies compared no treatment as a control (pycock and newcombe 1996; pascoe 1990; taha 2007; gores-lindholm et.al. 2013; noseir 2002; sharma et.al 2011), while 4/7 studies compared oxytocin at intervals ranging from 1-72 hours post mating [(pycock and newcombe 1996) 72 hours post mating, (noseir 2002) 4-12 hours post mating, (el-roos 2004) 1, 12, 16 hours post mating, (sharma et.al. 2011) unspecified time/s]. taya (2007) was the only study to evaluate the use of prostaglandin as an ecbolic agent. consistently it was observed that treatment of mares with endometritis improved pregnancy rates over no treatment at all (pycock and newcombe 1996; pascoe 1990; taha 2007; gores-lindholm et.al. 2013; noseir 2002; sharma et.al 2011). ecbolic agents and antibiotics had similar improvement to pregnancy rates when used alone (pycocok and newcombe 1996; noseir 2002). the combined effect of antibiotics and ecbolic agents were seen to act in synergy and further improve pregnancy rates (pycock and newcombe 1996; taya 2007; noseir 2002). intrauterine antibiotics have been postulated to not only aid in the treatment of potential pathogens but also by cervical dilation enhancing fluid removal (pycock and newcombe 1996). the combination of oxytocin to stimulate uterine evacuation and manual dilation of the cervix has been similarly treated with the use of plasma and uterine lavages (sharma et.al. 2011; gores-lindholm 2013; el-roos 2004). gores-lindholm (2013) demonstrated no significant difference in pregnancy rates for mares previously treated for endometritis with lavage and oxytocin (50%) compared to lavage, oxytocin and antibiotics (62%). similarly, sharma et.al (2011) showed no difference in day 16 pregnancy rates in mares treated with uterine lavage and oxytocin (52%) and intra-uterine antibiotics and oxytocin (45%). while the type, volume of antibiotic and method of antibiotic installation varied between the studies, all involved uterine placement which would have led to cervical dilation. supporting the use of antibiotics are culture and sensitivity studies. common bacterial isolates in endometritis include beta-haemolytic streptococcus, corynebacterium spp, and escherichia coli (assad et.al 2015). in all studies, the choice of antibiotic was empirical and not determined by culture and sensitivity results. four of the studies used a combination of procaine penicillin with streptomycin, gentamicin, framomycin, and or neomycin (pycock and newcombe 1996; pascoe 1990; taha 2007; noseir 2002) whilst one study used ceftiofur alone (gores-lindholm 2013). two studies did not comment on the antibiotic used (sharma et.al., 2011 ; el-roos 2004), and no studies commented on the use of systemic antibiotics. whilst the types of bacteria isolated are likely to vary geographically, assad et.al., (2015) showed all isolates were sensitive to gentamicin and ceftriazone (100%) followed by tetracycline and chloramphenicol (92.8%). there was widespread resistance against streptomycin (92.8%) and penicillin (50%) which were commonly used in the studies. sensitivity patterns varied based on which bacteria were isolated, with streptococcus spp having maximum sensitivity to gentamycin and tetracycline antibiotics (100%) and moderate sensitivity to penicillin (71.4%), while e. coli isolates were 100% resistant to ampicillin and streptomycin. indiscriminate use of antibiotics has shown to increase the risk of fungal and resistant bacterial species (assad et.al. 2015). further use of diagnostics to identify the bacterial isolate(s) involved, and antibiotic sensitivity, may aid in the reduction of restricted antibiotics such as tetracyclines and chloramphenicol. the outcome achieved varied between the studies, with different days of gestation considered. majority of the studies examined for pregnancy at 13-16 days (sharma et. al 2011; gores-lindholm et.al 2013; pycock and newcombe 1996), whilst two studies examined only later at 45 days (el-roos 2004), and 60 days (taha 2007). 2/7 studies (pycock and newcombe 1996; sharma et. al. 2011) commented on embryonic loss with uterine treatments by comparing pregnancy rates at 12-16 days to 28 days. there was no significant difference in embryonic loss in either study, however pycock and newcombe (1996) noted a higher embryonic loss when antibiotics were installed via a syringe compared to a catheter system. early embryonic loss is estimated to be between 2.6% to 24% due to progesterone deficiency or failure of maternal recognition (vanderwall 2008). such that the later scanning dates in the studies by el-roos (2004) and taya (2007) may have had a higher negative pregnancy rate from early embryonic loss rather than failure to conceive. post-service endometritis is a multifactorial disease and can be challenging to manage. currently the collective data supports the combined use of intrauterine treatments and ecbolic agents to increase pregnancy rates in mares with a history and or signs of endometritis. it is unclear if similar pregnancy results may be obtained with cervical dilation methods that do not include antibiotics in combination with ecbolic agents alone. further, this summary identifies the need for ongoing research into defining which mares have endometritis in order to determine those that may benefit from treatment. additional diagnostics such as culture and cytology of endometrial samples post-service could be utilised by clinicians to justify antibiotic usage. currently clinicians should use intrauterine antibiotics judiciously as they are unlikely to improve pregnancy rates and may be detrimental to fertility in mares with no history or signs of endometritis. glossary edta ethylenediaminetetraacetic acid lrs lactate ringer’s solution nac n-acetylcysteine pmn polymorphonuclear cell  methodology section search strategy databases searched and dates covered: search terms were applied in pubmed central accessed on ncbi website (1910-2017), cab abstracts database accessed on ovid platform (1973-2017) search terms: cab abs (equine* or horse* or equus or equid* or mare or mares or broodmares or 'brood mares' or pony or ponies).mp. or equidae/ or equus/ or horses/ or mares/ (endometritis or endometriosis or endometrial or metritis or uterine or uterus).mp. or endometritis/ or uterus/ (antibiotic or antibiotics or antimicrobial or antimicrobials or anti-microbial or anti-microbials or antibacterial or antibacterials or 'antiinfective agent' or 'antiinfective agents' or 'anti-infective agent' or 'anti-infective agents' or penicillin or gentamicin).mp. or exp antibacterial agents/ or exp antibiotics/ or exp antiinfective agents/ (post-service or 'post service' or postservice or mating or induced or breeding).mp. (pregnant or pregnancy or conception or conceiving or fertility or fertile or foal or foals).mp. or pregnancy/ or fertility/ 1 and 2 and 3 and 4 and 5   pubmed equine or horse or mare or mares or broodmares or brood mares or pony or ponies endometritis or endometriosis or endometrial or metritis or uterine or uterus antibiotic or antibiotics or antimicrobial or antimicrobials or anti-microbial or anti-microbials or antibacterial or antibacterials or 'antiinfective agent' or 'antiinfective agents' or 'anti-infective agent' or 'anti-infective agents' or penicillin or gentamicin post-service or post service or postservice or mating or induced or breeding pregnant or pregnancy or conception or conceiving or fertility or fertile or foal or foals 1 and 2 and 3 and 4 and 5 dates searches performed: march 2017 exclusion / inclusion criteria exclusion: non-english language, narrative or non-systematic review articles, unpublished data, pharmacokinetic, in vitro or in vivo experimental studies, artificial insemination protocols. inclusion: any reported use of antibiotics used in post-service treatment from natural coverings. search outcome database number of results excluded – non-english language publication excluded – non-systematic review article, conference proceeding or letter excluded – artificial chilled or frozen insemination excluded – pre-service treatment not post service excluded – did not answer pico question total relevant papers cab abstracts 53 3 15 6 2 20 7 ncbi pubmed 25 1 5 2 0 15 2 total relevant papers when duplicates removed 7 conflict of interest the authors declare no conflicts of interest. references ahmad, m., ahmad, n., mansoor, m.k. and samad, h.a., (2001) synergistic effect of antibiotics and oxytocin in the treatment of endometritis in mares. pakistan veterinary journal, 21 (4), pp. 202-205 assad, n.i., bugalla, n.s., chandolla, r.k. and sharma, a., (2015) isolation and antibiotic sensitivity of uterine microbial pathogensa study of 30 endometritis affected mares. intas pollivet, 16 (2), pp. 223-230 blanchard t.l., varner, d.d., schumacher j. love c.c., brinkso, s. and rigby s 2003, manual of equine reproduction ed. mosby, philadelphia, usa el-roos, m.e.a.a., (2004) some post-breeding treatments for improving fertility in mares. veterinary medical journal giza. 52, pp. 89-98 gores-lindholm, a.r., leblanc, m.m., causey, r., hitchborn, a., fayrer-hosken, r.a., kruger, m., vandenplas, m.l., flores, p. and ahlschwede, s., (2013) relationships between intrauterine infusion of n-acetylcysteine, equine endometrial pathology, neutrophil function, post-breeding therapy and reproductive performance. theriogenology. 80, pp. 218-227. doi: https://doi.org/10.1016/j.theriogenology.2013.03.026 leblanc, m.m. and causey, r.c., (2009) clinical and subclinical endometritis in the mare: both threats to fertility. reproduction in domestic animals. 44 (3), pp. 10-22. doi: http://dx.doi.org/10.1111/j.1439-0531.2009.01485.x morel m.c.g.d 2003. equine reproductive physiology, breeding and stud management 2 ed. wallingford, united kingdom: cabi noseir, w.m.b., (2002) effect of clearance of uterine fluid on pregnancy rate in mares susceptible to endometritis. veterinary medical journal giza. 50 (2), pp. 281-287 pascoe, d.r., 1990, effect of post breeding infusions on conception rates and foaling rates, proceedings of the twelfth bain-fallon memorial lectures, equestrian veterinarians australia, townsville, qld, pp. 187-192. pycock, j.f. and newcombe, j.r., (1996) assessment of the effect of three treatments to remove intrauterine fluid on pregnancy rate in the mare. the veterinary record. 138, pp. 320-323. doi: http://dx.doi.org/10.1136/vr.138.14.320 ricketts, s.w., (1997) treatment of equine endometritis with intrauterine irrigations of ceftiofur sodium: a comparison with mares treated in a similar manner with a mixture of sodium benzylpenicillin, neomycin sulphate, polymyxin b sulphate and furaltadone hydrochloride. pferdeheilkunde, 13 (5). pp. 486-489. doi: http://dx.doi.org/10.21836/pem19970510 sharma, s., dhaliwal, g.s., gosal, n.s. and varun., (2011) the impact of uterine therapies on reproductive efficiency in thoroughbred mares; the possible effect of mare age and reproductive status. veterinarski archiv, 81 (2), pp/ 163-173 taha, m.b., (2007) treatment of persistent mating induced endometritis in arabian maiden mares. journal of animal and veterinary advances.6 (5), pp. 718-722 vanderwall, d.k., (2008) early embryonic loss in the mare. journal of equine veterinary science, 28 (11). pp. 691-702. doi: http://dx.doi.org/10.1016/j.jevs.2008.10.001 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. tibial diaphyseal fracture rates following tibial tuberosity advancement rapid (ttar) and traditional tibial tuberosity advancement (ttta) a knowledge summary by wye li chong bvsc, manzcvs 1* 1canberra veterinary emergency service, 21 crinigan cir, gungahlin, act, 2912, australia *corresponding author (wyechong@gmail.com) vol 4, issue 1 (2019) published: 05 mar 2019 reviewed by: geoff robins (bvetmed, facvsc) and yves samoy (dvm, phd, dipecvsmr) next review date: 05 mar 2021 doi: 10.18849/ve.v4i1.179 pico question in dogs with cruciate disease, is the use of tta rapid (ttar) compared to traditional tta (ttta) associated with a higher risk of tibial diaphyseal fractures? clinical bottom line based on studies published between january 2013 and january 2018, the rate of tibial diaphyseal fractures as a complication of tibial tuberosity advancement rapid (ttar) surgery is within the published limits of traditional tibial tuberosity advancement (ttta). in this period, seven studies were related to ttta, comprising of four; one case series, two retrospective case-control studies, and one retrospective cohort study. five case series were related to ttar.  all evidence within this period has been observational (level 3 and 4 evidence). no direct head-to-head comparison between the techniques has been studied.  the evidence based on a literature search of the last 5 years (prior to 23 january 2018), there were seven pico related studies for ttta and five for ttar. of the articles for ttta, 3/7 were retrospective case series, 1/7 prospective case series, 2/7 retrospective case-controls and 1/7 retrospective cohort study. all ttar studies were case series. table 1: a summary of the strength of evidence summary of the evidence costa et al., (2017) ttta population: dogs sample size: 1613 intervention details: all dogs received perioperative cephazolin 22 mg/kg. all dogs received traditional tta procedure (kyon or medicatech vet). meniscal release or meniscectomy was performed based on preference. no bone grafts were placed on osteotomy site. all patients received postoperative coaptation. study design: retrospective case-control study outcome studied: major complication rates in dogs receiving tibial tuberosity advancement surgery and the effects of medial meniscal release on postoperative meniscal tear. main findings (relevant to pico question): major complication rate – 13.4% minor complications – not included medial meniscal tear 40.5% had medial meniscal injury and were treated with partial meniscectomy 59.4% had normal meniscus. 72.4% of these dogs had meniscal release. 0.5% of these dogs developed postliminary meniscal injury. 27.6% of dogs with normal meniscus did not receive meniscal release. 10.2% developed postliminary meniscal injury. postoperative patellar luxation 1.2% developed patellar luxation postoperatively. surgical site infection 6.9% of dogs developed superficial surgical site infection all were managed successfully with conservative treatment. 1.1% developed deep ssi necessitating surgical intervention. implant failure and fractures 1% of dogs had implant failure requiring revision surgery. 0.7% (11 dogs) developed fracture; 3/11 tibial diaphyseal fractures and 8/11 tibial tuberosity fracture. pico – three (0.18%) tibial diaphyseal fractures were reported. limitations: this study is retrospective and may be affected by bias in case selection and suitability for tta. factors that could have affected surgical outcome were not assessed, such as limb conformation or body condition score. minor complications were not assessed. being retrospective in nature, this study confuses the term incidence with prevalence. did not correlate the use of perioperative antibiotics and the development of surgical site infection. there was no power calculation. danielson et al., (2016) ttta population: dogs receiving single-session bilateral plated tibial tuberosity advancement. sample size: 148 stifle joints intervention details: single stage bilateral traditional tta. 68 tttas were performed with forked plates. 75 tttas were performed with screw plates. study design: retrospective case series outcome studied: short-term radiographic complication rates and healing scores in bilateral single-session ttas. main findings (relevant to pico question): overall radiographic complication rates of 17.6% (13/72 dogs), of which only one dog was considered to have major complications. minor complications in 12 dogs include forked plate displacement (6), tibial tuberosity fracture (4), screw failure (2) and cage displacement (1). forked plates had greater complications compared to screw plates. four stifle joints had tibial tuberosity fractures. pico – one stifle joint had tibial diaphyseal fractures (0.007%). limitations: the radiographic complications were evaluated by only one radiologist. the radiographic scoring system is subjective and may be prone to inter-operator variability. there is no control population (unilateral tta) used for comparison and testing of the null hypothesis. comparison was based on results of other studies. the outcomes of patients with major and minor complications were not reported. non-radiographic complications were not reported. statistical significance (p value) for comparing complications between forked and screw plates was not reported. proot & corr (2013) ttta population: 122 dogs sample size: 167 stifle joints intervention details: all dogs received plated tta by the same surgeon. dogs with meniscal pathology were partially or completely resected. dogs with intact meniscus were left in situ. consecutive records were plotted retrospectively using cumulation summation technique (cusum) to measure cumulative success for clinical audit and competence of a single surgeon over time. study design: retrospective case series outcome studied: cumulative success rates of a single general practitioner surgeon. major and minor complication rates. main findings (relevant to pico question): minor complications in 14/167 (8%) superficial wound infection (8/13) minor dehiscence (1/13) seroma (4/13) acute lameness responding to conservative treatment 3/13) septic arthritis not requiring surgery 1/13 major complications in 15/167 (9%) septic arthritis requiring surgery 3/15 tibial tuberosity fracture 3/13 medial patellar luxation 1/15 late meniscal injury (6/15) major dehiscence (1/15) severe patellar desmitis (1/15) overall success rate is 91% over 167 procedures. 22 procedures were required before the published veterinary surgeon became acceptably competent to perform ttta and have complications within published ranges. pico – 0 dogs had tibial diaphyseal fractures. limitations: this paper only measured success as the absence of complication rates, and not the clinical outcome. de lima dantas et al., (2016) ttta population: boxer vs. non-boxer dogs with cruciate disease sample size: 36 boxer stifle joints and 271 non-boxer stifle joints intervention details: all dogs received forked plate tta meniscus: 12/36 boxers and 94/271 non-boxers had cranial cruciate ligament remnant debrided. 8/36 boxers and 91/271 non-boxers had medial meniscal injury treated with partial meniscectomy. 2/36 boxers and 15/271 non-boxers had complete medial meniscectomy. 1/36 boxers and 3/271 non-boxers had medial meniscal release. 15/34 boxer and 111/250 non-boxer stifle joints received bone graft. antibiotics: 11/30 boxers and 123/264 non-boxers received amoxicillin-clavulanic acid perioperatively. 19/30 boxers and 141/264 non-boxers received cefuroxime perioperatively. 24/36 boxers and 152/271 non-boxers received antibiotics postoperatively. study design: retrospective cohort study outcome studied: incidence of major and minor complication rates associated with ttta in boxers vs. non-boxers. main findings (relevant to pico question): 14/36 (38.9%) boxers and 37/271 (13.6%) non-boxers had major complications (p < 0.001). 6/36 (16.7%) boxers and 6/271 (2.21%) non-boxers had minor complications (p = 0.003). 4/36 (11.1%) boxers and 22/271 (8.1%) non-boxers had late meniscal injury (p = 0.52). 7/36 (19.4%) boxers and 11/271 (4.1%) non-boxers had postoperative infections. boxers compared to non-boxers had an odds ratio of 5.78 of developing complication. 2/36 (5.6%) boxers had tibial tuberosity fractures compared to 1/271 (0.4%) non-boxers (p = 0.03). pico – 0 cases had tibial diaphyseal fractures. limitations: retrospective design predisposes the study population towards bias. complication rates were determined based on medical records of a referral hospital – this may have been underor over-estimated as it does not take into consideration complication rates detected by a referring veterinarian. this study includes complications by residents as well as specialists, which may influence the incidence due to the learning curve of residents. small number of boxer dogs compared to control population (36 vs. 271). no randomisation or blinding, which can lead to bias. kiefer et al., (2015) ttta population: dogs that underwent single-stage bilateral plated tta vs. unilateral plated tta sample size: 44 (88) bilateral tta (btta) vs. 86 unilateral tta (utta) intervention details: all dogs received plated tta system – manufacturer undefined. all dogs received commercial synthetic or cancellous bone graft on osteotomy site. some dogs received external coaptation (number undefined). all dogs were re-evaluated at: 10 weeks postoperatively to evaluate skin sutures 4 and 8 weeks for radiographs. study design: retrospective case-control outcome studied: major and minor complication rates of btta compared to utta at 4 and 8 weeks postoperatively. major complications defined as complications requiring further surgery. minor complications defined as any other complications. main findings (relevant to pico question): major complication rates (no significant difference) btta 11/88 (12.5%) vs. utta 2/86 (2.3%) minor complication rates (significantly different) btta 23/88 (26.1%) vs. utta 21/86 (24.4%) overall complication rate (no significant difference) btta 31/88(35.2%) vs. utta 21/86 (24.4%) fracture btta – 2/88 tibial diaphyseal fracture and 9/99 tibial tuberosity fracture utta – 1/88 tibial tuberosity fracture   pico – 2/88 (2.3%) tibial diaphyseal fracture in btta and 0/88 in utta limitations: retrospective design. ttta procedure was modified over time so there could have been more complications in earlier cases. postoperative care was not standardised. did not compare staged btta vs single-stage btta. relative risks were not reported. mcdonald et al., (2013) ttta population: skeletally mature dogs > 17 kg sample size: 24 dogs intervention details: all dogs underwent arthrotomy or arthroscopy. no dogs received meniscal release. partial meniscectomy performed in cases of meniscal injury. all dogs received plated securos surgical tta xgen system. all dogs received autologous cancellous bone graft into osteotomy space. all dogs received exercise restriction for 6 weeks. study design: prospective case series outcome studied: complications, lameness, thigh circumference, range of motion, radiographic osteoarthritis at 6 weeks, 6 months, and 1 year. main findings (relevant to pico question): postoperative complications 8/24 (33.3%) ssi 2/24 – resolved with antibiotics. fracture of tibial tuberosity 1/24. recurrent lameness 6/24 dogs – responded to conservative management. pico – 0 dogs had tibial diaphyseal fracture. limitations: very small sample size. utilised thigh circumference (tc) and range of motion (rom) as a measure of limb use, as opposed to peak vertical forces. postoperative rehabilitation was performed on some dogs and not others, which may influence tc and rom. clinical outcomes were subjectively measured using lameness score. follow up radiographic signs of osteoarthritis were measured subjectively by one certified radiologist. hans et al., (2017) ttta population: large breed dog > 50kg sample size: 145 stifle joints intervention details: 91 stifle joints received securos surgical tta xgen plated system 54 stifle joints received tibial plateau leveling osteotomy (tplo) study design: retrospective case-control outcome studied: major and minor complication rates of tta compared to tplo in large breed dogs. the null hypothesis is that there is a difference in major complications between the two techniques, based on medical records. main findings (relevant to pico question): tta group overall complication – 33% major complication rate 18/91 (19.8%) 14/91 surgical site infection 4/91 tibial tuberosity fracture 1/91 stifle joint receiving tta resulted in diaphyseal fracture 4/91 required implant removal one case concurrent tibial tuberosity fracture and ssi minor complication rate – 13/91 (13.2%) seroma – 7/91 minimally displaced tibial tuberosity fracture 3/91 remainder – patellar desmitis, incidental implant breakage and incisional dehiscence pico – 1/91 (1.1%) cases had tibial diaphyseal fracture                   tplo group major complications – 15/54 (27.8%) 14/54 (25.9%) surgical site infection 8/54 (14.8%) required implant removal minor complication – 12/54 (22.2%) 7/54 seroma 2/54 incisional irritation 2/54 fibular fracture limitations: surgeries were performed either by a specialist or resident. however, a comparison between the two groups was not analysed. the power of the study was not indicated. authors did not declare how many dogs were censored and excluded for not meeting the inclusion criteria. lack of randomisation. reliance on medical record accuracy. declared conflict of interest from one of the authors, who receives royalties for securos surgical xgen tta system. butterworth & kydd (2017) ttar population: dogs with cruciate disease sample size: 141 clinically lame dogs, 152 stifle joints intervention details: all dogs received ttar surgery. no dogs received meniscal release. all but four dogs received nanocrystalline hydroxyapatite paste on osteotomy gap. study design: case series outcome studied: subjective evidence of lameness and complications by clinical assessment at 3 months, and validated questionnaire at >6 months postoperatively. main findings (relevant to pico question): outcome was considered clinically satisfactory in 99% of 135 dogs 3 months postoperatively and 86% of 108 dogs in owner questionnaire. 44/152 (29%) of stifle joints had medial meniscal injury requiring meniscectomy 9/108 (8%) developed late meniscal injury 3/152 (1.97%) stifle joints developed ssi treated adequately with antibiotics 2/152 (1.3%) developed fracture of the tibial tuberosity tibial osteotomy gap healed at a mean and median of 7.94 and 7 weeks. pico – 1/152 (0.66%) developed tibial diaphyseal fracture treated by internal fixation. limitations: medium term follow-up was conducted using owner-assessed questionnaire. outcome was based on subjective clinical exam. number of cage size and number of breeds were reported but not correlated against each other. no control group for comparison. samoy et al., (2015) ttar population: dogs with unilateral cruciate disease sample size: 50 dogs intervention details: all dogs received amoxicillin clavulanic acid 8.75 mg subcutaneously preoperatively. all dogs received ttar surgery. all dogs received meniscal release. all dogs received hydroxylapatite bone paste onto osteotomy gap. all dogs had external coaptation for 2–3 days postoperatively. all dogs received postoperative antibiotics for 5 days. study design: prospective case series outcome studied: outcomes, minor and major complication rates. main findings (relevant to pico question): 42% of dogs had medial meniscal injury. all owners were satisfied with outcome of surgery. subjective assessment at 3 months postoperatively showed 28 dogs (56%) had an excellent outcome, 20 dogs (40%) had a good outcome and two dogs (4%) had a moderate outcome (one clinical healing and one complete healing of the osteotomy). 15/50 (30%) of dogs had undefined minor complication (undefined). 2/50 (4%) dogs developed tibial tuberosity fracture; only one required surgical revision. pico – 0% of dogs developed tibial diaphyseal fracture limitations: postliminary meniscal injury not reported. unclear if ssi did not develop or was unreported. small sample size. short follow-up times (3 months). not tested against a control group. not all dogs received surgery with the aid of a saw guide. outcome was based on subjective clinical exam only. conflict of interest that the developer of the technique is also the primary author. dyall & schmokel (2017) ttar population: small breed dog – mean weight 9 kg (4.8–15 kg) sample size: 48 stifle joints intervention details: 40 small breed dogs (48 stifle joints) received ttar surgery. 19/48 stifle joints received ttar with maquet hole, 29/48 had no maquet hole. no dogs received meniscal release. no dogs received bone graft. all dogs were on exercise restriction for 6 weeks. study design: retrospective case series outcome studied: lameness and postoperative complications at 6 weeks were measured by clinical examination and owner questionnaire assessment at midto long-term follow up (median 72 weeks). main findings (relevant to pico question): major complication rate 7/48 (14.6%) infection – 1/48 (0.02%) medial meniscal injury noted in 19/48 (40%) late meniscal injury rate 2/48 (4.7%) 2/48 developed tibial tuberosity fracture requiring surgical stabilisation 1/19 (5.26%) stifle joints with maquet hole resulted in tibial diaphyseal fracture 1/29 (3.45%) stifle joints without maquet hole resulted in tibial diaphyseal fracture 2/48 (4.17%) stifle joints in total resulted in tibial diaphyseal fracture pico – 2/48 (4.17%) developed tibial diaphyseal fracture limitations: small sample size. outcome was measured by subjective client questionnaire that has not been validated. no control group or comparison with an alternative technique. lack of objective outcome criteria. arican et al., (2017) ttar population: dogs receiving ttar sample size: 17 intervention details: 17 stifle joints received ttar surgery with maquet hole all dogs received perioperative antibiotics amoxicillin clavulanic acid (8.75 mg/kg subcutaneously) all dogs received carprofen 4 mg/kg perioperative analgesia all dogs received 3 days postoperative meloxicam 1 mg/kg (intramuscular) and 5 days amoxicillin clavulanic acid (undeclared dose). study design: case series outcome studied: minor complications and major complications. lameness and pain assessment 1, 2 and 3 months postoperatively. main findings (relevant to pico question): minor complication rate was 25%. major complication rate is 17.6% (4/17 dogs). tibial crest fracture occurred in 2/17 fractures; only one required surgery. pico – 0/17 stifle joints receiving ttar resulted in tibial diaphyseal fracture. limitations: meniscal findings and injury rate not reported. minor complications were not defined. the outcomes were measured subjectively using visual analogue scales. a clinician was used to assess outcome with blinding and control but the control was not defined. competency of the surgeon was not defined (specialist vs. resident vs. general practitioner). this study has a very small sample size for assessment of complication rates. there is no control group to assess if there would be improvement with no treatment. de sousa et al., (2017) plateless tta population: dogs that received plateless tta with complications of tibial diaphyseal fracture sample size: 17 dogs; 11/17 received orthofoam–mmp procedure, 6/17 received ttar procedure intervention details: all 17 dogs received revision surgery to correct tibial tuberosity fracture by various forms of internal fixation. study design: case series outcome studied: outcome, major and minor complication following repair of tibial diaphyseal fracture secondary to complication of plateless tta techniques. main findings (relevant to pico question): overall complication rate – 8/17 (47%) minor complication rate – 3/17 (17.6%) major complication rate – 5/17 (29.4%) surgical site infection – 4/17 (23.5%) pico ttar n = 6 major complication – 0/6 minor complication – 2/6 limitations: small sample size – 6 ttar and 11 orthofoam-modified maquet procedure. variation in surgeons managing complication – six boarded specialist vs. four rcvs certificate qualified veterinary surgeons. owner compliance to original procedure was not measured or accounted for. incidence of these tibial diaphyseal fractures could not be determined. no comparison with fracture complications from traditional tta methods. appraisal, application and reflection since the advent of ttta in 2002 (montavon et al., 2002), various second generation tta procedures have been invented. these techniques (ttar, orthofoam-mmp, mmt, tta–2) utilise custom saw guides to aid the surgeon in producing an incomplete osteotomy of the tibial tuberosity. they have different implant designs, and they eliminate the use of a supporting plate (ness 2016 samoy et al., 2015, bleakley 2015, brunel et al., 2013). these techniques are generally aimed at the non-specialist surgeon and are marketed to be simpler than ttta while offering comparable results. a recent case series of 17 dogs (de sousa et al, 2017) suggests that tibial diaphyseal fractures may be a well-recognised catastrophic complication of second generation tta techniques. however, the study design could not evaluate the actual incidence or prevalence of this complication. figure 1: example of tibial diaphyseal fracture as a complication of ttar technique. table 2: based on recent (< 5 years) studies relevant to the pico, tibial diaphyseal fractures are reported in the table. while not directly related to the pico, tibial tuberosity fractures are also included. from this table, the rate of tibial diaphyseal fractures from ttta (0–2.3%) compared to ttar (0–4.17%) are roughly comparable. in the ttar group, dyall & schmokel’s (2017) report of 4.17% tibial diaphyseal fractures using ttar on small breed dogs (< 15 kg) was notably higher than the other three studies. the higher fracture rate was attributed to the relatively large cage size, which may have overwhelmed the elasticity of the cranial tibial cortex, predisposing to fracture. if small breed dogs were excluded from the comparison then the rate of tibial diaphyseal fractures for ttar would be 0–0.7%, which is within the published limits for ttta (0–2.3%). a two-tailed t test (https://www.socscistatistics.com/tests/studentttest/default2.aspx) comparing ttar (0, 0, 0.7, 4.17) vs ttta (0.18, 0.7, 0, 0, 2.27, 0, 1.1) reveals t-value of 0.7246 and p-value of 0.487105, showing a lack of significance at p < 0.05, although the sample size is very small. interestingly, tibial tuberosity fractures, while not directly related to the pico, occur more commonly across studies. in ttta, a complete osteotomy of the tuberosity is held in place by a forked or screw plate. fractures are generally attributed to poor plate and cage positioning, as well as narrow tuberosity width postosteotomy (costa et al., 2017). in ttar, the osteotomy is incomplete leaving the distal hinge intact. fractures through the distal hinge were considered as tibial tuberosity fractures across the ttar studies (butterworth & kydd (2017), samoy et al., (2015), dyall & schmokel (2017), arican et al., (2017)). despite the added risk of the distal hinge fracture for ttar, the tibial tuberosity fracture rate of 0.5–9.1% for ttta and 1.3–11.7% for ttar does not differ significantly at p < 0.05, with two-tailed t test showing t-value of -0.91676 and p-value 0.378929. in addition, the 2/50 tibial tuberosity fractures in samoy et al. (2015) happened before the development of a dedicated saw guide. the ttar has since been modified to exclude the use of the maquet hole at the distal end of the incomplete osteotomy while utilising a longer osteotomy. this is facilitated by a dedicated saw guide, allowing an accurate cut. it is yet unknown if this will lead to reduced tuberosity and diaphyseal fractures. proot & corr’s (2013) clinical audit suggests that it takes 22 ttta procedures to gain acceptable competence. to date, a similar clinical audit has not been published for ttar and it is unknown if major complications such as tibial fractures are more common in the hands of inexperienced veterinary surgeons. it is also unclear from the data how often tibial fractures are due to faults in the technique or faults in the postoperative care. it should be noted that all evidence that met the inclusion criteria for this pico is of low grade evidence and to date no head-to-head control trials have been done comparing ttta to ttar or other second-generation plateless techniques. future studies could focus on which perioperative factors might have an impact on fracture complications. for example, the experience of the veterinary surgeon, the use of bone grafting, which may accelerate healing, the size and age of the patient, which may influence bone elasticity, as well as owner compliance and protective effect of external coaptation in the early postoperative period. based on current evidence however, the rate of tibial fractures does not differ between ttta and ttar. until data to the contrary becomes available, veterinary surgeons performing either technique should be cognizant of their ability to perform complex osteotomy, as well as audit their complications and compare them against published limits. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform 1973–week 4 2019 pubmed search terms: (canin* or dog*) and (cruciate) and (tibial tuberosity advancement or tta) or (tta rapid) and (fracture* or complication*) dates searches performed: 22/01/2018 exclusion / inclusion criteria exclusion: cab abstracts via the ovid platform covering from 1973 to 2013 weeks 1. pubmed with publication dates > 5 years non-english articles articles with contents irrelevant to pico. inclusion: all ttar papers and ttta related papers with data pertaining to tibial fractures and complications. search outcome database number of results excluded – non english excluded – publications > 5 years old excluded – irrelevant to pico total relevant papers cab abstracts 48 11 15 10 12 pubmed 37 0 17 11 9 total relevant papers when duplicates removed 12 conflict of interest the author declares no conflicts of interest. references arican, m., parlak, k., & åžahin, h. (2017). evaluation and application of the tta-rapid method in dogs with cranial cruciate ligament rupture. acta veterinaria, 67(2), 238–253. http://doi.org/10.1515/acve-2017-0020 brunel, l., etchepareborde, s., barthélémy, n., et al. (2013) mechanical testing of a new osteotomy design for tibial tuberosity advancement using the modified maquet technique. veterinary and comparative orthopaedics and traumatology 26, 47–53. bleakley, s. (2015) tta-2: research prokects, kyon symposium butterworth, s. j., & kydd, d. m. (2017). tta-rapid in the treatment of the canine cruciate deficient stifle: shortand medium-term outcome. journal of small animal practice, 58(1), 35–41. http://doi.org/10.1111/jsap.12610 costa, m., craig, d., cambridge, t., sebestyen, p., su, y., & fahie, m. a. (2017). major complications of tibial tuberosity advancement in 1613 dogs. veterinary surgery, 46(4), 494–500. http://doi.org/10.1111/vsu.12649 danielson, b., barnhart, m., watson, a., kennedy, s., & naber, s. (2016). short-term radiographic complications and healing assessment of single-session bilateral tibial tuberosity advancements. journal of the american animal hospital association, 52(2), 109–114. http://doi.org/10.5326/jaaha-ms-6194 de sousa, r., egan, p., parsons, k., butterworth, s., calvo, i., roch, s., & moores, a. p. (2017). treatment of tibial diaphyseal fractures following plateless tibial tuberosity advancement to manage cranial cruciate disease. journal of small animal practice, 58(7), 372–379. http://doi.org/10.1111/jsap.12673 de lima dantas, b., sul, r., parkin, t., & calvo, i. (2016). incidence of complications associated with tibial tuberosity advancement in boxer dogs. veterinary and comparative orthopaedics and traumatology, 29(1), 39–45. http://doi.org/10.3415/vcot-15-02-0036 dyall, b., & schmökel, h. (2017). tibial tuberosity advancement in small-breed dogs using tta rapid implants: complications and outcome. journal of small animal practice, 58(6), 314–322. http://doi.org/10.1111/jsap.12654 hans, e. c., barnhart, m. d., kennedy, s. c., & naber, s. j. (2017). comparison of complications following tibial tuberosity advancement and tibial plateau levelling osteotomy in very large and giant dogs 50 kg or more in body weight. veterinary and comparative orthopaedics and traumatology, 30 (4), 299–305. http://doi.org/10.3415/vcot-16-07-0106 kiefer, j. e., langenbach, a., boim, j., gordon, s., & marcellin-little, d. j. (2015). single-stage bilateral tibial tuberosity advancement for treatment of bilateral canine cranial cruciate ligament deficiency. veterinary and comparative orthopaedics and traumatology, 28 (3), 215–219. http://doi.org/10.3415/vcot-14-08-0130 macdonald, t. l., allen, d. a., & monteith, g. j. (2013). clinical assessment following tibial tuberosity advancement in 28 stifles at 6 months and 1 year after surgery. canadian veterinary journal, 54 (3), 249–254. montavon pm, damur dm, tepic s (2002). advancement of the tibial tuberosity for the treatment of cranial cruciate deficient canine stifle. proceedings of the 1st world orthopedic veterinary congress; 2002 september 5–8; munich, germany. 152. ness m (2016) the modified maquet procedure (mmp) in dogs: technical development and initial clinical experience, journal of the american animal hospital association, 52 (4), 242–250. proot, j. l. j., & corr, s. a. (2013). clinical audit for the tibial tuberosity advancement procedure. veterinary and comparative orthopaedics and traumatology, 26 (4), 280–284. http://doi.org/10.3415/vcot-12-04-0052 samoy, y., verhoeven, g., bosmans, t., van der vekens, e., de bakker, e., verleyen, p., & van ryssen, b. (2015). tta rapid: description of the technique and short term clinical trial results of the first 50 cases. veterinary surgery, 44 (4), 474–484. http://doi.org/10.1111/j.1532-950x.2014.12298.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. no evidence that therapeutic systemic corticosteroid administration is associated with laminitis in adult horses without underlying endocrine or severe systemic disease. a knowledge summary by catherine mcgowan bvsc, macvsc, deim, dipeceim, phd, fhea, mrcvs 1 daniel cooper bvsc, mrcvs 2 joanne ireland bvms, phd, certavp(em), mrcvs 3 1university of liverpool 2clent hills equine llp 3animal health trust *corresponding author (c.m.mcgowan@liv.ac.uk) vol 1, issue 1 (2016) published: 25 jan 2016 next review date: 26 may 2017 doi: 10.18849/ve.v1i1.12 clinical bottom line there is currently no conclusive evidence to support a causal association between therapeutic systemic corticosteroid administration and the development of laminitis in healthy adult horses/ponies. there is weak evidence of an association between administration of multiple doses of systemic corticosteroid and the onset of laminitis in adult horses/ponies with underlying endocrine disorders or severe systemic disease. question in reported cases of iatrogenic laminitis in adult horses and ponies, is therapeutic administration of systemic corticosteroid associated with the onset of laminitis? clinical scenario horses have been reported to develop laminitis following therapeutic systemic corticosteroid administration and the risk of laminitis induced by administration of exogenous glucocorticoids remains a contentious issue in equine medicine. previously the lack of reported adverse reactions to corticosteroids has been cited as evidence to suggest no association with laminitis. additionally, many studies investigating the use of corticosteroids in treatment of various conditions (such as recurrent airway obstruction and musculoskeletal disorders) have not observed induction of laminitis. it has been suspected that the development of laminitis following corticosteroid therapy is more likely in horses with an underlying disease that causes laminitis, specifically, systemic inflammatory response syndrome (sirs) or severe systemic disease and endocrine disease. johnson et al suggest that most widely recognised form of endocrinopathic laminitis occurs in association with steroid administration and that use of corticosteroids must be measured against the well-recognised risk of complicating laminitis (johnson et al 2004). johnson et al also state the likelihood of laminitis appears to be greater with the more potent agents such as triamcinolone laminitis (johnson et al 2004), while an earlier review suggests the association with laminitis has not been reported for use of prednisone or prednisolone (johnson et al 2002). early in vitro research demonstrated corticosteroid potentiation of the vasoconstrictor actions of catecholamines and serotonin, suggesting the resulting venous obstruction on the hoof may cause laminitis (eyre & elmes 1980). skin perfusion was decreased in a study using six days of daily dexamethasone and the authors suggested perfusion to the hoof may also be reduced, increasing the risk of laminitis (cornelisse et al 2006). following a standard overnight dexamethasone suppression test, non-obese ponies with a history of prior laminitis showed elevated insulin concentration and exaggerated production of insulin in response to corticosteroids compared to control ponies (bailey et al 2007). after a single administration of triamcinolone, one study reported a prolonged period (3 – 4 days) of hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia (french et al 2000). additionally, four of the five horses in this study developed laminar rings without clinical laminitis (french et al 2000). in a small cross-over study, healthy horses demonstrated marked insulin resistance following alternate day dexamethasone administration for three weeks (tiley et al 2007; tiley et al 2008). insulin resistance is associated with a predisposition to laminitis (mcgowan 2008); therefore it is possible that glucocorticoid-induced decrease in insulin sensitivity may increase the risk for development of laminitis although these studies demonstrate pathophysiological effects of exogenous steroid administration which offer plausible mechanisms by which corticosteroids may induce laminitis, particularly in those animals with existing predisposing factors, they do not provide sufficient evidence to support the hypothesis of increased risk of laminitis associated with the use of steroids in clinical practice. therefore, this knowledge summary aimed to identify cases of iatrogenic equine laminitis following systemic administration of corticosteroids and to appraise the evidence linking corticosteroid administration and laminitis onset. the evidence thirteen publications, reporting a total of 40 iatrogenic cases of laminitis following systemic corticosteroid administration, were identified in the literature searches (summarised in table 1). these comprised six single case reports, three case series, one non-randomised clinical trial of dexamethasone for the treatment of chronic respiratory disorders, a database of adverse drug events, a journalistic style anecdotal case report and a court case transcript. included publications were of level 4 (case series) or level 5 (mechanism-based reasoning) (ocebm levels of evidence working group). only one observational study aimed to evaluate the prevalence of laminitis amongst horses treated with triamcinolone (mccluskey & kavenagh 2004). no experimental studies investigating the frequency of laminitis following therapeutic corticosteroid administration were identified. three publications (including eight cases) did not report information regarding the type of corticosteroid administered (cripps & eustace 1999; lose 1980; slater et al 1995). of the 32 cases of iatrogenic laminitis reported in the other included publications, 53% (n=17) were reported to occur following administration of triamcinolone (cohen & carter 1992; mccluskey & kavenagh 2004; ryu et al 2004; u.s. fda), 34% (n=11) were reported to occur following administration of dexamethasone (fredrick & kehl 2000; humber et al 1991; muyelle & oyaert 1973; vandenabeele et al 2004; u.s. fda), 3% (n=1) occurred following administration of methylprednisolone (u.s. fda) and 3% (n=1) occurred following administration of betamethasone (u.s. fda). two further cases were reported to develop laminitis following the administration of more than one corticosteroid (anon 2005; winfield et al 2013). ten publications (including 14 cases) reported some information regarding duration of treatment or number of corticosteroid treatments, of which 79% of cases (n=11/14) developed laminitis following multiple doses of corticosteroid (cohen & carter 1992; fredrick & kehl 2000; humber et al 1991; muyelle & oyaert 1973; ryu et al 2004; vandenabeele et al 2004; winfield et al 2013). the remaining 21% of cases (n=3/14) developed laminitis following administration of corticosteroid on a single occasion; however two of these cases received multiple intra-articular doses of unknown corticosteroid (lose 1980) or triamcinolone (mccluskey & kavenagh 2004) and the other case received multiple doses of dexamethasone and possibly multiple intra-articular doses of triamcinolone (anon 2005). summary of the evidence muylle (1973) population: 10 normal horses and 15 horses with chronic respiratory disorders. respiratory cases referred to veterinary medical teaching hospital, ghent, belgium. sample size: 25 horses (predominantly standardbreds and hunter type) 15 horses administered dexamethasone study population included 2 iatrogenic laminitis cases. intervention details: intramuscular administration of dexamethasone 25 mg on alternate days for 4 – 6 treatments until remission of clinical signs achieved. study design: non-randomised, controlled clinical trial of dexamethasone for the treatment of chronic respiratory disorders. outcome studied: objective assessment: lung function test results in horses with chronic respiratory disorders compared to healthy controls and following dexamethasone treatment. main findings (relevant to pico question): 2 of the 15 dexamethasone-treated horses developed laminitis ‘a short time after discharge’. 1 of the 2 laminitis cases was treated successfully. limitations: primary objective of the study was investigation of lung function in response to dexamethasone treatment for chronic respiratory disease. no clinical details presented for iatrogenic cases and corticosteroid administration not evaluated as risk factor for development of laminitis. lack of temporal information precludes assessment of association between corticosteroids and onset of laminitis. lose (1980) population: 2 year old standardbred colt attended by a first opinion equine hospital, pennsylvania, usa. sample size: 1 intervention details: single intra-articular administration both tarsi. corticosteroid and dose not reported. study design: case report. outcome studied: objective assessment: description of treatment of single iatrogenic laminitis case. main findings (relevant to pico question): onset of laminitis affecting all four feet 8 days after corticosteroid administration. confirmed by radiography – rotation evident in all four feet (right fore most severely affected). no clinical details or information regarding diagnostic testing for underlying disease(s) reported. limitations: single case report, with primary focus on treatments used for laminitis. provides weak evidence of association between therapeutic administration of corticosteroids and onset of laminitis in a single horse. no details presented regarding presence or absence of underlying disease. humber (1991) population: 2 horses with immune-mediated thrombocytopaenia referred to veterinary medical teaching hospital, pennsylvania, usa. sample size: 1 iatrogenic laminitis case (8 year old thoroughbred mare). intervention details: intravenous administration of dexamethasone 0.16mg/kg every 12 hours for 3 days. study design: case report outcome studied: objective assessment: description of clinical presentation and treatment of immune-mediated thrombocytopaenia. main findings (relevant to pico question): onset of mild laminitis affecting all four feet 10 days after cessation of corticosteroid administration.confirmed by post mortem examination – slight displacement of the third phalanx in both forelimbs. affected horse had evidence of systemic disease (progressive epistaxis, ecchymotic haemorrhages involving the oral mucous membranes, hyphema, petechial haemorrhages on the sclerae, and nasal and vaginal mucous membranes). the horse also had swellings in the mid cervical region over the jugular veins. mucous membranes were pale. mild neutrophilic leucocytosis, anaemia, hypoproteinaemic and thrombocytopenic. blood in faeces. limitations: single case report. provides weak evidence of association between therapeutic administration of systemic corticosteroids and onset of laminitis in a single horse with severe systemic disease. cohen (1992) population: 10 year old quarter horse gelding referred to veterinary medical teaching hospital, texas, usa. sample size: 1 intervention details: 12mg (6ml) of triamcinolone administered; 2nd treatment 3 weeks later of 10mg (5ml) of triamcinolone (injected by owner without veterinary consult); 3rd treatment administered by owner 7 days after 2nd second treatment (dose details unknown but suspension was much stronger (40mg/ml)). study design: case report outcome studied: objective assessment: description of clinical presentation and treatment of steroid hepatopathy main findings (relevant to pico question): onset of bilateral forelimb laminitis 6 weeks and 6 days after first corticosteroid administration (2 weeks and 6 days after last). confirmed by radiography – rotation evident in both fore feet. affected horse had evidence of severe concurrent disease (hepatopathy and hyperadrenocorticism). limitations: single case report. laminitis developed approximately 3 weeks following cessation of corticosteroid treatment, which does not convincingly support a causal association. slater (1995) population: laminitis cases attended by 7 private practices and referred to veterinary medical teaching hospital, texas, usa. sample size: 108 laminitis cases study population included 3 iatrogenic laminitis cases intervention details: no details regarding corticosteroid administered, dose or duration of treatment. 3 cases in series reported to have received steroids ‘just prior to the onset of laminitis’ with no time frame stated. study design: case control study. outcome studied: objective assessment: horse level and clinical factors associated acute or chronic laminitis and description of treatments administered. main findings (relevant to pico question): 3 of 108 laminitis cases had a history of corticosteroid administration prior to the onset of clinical signs. limitations: no clinical details presented for iatrogenic cases and corticosteroid administration not evaluated as risk factor for development of laminitis. lack of temporal information precludes assessment of association between corticosteroids and onset of laminitis. cripps (1999) population: laminitis cases referred to a specialist equine laminitis referral centre, england, uk. sample size: 216 laminitis cases, of which 211 included in study study population included 4 iatrogenic laminitis cases. intervention details: no details regarding corticosteroid administered, dose or duration of treatment. 4 laminitis cases in series reported as iatrogenic ‘following injections of corticosteroids’ with no time frame stated. study design: case series – retrospective review of clinical records. outcome studied: objective assessment: horse level and clinical factors associated with outcome of treatment for laminitis (successful versus unsuccessful treatment). main findings (relevant to pico question): 4 laminitis cases in series reported as iatrogenic. 2 of the 4 iatrogenic cases were treated successfully. limitations: primary objective of the study was investigation of clinical parameters associated with outcome of treatment for laminitis. no clinical details presented for iatrogenic cases and corticosteroid administration not evaluated as risk factor for development of laminitis. lack of temporal information precludes assessment of association between corticosteroids and onset of laminitis. frederick (2000) population: 23 year old american saddlebred gelding, usa. sample size: 1 intervention details: single bolus injection of naquasone (trichlormethiazide 10 mg and dexamethasone acetate 0.55 mg/ml) followed by 4 days oral administration of naquasone tablets. dose not reported. study design: case report. outcome studied: subjective assessment: owner and veterinary surgeon account of single iatrogenic laminitis case. main findings (relevant to pico question): onset of laminitis affecting all four feet on 4th day of corticosteroid administration. confirmed by radiography – rotation evident in both fore feet. gelding was obese with regional adiposity (cresty neck). diagnostic tests for hypothyroidism and ppid inconclusive (neither specific tests nor results reported). limitations: very low quality non-peer reviewed single case report in journalistic style. provides very weak evidence of association between therapeutic administration of systemic corticosteroids and onset of laminitis in a single aged horse with clinical signs of underlying endocrine disease. ryu (2004) population: 3 year old thoroughbred filly referred to equine hospital, korea. sample size: 1 intervention details: intramuscular administration of triamcinolone acetonide 20 mg once daily for 10 consecutive days. study design: case report. outcome studied: objective assessment: description of clinical presentation and treatment of single iatrogenic laminitis case main findings (relevant to pico question): onset of bilateral forelimb laminitis 33 days after first corticosteroid administration (23 days after last). confirmed by radiography – severe rotation evident with eventual sole penetration. initially referred 25 days after first corticosteroid administration for haematuria and steroid hepatopathy with weight loss, vaginal hyperaemia, leukopenia and polyuria. affected horse had evidence of systemic disease (pyrexia, tachycardia, tachypnoea), congested mucous membranes, thrombophlebitis and neutrophilia). limitations: single case report. laminitis developed 23 days following cessation of corticosteroid treatment, which does not convincingly support a causal association. mccluskey (2004) population: adult horses treated with triamcinolone in an equine ambulatory practice, victoria, australia. sample size: 132 horses treated with triamcinolone (total 205 triamcinolone treatments). study population included 1 iatrogenic laminitis case (7 year old thoroughbred gelding). intervention details: intra-articular administration of triamcinolone acetonide 10 mg into 4 joints (40 mg total dose). study design: case series – retrospective review of clinical records. outcome studied: objective assessment: prevalence of laminitis in adult horses treated with triamcinolone main findings (relevant to pico question): single horse (n=1/132) developed laminitis one week after corticosteroid treatment. iatrogenic laminitis case reported to have previous episode of laminitis 7 months prior. no clinical details or information regarding diagnostic testing for underlying disease(s) reported. limitations: single case described within a case series with very limited clinical data reported. provides weak evidence of association between therapeutic administration of systemic corticosteroids and onset of laminitis in a single horse with previous history of laminitis. vandenabeele (2004) population: pemphigus foliaceus cases referred to a veterinary medical teaching hospital, california, usa. sample size: 20 pemphigus foliaceus cases study population included 4 iatrogenic laminitis cases: 2 year old quarter horse filly; 3.5 year old quarter horse filly; 4 year old standardbred mare; 5 year old quarter horse gelding. intervention details: oral dexamethasone 0.05-0.1 mg/kg per day (n=13). oral prednisone 1-2 mg/kg per day (n=3). oral prednisolone 1-2 mg/kg per day (n=4) duration of treatment not reported; however alternate-day dosing of corticosteroids was implemented when lesions were in remission (10–14 days of treatment). study design: case series – retrospective review of clinical records. outcome studied: objective assessment: description of clinical presentation and treatment of pemphigus foliaceus cases. main findings (relevant to pico question): 4 iatrogenic acute laminitis cases reported following dexamethasone treatment. 3 cases euthanased due to laminitis. 4th case treated successfully. serum albumin measured in 2 of the 3 non-surviving cases – both had hypoalbuminaemia. time frame of onset of laminitis relative to dexamethasone not reported. limitations: 4 laminitis cases described with very limited clinical data reported. lack of temporal information precludes assessment of association between corticosteroids and onset of laminitis. anon (2005) population: 14 year old mare, england, uk. sample size: 1 intervention details: dosage and nature of corticosteroids administered contested ad unclear. possible intra-articular administration of triamcinolone acetonide both tarsi (1 x 80mg/2ml in each joint) or intra-articular administration of dexamethasone both tarsi (1 x 4mg in each joint) multiple intra-muscular injections into back cumulatively of 20mg of dexamethasone. study design: court case transcript. outcome studied: subjective assessment: transcript of summary of evidence given during court case. main findings (relevant to pico question): laminitis diagnosed 11 days after corticosteroid treatment. euthanased due to laminitis 61 days post-diagnosis. received intra-articular administration of triamcinolone right fore fetlock 4 years previously – dose not reported – no adverse events. received multiple intra-articular and intra-muscular injections of dexamethasone 2 years – dose not reported – no adverse events. limitations: no clinical details or diagnostic information reported. court case assumes causal association between administration of corticosteroids and onset of laminitis. provides weak evidence of association between therapeutic administration of large doses of corticosteroids and onset of laminitis in a single horse. no details presented regarding presence or absence of underlying disease. center for veterinary medicine cumulative adverse drug event (ade) summaries report population: adverse drug event (ade) data from all reports received on paper by the u.s. food and drug administration center for veterinary medicine between 1987 and april 30, 2013, usa. sample size: 106 cases of equine laminitis reported as ade included 19 cases of laminitis reported as ade following corticosteroid administration. intervention details: not reported. study design: not applicable – database of reported ades. outcome studied: subjective assessment: laminitis reported as ade, by either veterinary surgeons or horse owners. main findings (relevant to pico question): laminitis reported as ade following administration of: parenteral betamethasone (n=1); oral dexamethasone (n=2); parenteral dexamethasone (n=1); parenteral methylprednisolone (n=1); parenteral triamcinolone (n=13); triamcinolone – route of administration unknown (n=1). limitations: no clinical details or diagnostic information reported; therefore iatrogenic laminitis cases not confirmed. lack of temporal information precludes assessment of association between corticosteroids and onset of laminitis. winfield (2013) population: 9 year old welsh pony stallion referred to a veterinary medical teaching hospital, california, usa. sample size: 1 intervention details: intramuscular administration of dexamethasone (0.05 mg/kg once daily for 3 consecutive days, followed by oral prednisolone (0.5-1.0 mg/kg once daily; plus topical administration of 0.015% triamcinolone acetonide spray. study design: case report. outcome studied: objective assessment: description of clinical presentation and treatment of a single pemphigus vulgaris case. main findings (relevant to pico question): onset of laminitis affecting all four feet within 4 months following initiation of corticosteroid administration (possibly after 6 weeks of treatment based on figure s5 legend in supplementary information). initial foot soreness developed as prednisolone dose was increased to 0.8 mg/kg/day. confirmed by post mortem examination – rotation and hoof wall separation in all four feet. in addition to pemphigus vulgaris, affected pony had evidence of chronic inflammation and systemic illness, considered by the authors to be contributing factors in the development of laminitis. limitations: primary objective of the report was to describe the clinical, histological and immunological findings of a case of pemphigus vulgaris. lack of accurate temporal information precludes assessment of association between corticosteroids and onset of laminitis. appraisal, application and reflection the aim of this knowledge summary was to critically appraise published evidence of iatrogenic equine laminitis following systemic administration of corticosteroids. it was beyond the scope of this review to evaluate the extensive published literature reporting on the therapeutic use of systemic corticosteroids where laminitis has not been observed or reported as an adverse event following treatment. the 13 included publications were predominantly descriptive studies and provided low level evidence pertaining to the potential association between therapeutic administration of systemic corticosteroid and the onset of laminitis (ocebm levels of evidence working group). no studies of an appropriate design to determine the incidence of laminitis following corticosteroid treatment or evaluate temporal relationships between corticosteroid administration and the onset of laminitis (i.e. longitudinal analytical studies) were identified. the only observational study investigating iatrogenic laminitis following treatment with triamcinolone reported a prevalence of 0.8% (n=1/132; 95% confidence interval 0 – 2.2%) (mccluskey & kavenagh 2004). in the same study, three other cases of laminitis were reported, of which two were diagnosed with laminitis prior to triamcinolone but did not develop laminitis subsequent to its use. therefore, laminitis following triamcinolone administration was observed in 33% of horses with a previous history of laminitis (n=1/3). the third horse developed laminitis 18 months after triamcinolone therapy as a result of post foaling toxaemic metritis (mccluskey & kavenagh 2004). of 106 equine laminitis cases reported as adverse drug events over a 26 year period, 18% (n=19) were attributed to corticosteroid treatment, whereas 35% of cases (n=37) were attributed to administration of anthelmintics and 32% (n=34) were reported following treatment with antibiotics or antiprotozoals (u.s. fda). only eight publications (each reporting a single case of iatrogenic laminitis) provided information regarding the time of onset of laminitis relative to corticosteroid administration (anon 2005; cohen & carter 1992; fredrick & kehl 2000; humber et al 1991; lose 1980; mccluskey & kavenagh 2004; ryu et al 2004; winfield et al 2013). one of the eight cases occurred during corticosteroid treatment (onset of laminitis reported on day 4 of a 5 day course) (fredrick & kehl 2000). onset or diagnosis of laminitis was reported to occur 7 days (mccluskey & kavenagh 2004), 8 days (lose 1980), 10 days (humber et al 1991), 11 days (anon 2005), 20 days (cohen & carter 1992) and 23 days (ryu et al 2004) after cessation of corticosteroid treatment. two of these cases, one with severe systemic disease (ryu et al 2004) and one with hepatopathy and hyperadrenocorticism (cohen & carter 1992), occurred three weeks after the last dose of corticosteroid. the longer the period of time between drug administration and disease onset, the less likely the drug was a contributing factor in the aetiology due to its reduced efficacy in the body as time passes (harkins et al 1993). the time frame for both these two cases appears to be too long to suggest a direct causal association, especially as in both cases laminitis occurred over a week after the onset of clinical signs of systemic disease. in the remaining case, laminitis was reported to have occurred within 4 months of commencing corticosteroid treatment (winfield et al 2013). seven publications provided diagnostic information, of which five (representing eight cases) reported confirmation of diagnosis via radiography (cohen & carter 1992; cripps & eustace 1999; fredrick & kehl 2000; lose 1980; ryu et al 2004) and two (representing two cases) reported confirmation via gross pathology at post mortem examination (humber et al 1991; winfield et al 2013). few included studies provided detailed clinical information regarding the presentation and severity of laminitis. two epidemiological studies of laminitis (cripps & eustace 1999; slater et al 1995) did not include any clinical information pertaining to iatrogenic laminitis cases, and reported only that animals had received corticosteroids prior to the onset of laminitis, while the center for veterinary medicine cumulative adverse drug event (ade) summaries report (u.s. fda) provided no details other than the type of corticosteroid administered prior to laminitis. where reported, laminitis most frequently affected all four feet (67%, n=4/6) (fredrick & kehl 2000; humber et al 1991; lose 1980; winfield et al 2013), and a further two cases (33%, n=2/6) (cohen & carter 1992; ryu et al 2004) developed bilateral forelimb laminitis. outcome was reported for 18 cases, of which 50% (n=9) were reported to have survived/recovered, although two cases were reported to have been retired from their previous athletic use due to laminitis (mccluskey & kavenagh 2004; ryu et al 2004). one non-surviving case was euthanased due to progression of pemphigus vulgaris rather than laminitis (winfield et al 2013) and the reason for euthanasia was unclear in one further non-surviving case (humber et al 1991). diagnostic evaluation of underlying disease(s) was infrequently reported. of the five laminitis cases occurring during treatment or within two weeks of corticosteroid administration, one horse was obese with marked regional adiposity, suggestive of equine metabolic syndrome (fredrick & kehl 2000); one horse had a previous history of laminitis (mccluskey & kavenagh 2004) and one had severe systemic disease (humber et al 1991). a further three cases had evidence of severe systemic disease (cohen & carter 1992; ryu et al 2004; winfield et al 2013). of four iatrogenic laminitis cases reported amongst horses treated with dexamethasone for pemphigus foliaceus, two non-surviving cases for which serum albumin was measured were hypoalbuminaemic (vandenabeele et al 2004). in conclusion, no studies that sought to investigate a potential causal association between therapeutic corticosteroid administration and laminitis were identified and there is currently insufficient evidence to support such an association in healthy adult horses. there is weak evidence of an association between administration of multiple doses of systemic corticosteroid and the onset of laminitis in adult horses with underlying endocrine disorders or severe systemic disease.   therefore, underlying diseases predisposing to laminitis should be considered prior to administration of corticosteroids, particularly where multiple or large doses are indicated. however, this knowledge summary has highlighted a paucity of information on iatrogenic laminitis and a well-designed cohort study is required to quantify the apparently small risk of iatrogenic laminitis following therapeutic administration of systemic corticosteroid. methodology section search strategy databases searched and dates covered: pubmed accessed via the ncbi website (1950 – present) thomson reuters web of science (1898 – present) cab abstracts on the cab direct interface (1910 – present) sciverse scopus (1823 – present) international veterinary information service (ivis) database (1997 – present) further relevant records were identified by the authors via the bibliographies and reference lists of retrieved publications and published conference proceedings. search terms: (equine or horse* or pony or ponies ) and (laminitis or laminitic) and (corticosteroid* or glucocorticoid* or dexamethasone or dex or prednisolone or methylprednisolone or triamcinolone or tmc or betamethasone) dates searches performed: 26/05/2015 and 27/05/2015 exclusion / inclusion criteria no limitations regarding study design, setting, sample size or study population were imposed. exclusion: non-english language, narrative or non-systematic review articles (or non-systematic reviews published in conference proceedings or as letters/correspondence), unpublished data, pharmacokinetic, in vitro or in vivo experimental studies. inclusion: any reported case of laminitis occurring in an adult horse or pony following the systemic administration of corticosteroid(s). search outcome database number of results excluded – nonenglish language publication excluded – non-systematic review article, conference proceeding or letter excluded – pharmacokinetic / in vitro / in vivo e xperimental study excluded – did not answer pico question/no iatrogenic laminitis case(s) reported total relevant papers ncbi pubmed 34 1 10 6 13 4 thomson reuters web of science 84 1 31 12 34 6 cab abstracts 86 1 44 13 24 4 sciverse scopus 66 5 30 7 19 5 international veterinary information service (ivis) database 70 0 69 0 1 0 other sources 7 0 1 0 1 5 total relevant papers when duplicates removed 13 references anon (2005) philip john glyn (t/a priors farm equine veterinary surgery) v jane mcgarel-groves, erik grandiere, clinique veterinaire equine de chantilly. case number: hq o3x 01706.[vlex: united kingdom] [online] available from: http://high-court-justice.vlex.co.uk/vid/hq-o3x-01706-52923646  [accessed 29/07/2015] bailey, s.r. et al., (2007) effect of dietary fructans and dexamethasone administration on the insulin response of ponies predisposed to laminitis. journal of the american veterinary medical association, 231 (9), pp.1365-1373. http://dx.doi.org/10.2460/javma.231.9.1365 center for veterinary medicine cumulative adverse drug event (ade) summaries report 01/01/1987 – 30/04/2013. [u.s. food and drug administration] [online] available from: http://www.fda.gov/animalveterinary/safetyhealth/productsafetyinformation/ucm055369.htm  [accessed 29/07/2015] cohen, n.d. and carter, g.k. (1992) steroid hepatopathy in a horse with glucocorticoid-induced hyperadrenocorticism. journal of the american veterinary medical association, 200 (11), pp. 1682-1684. cornelisse, c.j. et al., (2006) thermographic study of in vivo modulation of vascular responses to phenylephrine and endothelin-1 by dexamethasone in the horse. equine veterinary journal, 38 (2), pp. 119-126.  http://dx.doi.org/10.2746/042516406776563251 cripps, p.j. and eustace, r.a. (1999) factors involved in the prognosis of equine laminitis in the uk. equine veterinary journal, 31 (5), pp. 433-442. http://dx.doi.org/10.1111/j.2042-3306.1999.tb03845.x eyre, p and elmes, p.j. (1980) corticosteroid-induced laminitis? further observations on the isolated, perfused hoof. veterinary research communications, 4 (1), pp. 139-143. http://dx.doi.org/10.1007/bf02278492 frederick, d.m. and kehl, m. (2000) case report: back from the brink. equus, 272, pp. 34-41. french, k., pollitt, c.c. and pass, m.a. (2000) pharmacokinetics and metabolic effects of triamcinolone acetonide and their possible relationships to glucocorticoid-induced laminitis in horses. journal of veterinary pharmacology and therapeutics, 23 (5), pp. 287-292. http://dx.doi.org/10.1111/j.1365-2885.2000.00288.x harkins, j.d., carney, j.m. and tobin, t. (1993) clinical use and characteristics of the corticosteroids. veterinary clinics of north america: equine practice, 9 (3), pp.543-562. humber, k.a. et al., (1991) azathioprine for treatment of immune-mediated thrombocytopenia in two horses. journal of the american veterinary medical association, 199 (5), pp. 591-594. johnson, p.j. et al., (2002) glucocorticoids and laminitis in the horse. veterinary clinics of north america: equine practice, 18 (2), pp. 219-236. http://dx.doi.org/10.1016/s0749-0739(02)00015-9 johnson, p.j. et al., (2004) endocrinopathic laminitis in the horse. clinical techniques in equine practice, 3 (1), pp.45-56. http://dx.doi.org/10.1053/j.ctep.2004.07.004 lose, m.p. (1980) drug-induced laminitis in a colt. modern veterinary practice, 61 (7), pp. 608-610. mccluskey, m.j. and kavenagh, p.b. (2004) clinical use of triamcinolone acetonide in the horse (205 cases) and the incidence of glucocorticoid-induced laminitis associated with its use. equine veterinary education, 16 (2), pp. 86-89. http://dx.doi.org/10.1111/j.2042-3292.2004.tb00272.x mcgowan, c.m. (2008) the role of insulin in endocrinopathic laminitis. journal of equine veterinary science, 28 (10), pp. 603-607. http://dx.doi.org/10.1016/j.jevs.2008.08.004 muylle, e. and oyaert, w. (1973) lung function tests in obstructive pulmonary disease in horses. equine veterinary journal, 5 (1), pp. 37-44.  http://dx.doi.org/10.1111/j.2042-3306.1973.tb03191.x oxford levels of evidence 2 [oxford centre for evidence-based medicine – ocebm levels of evidence working group] [online] available from: http://www.cebm.net/index.aspx?o=5653 [accessed 11/08/2015]. ryu, s. et al., (2004) glucocorticoid-induced laminitis with hepatopathy in a thoroughbred filly. journal of veterinary science, 5 (3), pp. 271-274. slater, m.r., hood, d.m. and carter, g.k. (1995) descriptive epidemiological study of equine laminitis. equine veterinary journal, 27 (5), pp. 364-367.  http://dx.doi.org/10.1111/j.2042-3306.1995.tb04071.x tiley, h.a., geor, r.j. and mccutcheon, l.j. (2007) effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses. american journal of veterinary research, 68 (7), pp.753-759. http://dx.doi.org/10.2460/ajvr.68.7.753 tiley, h.a., geor, r.j. and mccutcheon, l.j. (2008) effects of dexamethasone administration on insulin resistance and components of insulin signaling and glucose metabolism in equine skeletal muscle. american journal of veterinary research, 69 (1), pp. 51-58. http://dx.doi.org/10.2460/ajvr.69.1.51 vandenabeele, s.i.j. et al., (2004) pemphigus foliaceus in the horse: a retrospective study of 20 cases. veterinary dermatology, 15 (6), pp. 381-388.  http://dx.doi.org/10.1111/j.1365-3164.2004.00423.x winfield, l.d. et al., (2013) pemphigus vulgaris in a welsh pony stallion: case report and demonstration of antidesmoglein autoantibodies. veterinary dermatology, 24 (2), pp. 269-e60 http://dx.doi.org/10.1111/vde.12002 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. the prevalence of positive urine cultures in 100 dogs with an inactive urine sediment rachel liebelt dvm, mrcvs1* armi pigott dvm, dacvecc2 1vets now hospital manchester, 98 bury old rd, whitefield, manchester, m45 6tq 2lakeshore veterinary specialists, 2100 w. silver spring drive, glendale, wi 53209 *corresponding author (rlliebelt@gmail.com) vol 4, issue 4 (2019) published: 19 dec 2019 reviewed by: conor o'halloran (bvsc, msc, mrcvs) and mary thompson (bvsc(hons), phd, dacvim, manzcv) doi: 10.18849/ve.v4i4.273 section index:    abstract | introduction | methods | results | discussion | footnotes | conflict of interest | references abstract objective: the purpose of this study was to determine the prevalence of positive quantitative urine cultures in dogs with an inactive urine sediment. background: a urinalysis is a useful screening tool for the evaluation of evidence of bacterial cystitis and a quantitative urine culture is used for definitive diagnosis. evidentiary value: a retrospective chart review from june 2012 to december 2017 at three private practice emergency and specialty referral hospitals examined urine samples obtained from 100 client-owned dogs. methods: the signalment and clinicopathologic data was recorded for all canine patients that had urine samples obtained by cystocentesis that had an inactive sediment exam on urinalysis and subsequent quantitative urine cultures were performed. results: the prevalence of positive quantitative urine cultures in all dogs with an inactive urine sediment at the aforementioned institutions was 6% (6/100). escherichia coli was the most commonly isolated bacteria. conclusion: given the low prevalence of positive quantitative urine cultures in dogs with an inactive urine sediment and current guideline recommendations for management of subclinical bacteriuria, we do not recommend urine cultures for dogs without lower urinary tract signs. further prospective study of patient subgroups, as well as controlled studies evaluating urine sample handling techniques using methods available to private practice practitioners are sorely needed. application: emergency and general practicing veterinarians should consider a quantitative urine culture for dogs with lower urinary tract signs, even with an inactive sediment examination, and on a case-by-case basis for dogs with pertinent systemic diseases or known risk factors for bacterial cystitis.   introduction urinalysis and quantitative urine culture (quc) are common diagnostics performed in a wide population of both human and veterinary patients. a urinalysis is a useful screening tool in the evaluation for supporting evidence of bacterial cystitis (weese et al., 2019), however urine culture is the gold standard to diagnose or rule out bacteriuria (ettinger, 2017). a quc should be performed in cases of known or suspected bacterial cystitis or pyelonephritis to determine the infectious agent and guide antimicrobial usage (weese et al., 2019; ettinger, 2017).  urinalysis and quc are also commonly performed as part of the routine diagnostic approach to determining sources of fever, causes for diabetic decompensation and ketosis, and as part of routine laboratory evaluation of the chronic kidney disease (ckd) or acute kidney injury patient (ettinger, 2017). there are occasions when a positive quc is obtained from urine that has no evidence of bacteria or inflammation on urinalysis. this scenario may be due to the limitations of light microscopy in detecting low numbers of bacteria compared to quc (ettinger, 2017). the literature states that 10,000 rods/ml to 100,000 cocci/ml of urine is required to consistently find bacteria on sediment evaluation, whereas a quc is much more sensitive for detecting bacteria present in smaller numbers (ettinger, 2017).   a quc is a relatively expensive test in comparison to the cost of a urinalysis, and it would be useful to know how often the quc is positive when patients have no evidence of bacteria or inflammation on urine sediment examination. the authors hypothesised that positive qucs occur in less than 10% of patients with an inactive urine sediment. the goal of this paper was to determine the prevalence of positive qucs associated with inactive urine sediments in all patients who had a quc performed at a private practice emergency and specialty referral hospital, which to the authors’ knowledge, has not previously been reported. the secondary aim of this paper was to describe the quc-positive patients.   methods results of all qucs performed between june 1st 2012 to december 31st 2017 at all three locations of the authors’ institutions were identified; 2,095 qucs in total. the corresponding urinalysis for each quc was then evaluated. an inactive sediment was defined as urine with colour descriptor recorded as yellow or colourless; turbidity descriptor recorded as clear; and the absence of epithelial cells, bacteria and pyuria (defined as greater than five white blood cells per high powered field) on urine sediment examination. dogs having urine collection by cystocentesis, urinalysis with inactive urine sediment, and quc, submitted on the same day that the urine for urinalysis was collected, were included in the study. dogs were excluded from the study if they had urinalysis and quc performed on separate days or at separate visits, did not have a urinalysis performed, had urine collected by a method other than cystocentesis or method not recorded, had urinalysis that did not meet the defined parameters for inactive sediment examination, or had a medical record that was otherwise insufficiently complete for data extraction, as depicted in figure 1. figure 1: flow chart depicting the exclusion process of the quantitative urine cultures (qucs) in this study. ua = urinalysis for dogs meeting the inclusion criteria the following data were extracted from the medical record: age sex and reproductive status (male vs female vs spay vs neuter) species breed urine culture result (positive vs negative) urine specific gravity (usg) laboratory performing the urinalysis (in-house vs commercial laboratorya) estimated time from collection of urine to culture plating (within 24 hours vs less than 40 hours vs greater than 40 hours) presence of crystalluria microscopic heamaturia (fewer than five red blood cells per high powered field vs greater than five red blood cells per high powered field) presence or absence of lower urinary tract signs (luts) if the visit was a recheck examination following treatment for bacterial cystitis the presenting complaint/clinical signs of each patient comorbidities that might result in decreased white blood cells in the urine despite active infection (hypothyroidism, chronic kidney disease (ckd), hyperadrenocorticism (hac), diabetes mellitus (dm), prostatitis, urolithiasis, neurogenic bladder, pregnancy, chemotherapy) recent steroid administration recent antimicrobial administration a culture was considered positive if any growth was detected, and the bacterial species and quantitative bacterial counts were recorded. additionally, select therapeutic data (antimicrobial prescribed, duration of antimicrobial prescription) and response to therapy (resolution of luts vs persistence of luts vs lost to follow-up) was obtained for dogs that presented for luts, had an inactive urine sediment and had a negative quc. the records of dogs that presented with and without luts, had an inactive urine sediment and a positive quc were also reviewed in more detail. during the study period the urine sediment was evaluated by either in-house technical staff trained in reading urinalysis or an outside commercial laboratorya. all qucs were performed by the same commercial laboratorya. routine handling of urine samples after collection at the authors’ institutions is as follows: immediately following collection the urine is transferred to preservative-free sample tubes (6 ml max volume; provided by the commercial laboratorya), and a patient identification label is applied to the tubes. the total volume collected is not standardised. the tubes of urine are subsequently stored in a refrigerator at 1.1°–2.2°c (34°–36°f) until the sample is collected by a courier provided by the commercial laboratorya. samples are transported to the laboratory in a cooler on ice. the qucs at the commercial laboratorya are plated on a blood ager/macconkey agar biplates (hardy diagnostics, ca). if the urinalysis was performed in-house it was done immediately following collection. the in-house urinalysis is performed as follows: usg is determined using a commercially available refractometer. protein, ph, blood, ketones, glucose, and bilirubin are evaluated using a commercially available colourimetric urine dipstick test according to manufacturer’s instructions. in instances where the usg was greater than the refractometers reference range the result was recorded in the medical record as >1.0xx (1.0xx being the highest mark on the refractometer in use at the time). when these data points were extracted from the record they were recorded as 1.0xx + 0.001. for example; >1.060 was recorded as 1.061. following dipstick testing, a urine sediment unstained wet mount is evaluated microscopically. this sample is prepared as follows: 1 ml of urine is centrifuged for 45 seconds at 9800 revolutions per minute (3900 x g) in a commercial centrifuge. the supernatant is decanted and sediment resuspended in the remaining fluid by gentle agitation. one drop is placed on a glass slide and covered with a cover slip for microscopic evaluation using the 10x and 40x objective. a minimum of 10 fields are evaluated to determine the average number of cells, casts and organisms per field. statistical methods data were analysed by means of descriptive and inferential methods using a commercial spreadsheet software programmeb. data were tabulated for descriptive purposes. data distribution was tested for normality using the shapiro-wilk test (vetter, 2017). comparison between groups was performed by means of mann-whitney tests for continuous variables, and fisher’s exact tests for categorical data (neely et al., 2003). values of p < 0.05 were considered significant.   results there were 100 canine qucs with an accompanying inactive urine sediment examination. the overall prevalence of positive qucs in this population of dogs with inactive urine sediment was 6% (6/100) when all cases were evaluated. when the 15 qucs that were performed specifically as a recheck examination following treatment for a recent diagnosis of bacterial cystitis were excluded, the prevalence of positive qucs with inactive sediments was 7% (6/85). a summary of the data obtained can be viewed in table 1.   all cases excluding recheck qucs following treatment for bacterial cystitis   positive negative total positive negative total total cases 6 94 100 6 79 85 age in years median (range) 7.5 (1–16) 8 (0.2–15) 8 (0.2–16) 7.5 (1–16) 8 (0.2–15) 8 (0.2–16) urine specific gravity median (range) 1.022 (1.008–1.038) 1.014 (1.002–1.051) 1.015 (1.002–1.051) 1.022 (1.008–1.038) 1.014 (1.002–1.051) 1.014 (1.002–1.051) reproductive status          intact male          intact female          castrated male          spayed female   0 0 2 4   5 5 22 62   5 5 24 66   0 0 2 4   5 4 20 50   5 4 22 54 lab performing ua          in-house          commercial laba   5 1   47 47   52 48   5 1   43 36   48 37 microscopic haematuria          absent          present   4 2   85 9   89 11   4 2   71 8   75 10 crystalluria          absent          present   5 1   84 10   89 11   5 1   70 9   75 10 time to plating          <24h          <40h          >40h   3 1 2   61 19 14   64 20 16   3 1 2   49 17 13   52 18 15 luts           absent           present   3 3   54 40   57 43   3 3   45 34   48 37 comorbidity/risk           hypothyroid           ckd           hac           dm           chemotherapy           urolithiasis           neuro. bladder           >1 of above 1 0 0 0 1 1 0 0 1 30 3 12 4 4 3 5 1 2 31 3 12 4 5 4 5 1 3 1 0 0 0 1 1 0 0 1 24 3 8 4 4 2 3 1 1 25 3 8 4 5 3 3 1 2 recent steroids           none           within 24h           >24h up to 30 days   6 0 0   88 6 0   94 6 0   6 0 0   74 5 0   80 5 0 recent antimicrobials          none          within 24h          2–7 days          8–30 days   6 0 0 0   58 23 7 6   64 23 7 6   6 0 0 0   56 16 5 2   62 16 5 2 table 1: summary of the number of patients with inactive urine sediments in various categories. quc = quantitative urine culture ua = urinalysis luts = lower urinary tract signs ckd = chronic kidney disease hac = hyperadrenocorticism dm = diabetes mellitus neuro. bladder = neurogenic bladder the breed distribution was as follows: 27% mixed breed, 13% labrador retriever, 4% golden retriever, 4% german shepherd, 3% corgi, 3% shih tzu, and all other breeds accounted for 2% or less each. the following primary presenting complaints and/or clinical signs were retrieved from review of the medical record in the following distribution: 33% with luts, 12% with aezotemia, 10% with fever, 9% with gastrointestinal tract signs, 5% with neurological signs, 4% with lethargy, 4% with dermatological concerns, 3% with anorexia, 3% for endocrine evaluation, and 2% for each of the following categories: hepatopathy, behavioural, polyuria/polydipsia, respiratory tract, orthopaedic, reproductive and weight gain. regardless of the primary presenting complaints and/or clinical signs further review of the patient’s history indicated that 44% of all dogs had luts described in their medical records. fourteen variables were compared between the positive and negative quc cases with no statistically significant differences identified. the analysis was repeated when the patients presenting for recheck following therapy for bacterial cystitis were excluded with the same (no difference) outcome. variables and results are shown in table 2. additionally, there was no difference between the sediment samples based on where the urinalysis was performed (in-house vs a commercial laboratorya) including rate of positive culture (p = 0.207). variable all cases excluding recheck qucs following treatment for bacterial cystitis   p p age >0.999 0.998 breed 0.174 0.14 urine specific gravity 0.886 0.831 reproductive status 0.833 0.842 microscopic hematuria 0.13 0.145 crystalluria 0.513 0.891 time to plating 0.264 0.445 luts 0.411 >0.401 comorbidity 0.431 0.668 recent steroids >0.999 >0.999 antimicrobials within 24 hours 0.334 0.336 antimicrobials within 7 days 0.072 0.33 antimicrobials within 30 days 0.085 0.184 presenting signs 0.464 0.489 table 2: variable comparison between groups by means of mann-whitney (continuous) and fisher's exact test (categorical). values of p<0.05 significant. quc = quantitative urine culture luts = lower urinary tract signs the most commonly isolated bacteria species was e. coli, accounting for half of the bacterial species grown (3/6; 50%). the results of the six positive qucs and the accompanying signalment and clinicopathologic data are displayed in table 3.   dog 1 dog 2 dog 3 dog 4 dog 5 dog 6 age in years 3 9 1 11 16 6 urine specific gravity 1.008 1.015 1.038 1.028 1.012 1.033 reproductive status  spayed female  spayed female  spayed female  neutered male spayed female neutered male lab performing ua  in-house inhouse commercial laba  in-house in-house  in-house organism cultured group d streptococci non-enterococcus e. coli proteus mirabilis e. coli e. coli enterrococcus spp. growth (cfu/ml) >100,000 >100,000 10,000–50,000 1,000 10,000–50,000 10,000–50,000 microscopic haematuria no yes no yes no no crystalluria no no no  yes no no time to plating >40h >40h <24h <24h <40h <40h luts  yes yes yes no no no comorbidity/risk none none none none none dm chemotherapy recent steroids  no no no no no no recent antimicrobials no no no no no no table 3: summary features of the six dogs with positive qucs with quantification of bacterial growth reported as colony forming units (cfu/ml). ua = urinalysis luts = lower urinary tract signs dm = diabetes mellitus of the six dogs that had an inactive urine sediment examination and a positive quc, three presented on an emergency basis for evaluation of luts (dogs 1–3). they had unremarkable histories and physical examinations otherwise. no significant work up was performed beyond a ua and quc. all three dogs were prescribed amoxicillin/clavulanic acid (clavamox®, zoetis, usa) by mouth (po) every (q) 12 (h) hours, at dosages ranging from 14.6–24 mg/kg for 7 to 10 days and their luts were reported to have resolved. the three dogs who had an inactive urine sediment examination and a positive quc that did not present with luts represented more complex cases. dog 4 presented as an emergency for non-specific lethargy and discomfort, difficulty ambulating and a fever of 40.7°c (105.3°f). initial bloodwork revealed a mild normocytic, normochromic non-regenerate anaemia (haematocrit of 28.9%; reference 37.0–55.9%), mild elevation in creatinine (141 mmol/l: reference 35.4–123.8 mmol/l; 1.6 mg/dl: reference 0.4–1.4 mg/dl), mild increase in aspartate aminotransferase (230 u/l: reference 0–60 u/l) and mild hypoglycaemia (3.9 mmol/l: reference 4.2–6.9 mmol/l; 71 mg/dl: reference 75–125 mg/dl). an abdominal ultrasound revealed mild pyelectasia of the left renal pelvis (2.8 mm) with mild dilation of proximal ureter. scant pericardial effusion was also documented. ultimately dog 4 was euthanised before a definitive diagnosis was achieved due to failure to respond to symptomatic and supportive care provided with intravenous balanced crystalloid therapy, various opioid analgesics and ampicillin sulbactam (unasyn, pfizer) at 21.8 mg/kg q 8 h. dog 5 presented as an emergency for acute haematochezia and chronic decreased appetite with weight loss. initial bloodwork revealed mild elevation in creatinine (175 mmol/l: reference 35.4–123.8 mmol/l; 2.3 mg/dl: reference 0.4–1.4 mg/dl), and blood urea nitrogen (23.3 mmol/l: reference 3.2–10.4 mmol/l; 65.4 mg/dl: reference 9.0–29.0 mg/dl). an abdominal ultrasound revealed bilateral renal mineralisation and a right-sided renal cyst. hypertension was also documented (232 mmhg as measured by doppler). dog 5 was diagnosed with ckd and was subsequently discharged with instructions to administer subcutaneous fluids (40 ml/kg q 24 h), amoxicillin/clavulanic acid at 12.5 mg/kg po q 12 h and an angiotensin converting enzyme inhibitor (generic benazepril hydrochloride, teva) at 0.5 mg/kg po q 12 h with chronic management via the internal medicine service. dog 6 had a previous incompletely excised nasal grade iii mast cell tumour for which he was actively receiving lomustine (gleostine®, amatheon) at 2.1 mg/kg po q 3–4 weeks. he had also developed dm during the course of his chemotherapy and was poorly controlled. he presented as an emergency for vomiting and diarrhoea and was subsequently diagnosed with diabetic ketoacidosis and pancreatitis. he was treated in routine fashion for his diabetic ketoacidosis. his treatment included a course of amoxicillin/clavulanic acid at 21.2 mg/kg po q 12 h and he continued to work with the internal medicine and oncology services for his dm and mast cell tumours, respectively.   discussion this population of canine patients evaluated at private practice emergency and specialty referral hospitals was determined to have a 6% prevalence of positive quc with an inactive urine sediment. the majority of the bacterial isolates were cultured in quantities >10,000 cfu/ml, with a single isolate at 1,000 cfu/ml. since > 100 cfu/ml is considered clinically significant in both canine and feline urine obtained by cystocentesis (ettinger, 2017; comer & ling, 1981) contamination, while still possible, is not considered likely to be a cause for any of the positive cultures in this report. previous studies have reported e. coli as the bacterial species most commonly isolated from the urinary tract (comer & ling, 1981; hallet al., 2013). older and female dogs (both intact and spayed) are more likely to have positive urine cultures (comer & ling, 1981). four of the six positive qucs in this report were from female dogs, two of which cultured e. coli. haematuria may suggest inflammation of the urinary tract and is a common clinical sign for patients with bacterial cystitis (ettinger, 2017). microscopic or occult haematuria may be associated with urinary tract inflammation, or may be secondary to cystocentesis collection technique (ettinger, 2017). for these reasons we chose to include patients with occult haematuria in the analysis rather than excluding them. there was no association between patients with microscopic haematuria and positive quc results. in an effort to further characterise which patients may benefit most from a quc if they have an inactive sediment examination, presenting complaints/clinical signs, pre-existing comorbidities and recent steroid and antimicrobial therapy were recorded. previous reports have identified antimicrobial or steroid administration within 60 days to be a risk factor for a positive urine culture in dogs (freshman et al., 1989). we did not identify an association between prior antimicrobial or steroid administration and positive quc in this population, and the lack of association persisted when the dogs presenting for rechecks following antimicrobial therapy for bacterial cystitis were excluded from the analysis. additionally, there was no association between specific presenting complaints/clinical signs, or pre-existing comorbidities in dogs with positive qucs.  three of the dogs with a positive quc (dogs 1–3) presented to the emergency service for evaluation of simple and straightforward luts and had no other comorbidities or history of drug administration. their histories and physical examinations were otherwise unremarkable. all three dogs were prescribed amoxicillin/clavulanic acid for a range of 7–10 days and follow-up records indicate that all dogs had resolution of their luts. unfortunately, no further diagnostic evaluation beyond the inactive sediment examination and positive quc was performed. their sediment examination may have been inactive because it was collected too early in the course of their infection. given their positive response to antimicrobial therapy, a sporadic bacterial cystitis is suspected. it should be noted that the international society for companion animal infectious disease guidelines for treatment of sporadic bacterial cystitis recommend 3–5 days of antibacterial therapy. these guidelines also recommend considering a course of analgesics, such as non-steroidal anti-inflammatory drugs, and if signs persist or worsen in 3–4 days, then considering antimicrobial therapy (weese et al., 2019). the other three dogs with a positive quc (dogs 4–6) presented for a variety of clinical signs with a host of pre-existing comorbidities. dog 4 was suspected of having pyelonephritis based on the presence of fever, mild aezotemia and pyelectasia with ureteral dilation, although the presence of additional disease processes could not be ruled out. despite timely administration of antimicrobial therapy, dog 4 failed to show any clinical improvement with hospitalisation and was ultimately euthanised <48 hours after presentation. dogs 5 and 6 were suspected of having subclinical bacteriuria, which is defined as a positive quc from a properly collected urine sample (i.e. via cystocentesis) in a patient with no luts (weese et al,. 2019), although pyelonephritis could not be entirely ruled out, it was considered less likely. dog 5 presented for haematochezia and was incidentally diagnosed with ckd during diagnostic evaluation. this is not unexpected, as it is common for dogs with ckd to have subclinical bacteriuria, although the clinical relevance of such a finding remains unknown (foster et al., 2018). dog 6 was a previously diagnosed diabetic who presented with ketoacidosis and was actively receiving chemotherapy for mast cell tumours. this is also unsurprising, as it is also common for dogs with dm to have subclinical bacteriuria (forrester et al., 1999). although both dog 5 and 6 received amoxicillin/clavulanic acid, antimicrobial treatment of subclinical bacteriuria is rarely indicated and actually discouraged in the international society for companion animal infectious disease guidelines (weese et al., 2019). of course, there are exceptions and treatment for subclinical bacteriuria should be considered in patients at high risk for ascending or systemic infections, patients unable to display luts (i.e. those with spinal cord injury) or following the culture of plaque-forming (i.e. risk for encrusting cystitis) or urease-producing bacterial (i.e. risk for struvite uroliths formation) (weese et al,. 2019). this study has several important limitations. due to the logistics of a private practice facility using an outside commercial laboratorya for urine cultures there is a long and variable time gap from the time the urine sample is obtained and when it is plated at the laboratorya. weekday business hour samples, weekday after-hours samples and weekend samples were compared with no differences identified. however, it remains less than ideal to be evaluating cultures plated greater than 24 hours after collection and is an unfortunate constraint of private practice facilities that do not have on-site laboratories. this delay may have led to falsely negative results, particularly if a patient had a low number of bacteria in the sample and the sample was stored for a longer period of time. the optimal handling and storage for urine samples for which plating will be delayed is not clearly defined in veterinary medicine. experiments by patterson et al. (2018) showed a statistically significant decrease in e. coli cfu/ml when urine was placed in either silicone clot tubes or urine transport tubes and stored in the refrigerator for 24 hours. conversely investigations by acierno et al. (2018) failed to find a difference in colony counts or positive culture rate when urine was plated immediately or stored in plain glass tubes in refrigeration for 24 hours. furthermore, padilla et al. (1981) supports the use of refrigeration over room temperature storage for urine samples that are not plated immediately after collection with only one false negative result out of 26 qucs and no false positive results after 24 hours of refrigeration. it is worth noting that patterson et al. (2018) used pooled sterile urine inoculated with e. coli while acierno et al. (2018) used clinical samples from dogs with a suspected bacteria cystitis. both techniques appear throughout the literature, however we were unable to find a good description of the differences in the urinary environment between naturally and artificially infected urine, and wonder if this might contribute to the difference between these two study outcomes. clearly this is an area that needs further study in many regards. for example, because long delays to sample plating at commercial laboratories are the challenging reality for most private practice institutions, it would be useful to repeat the current study with a prospective design that controls time from collection to urinalysis and culture plating to determine if there is a clinically important difference in the positive culture rate. additionally, inoculating sterile urine with a variety of different organisms at a range of different concentrations, storing that urine in the refrigerator for 24, 48 and 72 hours and then plating it utilising the commercial laboratory’s standard methods to determine if a positive culture rate compared to urine plated immediately after collection, would be useful information. similarly, studies evaluating the cost and reliability of in-house urine plating, and utilisation of techniques other than urine culture to identify causative organisms and predicted antimicrobial sensitivity would be of benefit to the veterinary community. qucs are a relatively expensive test compared to urinalysis alone and knowing the prevalence of a positive result in a dog with inactive urine sediment can assist clinicians in evaluating the medical and financial risks vs benefits of when to order this test. dogs displaying luts, even with an inactive sediment examination, may benefit from a quc. a quc should also be considered on a case-by-case basis for systemically ill patients with various comorbidities presenting to emergency services. ideally urine would be cultured within 24 hours post collection, however inability to do so should not preclude culture.  prospective studies evaluating the bacterial cystitis and subclinical bacteriuria prevalence in specific at-risk populations, studies that mimic the typical storage time and handling of urine samples submitted to commercial laboratories that are designed to determine the clinical impact of these practices, as well as research looking for rapid, point-of-care testing alternatives to urine culture and microbial sensitivity are needed in veterinary medicine.   footnotes footnotes aantech diagnostics 17620 mt. herrmann street, fountain valley, ca 92708 bmicrosoft office excel   abbreviations cfu = colony forming unit ckd = chronic kidney disease dm = diabetes mellitus hac = hyperadrenocorticism luts = lower urinary tract signs quc = quantitative urine culture usg = urine specific gravity ua = urinalysis   conflict of interest the authors declare no conflicts of interest.   references acierno, m.j., partyka, m., waite, k., cunha, a. & mitchell, m.a. ‘effects of refrigeration of clinical canine urine samples on quantitative bacterial culture’. journal of the american veterinary medical association (2018); 253(2): 177–180. doi: https://doi.org/10.2460/javma.253.2.177 comer, k.m. & ling, g.v. ‘results of urinalysis and bacterial culture of canine urine obtained by antepubic cystocentesis, catheterization and the midstream voided methods’. journal of the american veterinary medical association (1981); 179: 891–895. ettinger, s.j., feldman, e.c. & côté, e. textbook of veterinary internal medicine. 8th ed. st. louis: elsevier, inc. (2017). forrester, s.d., troy, g.c., dalton, m.n., huffman, j.w. & holtzman, g. retrospective evaluation of urinary tract infection in 42 dogs with hyperadrenocorticism or diabetes mellitus or both’. journal of veterinary internal medicine (1999); 13: 557–560. doi: https://doi.org/10.1111/j.1939-1676.1999.tb02209.x foster, j.d., krishnan, h. & cole, s. ‘characterization of subclinical bacteriuria, bacterial cystitis, and pyelonephritis in dogs with chronic kidney disease’. journal of the american veterinary medical association (2018); 252(10): 1257–1262. doi: https://doi.org/10.2460/javma.252.10.1257 freshman, j.l., reif, j.s., allen, t.a. & jones, r.l. ‘risk factors associated with urinary tract infection in female dogs’. preventive veterinary medicine (1989); 7(2): 59–67. doi: https://doi.org/10.1016/0167-5877(89)90037-8 hall, j.l., holmes, m.a. & baines, s.j. ‘prevalence and antimicrobial resistance of canine urinary tract pathogens’. vet record (2013); 173(22): 549. doi: http://dx.doi.org/10.1136/vr.101482 neely, j.g., hartman, j.m., forsen, j.w. jr. & wallace, m.s. tutorials in clinical research: vii. understanding comparative statistics (contrast)-part b: application of t-test, mann-whitney u, and chi-square. laryngoscope. (2003); 113(10):1719–1725. doi: https://doi.org/10.1097/00005537-200310000-00011 padilla, j., osborne, c.a. & ward, g.e. ‘effects of storage time and temperature on quantitative culture of canine urine’. journal of the american veterinary medical association (1981); 178: 1077–1081. patterson, c.a., bishop, m.a., pack, j.d., cook, a.k. & lawhon, s.d. ‘effects of processing delay, temperature, and transport tube type on results of quantitative bacterial cultures of canine urine’. journal of the american veterinary medical association (2016); 248(2): 183–187. doi: https://doi.org/10.2460/javma.248.2.183 vetter, t.r. fundamentals of research data and variables: the devil is in the details. anesthesia & analgesia. (2017); 125(4):1375–1380. doi: http://dx.doi.org/10.1213/ane.0000000000002370 weese, s.j., blondeau, j., boothe, d., guardabassi, l.d., gumley, n.,  papich, m.,  jessen, l.r., lappin, m., rankin, s., westropp, j.l. & sykes, j. ‘international society for companion animal infectious diseases (iscaid) guidelines for the diagnosis and management of bacterial urinary tract infections in dogs and cats’. the veterinary journal (2019); 247: 8–25. doi: https://doi.org/10.1016/j.tvjl.2019.02.008 intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. retrospective study on external canine limb prosthesis used in 24 patients brittany jean carr dvm, ccrt1* sherman canapp dvm, ms, ccrt, dacvs, dacvsmr1 julia l. petrovitch bvm&s1 derrick campana cpo2 debra canapp dvm, ccrt, cva, cvrat, dacvsmr1 christopher s. leasure dvm1 1veterinary orthopedic and sports medicine group, 10975 guilford road, annapolis junction, md 20701, usa 2animal orthocare, llc., 43760 trade center place, sterling, va 20166, usa *corresponding author (bjc0510@gmail.com) vol 3, issue 1 (2018) published: 09 mar 2018 reviewed by: alycen lundberg (dvm) and stephen jones (mvb, ms, dacvs) doi: 10.18849/ve.v3i1.118 section index:    abstract | introduction | methods | results | discussion | footnotes | conflict of interest | references abstract objective: the purpose of this retrospective study is to provide data regarding external prosthetic use in small animal patients, evaluate the common complications associated with external prosthetics, and evaluate the outcome of patients using an external prosthetic. background: the use of external canine limb prosthetics is relatively uncommon in veterinary medicine today.  however, there is growing interest in prosthetics and their clinical application because these devices may offer an alternative to euthanasia in severe cases where full amputation or alternative methods of limb spare are not an option. the goal of the prosthesis is to provide a better quality of life, help prevent further deformation and degeneration of existing joints, decrease leg length discrepancies, increase exercise and activity levels, provide a means to participate in rehabilitation therapy and maintain the ability to perform daily acts of living. to the author’s knowledge, there is no report of external prosthetic use in small animal veterinary medicine, providing the profession with baseline information for use in, not only general practice or referral practice, but also future research. evidentiary value: this retrospective study provides data regarding external prosthetic use in small animal patients, evaluates the procedures, manufacturing, rehabilitation and common complications associated with external prosthetics, and evaluates the factors that determine a patient’s prosthetic candidacy. methods: patients that had an external prosthesis custom manufactured for them at animal orthocare, llc and had a complete medical record were identified for this study.  a client survey was completed via e-mail or telephone to collect further data about the patients, including age, weight, breed, sex, affected limb(s), reason for prosthesis, level of amputation, activities patient could perform with prosthesis in place, prosthetic fit, prosthetic migration (e.g. rotating or slippage), quality of mobility comparing pre-prosthetic mobility to post-prosthetic mobility, prosthetic integrity, client’s post-prosthetic mobility expectations, complications encountered post-prosthetic application, and client’s perspective of patient’s quality of life comparing pre-prosthetic and post-prosthetic placement.  results: of the 76 patients who were identified for this study and received a survey, survey information was obtained for 24 patients. there were 50% (n=12) forelimbs affected and 50% (n=12) hind limbs affected. bilateral hind limb prosthesis was found in 8.33% (n=2) of the 24 cases included. causes for the prosthesis were found to be due to trauma in 37.5% (n=9) of cases, congenital causes in 37.5% (n=9) of cases, neoplasia in 16.66% (n=4) of cases, infectious in 4.17% (n=1) of cases, and unknown in 4.17% (n=1) of cases. of the 24 patients, 50% (n=12) of clients felt the prosthesis had an excellent fit; 20.83% (n=5) felt the prosthesis had a good fit; 16.67% (n=4) felt the prosthesis had an acceptable fit; 4.17% (n=1) felt the prosthesis had a less than satisfactory fit; lastly, 8.33% (n=2) felt the prosthetic had a poor fit. of the 24 patients, 91.66% (n=22) were able to stand using the prosthesis; 87.5% (n=21) were able to walk using the prosthesis; 79.17% (n=19) were able to trot using the prosthesis; 70.83% (n=17) were able to climb stairs using the prosthesis; 54.17% (n=13) were able to jump on or off furniture using the prosthesis; 79.17% (n=19) were able to play fetch using the prosthesis.  from these cases, 50% (n=12) of clients felt the patient’s mobility improved post-prosthetic placement. expectations were met in 70.83% (n=17) of cases; expectations were somewhat met in 4.17% (n=1) of cases; expectations were not met in 25% (n=6) of cases.  prosthetic migration affected 37.5% (n=9) of cases; residuum sore or infection affected 20.83% (n=5); refusal to use the prosthetic limb occurred in 20.83% (n=5) of cases; concurrent orthopedic disease occurred in 0% of patients; prosthetic failure (breaking) occurred in 20.83% (n=5) of cases. finally, clients were asked to rate the quality of life of patients after prosthetic placement when compared to pre-prosthetic placement on a scale of 1 – 5 (1 = much worse than before, 5 = much better than before). patients rated a quality of life of 5 were 20.83% (n=5); a rating of 4 was given to 20.83% (n=5); a rating of 3 was given to 45.83% (n=11); a rating of 2 was given to 4.17% (n=1); a rating of 1 was given to 8.33% (n=2).  conclusion: external prosthetics may help improve quality of life and should be considered as an alternative to euthanasia where full amputation or alternative methods of limb spare are not an option. application: these results should be considered by veterinarians and prosthetists when searching for an alternative to full amputation or other limb spare surgical methods. introduction the use of external canine limb prosthetics is relatively uncommon in veterinary medicine. there are a number of external prosthetics used in humans, utilising various methods of securing the artificial limb to the residual limb as well as various devices for different types of activity. in veterinary patients, we are limited in both areas, partially due to our patients’ anatomies and the limited amount of evidence-based knowledge available (canapp et al., 2012; seymour r., 2002). however, there is more interest in prosthetics and their clinical application because these devices may offer an alternative to euthanasia in cases where full amputation or alternative surgical methods of limb spare are not an option. the goal of the prosthesis is to provide a better quality of life, help prevent further deformation and degeneration of existing joints, decrease leg length discrepancies, increase exercise and activity levels, provide a means to participate in rehabilitation therapy and maintain the ability to perform daily acts of living. there are specific requirements for a prosthetic to be successful, and complications may arise if appropriate surgical planning, accurate manufacturing of the prosthetic, or proper introduction to the prosthesis are not performed. patients should be assessed carefully when recommending an external prosthesis. one of the most critical characteristics for prosthetic eligibility is the amputation level (canapp et al., 2012; canapp et al., 2014). in human studies, the most successful candidates have amputations performed as distally as possible, salvaging vasculature and soft tissue coverage over the residuum, as this has been shown to achieve the optimal potential for post-operative ambulation (bowker et al., 1992). when compared to non-amputees, patients with transtibial amputations were noted to have 9% higher oxygen consumption during ambulation, patients with transfemoral amputations were noted to have 49% higher oxygen consumption during ambulation and patients with bilateral transfemoral amputations were noted to have 280% higher oxygen consumption (huang et al., 1979). it is also widely accepted that patients with distal amputations have fewer planes of movement versus patients with proximal amputations, which improves patient control over the prosthesis during ambulation (bowker et al., 1992; canapp et al., 2014). due to the anatomy of our small animal patients, the hind limb offers an advantage for prosthetic success with distal amputations, while the forelimb’s anatomy offers better success with proximal amputations (canapp et al., 2012). the tarsus is an excellent suspension point to reduce prosthetic migration and has an anatomical advantage compared to other joints such as the carpus due to the acute angular nature of the joint, which reduces prosthesis axial rotation (canapp et al., 2012; canapp et al., 2014). in the forelimb, prosthetics may be utilised if the elbow joint is preserved (canapp et al., 2012; canapp et al., 2014). the humeral epicondyles provide a good prominence for self-suspension, and a circumferential strapping system used proximal to the elbow helps prevent migration and contributes to rotational stability (canapp et al., 2012; canapp et al., 2014). procedures requiring amputation proximal to the elbow have limited ability for prosthetic success as there are no ideal prominences for suspension and there are more planes of movement, which will reduce control over the limb and could even lead to humeral fracture if the prosthesis shank is too long (canapp et al., 2012).  proximal amputations in the hind limbs often have diminished success, unless a suspension system consisting of a harness is used.  further, the stifle joint provides minimal boney prominences to which an artificial limb may be suspended, making the prosthetic more prone to migration and excessive rubbing (canapp et al., 2014).   surgical planning for amputation should aim to maintain soft tissue coverage of the residuum while positioning nerve endings away from the distal residuum and preserving residual limb vasculature and smooth boney prominences to prevent residual limb sores (canapp et al., 2012; bowker et al., 1992; burgess et al., 1981; canapp et al., 2014). maintaining adequate soft tissue coverage will help reduce shear forces on the residual limb involved with prosthetic ambulation. in humans undergoing transtibial amputations, there is often discomfort due to instability between the tibia and fibula (bowker et al., 1992; ertl reconstruction website, 2015; decoster et al., 2006). in the human literature it is also proposed that an open medullary cavity will increase discomfort with end-bearing prosthesis by altering normal conditions of pressure and circulation within the bone (decoster et al., 2006). surgeons have developed a procedure to eliminate instability between the tibia and the fibula by using a tibiofibular bridge that creates a unified end-bearing limb and a callus over the medullary cavity to decrease disturbances in vascular supply to the end-bearing surface (decoster et al., 2006, ertl reconstruction website, 2015). currently, these techniques are infrequently utilised in veterinary surgery but could improve weight bearing and overall function in patients with a transtibial amputation (canapp et al., 2014). prior to surgery, the level of the amputation for the soft tissues is marked distally, while the boney anatomy is marked proximally on the skin. the initial incision should be planned so that the closed incision does not lie over the distal or palmar/plantar surface of the residuum to ensure that the incisional scar does not adhere to the underlying bone (canapp et al., 2012; canapp et al., 2014; bowker et al., 1992). it is vital that the soft tissues are handled carefully to prevent unnecessary trauma; good soft tissue coverage of the residuum will resist the shear forces involved in prosthetic ambulation and help maintain residual limb integrity (canapp et al., 2012; canapp et al., 2014; bowker et al., 1992). a transverse osteotomy, at the most distal level possible, is made across the bone(s), proximal to the initial skin incision and soft tissue transection, and the distal limb is removed. the cortical bone edges should be smoothed to prevent sharp edges causing soft tissue trauma (canapp et al., 2014; bowker et al., 1992; ert reconstruction technique, 2015; decoster et al., 2006). the medullary cavity should be packed with bone wax to help provide hemostasis from the medullary canal. hemostasis is especially important to obtain in amputations as hemorrhage will predispose the residuum to post-operative seromas (canapp et al., 2012; canapp et al., 2014; bowker et al., 1992). to begin closure, muscles, tendons and fascia from the caudal limb are wrapped around the end of the bone and apposed to the muscles, tendons and fascia on the opposite side of the bone in a mattress pattern using a long-lasting monofilament suture (canapp et al., 2012; canapp et al., 2014). while it is not well defined for small animals, it is recognised that weight bearing occurs at the caudodistal aspect of the residuum.  thus, the surgeon should avoid creating possible weak points over the caudodistal surface as it could predispose the residuum to future soft tissue break down (canapp et al., 2012; canapp et al., 2014). once all muscles, tendons and fascia are apposed, the skin incision should be closed over the cranial surface of the residuum with minimal to no tension to reduce the chances of ulcerations and to promote healing post-operatively (canapp et al., 2012; canapp et al., 2014). skin sutures may be preferred to skin staples as they are considered more comfortable and are associated with a lessened risk for post-operative incisional infection (smith et al., 2010). post-operatively, amputees are currently placed into a compression bandage to reduce swelling, protect the distal residuum from trauma and promote healing (canapp et al., 2012). prosthetic manufacturing should not begin until all swelling has resolved and muscle atrophy of the residual limb has occurred (canapp et al., 2012; canapp et al., 2014). typically, the residuum is fitted for a prosthetic at about 2-3 weeks post-operatively when the swelling has fully resolved, as this will help reduce further prosthetic revisions (canapp et al., 2012; canapp et al., 2014).   it is important that prosthetic professionals work directly with both the veterinary orthopedic surgeon and a veterinary rehabilitation team to reach the most successful outcome.  starting with prosthetic introduction, a close relationship between the prosthetist and the client should be maintained to ensure proper wear and care of the prosthesis and to prevent complications or further injury to the patient. firstly, the client should be instructed how to properly don and doff the prosthesis and a schedule for gradual introduction should be devised. schedules for introduction will vary case by case, but a generic schedule is 1 hour on day one, increased by 1 hour each day until it can be worn at all times. additionally, rehabilitation therapy is often recommended to help integrate the prosthesis into the everyday life of the patient and client. rehabilitation commonly focuses on increasing circulation, enhancing forelimb and hind limb strength and increasing range of motion; for prosthetic patients it must also provide prevention of contractures or correction of existing contractures, improvement in coordination, reduction of edema to promote healing and, lastly, promote mobility using the device (canapp et al., 2012; canapp et al., 2014). clients should also be made aware of signs of early complication (e.g. persisting erythema, etc.) so that earlier revisions may be made.  however, there is little in the literature regarding the most common complications observed in patients wearing external prosthetics. to the authors’ knowledge, there is no report of external prosthetic use in small animal veterinary medicine. the purpose of this retrospective study is to provide data regarding external prosthetic use in small animal patients, evaluate the common complications associated with external prosthetics, and evaluate the outcome of patients using an external prosthetic. methods patient selection patients that had an external prosthesis custom manufactured for them at animal orthocare, llc and complete records were selected from the database at animal orthocare, llc.  seventy-six candidates fit the inclusion criteria. information collected from the record included sex, age, weight, breed, and the affected limb. prosthetic fabrication each prosthesis was manufactured in a similar method for each patient.a each patient’s residuum had a cast made using several techniques – fiberglass cast, plaster of paris cast, 3d modeling, ct or mri image reconstruction, algination or biofoam techniques were employed. once a negative or positive cast was obtained, a positive mold was produced. manual sculpting or 3d digital modeling techniques were used in order to take down areas of pressure tolerance and build upon areas of pressure resistance to produce the final positive mold on which the definitive socket is manufactured. fabrication techniques used to form the socket include vacuum forming thermoplastics or carbon lamination. several materials were employed to improve comfort of the prosthesis including a soft liner made from plastazote, aliplast or volara. once the socket was created, methods of suspension were selected for each patient to help prevent migration of the device. thereafter, a shank was selected to ensure limb length was maintained and a foot for the prosthesis was designed to provide appropriate breakover, depending on the patient’s daily activity level. pending the patient’s response to the prosthetic design, adjustments were made accordingly so that the device maintained proper fit and to prevent migration. client survey for all patients identified for this study, a client survey was then completed via electronic email or telephone to provide further data about the patients, including age, weight, breed, sex, affected limb(s), reason for prosthesis, level of amputation, activities patient could perform with prosthesis in place, prosthetic fit, prosthetic migration (e.g. rotating or slippage), quality of mobility comparing pre-prosthetic mobility to post-prosthetic mobility, prosthetic integrity, client’s post-prosthetic mobility expectations, complications encountered post-prosthetic application, and client’s perspective of patient’s quality of life comparing pre-prosthetic and post-prosthetic placement.  results overall survey data seventy-six patients were identified for this study. the patient age ranged from 9 weeks to 15 years of age, with a mean of 4.7 years. the patient weight range was 4 to 155 pounds, with a mean of 61 pounds. surveys were sent via electronic mail to all 76 cases and followed up via telephone. of the 76 cases, survey information for 24 patients was obtained. from the 24 patients who responded to the survey, the patient age ranged from 5 months to 12 years, with a mean of 4 years. the patient weight ranged from 4 to 155 pounds, with a mean of 62.2 pounds. breeds included were mixed breed (n=7), golden retriever (n=4), pit bull terrier (n=2), border collie (n=1), south african boerboel (n=1), english mastiff (n=1), shiloh shepherd (n=1), german shepherd dog (n=1), labrador retriever (n=1), boxer (n=1), maltese (n=1), giant schnauzer (n=1), bassett hound (n=1) and coonhound (n=1). gender survey data from the 24 clients who responded to the survey, the patient sex ratio was 41.66% female (n=10), of which 70% (n=7) were altered. the male portion was a total of 58.33% male (n=14), of which 92.86% (n=13) were altered. affected limb survey data from the 24 patients who responded to the survey, 5 different affected limb categories were recognised. there were 50% (n=12) forelimbs affected and 50% (n=12) hind limbs affected. the left forelimb was affected 16.66% (n=4) of the time; the right forelimb was affected 33.33% (n=8) of the time. the left hind limb was affected 25% (n=6) of the time; the right hind limb was affected 16.66% (n=4) of the time. bilateral hind limb prosthesis was found in 8.33% (n=2) of the 24 cases included.  thus, there was a total of 26 affected limbs. reason for prosthesis survey data from the 24 patients who responded to the survey, reason for prosthetic application was recorded (figure 1). prosthetic application was elected following trauma in 37.5% (n=9) of limbs, congenital malformations in 37.5% (n=9) of limbs, neoplasia in 16.66% (n=4) of limbs, and other causes in 8.33% (n=2) of limbs, which included partial limb loss due to parvovirus (n=1) and an unknown cause (n=1) figure 1: this chart shows the pre-existing conditions that led to the use of an external limb prosthetic to improve mobility, provide a method of limb spare or improve quality of life. this data was collected from client answered surveys retrospectively. level of amputation survey data from the 24 patients who responded to the survey, the level of amputation was both obtained from the medical record and confirmed by having clients select the level of amputation from the amputation level diagram provided (figure 2). from the patients with a forelimb prosthesis, 75% (n=9) were amputees at the level of the metacarpus, while0% had amputation at the level of the carpus. amputation at the level of mid-diaphyseal radialulnar occurred 25% (n=3) of the time. from patients with a hind limb prosthesis, 50% (n=6) were amputees at the level of the metatarsus, while 41.66% (n=5) had amputation at the level of the tarsus. amputation at the level of mid tibial occurred 8.33% (n=1) of the time. figure 2: amputation level diagram. each letter denotes the level at which the limb was amputated. levels a, b, & c relate to the forelimbs: level a corresponds to amputation at the level of the metacarpus; level b corresponds to amputation at the level of the carpus; level c corresponds to amputation at the level of mid-diaphyseal radial-ulnar, or distal to the elbow. levels d, e, & f relate to the hind limbs: level d corresponds to amputation at the level of the metatarsus; level e relates to amputation at the level of the tarsus; level f relates to amputation at the level of mid-tibial or distal to the stifle. daily activities survey from the 24 patients who responded to the survey, information about daily activities was evaluated (figure 3). of the 24 patients, 91.66% (n=22) were able to stand using the prosthesis; 87.5% (n=21) were able to walk using the prosthesis; 79.17% (n=19) were able to trot using the prosthesis; 70.83% (n=17) were able to climb stairs using the prosthesis; 54.17% (n=13) were able to jump on or off furniture using the prosthesis; 79.17% (n=19) were able to play fetch using the prosthesis. figure 3: this graph shows data pertaining to daily acts of living for patients after prosthetic placement, obtained from client answered surveys. prosthesis fitting survey data from the 24 patients who responded to the survey, information about prosthetic fit was recorded. of the 24 patients, 50% (n=12) of clients felt the prosthesis had an excellent fit; 20.83% (n=5) felt the prosthesis had a good fit; 16.67% (n=4) felt the prosthesis had an acceptable fit; 4.17% (n=1) felt the prosthesis had a less than satisfactory fit; lastly, 8.33% (n=2) felt the prosthetic had a poor fit. prosthetic migration survey data from the 24 patients who responded to the survey, information about prosthetic migration (e.g. slipping) was gathered. of these patients, 45.83% (n=11) were reported to have no prosthetic slippage; 12.5% (n=3) were reported to have very occasional migration; 16.67% (n=4) were reported to have prosthetic slippage sometimes; lastly 25% (n=6) were reported to have prosthetic slippage often. prosthetic mobility survey data from the 24 patients who responded to the survey, subjective comparative data about patient mobility pre-prosthetic placement versus post-prosthetic placement was collected (figure 4). from these cases, 50% (n=12) felt the patient’s mobility improved post-prosthetic placement. no difference in mobility between pre-prosthetic and post-prosthetic placement was found in 37.5% (n=9) of patients. in 12.5% (n=3) of patients, clients rated mobility to be worse after prosthetic placement. figure 4: this graph shows data pertaining to the client’s subjective opinion on the patient’s mobility comparing pre-prosthetic placement to post-prosthetic placement. device integrity survey data from the 24 patients who responded to the survey, 75% (n=18) of patient’s prostheses did not break from the time of placement to the time of this study; 25% (n=6) of patient’s prostheses did break from the time of placement to the time of this study. mobility expectations survey data from the 24 patients who responded to the survey, clients rated how the prosthesis met their mobility expectations. the cases where expectations were met occurred in 70.83% (n=17) of cases; expectations were somewhat met in 4.17% (n=1) of cases; expectations were not met in 25% (n=6) of cases. complications survey data from the 24 patients who responded to the survey, information about complications encountered was gathered (figure 5). prosthetic migration occurring often affected 37.5% (n=9) of cases; residuum sore or infection affected 20.83% (n=5); refusal to use the prosthetic limb occurred in 20.83% (n=5) of cases; concurrent orthopedic disease occurred in 0% of patients; prosthetic failure (breaking) occurred in 20.83% (n=5) of cases. other complications encountered affected 8.33% (n=2) of patients. these complications included one patient never getting used to wearing the prosthesis and one patient who ‘didn’t like wearing’ the prosthesis. figure 5: this graph details incidence and types of complications clients experienced when using prosthetics. quality of life survey data from the 24 patients who responded to the survey, clients were asked to rate the quality of life of patients after prosthetic placement when compared to pre-prosthetic placement (figure 6). a scale from 1 – 5 was provided (1 = much worse than before, 5 = much better than before). patients rated a quality of life of 5 were 20.83% (n=5); a rating of 4 was given to 20.83% (n=5); a rating of 3 was given to 45.83% (n=11); a rating of 2 was given to 4.17% (n=1); a rating of 1 was given to 8.33% (n=2). figure 6: this graph details the comparison in quality of life between pre-prosthetic placement vs. post-prosthetic placement from the client’s perspective. discussion this study supports that external prosthetics may help improve quality of life and should be considered as an alternative to euthanasia where full amputation or alternative methods of limb spare are not an option. to the authors’ knowledge, this is the first report of external prosthetic use in small animal veterinary medicine, providing the profession with baseline information for use in, not only general practice or referral practice, but also future research.  furthermore, these results should be considered by veterinarians and orthotists when searching for an alternative to full amputation or other limb spare surgical methods. over 87% of clients reported that the prosthetic had both an acceptable fit or better and a quality of life that was equal to or better than the quality of life prior to prosthetic placement.  it is important to note that the majority of patients with a forelimb amputation had an amputation at the level of the metacarpus (75%) and all but one hind limb amputation patients were at the level of the metatarsus or level of the tarsus. as previously mentioned, forelimb prosthetics are typically preferred for more proximal amputations as the elbow joint typically provides a better suspension point than the carpus, whereas distal hind limb amputations offer an advantage for prosthetic success as the tarsus is an excellent suspension point to reduce prosthetic migration (canapp et al., 2012; canapp et al., 2014).  it is possible that the level of amputation contributed to the outcomes reported in this study; however, further study is necessary to determine if there is a correlation between amputation level and outcome measures. various complications were reported in this study, most notably prosthetic migration in 37.5% of cases and residuum sores or infection in approximately 20% of patients.  this is consistent with previous reports in both humans and dogs that report prosthetic migration and residuum sores are commonly noted complications (canapp et al., 2012; armstrong et al., 2007; bowker et al., 1992; seversky et al., 2005; canapp et al., 2014; ertl reconstruction website et al., 2015; decoster et al., 2006).  previous reports have also stated the initial prosthesis often requires revisions as the residuum changes in shape due to the patient’s altered ambulation (canapp et al., 2012; canapp et al., 2014). indications for prosthesis revision are prosthetic migration and the development of residuum sores.  client vigilance is necessary for monitoring the health of the residual limb to ensure prosthetic revisions are addressed in a timely manner to avoid excessive soft tissue damage or infection. otherwise, little daily maintenance is required if the prosthetic has an intimate fit and if it is used correctly (canapp et al., 2014).  many of the patients in this study were reported to be able to participate in a number of activities.  of the 24 patients, approximately 79% (n=19) were able to trot using the prosthesis, 70% (n=17) were able to climb stairs using the prosthesis, 54% (n=13) were able to jump on or off furniture using the prosthesis, and 79% (n=19) were able to play fetch using the prosthesis.  as one can imagine with frequent use and wear over time, repairs to the prosthesis may be needed.  approximately 25% of patient prostheses were reported to have broken from the time of placement to the time of this study.  it is important that owners are instructed on how to visually inspect the prosthesis for integrity and function as any damage to the prosthesis should be addressed promptly. this study demonstrated that a large percentage of dogs in this study were still able to participate in normal daily activities.  furthermore, the clients’ expectations for their patients’ mobility was met in over 70% of cases.  however, this study did not specifically inquire about or quantitatively analyze alterations in gait characteristic, which has been documented in dogs and humans who use external prosthetics (canapp et al., 2014; malchow et al., 2016; kendell et al., 2016). gait pattern changes often can occur due to a misaligned prosthesis or a leg length discrepancy. these problems should be addressed as soon as possible, and can often be remedied by simple alignment adjustments or by changing internal padding thickness in the prosthetic. depending on the case, joint abnormalities in other limbs may develop if the gait pattern is not corrected in a timely manner. the most common psychological abnormality occurs immediately when the patient is fitted with the device, where the patient rejects the prosthetic or refuses to use the limb (canapp et al., 2014). in this study, one patient would not use the prosthetic even after an appropriate acclimation period.  in most patients, a gradual introduction schedule is the method of choice to get the patient used to the device and reduce the risk of outright rejection. clients should be warned of all possible complications prior to electing limb spare involving external prosthesis. in the end, it is most important that the client is attentive to the possible complications and the veterinarian is adept at troubleshooting any situation which may occur. limitations of this study are predominantly related to its retrospective nature and subjective outcome measures as reported by clients.  future studies should be prospective, randomised and blinded and include objective outcome measures, such as goniometric measurements, limb circumference muscle mass measurements, and objective gait analysis.  nonetheless, this study provides data regarding external prosthetic use in small animal patients, evaluates the common complications associated with external prosthetics, and evaluates the outcome of patients using an external prosthetic that should be taken into consideration by veterinarians and prosthetists when searching for an alternative to full amputation or other surgical limb spare procedures. footnotes animal orthocare prosthesis, animal orthocare, llc., sterling, va, usa. conflict of interest acknowledgments: thank you katie cox, ms, for her help in collecting and organizing data for this manuscript. funding: no external funding was accepted for this project. competing interests: derrick campana, cpo, is the ceo and president of animal orthocare, llc. references armstrong pd. (2007). immediate postsurgical and early prosthetic management of lower extremity amputations, in lecture. the newington certificate program in orthotics and prosthetics, newington, ct. bowker jh, michael jw. (1992). atlas of limb prosthetics: surgical, prosthetic and rehabilitation principles. 2nd ed. st. louis, mo: mosby-year book, inc. burgess em, matsen fa. (1981). determining amputation levels in peripheral vascular disease. the journal of bone & joint surgery 63, 1493. doi: http://dx.doi.org/10.2106/00004623-198163090-00020 canapp so, campana dm, fair lm. (2012). orthopedic coaptation devices and small-animal prosthetics. in: tobias km, johnston sa. veterinary surgery: small animal volume 1. st. louis, mo: elsevier inc, 628–646. canapp so, petrovitch jl, leasure cs, et al. (2014). prosthesis: an alternative canine limb spare technique using partial amputation and external prosthetics, in proceedings. european society of veterinary orthopaedics and traumatology. decoster ta, homedan s. (2006). amputation osteoplasty. the iowa orthoaedic journal, 26, 54–59. ertl reconstruction website. the ertl osteomyoplastic transtibial amputation reconstruction description of technique and long term results. available at: http://www.ertlreconstruction.com/documents/transtibial-technique.pdf. accessed july 4, 2015. gailey rs, roach ke, applegate eb, et al. (2002). the amputee mobility predictor: an instrument to assess determinants of the lower-limb amputee’s ability to ambulate. archives of physical medicine and rehabilitation, 83, 613–627. doi: http://dx.doi.org/10.1053/ampr.2002.32309 huang c, jackson r, moore n, et al. (1979). amputation: energy cost of ambulation. arch phys med behahil, 60, 18. kendell c, lemaire ed, kofman j, dudek n. (2016). gait adaptations of transfemoral prosthesis users across multiple walking tasks. prosthetics and orthotics international, 40(1), 89-95. doi: http://dx.doi.org/10.1177/0309364614568410 malchow c and goeran f. (2016). effect on observation on lower limb prosthesis gait biomechanics: preliminary results. prosthetics and orthotics international, 40(6), 739-743. http://dx.doi.org/10.1177/0309364615605374 seversky n. (2005). theory and clinical applications of prosthetic gel liners, in lecture. the newington certificate program in orthotics and prosthetics, newington, ct. seymour r. (2002). prosthetics and orthotics: lower limb and spinal. baltimore, md: lippincott williams & wilkins. smith to, sexton d, mann c, et al. (2010). sutures versus staples for skin closure in orthopaedic surgery: meta-analysis. bmj, 340:c1199. doi: http://dx.doi.org/10.1136/bmj.c1199 supplementary files, images & tables all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. choosing treatment for dogs with generalised demodicosis – isoxazolines or imidacloprid and moxidectin? a knowledge summary by sarah long bvsc, certavp, mrcvs1* 1locum veterinary surgeon, united kingdom *corresponding author (sarahmlong@hotmail.co.uk) vol 4, issue 2 (2019) published: 23 apr 2019 reviewed by: constance white (dvm, phd) and roberta perego (dvm, phd) next review date: 1 mar 2021 doi: 10.18849/ve.v4i2.183 pico question in dogs with generalised demodicosis, are isoxazolines as effective as a combined formulation of imidacloprid and moxidectin at reducing mite count and the severity of associated clinical signs? clinical bottom line five single-blinded, randomised, positive control trials, most under laboratory conditions, directly compared the use of isoxazolines against moxidectin/imidacloprid to treat canine generalised demodicosis. all of them showed comparable efficacy of isoxazolines. three different isoxazolines were studied with two routes of administration (oral and topical) and four different dosing frequencies of moxidectin/imidacloprid. this made the papers more challenging to compare however, the evidence provided is sufficient to support their use. all of these trials were sponsored by the manufacturers of their respective isoxazoline products which may bias the study design and reporting of results. it is worth noting that sarolaner (simparica™, zoetis uk) was licensed in the uk for the treatment of canine demodicosis in january 2018 and that in the uk the cascade should be followed when prescribing treatments. the licensed use of isoxazolines in other countries is beyond the scope of this article and the reader is urged to check local regulatory body advice before prescribing the below medications. clinical scenario a seven-year-old male, neutered, long-haired, cross breed dog presented with a one month history of erythema, patchy alopecia and follicular casts to the feet, hindlimbs and dorsum. he had not been regularly treated with ectoparasiticides and had no previous history of skin disease. deep skin scrapings from the affected areas revealed two to eight live demodex canis mites per slide. cytology showed mild numbers of surface cocci only with no inflammatory cells. his clinical exam was otherwise unremarkable and full blood count, biochemistry and urinalysis were within reference intervals. the evidence a recent systematic review by perego et al. (2019) found good evidence for the use fluralaner and sarolaner with a good level of efficacy and safety, although long term follow up was lacking. they also found good evidence for the use of moxidectin/imidacloprid and noted improved efficacy with increased frequency of application (perego et al., 2019). moxidectin with imidacloprid is a good choice of positive control as it is a commonly used, licensed product for the treatment of canine demodicosis in the uk. amitraz (aludex®, msd animal health) is also licensed for this purpose in the uk but is less commonly used as it is more difficult to get hold of, is more labour intensive and perego et al. (2019) found insufficient evidence for its use. there is good evidence for the use of other treatment options that are not licensed in the uk for demodicosis, but may be licensed in other countries, such as milbemycin oxime and doramectin (perego et al., 2019). ivermectin has been used with good efficacy however, adverse effects are common and can be severe (perego et al., 2019). the five papers found were all single-blinded, randomised positive control trials with four performed under laboratory conditions. they all directly compared isoxazoline ectoparasiticides to moxidectin combined with imidacloprid. whilst the studies were small and their power was not calculated, they provide good evidence for the comparable efficacy of isoxazolines as a treatment for canine generalised demodicosis (perego et al., 2019). none of these studies calculated confidence intervals and this would have strengthened the evidence they provide. four of the five were also performed under laboratory conditions which may not represent conditions in the general population. summary of the evidence becskei, c., cuppens, o. and mahabir, s. p. (2018) population: client owned dogs with clinical signs of generalised demodicosis that showed: skin lesions on at least five body regions, entire body or pododemodicosis at least four live demodex canis mites found on skin scrapings patients were excluded if they were pregnant, lactating, intended for breeding, receiving immunosuppressive therapy, receiving systemic or topical antimicrobials, had been treated with an ectoparasiticide with residual activity against demodex canis, had sarcoptes scabiei mites or were under 8 weeks of age. the study population was recruited from centres in france, hungary, portugal and italy. sample size: 81 dogs intervention details: patients were split into two groups in a ratio of 2:1 53 dogs received sarolaner, 28 moxidectin/imidacloprid a randomised (one-way) block design was replicated in multiple clinics 53 dogs received sarolaner per os at 2–4 mg/kg on days 0, 30 and if necessary 60, 90, 120 and 150 28 dogs received a topical application of moxidectin combined with imidacloprid at a minimum dose of 10 mg/kg and 2.5 mg/kg respectively given monthly, or weekly in severe cases the severity of demodicosis was evaluated at every monthly visit study design: single-blinded, randomised non-inferiority trial outcome studied: the non-inferiority of sarolaner compared to moxidectin/imidacloprid objective – number of live demodex canis mites found in five deep skin scrapes taken from the same sites the sites were selected based on clinical exam. areas that had primary lesions and showed the most severe evidence of current mite infestation were chosen approximately 1 cm2 of skin was sampled at each site a one-sided 97.5% exact lower confidence limit for the difference between cure rates for each treatment group was used to assess non-inferiority of sarolaner at the 0.025 one-sided significance level at days 30 and 60 a non-inferiority margin of 15% was used subjective – the severity of clinical signs was graded absent mild (small body area affected, low intensity) moderate (great intensity and density of lesions over a small area) severe (great intensity and density of lesions over a large area) main findings (relevant to pico question): the parasitological cure rate for sarolaner was non-inferior to moxidectin/imidacloprid on day 60 but not day 30 (based on a present non-inferiority margin of 15%) there was no significant difference between cure rates for treatment groups on days 30 or 60 100% of dogs receiving sarolaner that completed the study (53/53) achieved parasitological cure 9% of the moxidectin/imidacloprid dogs that completed the study (24/27) achieved parasitological cure, one dog was withdrawn due to lack of efficacy at day 146 the percentage reduction in mean mite counts for sarolaner was non-inferior to moxidectin/imidacloprid at days 30 and 60 at day 90 (when approximately 80% of each group was still analysed) the total body area affected was 5% in the sarolaner group and 10% in the moxidectin/imidacloprid group no adverse events were associated with either treatment limitations: two of the dogs in the sarolaner group received systemic antibiotics during the trial and this may have hastened the improvement in their skin lesions, the authors do acknowledge this moxidectin/imidacloprid is licensed to apply once monthly although the data sheet notes (advocate™ spot-on solution, bayer plc, as published in the national office of animal health (noah) compendium 2019) that, at the case vet’s discretion, it can be applied weekly to treat demodicosis weekly treatments were administered at home by the owner, this may have led to variability in the dose received by the patient due to accuracy of application dogs in the moxidectin/imidacloprid group had different dosing intervals based on the severity of their condition, this may have added variance to the results the authors state that sarolaner appears to be at least as good as or better than most other miticides however, their study only proves non-inferiority not that sarolaner is a superior treatment ideally investigations for underlying disease should have been performed prior to enrolment e.g. blood and urine tests information regarding the age, breed and other baseline characteristics for each animal was not provided there is no calculation of the power of the study or explanation why a ratio of 2:1 was chosen confidence intervals are not calculated no justification for using mean rather than median age it is unclear if animals were assessed by one or multiple assessors all the authors were employees of zoetis uk who manufacture sarolaner (simparica™) six r. h. et al. (2016) population: dogs with naturally occurring demodex canis infestations that showed clinical signs of generalised demodicosis (alopecia, erythema, comedones, papules and pustules, casts, scales or crusts that involved five or more body regions or pododemodicosis). at least four live demodex canis mites seen on deep skin scrapings dogs were not treated with an ectoparasiticide for at least 90 days prior to the study they had not received a short acting corticosteroid for 1 week prior or a long acting corticosteroid for 4 weeks prior the dogs were recruited from south africa, they were ‘locally sourced’ mongrels over 6 months of age sample size: 16 dogs intervention details: dogs were housed individually 8 dogs were allocated to each group dogs were fed a commercial dry food for the duration of the study and given water ad lib dogs were acclimatised to the study conditions for at least 14 days before the first treatment was administered dogs were randomly allocated by ranking of mite count sarolaner was given per os at a dose rate of 2 mg/kg (tablets were shaved/sanded to aid accurate dosing) on days 0, 30 and 60 moxidectin/imidacloprid was applied topically at a minimum of 10 mg/kg and 2.5 mg/kg respectively given once weekly from day 0–81 deep skin scrapings were taken from five sites showing the most severe clinical signs based on visual examination the same sites were scraped each time clinical signs were assessed through surface area affected by: comedones/pustules/papules, casts/crusts/scales, alopecia and erythema examination and skin scraping was performed on days 14, 29, 44, 59, 74 and 91 the assessors were blinded to treatment group study design: single-blinded, randomised positive control trial under laboratory conditions (it is not stated if this is a superiority or non-inferiority trial) outcome studied: objective – live mite counts mite counts were transformed by loge (count + 1) prior to analysis to remove excessive variance differences were assessed at the two-sided significance level a = 0.05 geometric means were calculated from the least square means and used to minimise extreme outliers one dog was excluded from the moxidectin/imidacloprid group due to an accidental laceration requiring antibiotic treatment main findings (relevant to pico question): both treatments reduced live mite counts post-treatment compared to pre-treatment counts (p<0.0001) this was more rapid for the sarolaner group with a significant difference at day 14 (p = 0.0331) and day 29 (p = 0.0038) compared to the moxidectin/imidacloprid group mean counts were not significantly different after this at day 44 100% of sarolaner treated dogs had negative scrapes at day 59 100% of moxidectin/imidacloprid treated dogs had negative scrapes comedones, papules and pustules had resolved by day 29 in both groups casts, crusts and scales had resolved in seven dogs in each group by study completion one sarolaner and two moxidectin/imidacloprid treated dogs still showed erythema and alopecia at the end of the trial total area affected by lesions reduced from 65% pretreatment to 1–2% at study completion no adverse events were associated with either treatment limitations: information regarding the age, breed and other baseline characteristics for each animal was not provided it was not explained how the surface area affected was calculated dogs were examined clinically and considered in good health but there is no information as to how this was established e.g. were blood or urine tests performed to rule out underlying disease dogs were kept under laboratory conditions which may not be representative of a clinical scenario the sample size is small, there is no calculation of power or how the sample size was reached, this may have affected the outcome confidence intervals are not calculated it is unclear where these dogs came from raising ethical concerns enrolling them in the study as there is no mention of owner consent, if there was any financial gain or if they are strays it is not clear how dogs were randomly allocated to the two treatment groups or if they were evenly distributed based on mite count all of the authors were employees, directly or indirectly of zoetis uk who manufacture sarolaner (simparica™) another arm of this study involved infecting purpose bred laboratory beagles with otodectes cynotis and the control group were given a placebo treatment which represents a potential welfare issue for these dogs fourie j. j. et al. (2015) population: client owned dogs with naturally occurring generalised demodicosis that showed clinical signs (erythema, alopecia, comedones, follicular casts and crusts) and demodex canis mites found on deep skin scrapings. patients were otherwise healthy and had not been treated with a glucocorticoid or miticide for at least 12 weeks prior to the study. the study was conducted in south africa. sample size: 16 dogs intervention details: dogs were housed separately during the study period and were fed once daily and given water ad lib 8 dogs were allocated to each treatment group dogs were acclimatised to their new housing for at least 14 days before the study commenced all dogs were treated with a subcutaneous injection of cefovecin on days -14, -1, 13 and 27 for the treatment of pyoderma deep skin biopsies were taken from all dogs on days -14 and 27 group 1 were treated with fluralaner at a minimum dose of 24 mg/kg on day 0 group 2 were treated with 2.5 mg/kg moxidectin/10 mg/kg imidacloprid topically according to the manufacturer’s guidelines on days 0, 28 and 56 deep skin scrapings were taken from an area approximately 4 cm2 from five sites on days -4, 28, 56 and 84 and the same sites were sampled each time clinical signs were assessed on days -4, 28, 56 and 84, the body areas affected were sketched on a silhouette lesions recorded: erythema, casts, scales, crusts, alopecia percentage of hair regrowth was estimated colour photographs were taken to help compare lesions at each assessment study design: single-blinded randomised positive control trial under laboratory conditions (it is not stated if this is a superiority or non-inferiority trial) outcome studied: objective – mean mite number on skin scrapings efficacy was calculated using geometric means and abbot’s formula the groups were compared using an analysis of variance test (anova) with a treatment effect after a logarithmic transformation of the mite (count + 1) data for each study day subjective – improvement in clinical signs main findings (relevant to pico question): fluralaner reduced the mean mite number by 99.8% on day 28 and 100% on days 56 and 84 moxidectin/imidacloprid reduced the mean mite number by 98% on day 28, 96.4% on day 56 and 94.7% on day 84 p values were: day 28 = 0.0917, day 56 = <0.0001, day 56 = 0.0020 there was a significant difference between fluralaner and moxidectin/imidacloprid on days 56 and 84 both groups showed improvements in clinical signs no adverse events were associated with either treatment limitations: moxidectin/imidacloprid was used at the licensed dosing interval however, the data sheet (advocate ™ spot-on solution, bayer plc, as published in noah compendium 2019) states that for the treatment of demodicosis it can be used weekly at the case vet’s discretion. this may have affected the treatment response in this study there is limited information regarding the statistical analysis of the data (e.g. statistical package used, anova assumptions) and only geometric mean mite counts were provided information regarding the age, breed and other baseline characteristics for each animal were not provided dogs were kept under laboratory conditions which may not be representative of a clinical scenario the authors state the dogs were ‘healthy as far as could be determined’ but do not clarify what tests were performed one of the dogs was withdrawn from the moxidectin/imidacloprid group on day 59 due to the development of malignant lymphoma but the data before this date was included in the trial. this may have affected the treatment response for this group ideally antibiotics should have been used based on skin cytology and presence of pyoderma, presumably blanket treatment was chosen to avoid variance a sample size of 16 dogs is small and there is no justification of this or calculation of the power of the study. this may have affected the results confidence intervals were not calculated there was no information on recruitment measures (e.g. financial incentives) or source of cases five of the six authors were employees, directly or indirectly of msd animal health the manufacturers of fluralaner (bravecto®) beugnet, f. et al. (2016) population: client owned dogs over 6 months of age that showed signs of generalised demodicosis on days -14, -7, and -2 or -1. all dogs showed lesions (erythema, crusts, scales, alopecia, comedones or follicular casts) on either at least five body regions, an entire body region or two or more feet. all dogs had demodex canis mites confirmed on deep skin scrapings on day -1. none of the dogs were pregnant or had been treated with a glucocorticoid or ectoparasiticide for 12 weeks prior to the study. antibiotics and vitamin/mineral supplements were allowed during the trial. dogs were leased from their owners and recruited from south africa. sample size: 16 dogs split intervention details: dogs were randomised into treatment groups by ranking of pre-treatment mite counts and sex and 8 dogs allocated to each group dogs were housed in separate pens, fed once daily and water was given ad lib. they were moved to this housing for at least 14 days prior to the start of the study group 1 received afoxolaner and group 2 moxidectin/imidacloprid both dosed according to the manufacturer’s guidelines. no further information on dosing was provided doses were given on days 0, 14, 28 and 56 mite counts and clinical exams were performed on days 2, 28, 56 and 84 skin scrapings were taken from the same five sites at each exam a sketch was made of the body areas affected by: erythema, casts/scales/crusts, and alopecia. colour photographs were taken on days -2, 28, 56 and 84 study design: single-blinded, randomised positive control trial under laboratory conditions  (it is not stated if this is a superiority or non-inferiority trial) outcome studied: objective – mean mite counts the group mean, median, standard deviation, geometric mean, minimum and maximum counts were calculated pre and post-treatment administration mite counts were compared using anova and a significance level of 5% was set subjective – clinical lesions and hair regrowth main findings (relevant to pico question): there was a significant (p<0.05) reduction in mite count for both groups on all post-treatment assessments group 1 (moxidectin/imidacloprid) mite count reduced from a geometric mean of 808.1 before treatment to 82.4-119.9 after one month group 2 (afoxolaner) mite count reduced from a geometric mean of 650.8 before treatment to 0.0-5.3 after one month there was no significant difference in mean mite count (p = 0.8103) between the groups at the start of the trial significantly fewer mites were found on all post-treatment assessments for the afoxolaner group compared to the moxidectin/imidacloprid group (p<0.05) both groups showed improvements in clinical signs but no resolution of them no adverse events were associated with either treatment limitations: the dosing interval of moxidectin/imidacloprid was every 2 weeks for three doses then every 4 weeks. the authors acknowledge that weekly treatment, as suggested in the manufacturer’s guidelines, may have improved treatment outcome but do not state why they chose not to treat at this interval the authors chose eight dogs per group as it was higher than the six recommended by the committee for medical products for veterinary use guideline but do not calculate the power of the study confidence intervals were not calculated limited information is provided on statistical analysis e.g. anova assumptions dogs were leased from their owners indicating a financial gain and potential ethical implications afoxolaner was used off license at 2 weekly intervals, they acknowledge that further study of monthly administration is warranted the dogs were split into blocks of two based on sex and mean mite count, it is not clear if they were then randomly allocated to the two treatment groups or evenly distributed based on mite count dogs were kept under laboratory conditions which may not be representative of a clinical scenario information regarding the age, breed and other baseline characteristics for each animal is not provided all of the authors were employees, directly or indirectly of merial the manufacturer of afoxolaner (nexgard®) fourie, j. j., meyer, l. and thomas, e. (2019) population: client owned dogs, between 6 and 12 months of age, with naturally acquired generalised demodicosis defined as: more than five body areas affected, pododemodicosis involving two or more feet or an entire body region dogs must be older than 8 weeks acclimatised to the study site for at least 7 days presence of demodex canis mites on skin scrapings on day 2 otherwise clinically healthy on days -7 and -2 not pregnant not treated with glucocorticoids, ectoparasiticide or macrocyclic lactone for at least 12 weeks not excessively fractious (safe for personnel)  sample size: 16 dogs intervention details: dogs were ranked by mite count then randomly allocated to 1 of 2 groups using ms excel software, 8 dogs were allocated to each group age was assessed based on presence of permanent dentition dogs were transferred to the study site and housed individually indoors dogs were fed a commercially available dry dog food once daily with water ad lib group 1: 25 mg/kg fluralaner applied topically on day 0 group 2: at least 10 mg/kg imidacloprid and 2.5 mg/kg moxidectin applied topically on days 0, 28 and 56 four dogs in group 2 were treated weekly rather than every 4 weeks (based on manufacturer’s guidelines) cases classified as mild, moderate or severe based on clinical condition (crusts, casts, scales, hair loss and erythematous papules) by blinded veterinarian and examinations performed every 2 weeks all dogs were treated with cefovecin (convenia®) for potential pyoderma on days -7, 7, 21, 35 and 49 and a probioitic (protexin®) at least twice weekly skin biopsies were performed on days -7 and 27 to assess for demodex canis mites, acanthosis, hyperkeratosis, surface crusting, pigmentary incontinence, follicular keratosis, mural folliculitis, perifolliculitis, dermatitis, bacteria, granulomas and dermal stromal reaction skin scrapings and mite counts were performed on days -2, 28, 56 and 84 and were blinded deep skin scrapings were taken from an area approximately 4 cm² at the same five sites for each dog on every occasion only live mites were recorded study design: single-blinded, randomised, non-inferiority trial under laboratory conditions outcome studied: objective – percentage live mite reduction arithmetic means for each group preand post-treatment repeated measures analysis of covariance (rman-cova) was used to compare mite counts using sas institute analytical software version 9.3 significance level was set at 5% subjective – clinical signs mild, moderate or severe based on crusts, casts, scales and erythematous papules as percentage of group affected areas of hair loss scored 1 (0-50%), 2 (>50-90%) and 3 (>90%) main findings (relevant to pico question): no treatment related adverse events were noted fluralaner was significantly more effective than moxidectin/imidacloprid at eliminating live mites from dogs with generalised demodicosis (p<0.01) 0/8 dogs in group 1 had any live mites at day 84 1/8 dogs in group 2 was mite free at day 56 and 2/8 at day 84 2/8 dogs in group 2 showed an increase in live mite counts after treatment and this impacted significantly on efficacy calculations (based on mean mite counts for the group) limitations: group 2 dogs received two different treatment regimes (weekly and four weekly application) but results were not analysed separately all dogs were given 10 weeks of cefovecin regardless of the presence or absence of pyoderma, the authors note that diagnosis and treatment of pyoderma was not part of the treatment evaluation dogs were between 6 and 12 months of age indicating juvenile generalised demodicosis rather than adult onset which has the potential for self-resolution of signs, this may have affected results the age, sex and breed of dogs in each group is not recorded dogs were ranked by mite count before being randomly allocated to treatment groups but the reason for ranking before randomisation is not clear dogs were kept under laboratory conditions which may not be representative of a clinical scenario ideally antibiotics should have been used based on skin cytology and presence of pyoderma, presumably blanket treatment was chosen to avoid variance a sample size of 16 is small and there is no justification for this or calculation of the power of the study. this may have affected the results confidence intervals were not calculated no criteria for treatment success were outlined and results were only provided for live mite counts (not clinical signs or histopathology) no information on recruitment measures (e.g. financial incentives) or source of cases it is unclear what the aim of the study was, the authors state ‘to evaluate the efficacy… compared to moxidectin/imidacloprid’ but not if this is an inferiority or superiority study however, the authors then state superiority in the results and discussion all authors were employed (directly or indirectly) by msd animal health, the manufacturer of fluralaner (bravecto®) summaries of product characteristics for moxidectin/imidacloprid (advocate® spot-on solution, bayer plc) referenced are for cats and ferrets, not dogs appraisal, application and reflection three different, widely available, isoxazolines were studied in these five papers, two focused on sarolaner, two on fluralaner and one on afoxolaner. all five studies were sponsored by the pharmaceutical companies that make the isoxazoline preparations and nearly all authors were employees of these companies. this may bias study design and reporting of results as demonstrated in the study by becskei et al. (2018) where sarolaner is claimed to be as good as, if not better than moxidectin/imidacloprid, but the study was only designed to prove non-inferiority. in each paper the dosing frequency of moxidectin/imidacloprid varied making them harder to compare. the license for this product is for monthly application, however, the data sheet (advocate ™ spot-on solution, bayer plc, as published in noah compendium 2019) states that it can be used weekly to treat canine demodicosis in more severe cases at the case veterinarian’s discretion. ideally all papers would have used weekly dosing intervals as this is more effective (mueller et al., 2012, perego et al., 2019). monthly treatments may have only been successful in mild cases and this may be why fourie et al. (2015) found such a significant difference between the two treatment groups. generalised adult onset demodicosis can be associated with immunosuppression. the cause of this may be difficult to identify but ideally a full blood count, biochemistry, urinalysis, lymph node aspirates, thoracic radiographs and abdominal ultrasound should be performed to rule out underlying conditions (mueller et al., 2012). hyperadrenocorticism and hypothyroidism are important disorders to investigate as part of this process (mueller et al., 2012). the presence of an underlying condition could alter the treatment response and investigations should have been fully detailed or performed more thoroughly in these papers. all of the papers show that isoxazolines are at least as effective as moxidectin/imidacloprid at reducing the mean mite count from deep skin scrapings. deep skin scrapings are the gold standard diagnostic method to identify demodicosis and the area covered should be approximately 1 cm2 and focused on primary lesions (mueller et al., 2012). at least three to five areas should be sampled and this should be repeated until there are two consecutive negative scrapes one month apart (mueller et al., 2012).  cytology should also be performed to identify the presence of pyoderma, a common complication of demodicosis (mueller et al., 2012). fourie et al. (2015) and fourie, meyer and thomas (2019) treated all dogs with 8 weeks and 10 weeks respectively of a third-generation cefalosporin during the trial. this standardised treatment, but blanket antibiotic usage in these cases, would not be an advisable approach in practice. identification of pyoderma on cytology and ideally of the bacteria involved through culture and sensitivity is recommended. fourie, meyer and thomas (2019) took skin biopsies to assess for pyoderma however, they do not comment on the findings and note that it took 22 days for biopsy results to be available. as mentioned above, cytological evaluation and culture and sensitivity would have been a preferable method to assess for the presence of pyoderma. all of these studies use relatively small numbers of patients and four of the five kept animals under laboratory conditions that are unlikely to replicate those of our patients. confidence intervals are not calculated and some papers lack full detail regarding statistical analysis. addressing all of these points may increase the strength of evidence provided. another concern is the use of stray dogs and financial incentives to owners to enroll pets onto the treatment trials. this may compromise animal welfare through separation from owners, normal environments and routines.  the six et al. (2016) study also looked at the efficacy of sarolaner to treat artificial otodectes cynotis infestations in laboratory beagles. the control group in this arm of the trial was given a placebo treatment which again may compromise welfare. a recent systematic review by perego et al. (2019) found good evidence for the use of fluralaner and sarolaner in the treatment of generalised demodicosis. afoxolaner showed good efficacy but only one study was found providing limited evidence for their use. isoxazolines appear safe as well as efficacious, no adverse effects were noted in any of the studies reviewed here, but further long term follow up is required to confirm this. methodology section search strategy databases searched and dates covered: cab abstracts through cab direct platform 1973 – week 9 2019 pubmed through ncbi 1900 – week 9 2019 web of science 1900 – week 9 2019 scopus 1970 – week 9 2019 search terms: dog or dogs or canine* or bitch* or bitches or canis and demodicosis or demodex or demodectic and isoxazoline or isoxazolines or fluralaner or sarolaner or afoxolaner or lotilaner and imidacloprid or moxidectin or advocate or advantage multi   dates searches performed: march 1st 2019 exclusion / inclusion criteria exclusion: articles not available in english, narrative reviews, non-peer reviewed journals, book chapters, conference proceedings and articles that did not answer the pico question inclusion: original, peer reviewed articles that compared isoxazolines with moxidectin/imidacloprid search outcome database number of results excluded – review articles excluded – did not answer the pico question excluded – not available in english total relevant papers cab abstracts 3 2 0 0 1 pubmed 8 1 2 0 5 web of science 11 1 5 0 5 scopus 1 0 0 0 1 total relevant papers when duplicates removed 5 conflict of interest the author declares no conflicts of interest. references becskei, c., cuppens, o., & mahabir, s. p. (2018). efficacy and safety of sarolaner against generalized demodicosis in dogs in european countries: a non-inferiority study. veterinary dermatology, 1–7. https://doi.org/10.1111/vde.12526 beugnet, f., halos, l., larsen, d., & de vos, c. (2016). efficacy of oral afoxolaner for the treatment of canine generalised demodicosis. parasite, 23, 14. https://doi.org/10.1051/parasite/2016014 fourie, j. j., liebenberg, j. e., horak, i. g., taenzler, j., heckeroth, a. r., & frénais, r. (2015). efficacy of orally administered fluralaner (bravecto®) or topically applied imidacloprid/moxidectin (advocate®) against generalized demodicosis in dogs. parasites and vectors, 8(1), 1–8. https://doi.org/10.1186/s13071-015-0775-8 fourie, j. j., meyer, l., & thomas, e. (2019). efficacy of topically administered fluralaner or imidacloprid/moxidectin on dogs with generalised demodicosis. parasites and vectors. https://doi.org/10.1186/s13071-018-3230-9 mueller, r. s., bensignor, e., ferrer, l., holm, b., lemarie, s., paradis, m., & shipstone, m. a. (2012). treatment of demodicosis in dogs: 2011 clinical practice guidelines. veterinary dermatology, 23(2). https://doi.org/10.1111/j.1365-3164.2011.01026.x perego, r., spada, e., foppa, c., & proverbio, d. (2019). critically appraised topic for the most effective and safe treatment for canine generalised demodicosis. bmc veterinary research. https://doi.org/10.1186/s12917-018-1767-7 six, r. h., becskei, c., mazaleski, m. m., fourie, j. j., mahabir, s. p., myers, m. r., & slootmans, n. (2016). efficacy of sarolaner, a novel oral isoxazoline, against two common mite infestations in dogs: demodex spp. and otodectes cynotis. veterinary parasitology, 222, 62–66. https://doi.org/10.1016/j.vetpar.2016.02.027 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. is there any evidence to support the use of garlic as a wormer for dogs and cats in the uk? a knowledge summary by louise buckley phd, rvn 1* 1the royal (dick) school of veterinary studies, university of edinburgh *corresponding author (louise.buckley@ed.ac.uk) vol 4, issue 2 (2019) published: 29 may 2019 reviewed by: virginia fajt (dvm, phd, dacvcp) and william chandler (bvetmed, mrcvs) next review date: 20 feb 2021 doi: 10.18849/ve.v4i2.163 pico question in dogs and cats, is the oral administration of garlic, compared to no treatment, efficacious at preventing or reducing the intestinal worm burden (species found in the uk)? clinical bottom line no studies were identified that investigated the efficacy of garlic at preventing intestinal worm burden. garlic reduced egg and/or larvae counts in the worm species studied. however, where measured, egg and larvae count rapidly (2 days) returned to pretreatment levels once dietary garlic was discontinued. none of the studies included adulticidal action as an outcome measure. in the absence of research to demonstrate high levels of adulticidal action against a range of intestinal wormers at therapeutic, non-toxic levels in cats and dogs, clients should be advised that garlic has not been demonstrated to be an effective anthelmintic (either for multiple or single species use) for use in dogs and cats either to prevent or to treat an intestinal worm burden. clinical scenario the veterinary nurse is reading through the worming advice being given in a facebook group that encourages a natural approach to preventative medicine in dogs and cats. she notices that garlic is being recommended quite frequently by some pet owners as an alternative to a conventional anthelmintic and wonders what the evidence base is for this recommendation. she notes that some owners are recommending its routine use to prevent dogs or cats becoming parasitised and others are recommending it for dogs or cats known to have an intestinal worm burden so she includes both aspects in her pico. the evidence no papers were identified that addressed the use of garlic to prevent dogs and/or cats becoming parasitised by intestinal worm species. three papers were identified that either fully (bastidas, 1969; ronagh et al. 2015) or partially (andrei et al., 2011) addressed the intestinal worm reduction aspect of the pico. two of the studies focused on dogs (bastidas, 1969; andrei et al., 2011) and one of the studies focused on cats (ronagh et al., 2015). not all species of intestinal worm known to parasitise cats and/or dogs in the uk were represented, with tapeworm species being the notable exception. all three studies were clinical trials that either used the animal as its own control (andrei et al., 2011, bastidas, 1969) or allocated the animals to separate treatment groups (ronagh et al., 2015). random allocation of the latter was not reported. despite being clinical trials, all three studies are very limited with poor data handling and insufficient reporting of the methodology and/or results. the andrei et al. (2011) study used the garlic in conjunction with other herbs so any potential anthelmintic effect of garlic is totally confounded with the other components (n = 6, plus water) of the tincture and pumpkin oil preparation used. however, this tincture was associated with a greater than 90% reduction in eggs per gram of faeces for all species (toxocara canis, ancylostoma spp., trichocephalus spp.), with similar findings across both populations (shelter dogs: n = 37, owned dogs: n = 10)) studied. bastidas (1969), with a sample size of one, found that larvae count of ancylostoma caninum decreased during daily dosing with garlic, but eggs per gram of faeces was only slightly reduced. rapid recovery to pre-dosing levels (2 days) was observed following treatment cessation. finally, ronagh et al. (2015) found that cats dosed with garlic (n = 5) showed a numerical reduction in toxocara cati eggs on a faecal egg count and a numerical reduction in fecundity rate (number of eggs produced by a female adult toxocara cati worm). no such reduction in either parameter was observed for control cats (n = 5). none of the studies directly studied the effect of garlic as an adulticide and this remained an important practical limitation in the use of these findings. summary of the evidence andrei et al. (2011) population: two different populations of dogs were used. group one: unwormed dogs at a romanian rescue centre. group two: dogs owned by people living in timişoara (romania). both sexes, different breeds, and an age range of 2 months–4 years were used, but it is not possible to distinguish how this was distributed across the two groups. no further information is provided. sample size: group one: 37 dogs group 2: 10 dogs intervention details: the study design was a before/after design, with each dog used as its own control.   the intervention was a home prepared herbal tincture (10% solution), plus a dose of cold pressed pumpkin oil. the herbal tincture contained the following herbs: inula helenium tanacetum vulgare thymus serpyllum artemisia absinthium allium ursinum allium sativum (garlic) the quantities of each herbal are not stated, and the references cited are for resources reported in the romanian language. the dose administered of both the tincture and the pumpkin oil was weight dependent, and was given per os twice daily for 5 days.   experimental timeline day 0: a faecal sample was obtained from each dog. day 1–13: at some point over these 13 days each dog was given a weight dependent twice daily dose of the tincture plus the pumpkin oil for 5 days. the actual days this was administered on are not reported. day 14: a faecal sample was obtained from each dog.   the willis and mcmaster coproscopic method (no reference provided by the authors) was used to undertake the egg count. study design: non-randomised controlled trial (before/after design) outcome studied: worm eggs per gram of faeces, split down by species/class. samples taken before (day 0) and after (day 14) the intervention was applied. a percentage effectiveness score was then calculated: effectiveness (%) = ((epg day 0 – epg day 14) ÷ epg day 0) x 100 epg = eggs per gram main findings (relevant to pico question): in summary, for both groups of dogs, the egg count of the three species present was considerably lower following the intervention. the following values show the mean ± standard error of the mean, associated with each group/day/species. please note the authors do not conduct analytical statistics so there are no p values. they do report a confidence level of 95% but then appear¹ to report the confidence interval as a range, rather than as lower limit and higher limit.   group 1: toxocara canis: day 0: 1180.40 ±19 day 14: 121.70 ±61 effectiveness: 92.55%   ancyclostoma spp.: day 0: 1212.96 ±41 day 14: 131.40 ±39 effectiveness: 91.87%   trichocephalus spp.: day 0: 1011.54 ± 01 day 14: 123.00 ±34 effectiveness: 91.34%   group 2: toxocara canis: day 0: 800.00 ± 117.2 day 14: 50.00 ± 20.41 effectiveness: 93.86%   ancyclostoma spp.: day 0: 810.00 ± 182.62 day 14: 70.00 ± 30.00 effectiveness: 92.57%   trichocephalus spp.: day 0: 508.30 ± 83.08 day 14: 50.00 ± 18.26 effectiveness: 93.82%   ¹the interpretation made by the author of this knowledge summary. limitations: inadequate reporting of the scientific method (lacks detail, not reproducible given the level of detail reported) no information regarding the quantity of herbs present in a standardised dose of the tincture no information as to whether the scientists involved in this study were blinded data handling is poor: effect sizes calculated for values that are meaningless, confidence intervals are reported and labeled incorrectly the author uses parametric measures of central tendency and variation but does not report assessing the distribution of the data and no skew value is reported although the tincture appears to have a marked effect on worm burden in dogs it is impossible to quantify the effect, if any, of the addition of garlic to this preparation the sample size for treatment group two is small bastidas (1969) population: a dog weighing 10 kg and naturally infected with ancylostoma caninum no further information is available about the dog sample size: one intervention details: the intervention was the addition of garlic to the dog’s diet (ground meat, once daily). the dose varied daily (see below). experimental time line: day 1–5: before phase. dog was fed ground meat only. day 6–10: during phase. dog was fed ground meat plus garlic. day 11–12: after phase. dog was fed ground meat only. a faecal sample was collected on all 12 days, and a daily egg count (4 replicates, 50 mg samples) undertaken using the kato method (martin and beaver, 1968), and a culture (five replicates, 300 mg samples) per day were made and allowed to stand for 10 days (in a darkened room, at an ambient temperature of 21­–23˚c). the larvae were then killed using iodine and counted. the quantity of garlic fed/ingested was: day 6: 6.7 g day 7: 8.7 g day 8: 10.1 g day 9: 10.4 g day 10: 10.0 g study design: non-randomised controlled trial (before intervention/during intervention/after intervention) outcome studied: there were two outcome measures: daily mean egg count (eggs/smear) daily mean larvae count (larvae/culture) main findings (relevant to pico question): the author of the research paper reports only raw daily values in a table. with a sample size of one, there are no analytical statistics. to aid visualisation of the results, these raw values have been reported using line graphs created by the author of this knowledge summary. figure 1: mean daily egg count. nb. before phase/treatment (day 1–5); during phase/treatment (day 6–10); after phase/treatment (day 11–12) figure 2: mean daily larvae count. nb. before phase/treatment (day 1–5); during phase/treatment (day 6–10); after phase/treatment (day 11–12) the author of this knowledge summary also undertook the following analysis on the data reported in the original paper: using the formula reported in the andrei et al. (2011) study, the percentage of effectiveness was calculated. the mean value before feeding garlic (day 1–5) was used as the baseline measurement (epg day 0), and day 10 (last day that garlic was fed) as the comparator (epg day 10). the findings were as follows: effectiveness at reducing egg count by day 10: 14.75% effective¹ effectiveness at reducing larvae count by day 10: 81.77% effective² ¹ 14.75% = ((342.7 – 296)/342.7) x 100% ² 81.77% = ((927.2)/169)/927.2) x 100% limitations: there was a sample size of one there is no evidence that blinding was undertaken so the person handling the faecal sample was potentially aware of whether the sample corresponded to days on which garlic was administered the dose of garlic was not standardised per day (it is not clear whether this is because the quantity offered was different each day, or the quantity voluntarily consumed was different despite offering a fixed amount) the study findings could have been strengthened by a repeated measures design on this one subject, to help rule out stochastic or alternative explanations for the findings limited data handling ronagh et al. (2015) population: stray domestic shorthair female cats (weighing circa 3 kg), captured from the streets of tehran and naturally infected with toxocara cati roundworms (based on faecal egg counts). sample size: 25 cats (five per treatment group), drawn from a wider trapped sample of 100 cats. the 25 cats with the heaviest worm burden were selected from this larger sample. intervention details: cats were allocated to one of five treatment groups: control (no treatment) garlic (fed one 1.25 g garlic tablet daily) black seed (fed 12 g of black seed powder daily) pumpkin (fed 3 g of pumpkin seed powder daily) cloves (fed 6 g of clove powder daily) cats were trapped, housed separately, and given 3 days to acclimatise to their environment before the treatments were applied. experimental timeline: day 0 (prior to treatment): faeces were collected, and stored in a 10% formalin buffer solution to prevent decay. an egg count was performed at some point subsequent to this. day 7: cats were fed a standard feed ration (not defined in more detail by the authors), either without a supplement (control group) or with a supplement (experimental treatment groups). the supplement given is outlined in the treatment group description above. 7 days after treatments were applied (not clear whether this is 7 days after the start or end of the supplement phase): faeces were collected, and stored in a 10% formalin buffer solution to prevent decay. an egg count was performed (formalin-ether sediment method, no reference provided by the authors) at some point subsequent to this. cats were then euthanised, and the stomach and intestines removed and preserved in 10% formalin. sections of stomach, duodenum, jejunum and ileum were then stained (haematoxylin and eosin), and examined microscopically for damage). the number of intestinal adult female toxocara cati worms was counted. study design: controlled trial (not clear if randomised or nonrandomised) outcome studied: two outcome measures were relevant to the pico: faecal egg count (toxocara cati eggs) fecundity rate (toxocara cati worms) the fecundity rate was calculated using the following equation: fecundity rate = epg ÷ number of female adult worms epg = eggs per gram main findings (relevant to pico question): please note: only the control group and the garlic group results are reported here. faecal egg count: the mean (± standard deviation) toxocara cati eggs per gram of faeces were as follows: day 0: control group: 9.4 (±1); garlic group: 19.0 (± 2.2) day 7: control group: 9.0 (±6); garlic group: 8.8 (± 0.8) the authors also report that the control group versus garlic group was significantly different (t-test, p = 0.003). nb. they do not make clear what data this t-test was performed with (the raw data for day 0 or day 7, or a comparison between groups after calculating the difference in epg between day 0 and day 7 for each individual cat. no other statistical analysis is performed (e.g. within treatment differences) on this data. fecundity rate: the authors report only raw data (individual animals) for this data. the raw data can be seen in table 1 below. table 1: a comparison of the fecundity rate for cats in the control and garlic treatment groups descriptive statistics (below) have been performed on this data set by the knowledge summary author using the same parameters used by the paper authors in the first outcome measure. data distribution or skewness has not been evaluated. the mean (± standard deviation) fecundity rate was as follows: day 0: control group: 6.4 (±0); garlic group: 10.4 (± 3.5) day 7: control group: 6.1 (±9); garlic group: 4.9 (± 1.9) limitations: the authors do not report how they allocated the cats to the different treatment groups so it is not known whether cats were randomly allocated to receive the different treatments. there is no evidence that the researchers or any other personnel involved in the study (if any) were blinded as to the treatments when collecting/analysing data. insufficient experimental detail (in both the methods and results sections) is available to fully understand or interpret the study findings. there is insufficient detail in the methods to fully appraise scientific rigour (e.g. in relation to egg count methodology, use of duplicate samples, etc.) statistical analysis is limited and it is unclear what the p value reported relates to. the authors appear to have compared treatment groups before treatment application and not after. however it is possible that they have used ‘within treatment differences in egg count between day 0 and day 7’ data, and then conducted a between treatment group t-test on the ‘differences’ data. this would allow them to undertake one statistic test to compare between treatment groups, while also handling the data in a manner that would increase the likelihood of finding significant differences where there is a lot of variation between dogs in terms numbers of eggs present in faeces at either time point. the authors do not tell us though that they do this and this lack of detail is a study failing. the authors do not justify their use of parametric statistical analysis or choice of measure of central tendency. the sample size per treatment group is very small and does not appear to be based on a power calculation or other approach to determine an appropriate sample size. the treatment groups differed in mean number of eggs per gram of faeces (the garlic group had approximately double the number of eggs compared to the control group) on day 0 (prior to treatment application). likewise, the fecundity rate of the garlic group was higher than the control group at the start of the study (day 0). the authors report that garlic reduced the number of female adult worms and refer the reader to table 2 in demonstration of this. however, table 2 refers to fecundity rate (not the number of adult female worms) and this value cannot be used to quantify number of adult female worms present using the information provided. the number of adult female worms was not listed as a planned outcome measure, and is not reported anywhere else in the paper. appraisal, application and reflection plant-based anthelmentics have been suggested as a potential alternative to overcome increasing resistance to conventional anthelmentics (french, 2018). the use of garlic as a traditional anthelmintic for dogs with intestinal worms has been reported (n = 1 interviewee) in a study exploring central-southern italy’s ethno-veterinary practices (guarrera et al., 2008), and more widely elsewhere in pigs (lans et al., 2007; bartha et al., 2015) and ruminants (lans et al., 2007; bullitta et al., 2018). thus, the promotion of garlic as an anthelmintic in dogs and cats is probably derived from traditional ethnobotanical medical practices. more recently, there has been some growth in scientific interest in its potential anthelmintic properties in a range of mammalian and avian species. extracts from garlic bulbs shown to have in vivo (e.g. palacious-landin et al., 2015, but see e.g. worku, 2009; velkers et al., 2011) and/or in vitro (e.g. palacious-landin et al., 2015; orengo et al., 2016; tavassoli et al., 2018) efficacy (differing stages of the life cycle, dependent on the study) against various species of helminth. this includes in vitro activity against some species (toxocara canis, ancylostoma caninum) that infest dogs (orengo et al., 2016). consequently, scientific and veterinary growth in its interest in a wormer for dogs and cats may be likely to develop over time. no english language papers were identified that addressed the prevention aspect of the pico. three papers were identified that either fully (bastidas, 1969; ronagh et al., 2015) or partially (andrei et al., 2011) addressed the treatment aspect of the pico. two of the studies focused on dogs (bastidas, 1969; andrei et al., 2011) and one of the studies focused on cats (ronagh et al., 2015).  a further abstract (bekirov et al., 1979) that examined the use of garlic (in conjunction with other ingredients) as a canine anthelmintic effective against echinococcus or taenia hydatigena was excluded as the main paper was in russian but reported 92–94.8% and 100% efficacy respectively against each species. the relative lack of studies that addressed the pico also meant that some of the intestinal worms known to affect dogs and cats in the uk did not have any evidence available to address the use of garlic as an anthelmintic for that species. studies focusing on tapeworm species were notably absent, with the exception of the bekirov study, which combined garlic with several other products thereby confounding interpretation of the efficacy of garlic per se as an anthelmintic. thus, any positive anthelmintic effects at the level of the individual species may still limit clinical use to the practitioner or owner when seeking an anthelmintic effective against a broad range of intestinal worms. all three studies included in this knowledge summary were clinical trials, which either used the animal as its own control (andrei et al., 2011, bastidas, 1969) or allocated the animals to separate treatment groups (ronagh et al., 2015). however, despite being clinical trials, all of the studies showed clear limitations in terms of methodological approach and/or study methodology reporting and/or results reporting and highlight the importance of not using the evidence pyramid (see: o’connor, 2017 for a discussion on the limitations to the evidence pyramid) in isolation when evaluating the relative quality of a study. furthermore, the outcome measures used by each of the studies used are unlikely to address the clinical need of veterinary practitioners or clients seeking an anthelmintic that will kill intestinal worms present at the point of dosing the dog or cat. in the andrei et al. (2011) study a 90% reduction in eggs per gram of faeces for all species (toxocara canis, ancylostoma spp, trichocephalus spp.) following a twice daily weight dependent dose of their worming preparation (tincture and pumpkin oil). similar results were obtained for both populations (shelter dogs: n = 37, owned dogs: n = 10)) studied. however, this worming preparation used the garlic in conjunction with other herbs so any potential anthelmintic effect of garlic is totally confounded with the other components (n = 6, plus water) of the tincture and pumpkin oil preparation used. thus, it is impossible to quantify the relative contribution (positive, negative, additive, synergistic, or no effect at all) of garlic to these findings. in defence of the authors, this study was designed to test the efficacy of this worming preparation rather than to investigate the efficacy of garlic in isolation as an anthelmintic. however, this study is also problematic in terms of its scientific quality, with authors failing to report tincture composition in sufficient detail, with no detail available on the quantity of each herb added to the tincture preparation. dosing standardisation was achieved through product dosing based on the weight of the dog, but this is only described in terms of quantity of the tincture plus pumpkin oil supplied. despite the most impressive sample size (relative to the other two studies reported here), the authors do not perform analytical statistics on their findings, and while they describe reporting the confidence intervals (which can be used in preference to p values), they appear to be reporting this as one value rather than as an upper and lower limit which limits its value in interpreting the data. however, the descriptive statistics do suggest that the before and after treatment faecal egg counts would be significantly different across all three of the worm species studied (and the direction of the effect is similar for both shelter and owned dogs) should a suitable analytical test be performed. despite this, the study suffers from another key issue when considering the clinical application of this tincture, and that is that the outcome measure assessed did not include either a direct or indirect (proxy) measurement of the effect of the preparation on adult worm mortality and/or long-term fecundity. the study finished immediately after the end of the tincture and pumpkin oil dosing period. thus, all that is known is that this worming preparation had effects on egg production during the period of dosing, without anything to indicate the possible reason for this reduction. this is a clinically important issue that is of relevance to any anthelmintic product selection, and represents a major study limitation within the context of any clinician considering using this worming preparation in preference to any product with known adulticidal efficacy. the second of the studies evaluated (bastidas, 1969) was included as a clinical trial based on its study methodology (before, during, after treatment) allowing it to meet the inclusion criteria but it had a sample size of one dog, and with each study phase undertaken only once, findings were potentially explicable, either partially or fully, by other undefined or unreported effects. this should be borne in mind when considering the reported findings. this study found that larvae count of ancylostoma caninum decreased during daily dosing with garlic (non-standardised dose), but eggs per gram of faeces remained similar following a five-day dosing period. application of the andrei et al. (2011) equation for evaluating anthelmintic efficacy to bastidas’ (1969) raw data indicated that efficacy at reducing egg count after 5 days of garlic treatment was only 14.75%. this was much lower than the andrei et al. (2011) study, and suggests that other components of the andrei et al. study’s worming preparation may have explained the increased efficacy at reducing egg count identified in that study. however, there are other differences in the study methodology and lack of detail regarding the tincture preparation mean that meaningful comparisons are difficult to draw. garlic appeared more effective at reducing larvae count and was 81.77% effective at reducing larvae count by day 5 (the last day) of treatment. however, it is important to note that this effect was very short lived and mean larvae count increased rapidly (1 day) following discontinuation of the garlic and returned to approximately pretreatment levels only 2 days after discontinuation of the garlic. again, while the presence of viable adult female worms was not an outcome measure of this study, these post-treatment changes in larvae count suggest that the addition of garlic to the diet at this dosage and dosing period did not affect adult female worm mortality or longer-term fecundity rates. finally, ronagh et al. (2015) found that cats dosed with garlic (n = 5) showed a numerical reduction in toxocara cati eggs on a faecal egg count and a numerical reduction in fecundity rate (number of eggs produced by a female adult toxocara cati worm). no such reduction in either parameter was observed for control cats (n = 5). however, this study euthanised the cats at the end of the study (to assess fecundity rate and gastrointestinal damage to the mucosa) and did not measure faecal egg counts for a few days post-treatment cessation. thus, while it is known that egg counts were lower, and this reduction was probably due to a reduction in the number of eggs produced by each viable female, it is not known whether any inhibitory effect of the garlic is temporary (i.e. females will increase egg production when the garlic is discontinued) or whether it is more permanent (e.g. through increased morbidity/mortality rates of adult female worms). in the light of the bastidas (1969) study findings this is an important consideration. this study did count the number of adult female worms present within the intestines at the point of euthanasia of both the control group and the garlic group but does not report this information. however, the authors do not report how the cats were allocated to their respective treatment groups. frustratingly, the pretreatment faecal egg count demonstrates that the control cats had a lower mean (± standard deviation) faecal egg count (9.4 ± 1.1) and fecundity rate (6.4 ± 2.0) than the garlic group (egg count: 19.0 ± 2.0; fecundity rate: 10.4 ± 3.5), with important implications for data handling, analysis and interpretation. the authors’ report a significant effect of treatment group (garlic versus control) but fail to report what data was analysed to obtain this probability value, and its value to the data interpretation is thereby questionable. with better management of subject allocation to the treatment groups (for example by using faecal egg counts to rank cats according to worm burden severity and then allocating to treatments using a randomised block approach) this study could have been strengthened. it is not clear why this was not undertaken as the authors originally trapped 100 cats, and retained the 25 most toxocara cati parasitised cats to use in this study, so this limitation could have been addressed at the study outset. in summary, based on the limited and relatively poor quality studies available to address the pico, garlic may have a temporary inhibitory action on larvae and/or egg production of the intestinal worm species studied but none of the studies directly investigated the effect of garlic on adult worm mortality or viability. however, where a proxy measure was used (egg/larvae production after treatment cessation) this suggested that garlic did not have adulticidal action against ancyclostoma caninum. in the absence of research to demonstrate high levels of adulticidal action against a range of intestinal wormers at therapeutic, non-toxic levels in cats and dogs, clients should be advised that garlic is not proven as an effective anthelmintic (either against multiple species or a single species) for use in dogs and cats with to prevent, or to treat, an intestinal worm burden. methodology section search strategy databases searched and dates covered: pubmed, accessed  via the ncbi website (01/01/1900 – 20/02/2019); web of science (1990 – 20/02/2019) search terms: pubmed & web of science search: (dog or dogs or canine or canid or canis or bitch or bitches or pup or puppy or puppies or cat or cats or feline or felid or kitten or kittens) and (garlic or “allium sativum”) and (worm or tapeworm or tape-worm or “tape worm” or roundworm or round-worm or “round worm” or hookworm or hook-worm or “hook worm” or whipworm or whip-worm or “whip worm” or flatworm or “flat worm” or flat-worm or endoparasite or endo-parasite or parasite or parasitic or anthelmintic or ascarid or ascaris or larvae or toxocara or toxascaris or ancylostoma or trichuris or uncinaria or dipylidium or taenia or echinococcus or cestode or cestodes or nematode or nematodes or trematode or trematodes or fluke or flukes or nanophytus or heterophyes or cryptocotyle or apophallus or alaria) cab abstract search: (dog or dogs or canine or canid or canis or bitch or bitches or pup or puppy or puppies or cat or cats or feline or felid or kitten or kittens).mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (garlic or allium sativum).mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (worm or tapeworm or tape-worm or tape worm or roundworm or round-worm or round worm or hookworm or hook-worm or hook worm or whipworm or whip-worm or whip worm or flatworm or flat worm or flat-worm or endoparasite or endo-parasite or parasite or parasitic or anthelmintic or ascarid or ascaris or larvae or toxocara or toxascaris or ancylostoma or trichuris or uncinaria or dipylidium or taenia or echinococcus or cestode or cestodes or nematode or nematodes or trematode or trematodes or fluke or flukes or nanophytus or heterophyes or cryptocotyle or apophallus or alaria).mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] 1 and 2 and 3 dates searches performed: pubmed (20/02/2019); web of science (20/02/2019); cab abstracts (20/02/2019) exclusion / inclusion criteria exclusion: pre-defined exclusion criteria: non-english language, popular press articles, in vitro studies, conference abstracts inclusion: any comparative study in which the effect of garlic on intestinal worms in dogs or cats was studied search outcome database number of results excluded – did not answer the pico question excluded – not english language excluded – conference abstract only excluded – duplicates total relevant papers pubmed 8 7 0 0 0 1 web of science 10 0 0 0 0 0 cab abstracts 17 14 1 0 0 2 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflicts of interest. references andrei, s., ilie, m. s., mederle, n. & darabus, g. (2011) testing the effectiveness of a plant extract in the therapy on some endoparasites in dogs. lucrari stiintifice medicina veterinara, universitatea de stiinte agricole si medicina veterinara "ion ionescu de la brad" iasi, 54(3), pp. 247–254. bartha, s. g., quave, c. l., balogh, l., papp, n. (2015) ethnoveterinary practices of covasna county, transylvania, romania. journal of ethnobiology and ethnomedicine 11: 35 [online] available from: https://ethnobiomed.biomedcentral.com/articles/10.1186/s13002-015-0020-8 (accessed: 16/05/2019) doi: http://dx.doi.org/10.1186/s13002-015-0020-8 bastidas, g. j. (1969) effect of ingested garlic on necator americanus and ancylostoma caninum. the american journal of tropical medicine and hygiene, 18(6), pp. 920–923. doi: http://dx.doi.org/10.4269/ajtmh.1969.18.920 bekirov, r. e., azimov, sh. a., oripov, a. o., & dzhumaev, z. 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(2015) in vitro and in vivo nematocidal activity of allium sativum and tagetes erecta extracts against haemonchus contortus. turkish journal of parasitology 31: 277–282. doi: http://dx.doi.org/10.5152/tpd.2015.4523 ronagh, k., gharouni, a., bahadori, s. r., zakian, a., gholami, n., rezaeian, h. & shahraki, m. s. (2015) effect of nigella sativa, allium sativum, syzgium aromaticum and cucurbita maxima on toxocara cati fecal egg count in stray cats. online journal of veterinary research, 19(5), pp. 325–330. tavassoli, m., jalilzadeh-amin, g,. fard, v. r. b., & esfandiarpour, r. 2018. the in vitro effect of ferula asafoetida and allium sativum extracts on strongylus spp. annals of parasitology 64(1): 59–63. velkers, f. c., dieho, k., pecher, f. w. m., vernooij, j. c. m., van eck, j. h. h., &landman, w. j. m. (2011) efficacy of allicin from garlic against ascaridia galli infection in chickens. poultry science 90(2): 364–368. doi: http://dx.doi.org/10.3382/ps.2010-01090 worku, m., franco, r., & baldwin, k. (2009) efficacy of garlic as an anthelmintic in adult boer goats. archives of biological sciences 61(1): 135–140. doi: http://dx.doi.org/10.2298/abs0901135w intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. when preparing veterinary patients for surgery is the friction (back and forth) method of scrubbing the skin more effective than concentric circles at reducing bacterial levels on the skin? a knowledge summary by alison mann bsc (hons), dipavn (small animal), afhea, rvn 1* 1langford vets, university of bristol vet school, langford house, north somerset, bs40 5du *corresponding author (alison.mann@bristol.ac.uk) vol 3, issue 2 (2018) published: 25 apr 2018 reviewed by: constance white (dvm, phd) and brian pound (fcim) next review date: 25 apr 2020 doi: 10.18849/ve.v3i2.157 pico question: in veterinary patients is the friction (back and forth) method of scrubbing the skin more effective than concentric circles at reducing bacterial levels on the skin? clinical bottom line: currently there is insufficient evidence to indicate whether the friction (back and forth) method of scrubbing the skin is more effective than the concentric circle method at reducing bacterial levels on the skin. clinical scenario a student veterinary nurse is preparing a bitch spay for surgery and asks what is the best method for preparing the surgical site as they had seen in some literature that the friction (or back and forth) method may be better than the more traditional circular method. historically veterinary patients undergoing surgery have been prepared for surgery by applying scrub solutions on a swab in a circular motion, working from the surgical site outwards towards the periphery before repeating until the skin is clean. the performance of this method has been questioned in recent years with people claiming that the circular method means that the actual surgical site doesn’t get adequately disinfected or that the circular motion risks bringing bacteria from the periphery back to the surgical site. another method has been suggested to be superior to this; the friction method involves a short back and forth, side to side motion of scrubbing which starts over the proposed surgical site and works outwards, discarding the swab once the periphery is reached. by looking into the evidence the author hopes that the results will help in educating both students and qualified veterinary nurses on the gold standard of patient preparation. the evidence two studies were found which could be used in this knowledge summary, one human and one veterinary. the human study refers to donor arm disinfection so there are stark differences in the surfaces and the size of areas being prepared, in this instance the site being prepared is very small. the first trial within this study is probably the most relevant to the scenario due to the second and third trials using a ‘no touch’ preparation kit containing iodine tincture. these kits are beginning to be used more in veterinary hospitals and practices but the disinfectants used are different. the first trial produced poor results for all the preparation methods used, in that large numbers of bacteria were yielded post disinfection and so no relevant evidence can be gained from this. the veterinary study found is taken from a veterinary nurse undergraduate dissertation published in a veterinary nursing publication. although it is very relevant to the pico the sample size is too small to find a significant difference between the two techniques. summary of the evidence mcdonald (2001) evaluation of donor arm disinfection techniques population: trial no 1 – routine blood donors trial no 2 – blood donation staff trial no 3 – routine blood donors sample size: trial no 1 – 314 donors trial no 2 – 198 staff trial no 3 – 300 donors intervention details: trial 1 3 methods of donor arm disinfection were adapted from donation centres. the sample size was split into 3 groups according to the 3 disinfection techniques. pre disinfection swabs were taken from each arm. one technique involved using the circular motion the second was the same as the first but the technique was carried out twice and the third involved wiping either side of the vein once then over the vein low bacterial reductions were gained from these techniques and so none were adopted for the rest of the study. trial 2: a second trial was carried out with seven techniques. the two best performing techniques at reducing bacterial levels from the second trial were chosen for the third trial.  these were applying iodine tincture (commercial, no touch kit) using the back and forth motion and the second was two applications of alcohol using back and forth motion followed by the application of iodine tincture (commercial, no touch kit) in a circular motion. trial 3: the methods were selected as above with the addition of a control method consisting of chx and ipa wipe being used in a circular motion before being allowed to dry.  the commercial kit used in the other preparation methods consisted of a device designed so that the hands of the operator are nowhere near the skin at the time of using it thus making it ‘no touch’ technique. there were 100 participants in each of these groups. study design: prospective trial outcome studied: post disinfection bacterial counts at the donation site, in this case the antecubital fossa of the arm. main findings (relevant to pico question): the first trial was mainly to find a technique which they could take forward into further trials.  the methods adapted are discussed in the intervention details section.  results found that low bacterial reductions were gained from these techniques and so none were adopted for the rest of the study. in the second trial the technique that involved using an up and down motion with a commercial kit (after initial application of ipa) was found to be most effective although not significant in the 3rd trial, the technique using the up and down motion using the commercial ‘no touch’ kit was found to be superior (p< 0.001) to the method that applied the tincture of iodine in a spiral method. however, the absence of confidence intervals makes statistical reporting poor and there can be some question about whether a difference in bacterial reductions of 1.64% can be called significant. limitations: this is carried out on humans not animals. there was no indication that those who were collecting the swabs for bacterial counts were blinded to the methods used. it is only carried out on one small area of skin, which due to location may not be exposed to high bacterial counts in the first place. it wasn’t the same person carrying out all the arm disinfections and people’s technique may differ slightly. a commercial ‘no touch’ kit was used. although such kits are available to veterinary practices, patients are often prepped for surgery with swabs held by gloved or sometimes non gloved hands rather than the ‘no touch’ method. the ‘no touch’ kit methods included the use of iodine rather than chx and so cannot be transferred to veterinary practice where chx is used the majority of the time. swales (2017) failure to achieve asepsis following surgical skin preparation is influenced by bacterial resistance to chlorhexidine, but not skin preparation technique population: client owned dogs admitted to a university teaching hospital for abdominal surgery. sample size: 25 dogs intervention details: the dogs were clipped from the thoracic outlet to the pubic symphysis and to lateral skin edges. post preparation swabs were taken before any product was applied to the skin. the patient was then prepared for surgery using one of two methods, either the concentric circle method or the linear (back and forth or friction) method using a 2% chlorhexidine (chx) solution. the methods were alternated and carried out by the same person each time.  there were 13 dogs who were prepared using the back and forth method and 12 who had concentric circles the patients were prepped for five minutes or until a plain swab wiped over the surgical incision site came away clean. another swab was taken after preparation. the swabs were cultured on mannitol salt agar or macconkey agar and these were incubated for 24 hours. colonies found from the post preparation swabs were subcultured into blood culture bottles for identification of bacterial species. study design: prospective trial outcome studied: whether reduction in bacterial count differed between the two scrub methods. main findings (relevant to pico question): both methods significantly decreased bacterial counts on the skin but there was no significant difference in the post preparation bacterial counts between the two methods. 32% of the dogs had bacteria present after skin preparation, 8 dogs in total but two had two species present. three were prepared using concentric circles and five using the linear method.  4 out of the 10 species of bacteria present were reisitant to chx at the dilutions tested.  there was no significance between the groups of the likeliness of bacteria remaining. due to the lack of significance between the 2 methods and with the fact that some bacteria were resistant to chx, the authors concluded that resistance may be more of an issue with products used for patient preparation rather than the method in which they are applied limitations: small sample size, probably due to the limited data collection window. the subjectivity of when preparation was deemed finished, by either timing for 5 minutes or until a clean dry swab came away from the skin clean the patients were all dogs but sizes, lifestyle and coat may have differed greatly, meaning that some may have had a higher bacterial burden on the skin. the study method states that no exclusions were made due to age, breed or sex. appraisal, application and reflection one human study was found to be relevant to the pico which reports superior action of the up and down friction method compared with the circular technique, however, results may be confounded by the use of different products; it is unclear whether the treatment effect was due to the scrub technique or the disinfectant applied. the main limitation to this study is its application in the veterinary world due to the nature and site of the areas being prepared in the human study. the veterinary study found is taken from a veterinary nurse undergraduate dissertation published in a veterinary nursing publication. although the study is very good, the sample size is small and the study likely to be underpowered, meaning that due to it not being a true representation of a population it may miss out on a significant result. it is not known whether a significant difference may be found with a larger sample size, as there are no similar studies carried out in this area. there is still a gap in the evidence for a larger scale veterinary study to be carried out in this area which could provide some usable evidence through controlling aspects such as species, type of disinfection used, contact time and method of application. not every clinical decision made comes down to only evidence. based on experience and opinion it may be argued that the circular method a) doesn’t thoroughly disinfect the proposed incision site and b) risks bringing bacteria from the periphery back over the proposed incision site before the swab is discarded. the back and forth method could produce more friction, and it is this mechanical action which could help to reduce bacterial levels on the skin (davids et al 2015). however, in the absence of evidence, protocol should be made based on what works best for the practice and has proven to be most efficient and achieves the best results. methodology section search strategy databases searched and dates covered: cab abstracts and pubmed 1973-2017 week 26 search terms: cab abstracts: (preoperative or pre-operative or presurgery or presurgical or pre-surgery or pre-surgical) ((site or skin) and (technique or techniques or method or methods or preparation)) ((scrub or scrubs or scrubbing) and (technique or techniques or method or methods or preparation)) 1 and (2 or 3)   pubmed: (((preoperative or pre-operative or presurgery or presurgical or pre-surgery or pre-surgical)) and ((site or skin) and (technique or techniques or method or methods or preparation))) and ((scrub or scrubs or scrubbing) and (technique or techniques or method or methods or preparation)) dates searches performed: 13/07/2017 exclusion / inclusion criteria exclusion: review articles inclusion: those relevant to pico including human literature search outcome database number of results excluded – not relevant to pico excluded – review article excluded – due to methodology total relevant papers cab abstracts 203 202 0 1 0 pubmed 129 129 0 0 0 hand search 3 0 1 0 2 total relevant papers when duplicates removed 2 conflict of interest the author declares no conflicts of interest. references davids, b. i., davidon, m. j., tenbroeck, s. h., colahan, p. t. and oli, m. w. (2015) ‘efficacy of mechanical versus non mechanical sterile preoperative skin preparation with chlorhexidine gluconate 4% solution’, veterinary surgery, vol 44 (5), pp 648-652. doi: http://dx.doi.org/10.1111/vsu.12335 mcdonald, c. p., lowe, p., roy. a., robbins. s., hartley, s., harrison, j. f., slopecki, a., verlander, n. and barbara, j. a. j. (2001) ‘evaluation of donor arm disinfection techniques’, vox sanguinis, vol 80 (3), pp 135-141. doi: http://dx.doi.org/10.1046/j.1423-0410.2001.00029.x swales, n. and cogan, t. (2017) ‘failure to achieve asepsis following surgical skin preparation is influenced by bacterial resistance to chlorhexidine, but not skin preparation technique’, veterinary nursing journal, vol 32, (8), pp224-227. doi: http://dx.doi.org/10.1080/17415349.2017.1328994 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. in an adult horse with severe asthma (previously recurrent airway obstruction) does using inhaled corticosteroids result in an equal improvement in clinical signs when compared to systemic corticosteroids? a knowledge summary by natasha a jocelyn ma vetmb mrcvs 1* 1 the royal veterinary college, hawkshead lane, north mymms, hatfield, hertfordshire, al9 7ta *corresponding author (njocelyn@rvc.ac.uk) vol 3, issue 2 (2018) published: 10 apr 2018 reviewed by: kate mcgovern (bvetmed certem(int.med) ms dacvim dipeceim mrcvs) and tim brazil (bvsc phd cert em (internal medicine) deceim mrcvs) next review date: 20 jul 2019 doi: 10.18849/ve.v3i2.139 pico question in an adult horse with severe asthma (previously recurrent airway obstruction (rao)) does using inhaled corticosteroids result in an equal improvement in clinical signs when compared to systemic corticosteroids? clinical bottom line the level of confidence in the outcomes from the body of evidence in the 4 papers identified is high. this suggests inhaled corticosteroids (fluticasone and beclomethasone) when used at an appropriate dose can have equivalent effects on severe equine asthma as systemic intravenous dexamethasone. inhaled corticosteroids can take longer to have the desired effects.  clinical scenario a 12-year-old cob mare presents to you with increased respiratory effort and rate at rest. radiographs and ultrasound of the lungs are unremarkable. a bronchoalveolar lavage indicates inflammation and neutrophilia (>20% neutrophils) with no evidence of bacterial infection. you diagnose equine severe asthma (previously called recurrent airway obstruction) and need to decide the best treatment option for the mare. the owner is concerned with the potentially long term use of systemic steroids and wants to know if other routes of administration for steroid treatment are effective. the evidence following refinement of the initial search and exclusion of unsuitable publications, four studies were found that were directly applicable to the pico question (rush et al. 1998; couëtil et al. 2005; couëtil et al. 2006; robinson et al. 2009). all four were clinical trials, with three  being crossover in design (rush et al. 1998; couëtil et al. 2006; robinson et al. 2009). three were blinded (rush et al. 1998; couëtil et al. 2005; couëtil et al. 2006). none of the studies were completely comparable because each had slightly different interventions and outcomes but overall the evidence was of high quality. summary of the evidence rush (1998) – published as 3 parts but one study population: adult horses with a diagnosis of severe equine asthma recurrent airway obstruction (rao) which could be induced with the moldy hay challenge. sample size: 6 intervention details: severe equine asthma was induced via the moldy hay challenge over 7 days. then in a cross over design the following were administered for 7 days: inhaled beclomethasone (1,320mg twice a day (bid)) via 3m metered dose delivery device + 20mls saline iv sid iv dexamethasone (0.1mg/kg once a day (sid)) + aerosolized propellant (10 actuations bid) aerosolized propellant (10 actuations bid) + 20mls saline iv sid horses were maintained in the moldy environment for a further 7 days. there was a two-month washout period between treatments. study design: prospective crossover, blinded, controlled clinical trial outcome studied: clinical scoring (bid days 0-21) plus pulmonary function testing (max trans pulmonary pressure change, pulmonary resistance and dynamic compliance) and bronchoalveolar lavage were performed at days 0, 7, 10, 14 and 21. main findings (relevant to pico question): clinical score and pulmonary function improved after 3 days of beclomethasone compared to the control. the improvement was greater with iv dexamethasone compared to beclomethasone. the beneficial effects actions of beclomethasone did not extend beyond the treatment period for clinical score outcome but did for pulmonary function. bronchoalveolar lavage cytology identified neutrophilia induced by the moldy hay challenge which was significantly improved by both corticosteroids. the neutrophilia rebounded after treatment discontinuation for both treatment options. limitations: small sample size couëtil (2005) population: adult horses with a history consistent with severe equine asthma (rao) sample size: 28 intervention details: horses assigned to either mild, moderate or severe clinical groups based on initial clinical examination and pulmonary function testing. horses within each group were randomly assigned to one of the following treatments: inhaled fluticasone via metered dose inhaler using equine aeromasktm inhaled control substance oral prednisone all 3 treatments were given in a tapering regime over 4 weeks. all horses kept outdoors at pasture and fed a pelleted feed for duration. study design: prospective, randomised, double blind, controlled clinical trial outcome studied: clinical scoring, pulmonary function testing (extensive) and bronchoalveolar lavage were performed at week 0, 2 and 4. main findings (relevant to pico question): in those animals with the most marked disease, treatment with fluticasone (1980mg bid) for 2 weeks had a significant improvement in pulmonary function compared to prednisone or control. irrespective of treatment group all animals had improved clinical scores over the 4 weeks indicating environment is critical. cytology of bronchoalveolar lavage was not statistically different between the groups. limitations: various degrees of severe equine asthma with various confounding factors prior to enrollment. 54% were discharged for treatment by owner at home. prednisone is a pro drug considered to have low bioavailability, inefficiently converted in the horse and not available in the uk. only 1 of the treatment options given to each horse. couëtil (2006) population: adult horses with a diagnosis of severe equine asthma (rao). diagnosis by asthma induction following moldy hay challenge, with abnormal pulmonary function testing, >25% neutrophilia in bal and normal haematology and biochemistry. sample size: 7 intervention details: severe asthma was induced via the moldy hay challenge. then in a crossover design the following were administered: inhaled beclomethasone dipropionate, 500mg bid for 10 days using 3m hand held delivery device a single im injection of dexamethasone 21-isonicotinate 0.06mg/kg a single im injection of sterile saline a 4 week wash out period between interventions was employed with repetition of the moldy hay challenge before each intervention. study design: prospective crossover, blinded, controlled clinical trial outcome studied: clinical scoring (days 0, 1, 4,7,10), pulmonary function testing (max trans pulmonary pressure change, pulmonary resistance and dynamic compliance), bronchoalveolar lavage and bronchial brushing (day 0 and 10) main findings (relevant to pico question): 10 days of low dose inhaled beclomethasone significantly improved pulmonary function but failed to alter airway cytology or clinical score a single injection of long acting dexamethasone failed to improve any of the outcome variables examined limitations: under powered. low dosage of drugs used. short study period. randomisation not described. no inhaled control substance. robinson (2009) population: adult horses with previous diagnosis of severe equine asthma (rao) which demonstrated atropine-reversible airway obstruction when housed and fed hay. sample size: 8 in first protocol and 6 in second intervention details: two protocols: 1. severe asthma was induced via stabling on straw and hay. then in a crossover design the following were administered for 3 days: -  fluticasone 3mg inhaled bid using equine halertm -  fluticasone 6mg inhaled bid using equine halertm  dexamethasone 0.1mg/kg sid iv a 21-day washout period at pasture with a pelleted diet between the 3 treatments was undertaken. 2. animals which had been at pasture for 21 days were confirmed to be in remission, and then in a cross over design the following were administered for 7 days: fluticasone 6mg inhaled bid using equine halertm dexamethasone 0.1mg/kg sid iv no treatment for the first 3 days horses remained at pasture then moved into stables on straw and fed hay. a 21 day washout period at pasture with a pelleted diet between the treatment protocols was undertaken. study design: prospective, non-blinded, crossover, controlled clinical trial outcome studied: clinical scoring (respiratory and lameness) and pulmonary function testing (maximal change in pleural pressure) (0, 24, 48, 72hrs) and bronchoalveolar lavage (0 and 72hrs). clinical scoring (respiratory and lameness) and pulmonary function testing (days 0, 4-8), bronchoalveolar lavage (days 0 and 8). main findings (relevant to pico question): inhaled fluticasone at a dose of 6mg bid, but not 3mg bid, significantly improved respiratory clinical score and pulmonary function in horses with active asthma but only after 72 hours of treatment. intravenous dexamethasone was equally effective but had a faster onset of 24 hours after treatment initiation. both corticosteroids were effective when compared to no treatment at preventing acute exacerbation of asthma. no significant difference in bronchoalveolar lavage cytology was seen with any of the treatments or doses in either protocol. no signs of acute laminitis were observed in either protocol using the clinical lameness scoring. limitations: short study period (3 days of treatment only for initial study and 8 days for 2nd protocol). ideally the control group should have received placebo (inhaled +/im injection). low sample size and not blinded. limited pulmonary function tests. appraisal, application and reflection three out of the four studies (rush et al. 1998; couëtil et al. 2006; robinson et al. 2009) used a very similar design which involved inducing clinical disease by exposure to hay and or straw, using highly controlled environments and comparing inhaled and systemic corticosteroids to a control. the studies used clinical scoring systems for assessment of clinical signs, and used other similar outcome measures such as bal cytology and pulmonary function testing, which allowed comparison between studies. all three of the above studies used pleural pressure changes to initiate the start of the treatment period, with the cut off value being equivalent in rush et al. (1998) and couëtil et al. (2006), and similar in robinson et al. (2009). the populations were different and geographical location also varied. as is often the case, the clinical trials used small numbers of animals and relatively short study periods treatment protocols varied from three days to four  weeks with the largest and longest study (couëtil et al. 2005) being the least controlled. couëtil et al. (2005) differed in methodology to the other papers but, importantly, it was not crossover in design and still employed clinical scores, pulmonary function and cytology to compare the groups. two different inhaled corticosteroids were investigated (beclomethasone and fluticasone) in all four studies, but at different doses. two studies (rush et al. 1998; robinson et al. 2009) used systemic dexamethasone at the same dose for varying lengths of time. the two studies that compared systemic dexamethasone to the inhaled steroids found them to be broadly equivalent at specific doses except that the onset of beneficial actions was slower with the inhaled steroids. the other two studies found that the systemic corticosteroid used, either oral prednisone (couëtil et al. 2005) or a long-acting intramuscular preparation of dexamethasone (couëtil et al. 2006), was not effective. the low bioavailability of prednisone in horses makes its use in the couëtil et al. 2005 paper highly questionable.  couëtil et al. (2005) also modified the environment for all animals. this had a significant effect on outcome, which may have confounded the results. two studies used the same inhaler device (hand held metered device 3mtm) for administering beclomethasone (rush et al. 1998; couëtil et al. 2006) whereas the other two used different devices, thus adding a further potential variable when comparing the studies. only one study (rush et al. 1998) observed significant differences in airway cytology, specifically reduction in bal neutrophilia, as a result of corticosteroid treatment. bal is widely used for diagnosis and monitoring of equine severe asthma but the evidence from the other three of these studies suggests it may not be a useful outcome for monitoring response to treatment. the available evidence is of sufficient quality that clinicians should be able to apply the findings to clinical scenarios. the most effective inhaled corticosteroid appears to be fluticasone at 6mg bid which seems to be able to prevent exacerbation of asthma in horses moving from pasture to a stabled environment. the use of iv dexamethasone may be preferable in the acute case as the onset of clinically-apparent action was reported in these studies to be faster. the literature is lacking comparison of inhaled corticosteroids and prednisolone. prednisolone is a widely used oral corticosteroid in the uk with a product licensed for equine asthma specifically. since these studies were published, ultrasonic nebulisers (which provide an alternative to metered dose inhalers as a means of delivering inhalation therapy) have come to the market in the uk and these also warrant comparison in clinical settings. methodology section search strategy databases searched and dates covered: cab abstracts 1973week 29 2017 pubmed 1900week 29 2017 search terms: equine or horse and recurrent airway obstruction or rao or equine asthma and corticosteroids or corticoids dates searches performed: 19/07/2017 exclusion / inclusion criteria no limitations regarding study design, setting, sample size or study population were imposed. exclusion: articles not relevant to the pico question, in vitro studies, book chapters or conference proceedings. inclusion: relevant to pico question, more than 1 animal, in vivo search outcome database number of results excluded – irrelevant to pico question excluded – duplicates excluded – conference proceedings or review articles excluded – in vitro studies total relevant papers cab abstracts 23 20 0 2 0 1 pubmed 37 30 1 0 3 3 total relevant papers when duplicates removed 4 conflict of interest the authors declare no conflicts of interest. references couëtil, l.l. et al., 2006. effect of beclomethasone dipropionate and dexamethasone isonicotinate on lung function, bronchoalveolar lavage fluid cytology, and transcription factor expression in airways of horses with recurrent airway obstruction. journal of veterinary internal medicine / american college of veterinary internal medicine, 20(2), pp.399–406. doi: http://dx.doi.org/10.1111/j.1939-1676.2006.tb02875.x couëtil, l.l. et al., 2005. randomized, controlled study of inhaled fluticasone propionate, oral administration of prednisone, and environmental management of horses with recurrent airway obstruction. american journal of veterinary research, 66(10), pp.1665–1674. doi: http://dx.doi.org/10.2460/ajvr.2005.66.1665 robinson, n.e. et al., 2009. fluticasone propionate aerosol is more effective for prevention than treatment of recurrent airway obstruction. journal of veterinary internal medicine, 23(6), pp.1247–1253. doi: http://dx.doi.org/10.1111/j.1939-1676.2009.0382.x rush, b.r. et al., 1998. pulmonary function in horses with recurrent airway obstruction after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively. american journal of veterinary research, 59(8), pp.1039–1043. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. the veterinary clinical trials network a pragmatic approach to filling the evidence gaps for veterinary practice hannah doit phd student1* 1cevm, university of nottingham, sutton bonington campus, sutton bonington, loughborough le12 5nt *corresponding author (hannah.doit@nottingham.ac.uk) vol 2, issue 2 (2017) published: 26 apr 2017 doi: 10.18849/ve.v2i2.110 including current published evidence is vital as part of evidence-based decision making in veterinary practice. sometimes there is no published evidence which is relevant or applicable to the clinical situation. this can be either because it refers to patients with experimentally induced conditions, from a referral population or who lack the co-morbities often seen outside of the experimental context. the veterinary clinical trials network is unique. it is a rapidly expanding network of veterinary practices, with whom we are working to establish methods for running prospective, pragmatic, practical clinical trials in veterinary practice. data is extracted from the patient record using an xml schema. the data extracted is already captured by the practice management software (pms) system as part of the consultation, no extra information is required, and the extraction method is automated. this improves participation as it minimises the time input required from vets and vet nurses. other data is obtained directly from owners of the animals involved. by working with a large number of first opinion veterinary practices we are able to include enough patients to ensure that our trials are suitably powered, and the participants will be representative of the wider vet-visiting pet population. the research generated from this clinical trials network will help strengthen the evidence base to aid decision making by veterinary practitioners. find out more about hannah. comments: percutaneous drainage in the management of urethral blockages in cats a knowledge summary by david l haine ma, vetmb, mrcvs 1* emma place ma, bsc 1 1university of bristol, senate house, tyndall avenue, bristol, bs8 1th, uk *corresponding author ( davidhaine@gmail.com) vol 3, issue 4 (2018) published: 20 nov 2018 reviewed by: wanda gordon-evans (dvm, phd, dacvs, dacvsmr) and jacqueline cole (bsc, bvetmed, mrcvs) next review date: 20 nov 2020 doi: 10.18849/ve.v3i4.171 pico question in adult male cats with a urethra blockage, is indwelling catheterisation more effective than percutaneous drainage in reducing the incidence of recurrence? clinical bottom line based on the available literature, it would appear that recurrence rates following percutaneous drainage are broadly similar to those managed with indwelling catheterisation. however, the level of evidence supporting the use of percutaneous drainage is very low and there are significant uncontrolled variables between all available studies, with the consequences that meaningful comparisons between recurrence rates are not possible. more studies are needed before routine use of percutaneous drainage as an alternative to indwelling catheterisation can be advocated. clinical scenario a 7y mn dsh cat presents to your clinic with a 24-hour history of pollakiuria and haematuria, and a 4-hour history of non-productive stranguria. abdominal palpation reveals a firm distended bladder which cannot be manually expressed, biochemistry reveals a moderate azotaemia, lateral abdominal radiographs do not suggest the present of any calculi. the owner has significant financial restrictions and would like to know if any other options for management other than indwelling catheterisation are available and how likely the problem would be to recur. summary of the evidence gerber, b. et al. (2008) population: male cats diagnosed with urethral obstruction admitted to the clinic for small animal internal medicine, university of zurich, between december 2000 and november 2002. sample size: forty-five male cats with urethral obstruction. study design: retrospective single centre case series. outcome studied: time to recurrence of signs, if deceased, whether death was related to lower urinary tract disease. assessed through reviewing clinical records and telephone interview with owner. main findings (relevant to pico question): cats in the study had an age range of 1-15 years, with a mean of 5 years. 24/45 were diagnosed with idiopathic urethral obstruction, 13/45 had urolithiasis, and 8/45 had urethral plugs. 32/45 cats were managed non-surgically, with a median hospitalisation period of 4.5 days and a range of 1-12 days. 29/32 non-surgical cats were managed with indwelling urethral catheterisation. a variety of different medication regimens were used for different cats including: diazepam, flavoxat, phenoxybenzamine, non-steroidal anti-inflammatories, heparin, amitriptyline, n-acetyl-glucosamine, and a variety of antibiotic therapies. follow up was available for 39 cases (8 managed surgically, 31 managed non-surgically), for a range of 5-868 days and a median of 432 days. 15/31 cats with follow up managed non-surgically developed recurrent signs of flutd and 11/31 (35%) re-obstructed, with a range of 3-728 days to obstruction and a mean of 18 days. frequency of re-obstruction was not significantly correlated with the primary cause of the obstruction (p > 0.05). limitations: retrospective case series, low on evidence hierarchy. there was a significant variability in medical management between cases. follow up was for a wide range between cases, meaning re-obstruction may have occurred without being reported. the series describes a single centre referral population, which may not be directly comparable with other populations. no control group. cooper, e.s. et al (2010) population: male cats brought to the ohio state university veterinary teaching hospital for treatment of naturally occurring urethral obstruction between june 2007 and june 2008, and in which the owners had declined conventional treatment (catheterisation and intensive care). cases were excluded if severe metabolic derangements or radiographically visible uroliths were present. sample size: fifteen male cats. intervention details: cats were sedated with a combination of acepromazine, buprenorphine and medetomidine and placed in a dark environment. decompressive cystocentesis and subcutaneous fluid administration was performed as necessary. intervention was charged at a fixed price significantly lower than the clinics normal protocol of hospitalisation in an intensive care unit with an indwelling urinary catheter. treatment success was defined as spontaneous urination within 72 hours of starting therapy. study design: prospective case series. outcome studied: time to spontaneous urination, incidence of recurrence. main findings (relevant to pico question): intermittent percutaneous drainage was successful in treating 11/15 cats (73%). mean time to spontaneous urination was 34.6 hours. of those successfully treated, recurrence rate at three days was 0/11 cats (0%) and 2/11 (18%) cats at three weeks. 4/15 (27%) cats were euthanised due to treatment failure (failure to spontaneously urinate). limitations: single centre case series, low on evidence hierarchy. the study described a small sample size, meaning that conclusions are less statistically robust and the extent to which they can be extrapolated to other populations is limited. the series describes a single centre referral population, which may not be directly comparable with other populations. no control group. eisenberg, b.w. (2013) population: male cats presented to the emergency departments of three referral hospitals due to acute urethral obstruction between april 1, 2010, and april 30, 2011. cases were excluded if an indwelling urinary catheter had been placed prior to arrival at the participating hospital. further exclusion criteria included catheterisation for < 1 hour, death or euthanasia prior to urethral catheter placement, and incomplete medical records. all cats treated surgically during the initial hospitalisation period were excluded from the study population. sample size: 83 male cats. intervention details: cats were sedated and an indwelling urinary catheter was placed. the urinary catheter was removed after stabilisation of azotaemia, resolution of haematuria, or after 24 hours had passed. follow up information was surveyed from telephone or email conversations 30 days post discharge. study design: prospective multi-centre (three) case series. outcome studied: incidence of, and time to, re-obstruction. duration of catheterisation. main findings (relevant to pico question): 68 cases had follow up, of these 10/68 (15%) had a repeat episode of obstruction during the follow up period (median follow up period 41 days, range 25-110 days). shorter duration of catheterisation was significantly associated with a higher probability of recurrent obstruction in the follow-up period (p = 0.03) (median 24.5 hours [range, 1 to 54 hours] vs median, 26.5 hours). catheterisation with a smaller catheter (3.5fr vs 5fr) was not significantly (p = 0.99) associated with the risk of recurrent urethral obstruction. limitations: case series, low on hierarchy of evidence. the study described a relatively small sample size (83 cats), meaning that conclusions are less statistically robust and the extent to which they can be extrapolated to other populations is limited. the study describes a referral population, which may not be directly comparable with other populations. 15/83 cases were lost to follow up, which may affect reliability of results. treatment interventions were not standardised, with interventions (for example medical therapy protocol) varying at the discretion of the attending veterinarian. no control group. hetrick, p.f. and davidow, e.b. (2013) population: male cats with urethral obstruction (excluding urolithiasis, neoplasia, or toxicosis) that were treated at an emergency and specialty centre from january 2004 through december 2010 with an indwelling urinary catheter. sample size: 192 male cats with follow up data for the 24-hour period after removal of a urinary catheter, of which 157 had follow up for 30 days. intervention details: all cats were managed with an indwelling polyvinyl chloride urinary catheter, size chosen at clinicians’ discretion. cats were prescribed either prazosin or phenoxybenzamine following removal of the indwelling urinary catheter. study design: retrospective single centre case series. outcome studied: rate of recurrent urethral obstruction (ruo). main findings (relevant to pico question): mean duration of urinary catheterisation was 36 hours. there was a lower rate of ruo in cats that had a 3.5fr urinary catheter as compared to cats with a 5fr catheter. overall ruo rates were 11% (21/192 cats) at 24 hours and 24% (37/157 cats) at 30 days after iuc, with 86% of ruo (32/37 recurrences) occurring within 4 days of indwelling catheter removal. administration of analgesia (meloxicam/opioids) did not make a significant difference to rates of ruo (p > 0.05). limitations: significant variation between treatment protocols and follow up, including a hospital protocol shift halfway through the series, also a potential source of bias. retrospective single centre case series, low down the hierarchy of evidence. some cases (35/192 cats) were lost to follow up, which may affect the reliability of results. cases are from 2004-2010, so medications, equipment and management techniques may have changed since the study period. population data including weight and breed were not described, making it difficult to compare to other populations. all cats in the study had polyvinyl chloride infant feeding tubes placed as urinary catheters. these may not be directly comparable to urinary catheters used in other studies or institutions. no control group. appraisal, application and reflection this search presented few studies that assessed the incidence of recurrence in cats managed with either indwelling urinary catheterisation or percutaneous drainage, of which none directly compared the two approaches, meaning that more studies are needed to draw firm conclusions as to the comparative efficacy of these techniques. all of the studies described case series in referral populations, which may not be applicable to the majority of cases managed in first opinion practice, as these are often cases deemed by a primary vet to be more challenging to manage. there is significant variation in treatment protocols between and within different centres, leading to a significant number of uncontrolled variables. all of the data used is more than 5 years old, leaving the potential for treatment protocols to have changed and evolved since publication – in one study there was a significant evolution in protocol during the study (hetrick & davidow, 2013). several of the studies with relevant data are retrospective studies, so there is potential for significant bias in the selection and treatment of cases. there is variation in the time scale of follow up between studies, meaning that re-obstruction in one study could have occurred without being included in the results (gerber, eichenberger, & reusch, 2008) and the measures for outcome are not consistent between studies, with death and recurrence of obstruction both used as endpoints for treatment failure. there is only one study evaluating the effect of percutaneous drainage on time to recurrence, which has a small sample size of just 11 cats with follow up to 30 days. overall the quality and extent of the evidence is limited, meaning that significant conclusions are hard to draw from the data. considering the studies generated through this search strategy, there is no evidence to support the advantage of either percutaneous drainage or indwelling catheterisation over each other in reducing recurrence rates when managing urethral obstruction in cats. cats managed with an indwelling urethral catheter report recurrence rates of 24% in one study evaluating 30 day follow up (hetrick & davidow, 2013) and 15-31% in studies with longer, variable follow up (gerber, eichenberger, & reusch, 2008) (eisenberg, et al., 2013). cats managed with percutaneous drainage reported a recurrence rate of 18% at three weeks, although this is based on just 11 cases (cooper, owens, chew, & buffington, 2010). based on these data, it could be suggested that recurrence rates between these two techniques are broadly similar. however, the level of evidence supporting the use of percutaneous drainage is extremely limited, meaning that further studies are necessary, ideally comparative, prospective multi-centre studies with significant sample sizes, before any significant conclusions can be made about the true incidence recurrence after use of the technique. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform 1973-2017 medline on ovid platform 1946-2017 search terms: cab abstracts: [[cat disease/or cats] or [(cat or cats or feline* or felis or felid*).mp.]] and [[(obstruction or urinary tract disease or urethra* or urinary calculi or urolithiasis).sh.) or [urinary tract/] or [(urethra or “urinary tract”).mp.]] and [[(catheter or catheterization).sh.] or [(catheter* or catheteri?ation).mp.]] and [limit to english language] medline: [felis/ or cats/] or [(cat or cats or feline* or felis or felid*).mp.] and [[urethral obstruction/ or urolithiasis/] or [(urethra* or “urinary tract”).mp.]] and [[catheterization/ or urinary catheterization/ or intermittent urethral catheterisation/] or [(catheter* or catheteri?ation).mp.]] and [limit to english language] dates searches performed: 18th december 2017 exclusion / inclusion criteria exclusion: single case reports, book chapters/opinion, conference proceedings, correspondence, articles not relevant to pico question. inclusion: articles relevant to pico question. search outcome database number of results excluded – single case report excluded – book chapter/opinion excluded – conference proceedings excluded – correspondence excluded – irrelevant to pico total relevant papers cab abstracts 193 31 (162) 22 (140) 20 (120) 1 (119) 116 (3) 3 medline 165 16 (149) 1 (148) 0 (148) 1 (147) 143 (4) 4 total relevant papers when duplicates removed 4 conflict of interest the authors declare no conflicts of interest. references cooper, e. s. et al., 2010. a protocol for managing urethral obstruction in male cats without urethral catheterization. journal of the american veterinary medical association, 1 december, 237(11), 1261-1266. http://dx.doi.org/10.2460/javma.237.11.1261 eisenberg, b. w. et al., 2013. evaluation of risk factors associated with recurrent obstruction in cats treated medically for urethral obstruction. journal of the american veterinary medical association, 15 october, 243(8), pp. 1140-1146. http://dx.doi.org/10.2460/javma.243.8.1140 gerber, b., eichenberger, s. & reusch, c. e., 2008. guarded long-term prognosis in male cats with urethral obstruction. journal of feline medicine and surgery, 1 february, 10(1), pp. 16-23. https://doi.org/10.1016/j.jfms.2007.06.007 hetrick, p. f. & davidow, e. b., 2013. initial treatment factors associated with feline urethral obstruction recurrence rate: 192 cases (2004–2010). journal of the american veterinary medical association, 15 august, 243(4), pp. 512-519. https://doi.org/10.2460/javma.243.4.512 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, 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no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. are pressure vests beneficial at reducing stress in anxious and fearful dogs? a knowledge summary by louise anne buckley phd, rvn * *corresponding author (louisebuckleydyson@msn.com) vol 3, issue 1 (2018) published: 02 mar 2018 reviewed by: sue badger (med, cert ed, rvn) and erik fausak (mslis, ma, cvt, lvt, rlat) next review date: 02 sep 2020 doi: 10.18849/ve.v3i1.152 pico question in fearful or anxious dogs does wearing a pressure vest, compared to not wearing one, result in reduced behavioural and physiological signs of stress? clinical bottom line four studies of variable quality and limitations were identified that investigated the use of pressure vests, using various physiological and behavioural proxy measures of anxiety. most behavioural outcome measures associated with a positive effect were subjective assessments, with unblinded assessors. subjectively, many of the owners believed that pressure vests had a positive effect on their dogs’ anxiety levels. the take home message for the veterinary professional is that pressure vests may have small but beneficial effects on canine anxiety and that habituating the dog to the vest, assessing for comfort and using repeatedly may improve the likelihood of any benefit. however, the owner should be cautioned that they should not expect their dog’s anxiety to be fully alleviated or prevented, and it may have no beneficial effect at all.  clinical scenario during veterinary nursing clinics, the veterinary nurse encounters dogs that the owners describe as being fearful, anxious or stressed in a range of situations (e.g. separation anxiety, noise phobia, etc). aware that there is a plethora of products available on the market aimed at reducing negative emotional states in dogs, she is keen to ensure that she only recommends products to these clients when there is evidence to support their use. a couple of clients have mentioned the use of pressure vests and have suggested that the veterinary practice stock them for use with other clients, therefore she decides to examine the evidence base for these products. the evidence three studies were identified (cottam et al., 2013; king et al., 2014; pekkin et al., 2016) that specifically aimed to test the efficacy of commercially available pressure vests at reducing indices of stress in canines. of these, only one (pekkin et al., 2016) reported measuring and standardising the pressure exerted by the vests, the other two papers reported fitting (or asking owners to fit) the vests firmly in accordance with the manufacturers’ instructions. on this basis, a fourth paper (fish et al., 2017) that looked at the effect of fitting a telemetry vest (the authors report snuggly fitting these spandex vests) on physiological and behavioural parameters of dogs exposed to a stressor was also included. a fifth paper (cottam and dodman, 2009) was identified that also used an item of torso clothing (a cape) to use reduce stress in dogs naturalistically exposed to thunderstorms. however, this study was devised to examine the effects of an anti-static lining, and both the control and the experimental dogs wore capes (both of which reduced the anxiety levels of dogs exposed to thunderstorms). furthermore, the authors do not report fitting the cape firmly (or any other adjective to indicate that the cape exerted pressure on the torso). thus, this paper was not included in the evidence summary. summary of the evidence cottam (2013) population: healthy, house-trained dogs fearful of thunderstorms and living in one of 11 american states known for having frequent thunderstorms and whose owners responded to an advert in the vet school newsletter. dogs had to meet the inclusion criteria to be designated ‘thunderstorm wary’ and not currently be on any pharmacological treatment for this fear. inclusion criteria (based on owner self-reporting): dogs had to show anxiety during thunderstorms at least 85% of the time. during thunderstorms, dogs had to show three (or more) of the following signs of anxiety: panting shaking escape attempts or damage property inappropriate elimination pacing attention seeking whining inappetence salivation hiding sample size: 32 dogs started the study, but only 18 dogs could be used for the thunderstorm anxiety score analysis, and only 19 dogs could be used to answer the overall effectiveness of the anxiety wrap analysis. further details. 32 dogs started the study. this reduced to 26 at the end of the baseline phase. this reduced to 21 dogs by the end of the experimental phase, but not all these provided enough material to be used in all analyses. drop-outs were defined based upon completed surveys at the end of each stage. no explanation is given for the drop outs at the end of the baseline phase. of the five owners who did not complete the survey at the end of the experimental phase, the reasons were as follows (one dog per reason): risk of aggression during fitting vest, medical illness, no reason, failed to return form, and vest the wrong size. of the 21 remaining dogs, three failed to complete surveys for five thunderstorm episodes during the experimental phase (reduced to 18 for the related analysis). for the overall effectiveness score, owners of dogs that had experienced three or more thunderstorms while wearing the anxiety wrap were eligible to be included. this reduced the sample from 21 to 20. a further owner failed to provide an overall effectiveness score, reducing the sample for this section to 19.   intervention details: the intervention evaluated for efficacy at reducing anxiety during thunderstorms was the commercially available anxiety wrap (animals plus llc, huntington, in), and animals were used as their own control in a before treatment/during treatment clinical trial. study design: the clinical trial was divided into two phases: baseline phase (control/no treatment during two thunderstorms) treatment phase (experimental phase/pressure vest worn during five thunderstorms) owners completed a questionnaire after each thunderstorm, that asked the owner to provide the following information: the existence and severity of specific anxiety behaviours (except escape/damage) listed in the inclusion criteria. interactions with their dog during the thunderstorm severity of the thunderstorm owners of dogs included were requested to discontinue (for the duration of the study) any other treatments they currently used for the treatment or management of thunderstorm fear. post-trial: owners were asked to complete a survey that assessed how effective they felt the anxiety wrap was at reducing their dog’s thunderstorm phobia. further information: sample selection: the first 32 dogs whose owners responded to the newsletter advert and who met the inclusion criteria were included in this study. exposure to the anxiety wrap: owners were provided with an anxiety wrap given directions on how to fit and remove it and instructed to fit it during thunderstorms. they were also asked to practice fitting it once before a thunderstorm (and to associate its fitting with a reward for the dog) and three times during non-stormy days (to prevent the dog associating the vest with thunderstorms). study design: clinical trial outcome studied: the main three outcome measures relevant to answering this pico were: thunderstorm anxiety score presence (yes/no) of the nine individual anxiety behaviours exhibited by the dogs during thunderstorms. owner’s subjective assessment of the overall effectiveness of the anxiety wrap at reducing anxiety during thunderstorms (scored as: 0%, 1 – 24%, 25 – 49%, 50 – 74%, 75 – 100% effective). the thunderstorm anxiety score was generated from the nine inclusion criteria behavior (except escape/damage). for each storm, owners had to report whether the dog showed the specific behavior (yes / no?). if yes, the owner was asked additional question(s) about the intensity/frequency/duration of the behavior (varied according to behavior). this was done to assess anxiety severity and a score (maximum 5 per behavior, 45 if all behaviours exhibited at maximum severity) awarded. as not all dogs showed all behaviours, the authors converted the resultant score into a ratio based upon the number of points awarded for behavior severity, divided by the maximum number of points it could have obtained given the behaviours shown: i.e. the actual score divided by (5 multiplied by the number of behaviours for which the owner answered “yes” the dog displayed this behavior during the thunderstorm) = the standardised ratio score. thunderstorm severity was also analysed to look for interactions between thunderstorm anxiety score and thunderstorm severity (e.g. do dogs show more severe levels of thunderstorm anxiety score when thunderstorms are particularly bad?) main findings (relevant to pico question): thunderstorm anxiety score: no significant differences were found between baseline thunderstorm 1 and 2 there was no significant effect of thunderstorm severity on baseline thunderstorm anxiety score. a significant difference (f5,102 = 3.99, p = 0.002) was found between the mean baseline thunderstorm anxiety score and the thunderstorms during which an anxiety wrap was worn (experimental thunderstorm anxiety score). post-hoc testing indicated that the treatment thunderstorm anxiety score was significantly lower than the baseline thunderstorm anxiety score for thunderstorms 4 and 5 (both p = 0.003). however, numerically, the mean ratio treatment thunderstorm anxiety score was lower than the baseline thunderstorm anxiety score for all five thunderstorms.   individual anxiety signs: baseline thunderstorm 1 versus treatment thunderstorm 5 (treatment phase): no significant differences were observed in the presence of any of the nine anxiety signs. there was a tendency for shaking (p = 0.08) , pacing (p = 0.07) and salivation (p = 0.07) to be different, but the authors do not report the direction of the effect. baseline thunderstorm 2 versus treatment thunderstorm 5 (treatment phase): the percentage of dogs that exhibited shaking (p = 0.03) and pacing (p = 0.03) behaviour during the thunderstorm was 33% lower in thunderstorm 5. no other behaviours showed a significant difference or a tendency to be different. the authors did not compare behaviours between baseline and treatment thunderstorms 1 – 4. overall effectiveness: significantly more owners (n = 17) rated the anxiety wrap as effective, than those who said it was not effective (n = 2) (χ2= 11.842, p = 0.001). the overall level of effectiveness at reducing thunderstorm anxiety reported by the owners who used the anxiety wrap on three or more thunderstorms was: 1 – 24% effective: n = 2 25 – 49% effective: n = 3 50 – 74% effective: n = 7 75 – 100% effective: n = 5 eighty percent of owners said they would continue to use the anxiety wrap now the study had finished. limitations: the study was supported financially by the manufacturers of the anxiety wrap. the owners were directed to fit the vest in accordance with the manufacturer’s directions but no attempt was made to quantify what level of pressure this exerted or to ensure this was standardised between dogs. there was a high drop-out rate plus additional individuals that, while not classified as a drop-out, nevertheless failed to provide enough information to be included in at least one of the analyses. if this was influenced by perceived product efficacy, then it will have introduced bias into the data set. the study relied entirely on owner reporting of clinical signs. owners not blinded to treatment. high risk of placebo effect/bias. the authors rely heavily on the results of thunderstorm anxiety score. this is an un-validated method for assessing canine anxiety during a thunderstorm. the analysis and reporting of the individual behaviours could be improved. it is not clear why the authors chose to analyse each baseline measurement separately (instead of the mean of both), but this meant that 18 tests needed to be performed. no allowance has been made for this statistically (e.g. by applying a bonferroni correction). the authors report that for the two behaviours that were significantly reduced between baseline 2 and treatment thunderstorm 5, that there was a 33% reduction in owners reporting each of these two behaviours, but it is not clear how much of a reduction this represents in numerical terms (i.e. how many owners/dogs stopped seeing these signs?). some of the discussion does not match up with the tables that the text signposts the reader towards. king (2014) population: anxious juvenile and adult (i.e. > 6 months) pet dogs with no other health problems. to qualify as “anxious” dogs needed to be diagnosed by a veterinarian or animal behaviourist as having one of the following conditions: separation anxiety (sa) generalised anxiety condition (gac) no breed restrictions were in place and the dogs used were a variety of sizes and breeds or crossbreeds. some dogs were on anti-anxiety medications at the time of the study. sample size: total number of dogs used: 90 (sa: n = 50; gac: n = 40), with 30 dogs per treatment group. intervention details: the intervention that was evaluated for efficacy was the thundershirt® (a commercially available pressure vest). dogs were randomly allocated to one of three treatment groups (all n = 30): control group (no pressure vest worn) snug fit vest (pressure vest worn and fitted snugly, as per the manufacturer’s instructions) loose fit vest (pressure vest worn and fitted very loosely so that it exerted no pressure) all dogs also wore a heart rate monitor strapped over their chest. experimental design: dogs were fitted with the equipment (heart rate monitor ± the pressure vest) a 1-minute baseline heart rate was recorded the dog was put into a walk-in kennel (1.2m x 3m) and kept in this kennel for 15 minutes while the dog was in the kennel their behaviour was video recorded for later analysis immediately after putting the dog into the kennel, owner and experimenter left the room and monitored the dog’s response remotely each dog was tested individually and the kennel cleaned before the next dog was tested. the outcome measures studied (heart rate and behaviour) are detailed below. heart rate was measured non – invasively and remotely using a heart rate monitor. behaviour was video recorded and each video watched independently by two researchers. the researchers were not blinded to the treatment received. observations recorded by each were assessed for inter-observer agreement and correlations between the behaviour assessments were good for most parameters (raverage = 0.99) (exception: licking, r = 0.64). study design: randomised controlled trial outcome studied: heart rate (average heart rate and maximum heart rate) baseline (before entering kennel) experimental (during the 15 minutes housed in kennel) behavioural signs of anxiety (pacing, panting, yawning, tongue-flicking, drooling, elimination, barking, stress-whining, howling, licking, orientation towards door) or non-anxiety (calm presentation) main findings (relevant to pico question): average heart rate: there was a significant interaction (f2, 1618.93 = 8.53, p < 0.01) between time (change in hr between baseline measurement and hr averaged over the 15-minute period of kenneling) and treatment group. post-hoc, pairwise comparisons indicated that the change in hr over time of snug fit vest dogs differed from both control groups (p = 0.022) and loose fit vest dogs (p = 0.001). snug fit dogs showed a decrease in hr over time; the other two groups showed an increase in average heart rate. removal of the dogs on anxiety medication (new treatment group sample sizes: control: n =27; snug fit: n = 21; loose fit: n = 25), and re-analysis of the remaining data found the same direction of effect, with snug fit dogs differing from both control dogs (p < 0.001) and loose fit dogs (p < 0.001). maximum heart rate: significant differences in increase in maximum heart rate (from baseline) were found between groups (f2,86= 4.51, p = 0.01). post-hoc testing indicated that snug fit dogs had a lower maximum heart rate increase than loose fit dogs (p = 0.02); but neither experimental group differed significantly from control dogs. the author’s report removal of the dogs on anxiety medication (numbers removed from each group: control: n =3; snug fit: n = 9; loose fit: n = 5), and re-analysis of the remaining data but they then describe this data in terms of average heart rate (despite starting off describing the analysis in terms of maximum heart rate). therefore, it is not clear what they are reporting here (average or maximum) and so it is not reported here. behavioural signs of anxiety: the only behavioural parameter that was significantly different (p = 0.02) between groups was orientation towards the kennel door. ninety percent of control dogs orientated towards the door, whereas only 53% of snug fit vest dogs and 67% of loose fit vest dogs did. the authors report that the dogs in the snug fit vest group showed a statistical tendency to show less yawning and tongue flicking compared to the other two treatment groups but the statistical handling of this data is problematic (see limitations). limitations: the authors report a statistical tendency for dogs in the snug fit vest group to show less yawning and tongue flicking. however, this claim is based upon a kruskal wallis test which indicates that a significant difference exists between the medians of at one least of the treatment pairs (but not one(s)). the authors do not undertake post-hoc testing. despite reporting, this behavioural data was often highly skewed, they present this data using means and standard deviations which conceals the true spread of values. the owners were directed to fit the vest in accordance with the manufacturer’s directions (snug fit dogs only) but no attempt was made to quantify what level of pressure this exerted or to ensure this was standardised between dogs. two types of anxiety condition were accepted under the inclusion criteria, but no attempt was made to undertake a randomised block design in which each condition was equally/near equally distributed across the three treatment conditions. observers were not blinded to treatment. dogs were not habituated to vest wearing before the study. the baseline heart rate measurement was recorded after the pressure vest was fitted, and both loose and snug fit groups had a mean baseline heart rate that was numerically higher (the authors do not report analysing baseline group differences) than the control group, suggesting that the vest was initially anxiety-inducing. pekkin (2016) population: finnish-based adult dogs (various breeds, both genders and either neuter status) known to usually (60 – 100% of occasions) react fearfully to fireworks. firework fear was assessed using a validated questionnaire (tiira & lohi, 2014) that had a good test-retest reliability when assessing noise-related fears. the questionnaire was completed by the dogs’ owners. the questionnaire provided the authors with a measure of the dogs’ noise reactivity, noise fear frequency, and general fearfulness. exclusion criteria: fear towards strange people or situations, bitches in season, dogs using regular medication (other than non-steroid anti-inflammatories). sample size: 28 dogs were recruited to the study. a full set of data was not collected for each dog. for the oxytocin analysis, two urine samples were obtained from 24 of the dogs. for the cortisol analysis, four saliva samples were obtained from 20 dogs. for the behavioural analysis, 25 dogs participated in all tests. intervention details: the intervention that was evaluated for efficacy was the lymed animaltm supporting garments (a commercially available pressure vest). there were three treatment groups, with each dog planned to experience each of the treatments. the three treatment groups were: control (no pressure vest fitted) light pressure (pressure vest fitted lightly, exerting a pressure on the dog of approximately 2 – 3mmhg) deep pressure (pressure vest fitted firmly, as per the manufacturers’ recommendations, and exerting a pressure on the dog of approximately 10 – 12mmhg) dogs were semi-randomly allocated (balanced for gender) to one of three groups, with each group experiencing the three treatments in a different order. the study was divided into three main sections: urine sampling (to measure oxytocin), vest fitting, and experimental enclosure habituation three episodes (one per treatment) of exposure to noise in the experimental enclosure, behavioural data collection, and saliva sampling (to measure cortisol) post-study owner self-reporting of deep pressure vest efficacy in the home environment further details of each phase are below: first section: the dog (and owner) are given 30 minutes to habituate to the experimental room before a urine sample is taken. a pressure vest is then fitted, and a 30-minute habituation period allowed before a second urine sample is taken. the vest is then removed. second section: this section is repeated three times (one per treatment), a minimum of one week apart. a saliva sample is taken and then the dog has a vest is fitted / handled as if one was being fitted (dependent upon treatment phase). the dog and owner (separated from dog) then wait in the test arena for 20 minutes before a second saliva sample is taken. video recording then commences (no experimenter present) for six minutes to identify the dog’s behavior under the following conditions: first 2mins: no noise. 2 – 4 mins: fireworks noise (track from sounds scary cd, sound therapy for dogs, 4 pets, uk) played at 70 – 73db. 4 – 6 mins: no noise. third and fourth saliva samples are taken after a further 18 and 38 minutes respectively. a person that was blind to both the study aims and treatment then watched the videos and recorded the dogs’ behaviour using the ethogram provided (see outcome measures). third section: the owner was sent two follow up questionnaires (one two months after the study finished, one just after new year’s eve) that asked about vest use and perceived efficacy generally or specifically on new year’s eve. study design: randomised controlled trial outcome studied: the outcome measures studied that were relevant to addressing the pico included: physiological: urinary oxytocin levels saliva cortisol levels behavioural: body positions lying sitting standing motor activity – fence manipulation tail position location location in arena (divided into grids) location in relation to a table (under table? yes / no) vocalisation oral behaviours lick nose or lips pant other – trembling owner self – reporting (survey data): did the owners use the vest during daily life? did the owners use the vest on their dog on new year’s eve? did they think it was useful for their dog? main findings (relevant to pico question): selected findings (directly relevant to the pico): physiological: oxytocin: there was no significant effect of wearing a deep pressure vest on urinary oxytocin levels. cortisol: there was no significant effect of treatment on saliva cortisol levels. however, saliva cortisol levels were significantly higher 20 minutes after the fireworks cd finished playing (cortisol sample 3), than immediately before the noise test (cortisol sample 2), or after a 40-minute recovery period (cortisol sample 4). behavioural: dogs spent less time lying down during the two-minute period during which the fire work noise was being played when they were wearing the deep pressure vest, compared to when they were wearing no vest (control) (p < 0.03). the median (interquartile range) seconds spent lying down was: deep pressure: 0.0 (66.9); light pressure: 12.7 (110.1); control: 39.0 (209.0). there was a positive correlation between duration of time spent lying down and general fearfulness (p < 0.05) and noise fear frequency (p < 0.05). no other behavioural treatment effects were identified (p > 0.05). owner reports: of the 28 owners who completed the first post-study survey, 17 had used the pressure vest at home. of these, 14 reported that its use had mainly positive effects, and three were neutral. of the 26 owners who completed the second post-study survey (regarding its use on new year’s eve), 20 dogs had worn the vest on new year’s eve. of these, 16 reported positive effects, and four were neutral about its use. limitations: authors report semi-randomly allocating dogs to the order of treatment, but do not report what they mean by ‘semi’ or how this was achieved. only 25 dogs took part in all three treatments. however, the authors report using all 28 dogs in the analysis. this may have introduced bias into the study. they fail to report in sufficient detail which dogs dropped out, at what stage, and which treatment(s) they had completed (i.e. were included in the statistical analysis) and which they hadn’t. behavioural outcome measures were often proxy measures that do not necessarily measure anxiety. exposure to the firework stimulus acted as a very short acute stimulus and may not represent the normal conditions under which a dog is exposed to noise stressors like fireworks. the study reports that the observer was blinded to treatments but it is not clear how that blinding was achieved (e.g. were the vest images pixelated? did the authors mean blinded to when the audio-recording was being played?). the study was supported financially by the manufacturer of the pressure vest used in the study. fish (2017) population: adult, male and female field-trial-bred labrador retrievers purchased by a military training facility and kennel housed at the research facility that carried out this study. dogs had been used in previous studies, including one using telemetry vests and one utilizing the open-field test (oft). sample size: 16 dogs (8 per treatment group) intervention details: the intervention was the wearing of a telemetry vest during testing within the oft. two treatment groups: vest (n = 8) no vest (n = 8) each dog was given three ofts, held on three consecutive days, and each of nine minutes duration. during tests one and three, dogs were exposed to no auditory stimuli while in the oft area. during test two, dogs were exposed to a thunderstorm audio recording during the middle three minutes of the nine-minute test. dogs were filmed during the oft for later anxiety scoring using one partially-blinded, trained observer (blind to thunderstorm stimulus occurrence, not blind to vest wearing). immediately prior to each oft, a telemetry vest was fitted to each dog, and the dog’s heart rate and temperature were then manually recorded. the vest was then left on (vest dogs) or removed (no vest dogs) for the oft. immediately after the oft, the dog’s heart rate and temperature were manually recorded again.  further detail: the spandex vest was standardised for pressure by fitting the vest to each dog tight enough to only allow two fingers to be inserted under the vest. dogs were allocated to treatment group using a randomised match-pairs design. they were pair ranked (lowest to highest value) according to their global anxiety score (obtained in a previous study, gruen et al. 2015), and then the first of each pair member randomly allocated to either the vest or no vest group, and the remaining pair member allocated to the alternative group. study design: randomised controlled trial outcome studied: outcomes relevant to addressing the pico included: physiological data: heart rate (beats per minute, bpm) rectal temperature (centigrade, ëšc) were recorded immediately after fitting the vest (both treatment groups, just before entering the oft arena) and immediately after the nine-minute oft. behavioural data: mean anxiety score during each three-minute period of the oft. anxiety assessment was subjective and based on a subjective qualitative ordinal scale (1 – 6, 1 = no anxiety behaviours observed, 6 = severe anxiety observed most of the time). dogs were initially scored separately for negative/passive anxiety (e.g. freezing, hiding, etc) and positive/active anxiety (e.g. escape attempts, bolting, etc). the mean of these two scores was used in the analysis. main findings (relevant to pico question): findings relevant to the pico: physiological data: heart rate: on oft days (pooled data from the three days), vest dogs had significantly (f = 11.7, p = 0.0009) lower heart rates than no vest dogs. the mean (standard error of the mean, s.e.m.) was: vest dogs: 95.5 (± 1.5 bpm); no vest dogs: 103.9 (± 2.0 bpm). rectal temperature: on oft days (pooled data), mean rectal temperature did not differ between vest dogs and no vest dogs. the mean (s.e.m.) temperature was: vest dogs: 39.1 (±1ëšc); no vest dogs: 39.0 (± 0.2ëšc). behavioural data: mean anxiety score: on oft days (pooled data), the mas of vest dogs was significantly (f = 0.241.3, p = 0.0031) lower than no vest dogs. the overall (mean, ±e.m.) mas was: vest dogs: 1.9 ± 0.4; no vest dogs: 2.9 ± 0.4 (t = 1.80, p = 0.0471). there was a statistically significant (no test statistic reported, p < 0.05) difference between vest and no vest dogs in terms of the change in mas between the pre-phase and the during-phase of day 2. vest dogs had a 40% lower mas during the thunderstorm stimulus than no vest dogs.   limitations: the most severe limitation is the reporting that heart rate was higher in no vest dogs, but the pre-oft heart rate was taken while both vest and no vest dogs were wearing the vest (i.e. dogs were being treated identically at this point). the authors do not report accounting for this issue in their data handling (e.g. by only using post oft heart rate data). pairwise comparisons were performed using a one-tailed student t-test. the authors report adopting this approach because of their directional hypothesis, but it is possible that vest wearing could have had the opposite effect and this would also be clinically relevant to the study’s aim. the analysis and reporting would have been more robust if a two-tailed approach had been taken. if it had been adopted, the overall mean mas would not have been significant as the p value would have been p = 0.0942. some data reporting is not precise enough to allow the reader to determine how the data was handled/being reported. for example, what does “overall” mas mean? how was it determined? the authors report using data pooled from the three days for some of the statistical analyses, but they do not report how this data was pooled or the rationale for this. it was a very small sample size (n = 8 per treatment) and the authors do not report using a power calculation to determine the appropriate sample size. the population of dogs studied was not like the pet dog demographic that pressure vests might be recommended for. these were not pet dogs raised and living in a pet environment. only one breed of dog was used in the study. dogs were not selected for the study based on known anxiety/fear towards thunderstorms (the stressor applied) or exceeding a more general threshold for anxiety. these were not particularly anxious dogs. the global anxiety score (gas) ranged from 1 – 6. the mean (s.e.m.) gas was: vest dogs: 1.16 (±30); no vest dogs: 1.36 (± 0.33). it is not clear how the authors obtained baseline gas scores (used for treatment allocation) of < 1.0, as these were obtained from a previous study (gruen, et al. 2015) that assessed anxiety levels using the same ordinal scale reported in the current study (with values ranging from 1 – 6). the purpose of this study was not specifically to look at the role of pressure vests in reducing anxiety in dogs. observers were only partially blinded to which treatment the dogs were receiving. they could not hear the auditory stimuli but could see which dogs were wearing vests. appraisal, application and reflection in terms of external relevance, of the studies that were included, three of the papers (cottam et al., 2013; pekkin et al., 2016; fish et al., 2017) used noise stressors (thunderstorm, firework or thunderstorm sound recordings respectively) to induce an anxiety or fear response. the stressors have external relevance as thunderstorms, fireworks and separation-related stress are all stressors that clients will frequently approach veterinary professionals to seek assistance with the management or treatment of their dog’s negative response towards. however, whilst the cottam et al. (2013) study used field data based on known thunderstorm-fearful dogs’ responses to actual thunderstorms whilst in their home environment, the other studies used study designs that may have reduced the applicability of the study findings in a real-life scenario. the three studies investigating commercially available pressure vests all selected pet dogs drawn from a population of dogs known to be fearful or anxious of either the sound stressor used in the study (cottam et al., 2013; pekkin et al., 2016) or of having separation anxiety or a generalised anxiety disorder relevant to triggering anxiety under the isolation kennel facilities (king et al., 2014). thus, applicability to client-owned dogs is likely to be good from this perspective. the fish et al. (2017) study was more problematic in this respect. these were kennelled dogs, drawn from military working dogs and housed under research conditions. although the dogs were scored using a global anxiety score (scores carried over from a previous study, gruen et al., 2015) this was undertaken to allocate dogs evenly across treatment groups, and being anxious (either specifically in response to thunderstorms or more generally) was not part of any inclusion criteria. although dogs per se will clearly all experience fear and anxiety at some point (and the data in this study indicates that these dogs did show an increase in their anxiety score during testing compared with the mean global anxiety score), clients seeking assistance or advice may be disproportionately drawn from dogs known to be fearful or anxious (or, more severely so) in the presence of a given stressor. thus, the dogs studied in this study may differ from those we wish to apply any findings too and this should be borne in mind. in terms of internal validity, each of the studies had its merits and limitations. the cottam et al. (2013) study was a field-based, clearly client-relevant, commercially funded study that relied heavily on owner reporting of behaviour. the authors reported that the use of a pressure vest, compared with baseline measurements, was associated with a numerical reduction on the anxiety scores during all thunderstorms in the treatment phase. however, only during treatment thunderstorms 4 and 5, was the mean anxiety score sufficiently lower than the baseline anxiety score for any potential difference to be significant. this downward trend in anxiety scores may suggest that there may be an element of associative learning to any therapeutic effect of pressure vest use. owners reported a variable level of efficacy, but most owners felt that the vest had some positive effect on their dog’s thunderstorm fear. however, the owners were not blinded to treatment, and thus there is a high risk of placebo effect or bias being present in the reporting of these results. however, with a cautionary note that the thunderstorm anxiety score is an un-validated method for quantifying thunderstorm anxiety severity, this study does provide some limited evidence of a beneficial effect of pressure vests on dog anxiety during thunderstorms.  the king et al. (2014) paper used a positive control (loose fitting vest) as well as a traditional control group that allowed the authors to identify whether any apparent benefit of wearing a pressure vest was due to simply wearing an item of clothing (e.g. dogs associated it with going for a pleasant walk) or genuinely an effect of pressure exerted on the dog’s torso. the strongest finding in this study was the demonstration that dogs in the snug fit vest group showed a decrease in heart rate between the baseline (pre-kennel/isolation) and the average heart rate of the dog when in the kennel for 15 minutes. this contrasted with both other treatment groups which demonstrated the converse. the behavioural data also demonstrated that snug fit dogs spent less time orientating towards the door (53% of dogs, as compared to 67% of loose fit dogs, and 90% of control dogs). this is more problematic to interpret as this would suggest that wearing a vest per se reduced door orientation behaviour. these dogs were not habituated to pressure vest wearing at the start of the study and the authors do not report information regarding the dogs’ prior coat-wearing history so it is difficult to assess the likelihood of this alternative interpretation. the authors report a statistical tendency for snug fit dogs to show less yawning and tongue flicking but their statistical handling and reporting of this data made it more problematic to draw conclusions from the behavioural output. they report the data was highly skewed and use a non-parametric test to undertake inferential testing but then report the data using the mean (± standard deviation) which makes independent interpretation of the data problematic. however, the study does provide some evidence that a pressure vest can reduce a physiological measure of arousal during short term isolation from the owner/confinement to an unfamiliar area. also commercially funded, the pekkin et al. (2016) study found very little evidence of pressure vests having a beneficial effect in their main study (though the owners, when surveyed, subsequently reported a positive effect under field conditions). no physiological parameters (oxytocin, cortisol) were affected by wearing a pressure vest (either fitted loosely or firmly), but the cortisol levels increased post-audio stressor across all treatment groups, suggesting that the dogs did find the audio-stressor stressful. however, when the dogs were wearing a firmly fitted vest they spent less time laying down during the audio-stressor than under either other treatment condition, and laying down behaviour was (independent of treatment) shown to be positively correlated with fear. this might indicate that, when wearing a firmly fitted vest, dogs felt less fearful during the audio recording of fireworks. however, it cannot be discounted that lying down in a tight-fitting vest is less comfortable than when wearing a vest loosely or no vest at all. no other behaviour parameters were affected by treatment. the weakest part of this study was the owner survey which was very sensitive to bias and the placebo effect. however, the main study may provide some very limited evidence that firmly fitted pressure vests may have a positive impact on one behavioural sign of canine anxiety, but this would be more convincing if more of the outcome variables were affected by a firmly fitted pressure vest and more research is needed here.   the fish et al. (2017) study reported that the use of a telemetry vest resulted in a lower heart rate, lower anxiety scores during the open field tests and reduced increase in anxiety score during the audio recording of thunder, compared with dogs not wearing a vest. however, a small sample size (n= 8 per group) and methodological issues reduce the reliability of these findings (particularly, the significant difference in heart rates between treatment groups). further research, using a large sample size (determined using a power calculation) would be beneficial here.    in conclusion, four studies of variable quality and limitations were identified that investigated the use of pressure vests, using various physiological and behavioural proxy measures of anxiety. most behavioural outcome measures associated with a positive effect were subjective assessments, with unblinded assessors. differences between study designs, stressors and outcome measures used, and what parameters were affected by pressure vest wearing make it difficult to meaningfully triangulate findings and draw firmer conclusions. the take home message for the veterinary professional is that pressure vests may have small but beneficial effects on canine anxiety and that habituating the dog to the vest, assessing for comfort and using repeatedly may improve the likelihood of any benefit. however, the owner should be cautioned that they should not expect their dog’s anxiety to be fully alleviated or prevented, and it may have no beneficial effect at all.  methodology section search strategy databases searched and dates covered: pubmed (1900 – 14/09/2017); science direct (1901 – 14/09/2017); cab abstracts (1973 – 2017, week 35) search terms: pubmed: (dog or dogs or canine or bitch or bitches or canid or puppy or puppies) and (vest or shirt or jacket or coat or wrap or cape) and (anxiety or anxious or fear or fearful or stress or stressed or stressful or panic or phobi*) science direct: restricted to: <advanced search><journals only><title-abstr-key> (dog or dogs or canine or bitch or bitches or canid or puppy or puppies) and (vest or shirt or jacket or coat or wrap or cape) and (anxiety or anxious or fear or fearful or stress or stressed or stressful or panic or phobi*) cab abstracts: 1 (dog or dogs or canine or bitch or bitches or canid or puppy or puppies).mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (195323) 2 (vest or shirt or jacket or coat or wrap or cape).mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (40414) 3 (anxiety or anxious or fear or fearful or stress or stressed or stressful or panic or phobi*).mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (311937) 4 1 and 2 and 3 (36) dates searches performed: pubmed: 14/09/2017; science direct: 14/09/2017; cab abstracts: 11/09/2017 exclusion / inclusion criteria exclusion: pre-defined exclusion criteria: non-english language, popular press articles, conference abstracts inclusion: any comparative (control group utilised) study in which the effect of pressure vests on anxiety (or similar) in dogs was studied. search outcome database number of results excluded – did not answer pico question excluded – not english language excluded – conference abstract only excluded – duplicates total relevant papers pubmed 41 40 0 0 1 1 science direct 35 32 0 0 0 3 cab abstracts 36 30 0 1 5 0 total relevant papers when duplicates removed 4 conflict of interest the author declares no conflicts of interest. references cottam, n, dodman, n. h. 2009. comparison of the effectiveness of a purported anti-static cape (the storm defender®) vs. a placebo cape in the treatment of canine thunderstorm phobia as assessed by owners’ reports. applied animal behaviour science 119: 78 – 84 doi: https://doi.org/10.1016/j.applanim.2009.03.014 cottam, n., dodman, n. h., ha, j. c. 2013. the effectiveness of the anxiety wrap in the treatment of canine thunderstorm phobia: an open – label trial. journal of veterinary behaviour 8: 154 – 161 doi: http://dx.doi.org/10.1016/j.jveb.2012.09.001 fish, r.e., foster, m. l., gruen, m.e., et al. effect of wearing a telemetry jacket on behavioral and physiologic parameters of dogs in the open – field test. journal of the american association for laboratory animal science 56: 382 – 389 gruen, m. e., case, b. c., foster, m. l., et al. the use of an open field model to assess sound-induced fear and anxiety-associated behaviours in labrador retrievers. journal of veterinary behavior 10: 338 – 345 doi: 10.1016/j.jveb.2015.03.007 king, c., buffington l., smith, t. j., et al. the effect of a pressure wrap (thundershirt®) on heart rate and behavior in canines diagnosed with anxiety disorder. journal of veterinary behaviour 9: 215 – 221 doi: https://doi.org/10.1016/j.jveb.2014.06.007 pekkin, a., hänninen, l., tiira, k. et al. the effect of a pressure vest on the behavior, salivary cortisol and urine oxytocin of noise phobic dogs in a controlled test. applied animal behaviour science 185: 86 – 94 doi: https://doi.org/10.1016/j.applanim.2016.09.003 tiira, k., lohi, h., 2014. reliability and validity of a questionnaire survey in canine anxiety research. applied animal behaviour science155: 82 – 92: http://dx.doi.org/10.1016/j.applanim.2014.03.007 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. investigating the use of gastroprotectants as a means of preventing iatrogenic gastrointestinal signs associated with immunosuppressive corticosteroid therapy. a retrospective study adam swallow bvsc, mrcvs1* 1university of cambridge, the old schools, trinity ln, cambridge, cb2 1tn * (adamswallow26@gmail.com) vol 2, issue 3 (2017) published: 20 sep 2017 doi: 10.18849/ve.v2i3.150 background: gastroprotectants are commonly prescribed in patients receiving immunosuppressive therapy with glucocorticoids. presently, there is limited evidence to support such use of gastroprotectants. gastroprotectants are commonly prescribed in patients receiving immunosuppressive therapy with glucocorticoids. presently, there is limited evidence to support such use of gastroprotectants. the objective of this study was to establish if the prophylactic use of gastroprotectants was associated with a reduced incidence of gastrointestinal signs in dogs receiving immunosuppressive doses of glucocorticoids, compared to not receiving prophylactic gastroprotectants. find out more about adam. comments: in dogs with a european adder bite, does the use of antivenom with supportive treatment compared to supportive treatment alone improve time to recovery? a knowledge summary by lindsay hodgson bvsc 5 1* giorgia brambilla bvsc 5 1 1university of bristol, senate house, tyndall ave, bristol bs8 1th *corresponding author (lh12819.2012@my.bristol.ac.uk) vol 2, issue 4 (2017) published: 06 nov 2017 reviewed by: jackie belle (rvn, certsan, certfn, certvnes, dipcabt, dipesm, dip, br, dipendv, ptlls, bsc, msc) kit sturgess (ma, vetmb, phd, certvr, dsam, certvc, mrcvs) and nicola bates (bsc msc ma) next review date: 06 nov 2019 doi: 10.18849/ve.v2i4.114 clinical bottom line the current literature does not offer convincing evidence for the positive effect of antivenom on time to recovery in dogs envenomated by the european adder. it appears that the use of antivenom in addition to supportive treatment may positively affect local swelling if given within 24 hours of the bite, but the evidence is low quality and further studies are required before a more definitive answer can be reached. question in [dogs with european adder bites] does the use of [antivenom and supportive treatment] compared to [supportive treatment only] [improve time to recovery]? clinical scenario a dog has been brought into your practice with a suspected european adder bite. you do not stock antivenom in the practice and you are aware that it can be difficult to access a source. you wish to know if there is any evidence that giving antivenom will improve the dog’s recovery time, compared to supportive treatment alone. the evidence the quality of the evidence available to answer the pico question is limited by the lack of studies directly comparing the addition of antivenom to  supportive treatment alone. at the time of writing no studies were found for the use of antivenom to treat european adder envenomation of dogs with time to recovery used as an outcome. current studies are limited by bias; the decision to use antivenom is often made on severity of clinical signs, so that only the most severely affected dogs receive it different sized dogs will also be affected with varying degrees of severity, with some dogs presenting asymptomatically. in addition, different amounts of venom may be injected with some bites injecting no venom (sutton et al, 2011) so every dog is not subjected to the same amount of venom. these limitations influence the conclusions that can be drawn about the effect of antivenom on time to recovery. in conclusion, a convincing body of evidence to influence the clinician’s decision whether or not to use antivenom in the dog, in addition to supportive treatment, does not currently exist. other considerations include difficulty in sourcing antivenom (sutton et al, 2011), so if clinicians decide its use is warranted, they should begin locating a source as soon as possible. adverse reactions to antivenom have also been reported and a study conducted on 54 dogs found that 7% of the patients developed at least one side effect after administration of f(ab)2 antivenom. the reactions reported in this paper included facial swelling unrelated to the snake bite, profound panting and non-productive cough (lund et al, 2013); anaphylaxis (turkovic et al, 2015)  has also been reported. at the time of writing, the authors were unable to find any reports of death in dogs directly caused by  antivenom administration and lund et al (2013) state that adverse effects appear to be “relatively mild and self-limiting”. as with any drug, the side effects should be considered as part of the decision making process about whether or not to use antivenom. summary of the evidence lund (2013) population: dogs presented with clinical signs consistent with european adder envenomation and treated with antivenom. dogs were included if either a snake or bite incident was witnessed by the owner or the clinician had identified wounds consistent with fang marks of the european adder. sample size: owner questionnaire for 54 dogs envenomated with the european adder and treated with antivenom blood and urine collected and analysed from 35 of the 54 dogs. this was compared to blood and urine collected from a control group of 16 dogs envenomated but not treated with antivenom. intervention details: administration of 1000 mg f(ab)2 antivenom following envenomation from the european adder. study design: case series outcome studied: questionnaire: part 1 = signalment (breed, gender, age, weight); bite information (date and time of day of the bite) and whether the owner witnessed the episode; description of dog’s reaction and clinical signs; administration of prednisolone by the owner prior to admission. part 2 = time from bite to admission; dog’s mental and physical status; clinical signs at admission; location of the bite; presence of fang marks; type/dosage/effect of treatment. part 3 = time from bite to administration of antivenom; dose and infusion rate of antivenom; heart rate at 5 minutes intervals following administration of antivenom; resolution of clinical signs and development of adverse effects (type, onset, duration). in case of adverse reactions type, dose and effect of treatment administered was recorded. part 4 = progression in mental and physical status and clinical signs 24 hours after admission, as well as follow up information at 1 and 2 weeks following admission. blood and urine analysis: samples were obtained on admission and at 1 and 2 weeks following treatment. samples were screened for serum globulin, albumin and urine protein levels. main findings (relevant to pico question): administration of antivenom resulted in a positive effect on mental status and local swelling in all dogs receiving antivenom within 24 hours of the bite occurring. 4/54 dogs (7%) developed acute adverse reactions to antivenom: o   2 dogs developed facial swelling o   1 dog developed non-productive cough o   1 dog developed sudden, profound panting dogs treated with antivenom had a lower percentage of proteinuria after 2 weeks compared to dogs not treated with antivenom (p = 0.03). no differences in serum albumin or globulin were observed between the 2 groups. 2/54 dogs treated with antivenom died: 1 due to multiple organ failure after 4 days 1 was euthanased after 5 days due to kidney failure limitations: decision to use antivenom was made by different vets on a subjective basis leading to a non-standardised intervention protocol. as a result, the group of dogs receiving antivenom could have been more severely affected compared to the control group of dogs. multiple observers throughout the study and no standardised method for assessment of mental status or local swelling were reported, leading to lack of objectivity in improvements seen with antivenom use. small sample size. study group and control group were not randomly allocated. control group was composed of animals that could not receive antivenom due to cost, lack of availability or deemed unnecessary by the clinician in charge. as a consequence, the control group may include dogs with less severe presentations. sutton (2011) population: dogs in the uk reported to the veterinary poisons information service (vpis) between september 1985 and december 2010, with european adder bites. questionnaires requesting details of clinical effects, onset and duration of effects, treatments given and clinical outcome are sent to around 55% of enquirers, and patient records were only included if this follow up was complete. sample size: 985 enquiries with follow up information from 422 cases and outcomes reported in 411 cases. intervention details: ivft used in 241 dogs (57.1 %). antivenom used in 236 dogs (55.9%). supportive treatment included: glucocorticoids used in 216 dogs. antibacterial agents used in 235 dogs. antihistamines used in 84 dogs. combinations of supportive treatments given to individual dogs were not reported. study design: case series outcome studied: age of dog, weight, sex, breed, month and time of bite and postcode of reporting practice. clinical signs reported, onset and duration of clinical signs. time to response to antivenom. duration of oedema. death. main findings (relevant to pico question): duration of oedema was reported as 46.8 hours in dogs that received antivenom (n=39) and 94.1 hours in those that did not receive antivenom (n=52)(significance unknown sutton et al acknowledge that more data is required to calculate significance due to the small number of cases where this outcome was reported). response to antivenom reported in 15 dogs; average response time was 74.3 minutes (range 20 minutes to four hours). method of assessment was not stated. death occurred in 7 dogs of 236 receiving antivenom (3%) (unknown if euthanased or died). death occurred in 9 dogs of 186 not receiving antivenom (4.8%) (unknown if euthanased or died). of the 189 vets that had completed the free comments area of the follow up questionnaire, 33 vets commented that antivenom gave a good clinical response, 18 vets commented that antivenom response time was quick, 11 vets commented that antivenom visibly improved oedema and one vet commented that improvement was faster than without antivenom. three vets noted that antivenom appeared to have no effect, two vets commented that antivenom made oedema worse and anaphylaxis was reported in one dog following antivenom administration. authors of study note that no studies exist on the use of antihistamines for envenomation. as venom causes local histamine release, this may be a future area to study. limitations: limited evidentiary value as retrospective review of records. no controls used. no information given regarding which dogs received which supportive treatments, so unknown which treatment had effect on clinical signs and time to recovery. outcomes were not reported in all dogs, reducing the sample size. duration of oedema reported in small number of cases (n=91). limited follow up information given and quality of response varied widely. no statistical analysis of results given, so unknown if outcomes are significant, although author notes that “antivenom administration did not appear to affect mortality”. not reported how duration of oedema or response to antivenom was assessed. doses of antivenom not reported, so unknown if same dose given to all dogs. information from the free comments area of the questionnaire is opinion. variations in time from envenomation to administration of antivenom may negatively impact effect of antivenom. turkovic (2015) population: dogs in germany bitten by the european adder, presented to the small animal clinic at ludwig-maximilians university, munich, between 1st january 2008 and 31st august 2014. sample size: 15 intervention details: figure 1: breakdown of treatment combinations given to dogs in the study by turkovic et al, 2015. ivft used in 15 dogs (crystalloids in all 15 adjusted to hydration status, three also received synthetic colloids). antivenom (zagreb european viper venom antiserum, 10ml iv) used in eight dogs. supportive treatment included: fresh frozen plasma (20ml/kg iv) used in five dogs due to coagulopathy. steroids (prednisolone, 1-2 mg/kg iv) used in ten dogs. antihistamines (diphenhydramine, 1-2mg/kg iv) used in 13 dogs. dopamine cri (5-10µg/kg/min) used in one dog (due to persistent hypotension & tachycardia). antibacterial drugs and analgesia used in all dogs. ranitidine (2mg/kg) used in two dogs. lmw heparin (100-150 iu sc q 12h) used in eight dogs.         study design: case series outcome studied: signalment, date and time of bite, time until presentation, presenting complaint, location of bite, duration of hospitalisation and outcome were studied (if recorded). heart rate, respiratory rate, body temperature, mucous membrane colour, capillary refill time, systolic blood pressure, local swelling, packed cell volume (pcv), serum biochemical parameters, electrolytes, platelet count, leukocyte count, blood glucose, activated partial thromboplastin time (aptt) and prothrombin time (pt) were studied (if recorded). main findings (relevant to pico question): antivenom administration did not have a significant positive clinical effect on local swelling in the 24 hours following envenomation. authors of study note that research into the effects of antihistamines and heparin for treating envenomation in dogs is of interest. no anaphylaxis was noted following administration of antivenom. limitations: individual patient parameters were not reported despite statistical analysis being carried out. data was incomplete and so correlations between treatments and individual changes could not be made or analysed. treatment and outcome monitoring protocols were not standardised making it difficult to compare effects. duration of hospitalisation was recorded for the dogs that did and did not receive antivenom but results were not analysed for significance. no controls were used and so it is not possible to demonstrate if antivenom affected outcome. small study size. method of measuring local swelling not stated. retrospective study of patient records so low evidentiary value. appraisal, application and reflection the literature search performed by the authors found three papers which partially addressed the pico question. the study by lund et al (2013) reports an improvement in local swelling and mental status in animals that received antivenom within 24 hours of the european adder bite. the group of dogs receiving antivenom also showed decreased proteinuria levels two weeks after the bite. these findings could be considered of interest when answering the pico question; the study, however, presents some significant limitations which affect the quality of the evidence produced. the dogs recruited for the study had not been randomly assigned to the antivenom or the control group. the choice to administer antivenom was based on the clinician’s subjective assessment of the severity of the clinical signs, the financial situation of the owner and the availability of antivenom. this could have led to the introduction of bias in patient selection. moreover, the study was not blinded and the subjective improvement noted by the clinicians in swelling and mental status of dogs receiving antivenom cannot be regarded as good quality evidence for the pico question. in the sutton et al (2011) study of cases reported to the vpis, it was found that in dogs receiving antivenom, oedema lasted an average of 46.8 hours, compared to dogs that did not receive antivenom, where oedema lasted an average of 94.1 hours. this was the most significant finding to the pico question in this paper but is limited by several factors. duration of generalised oedema was not reported in all dogs, decreasing the sample size, and objective method of oedema measurement was not given. statistical analysis of the findings was not reported, so it is not known if the findings are significant. death occurred in 3% of dogs receiving antivenom and 4.8% of dogs not receiving antivenom, which appears similar, but unfortunately no conclusions can be drawn due to the lack of statistical analysis. the study looked at broad risk factors for envenomation and mortality and the scope of treatment, rather than evaluating the effect of any individual treatment, and this was a common theme among the evidence found. turkovic et al (2015) found that antivenom administration did not significantly clinically affect local swelling 24 hours after envenomation, which appears to contrast to the finding from the lund paper (2013). this paper was another case series studying risk factors, treatments and outcomes, with a very small study size and data relevant to the pico question was incomplete. duration of hospitalisation was recorded for dogs receiving and not receiving antivenom but the results were unfortunately not analysed for significance. the use of heparin and antihistamines in treating envenomation were highlighted as future areas of research. the majority of the studies found by the authors examine risk factors for envenomation, adverse effects of antivenom administration and common treatment choices. furthermore, most studies were retrospective, considered envenomation by other species or studied the effects of other elements of the treatment regime, such as glucocorticoids. there is wide variation in the combinations of supportive treatment given in the literature; combinations of intravenous fluid therapy (ivft) with crystalloids, colloids or blood products, analgesia, antibacterial agents, glucocorticoids, antihistamines and heparin (sutton et al, 2011, turkovic et al, 2015 and lund et al, 2013). this lack of a standardised treatment protocol makes direct comparison of the effect of antivenom more difficult to assess. these variations affect the analysis of the impact of antivenom on time to recovery. the best study design to answer this pico question would directly compare the outcomes when the use of antivenom is the only variable imposed by the study authors.   the pico question could be best answered by a prospective, randomised, double-blinded controlled trial, comparing the effects of the addition of antivenom to supportive treatment alone. this could be considered as a research prospect; although a lack of antivenom licensed in dogs and the need to envenomate dogs would render such a study unlikely to pass ethics approval. the relatively small number of dogs envenomated each year in the uk could potentially render such a study financially unviable for antivenom manufacturers. objective judgement of the clinical effects of antivenom, such as reduction of oedema, also generates difficulties. as such, the proposed clinical trial using viperavet may be of interest in revisiting this clinical question in the future; although at the time of writing the study was postponed (vpis, 2017). methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform 1973 week 7 2017 thomson reuters web of science 1900-2017 pubmed (any date) search terms: dog* or cani* or bitch* or pup* ‘viper* berus’ or ‘european adder*’ or ‘european viper*’ or adder antiven* or antiser* or anti-ven* or anti-ser* 1 and 2 1 and 2 and 3 please note the terms “adder bite*” and “envenomation” were also included in the search strategy, but yielded fewer results than the terms used above and yielded no additional papers. dates searches performed: 23/03/2017 exclusion / inclusion criteria exclusion: reviews of available treatments expert opinion letters book chapters papers studying envenomation by species other than the european adder or envenomation of humans papers in a foreign language (that could not reasonably be translated) papers that could not be accessed by authors or library staff inclusion: studies regarding the use of antivenom for treatment of envenomation of dogs by the european adder, vipera berus. search outcome database number of results excluded – species other than the european adder excluded – did not meet pico question excluded – cannot access paper excluded – foreign language excluded – book chapter excluded – duplicate paper total relevant papers cab abstracts 18 3 6 0 5 1 0 3 web of science 32 2 17 2 0 0 11 0 pub med 13 0 2 0 0 0 11 0 total relevant papers when duplicates removed 3 conflict of interest the authors declare no conflicts of interest. the authors wish to thank clare boulton for her assistance with the literature search and emma place for her assistance with locating papers. references lund, h., kristiansen, v., eggertsdóttir, a. et al . (2013). adverse reactions to equine-derived f(ab’)2-antivenin in 54 dogs envenomated by vipera berus berus. journal of veterinary emergency and critical care. 23 (5), 532–537. 2013. 1111/vec.12099 sutton, n., bates, n. and campbell, a. (2011). canine adder bites in the uk: a retrospective study of cases reported to the veterinary poisons information service. veterinary record. 169 (23), 607. 2011. http://dx.doi.org/10.1136/vr.d4695 turkovic, v., teichmann, s. and doerfelt, r. (2015). european adder bites in dogs in southern germany. a retrospective study over a 6.5-year period. tieraerztliche praxis ausgabe kleintiere heimtiere . 43 (4), 221-230. 2015. https://doi.org/10.15654/tpk-140364 veterinary poisons information service. (2017). clinical trial for veterinary adder antivenom – invitation to take part. available: https://vpisglobal.com/adder-antivenom/ last accessed 26th july 2017. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. use of a reverse thermodynamic gel to manage chronic shedding in equine strangles mark bowen bvetmed mmedsci phd certva certem(intmed) dipacvim-laim pfhea frcvs1* 1oakham veterinary hospital, ashwell road, oakham le15 7qh *corresponding author (mark.bowen@nottingham.ac.uk) vol 2, issue 3 (2017) published: 24 jul 2017 reviewed by: tim mair (bvsc phd deim dests dipeceim assocecvdi mrcvs) kate mcgovern (bvetmed certem(int.med) ms dacvim dipeceim mrcvs) doi: 10.18849/ve.v2i3.109 strangles is a common condition in equine practice with high morbidity. management of outbreaks is complicated by the development of asymptomatic carriers with the causative organism (streptococcus equi var equi) being retained within the guttural pouch1,2. treatment of carriers relies upon removal of physical infection and locally administered antimicrobials. combinations of penicillin with gelatin has been recommended3 to prolong antimicrobial concentrations within the guttural pouch.. this involves the melting of gelatin, to allow mixing and infusion of the warm liquid. the horses head is raised for 20 minutes while the solution sets as it cools, preventing loss of solution. these steps are often difficult to achieve outside of a hospital environment. the availability of reverse thermodynamic agents, that are liquid when cool and solidify as they warm, have been used for local delivery of medicines when treating otitis externa in dogs. these create an opportunity to retain antibiotics in the guttural pouch without the complexity of melting gelatin in a field setting. benzylpenicillin in poloxamer gel was specially formulated at a concentration of 120mg/ml in a 25ml solution by a commercial specials manufacturer (bova uk). an asymptomatic strangles carrier was identified based on pcr detection of bacterial dna from a guttural pouch lavage. after sedation, a stainless steel uterine catheter (nielson catheter) was adapted by manually placing a 30 degree bend at the distal 3cm tip of the catheter and approximately a 10 degree curve along the distal 15cms of the catheter (figure 1). the catheter was placed along the ventral meatus with the tip angled ventrally. once the catheter was in the pharynx, the tip was rotated ventrally and abaxially as the catheter was advanced into the guttural pouch; location was confirmed endoscopically (figure 2). cooled, pre-formulated poloxamer gel was infused through the urinary catheter and the catheter immediately removed. the head was maintained in a neutral position and a small amount of gel that exited the pouch as the catheter was removed, remained adherent to the pharyngeal wall demonstrating that it had already partially set. endoscopic assessment of the guttural pouch immediately after the infusion demonstrated that the poloxamer gel had partially set within the floor of the medial compartment of the treated pouch (observed 4 minutes 25 seconds after infusion: figure 3). treatment was repeated on three consecutive days and cure was determined by three guttural pouch lavages taken at weekly intervals, starting one week after the last treatment. this confirms the value of locally infused antibiotics in the management of strangles carriers. the reverse thermodynamic poloxamer gel provided a practical method for retaining antibiotics within the pouch with the need for complex mixing or prolonged raising of the horses head. this will facilitate management of this frustrating condition in the field. administration through an endoscopic catheter is not recommended since the poloxamer gel partially solidifies within the biopsy channel due to the heat from the light source. this case highlights the value of specially formulated medicines in the management of complex diseases by providing novel delivery vehicles. figure 1: (a) the nielson catheter that has been manually adapted to include a 30 degree distal bend at the tip and a 10 degree mid-shaft curve. (b) shows a close up of the distal tip. figure 2: endoscopic appearance of the pharynx showing the appearance of the nielson catheter within the horse’s right guttural pouch. figure 3: endoscopic appearance of the partially solidified poloxamer gel 4 minutes 25 seconds after infusion into the guttural pouch of a strangles carrier. lifiting of the head did not change the appearance of the meniscus within the pouch demonstrating it was already partially set. arrows show meniscus of solidified gel against retropharyngeal mass (lymph node). conflict of interest the author declares no conflict of interest. references george, j. l. et al. (1983) identification of carriers of streptococcus equi in a naturally infected herd. journal of the american veterinary medical association, 183 (1), pp. 80-84. newton, j. r., verheyen, k., talbot, n. c., timoney, j. f., wood, j. l. n., lakhani, k. h. and chanter, n. (2000), control of strangles outbreaks by isolation of guttural pouch carriers identified using pcr and culture of streptococcus equi. equine veterinary journal, 32 (6), pp. 515–526. http://dx.doi.org/10.2746/042516400777584721 verheyen, k., newton, j. r., talbot, n. c., brauwere, m. n. d. and chanter, n. (2000), elimination of guttural pouch infection and inflammation in asymptomatic carriers of streptococcus equi. equine veterinary journal, 32, pp. 527–532. doi:10.2746/042516400777584703 treatment duration with steroid monotherapy in dogs with steroid responsive meningitis-arteritis a knowledge summary by richard william lawn bvsc, certavp, mrcvs1* 1university of bristol, langford vets, langford, somerset, bs40 5du university of bristol *corresponding author (richard.lawn.2017@my.bristol.ac.uk) vol 4, issue 1 (2019) published: 28 mar 2019 reviewed by: simon platt (dvm, bvm&s, mrcvs, dacvim (neurology), decvn) and conor o'halloran (bvsc, mrcvs) next review date: 28 mar 2021 doi: 10.18849/ve.v4i1.221 pico question in dogs suspected of having steroid responsive meningitis-arteritis (srma), how long should immunosuppressive monotherapy with steroids be undertaken in order to achieve clinical resolution without relapse of clinical signs? clinical bottom line based on the currently available literature, steroid treatment using the protocol outlined in lowrie et al. (2009) at a gradually tapering dose over a course of 6 months, appeared to lead to clinical remission in all cases, with a disease free post treatment interval of at least 6 months. however, further research is needed as there are currently three published papers with a low number of cases, so a definitive time course cannot be suggested until stronger evidence is available. clinical scenario you are presented with an 18-month-old female neutered beagle with a history of anorexia and lethargy. on examination the dog shows cervical hyperesthesia and has a rectal temperature of 39.8°c. cerebral spinal fluid (csf) analysis reveals a marked neutrophilic pleocytosis with elevated protein. a presumptive diagnosis of steroid responsive meningitis-arteritis (srma) is made, and you wish to start the dog on immunosuppressive monotherapy with steroids, however you are unsure as to how long the dog will require treatment to achieve clinical resolution and without relapse of clinical signs. the evidence there is limited available evidence regarding treatment duration of dogs with srma with steroid monotherapy. three studies were located which investigated steroid treatment protocols and follow-up however these all had a small population size. one study did not define how the follow-up data was obtained (tipold & jaggy, 1994), and another was a retrospective study which sits low on the hierarchy of evidence (cizinauskas et al., 2000). only one study standardised treatment and follow-up on cases (lowrie et al., 2009). the available evidence is therefore limited and would benefit from studies of a higher power i.e. prospective, randomised, blinded studies, before a definitive recommendation of treatment duration can be made. a repeat literature search including combination therapies for treatment of srma may be beneficial at identifying more papers with a stronger evidence base to establish a treatment duration. summary of the evidence tipold & jaggy (1994) population: dogs with clinically confirmed srma referred to the institute of animal neurology, university of berne, brem-gartenstrasse, switzerland during an unspecified time frame sample size: 20 dogs intervention details: all cases were diagnosed based on clinical and neurological examination, complete blood count (cbc) and serum biochemistry and csf analysis. some dogs had additional testing including electromyography (emg), electroencephalography (eeg), myelography , computed tomography (ct) and cisternography dogs received prednisolone at 4 mg/kg/day. this was reduced to 2 mg/kg/day after 2 days and maintained for 2 weeks, followed by 1 mg/kg/day for a further 2 weeks at this point dogs returned for examination to include csf analysis, blood profile and eeg. these were repeated every month since the beginning of the treatment for at least 6 months as soon as neurological exam and csf analysis were normal, the prednisolone dose was reduced from 1 mg/kg/day until 0.5 mg/kg every other day was achieved for 6 months. the treatment was stopped when dogs presented clinically normal with normal csf and blood profile when pleocytosis was still detected, the same dosage was maintained for 6 months study design: prospective single centre case series outcome studied: the diagnostic usefulness of ancillary testing and response to a treatment protocol subjective: follow-up of dogs for up to 4 years after cessation of treatment protocol objective: occurrence of abnormalities in csf analysis, blood profile and eeg at monthly follow-ups main findings (relevant to pico question): 12/20 dogs that entered the study had no clinical signs following the described treatment regimen and were free of neurological signs for up to 4 years after treatment was stopped 2/20 improved but were still under treatment at the time of the article’s publication 3/20 cases relapsed after stopping the 6 month treatment schedule one dog was euthanised the outcome was unknown in the two others limitations: cases are from a single referral hospital; this population may not be directly comparable with other populations i.e. those seen in first opinion practice small population size the study is 23-years-old there is minimal to no statistical analysis no details on how 4 year follow-up was obtained cizinauskas, jaggy & tipold (2000) population: dogs with clinically confirmed srma referred to the small animal neurology department, university of bern, between march 1995 – may 1997 sample size: 9 dogs intervention details: all cases were diagnosed based on clinical and neurological examination, complete blood count (cbc) and serum biochemistry and cerebral spinal fluid (csf) analysis. some dogs had additional mri and infectious disease pcr testing. all dogs were treated with a standard protocol initiated with oral prednisolone at 4 mg/kg/day. after 2 days this was reduced to 2 mg/kg/day orally for 2 weeks, followed by 1 mg/kg/day orally for 1 month. dogs were rechecked at one to three month intervals which included clinical examination, complete blood count and biochemistry, and csf tap once results of neurological and csf examination were found to be in normal range, prednisolone dose was reduced to half the previous dosage until 0.5 mg/kg every alternate day was reached if pleocytosis was present in csf, initial dosage was maintained. this therapeutic regimen was maintained for at least 4 months until there were no clinical signs of srma and csf tap and blood results were normal in the two latest follow-up examinations in dogs that relapsed, the prednisolone dose they were on at the time was doubled. dogs with frequent and severe relapses, which did not respond to routine treatment (prednisolone 1 mg/kg/day), received additional immunosuppressive therapy with mycophenolate mofetil at 20 mg/kg every other day, alternating with prednisolone (0.5 or 1 mg/kg). prednisolone was continuously reduced down to 0.5 mg/kg every third day, then once a week and later withdrawn if clinically improving two dogs were treated initially with meloxicam 0.1 mg/kg once daily. one dog was put on prednisolone treatment after relapsing, while the other was treated with meloxicam only study design: retrospective single centre case series outcome studied: response to treatment and side effects of long-term glucocorticoid steroid therapy subjective: long term follow-up of 8–34 months; for 7 dogs this was longer than 18 months final examination 2–8 months after treatment terminated, regularly contacted thereafter via telephone objective: cbc, biochemistry and csf analysis at 1–3month intervals relapse of cases demonstrated by recurrence of clinical signs and abnormal csf analysis results of clinical examination and csf analysis at follow-up at 18 months main findings (relevant to pico question): side effects included poly uria and poly dipsia (n=7), polyphagia (n=6), urinary tract infection (n=3), hyperpigmentation, alopecia, gastrointestinal signs and hepatomegaly (n=2) 8/9 dogs were free of neurological signs up to 29 months after termination of treatment 4/9 dogs were disease free throughout the follow up period three dogs on steroids alone finished treatment at 4, 7, and 9 months after diagnosis without relapse. these were observed for 28, 26 and 8 months respectively, and were relapse free. one dog on meloxicam alone finished treatment 2 months after diagnosis without relapse. it was observed for 11 months and was relapse free 4/9 had relapses of srma of these four dogs, one dog stopped all treatment 13 months after diagnosis, one dogs’ follow up period ended at 12 months whilst on steroids and mycophenolate mofetil, one dog stopped all treatment 20 months after diagnosis and one dog stopped taking steroids and mycophenolate mofetil at 19 months and 27 months after diagnosis respectively case 9, 5, 7 and 10 were observed for 11, 0, 5 and 4 months respectively and showed no signs of relapse in this period one dog was euthanised at 8 months following relapse on steroids alone, at the owners’ request limitations: retrospective study cases are from a single referral hospital; this population may not be directly comparable with other populations i.e. those seen in first opinion practice small population size four dogs were treated with steroids prior to study abstract identifies ten dogs, however only nine in study and eight available for follow-up. one dog is missing from the follow-up and not accounted for. the discrepancy in numbers is not explained the study is 18-years-old there is minimal statistical analysis no standard treatment protocol between animals no standardised duration of observation period lowrie et al. (2009) population: client owned dogs with clinically confirmed srma presenting to the small animal neurology service at university of glasgow small animal hospital (ugsah) between may 2006 – may 2008 sample size: 20 dogs intervention details: all dogs received a physical examination, complete blood count, biochemistry, orthogonal cervical radiographs and csf analysis of cytology and total protein concentrations dogs with neurological deficits underwent polymerase chain reaction (pcr) for infectious diseases and magnetic resonance imaging (mri) to rule out other disease all dogs were treated with a standard protocol initiated with oral prednisolone at 2 mg/kg q. 12 hours for 2 days, then 1 mg/kg q. 12 hours for 12 days if remission was achieved, prednisolone was continued at 0.5 mg/kg orally q. 12 hours for 6 weeks, then reduced to 0.5 mg/kg orally q. 24 hours for 6 weeks, then reduced to 0.5 mg/kg orally q. 48 hours for 6 weeks, then reduced to 0.5 mg/kg orally every third day for 6 weeks before stopping, and resolution considered if a putative relapse was considered, the protocol was restarted with prednisolone at 1 mg/kg orally q. 12 hours for 2 weeks a recheck examination was scheduled 2 weeks after starting treatment and involved a clinical examination and csf analysis remission was defined as absence of clinical signs in addition to normal csf analysis a failure to achieve clinical remission at recheck involved following the above protocol with a further second recheck 2 weeks later failure of the protocol was defined as two consecutive cycles without achieving clinical remission once clinical remission was achieved, no further csf samples were obtained unless relapse suspected at presentation, remission, and putative relapse, a history, general and neurological examination, complete blood count (cbc), serum biochemistry and acute phase protein (app) panel were obtained serum samples were taken at resolution, defined as 4 weeks after cessation of therapy without the recurrence of clinical signs the minimum follow-up for each case was 6 months after cessation of prednisolone study design: prospective single centre case series outcome studied: response to therapy, long term outcome and expression of potential disease markers of srma as potential diagnostic indicators objective: cbc, biochemistry and csf analysis at presentation, remission (2 weeks into treatment) and resolution (4 weeks after cessation of treatment) main findings (relevant to pico question): all 20 dogs responded to the 6 month course of prednisolone therapy four out of 20 dogs were suspected of suffering putative relapses with 1 dog having two separate episodes all four dogs suspected of relapsing remained on treatment protocol and increased prednisolone dose as described, resulted in resolution of clinical signs with a 6 month follow-up period prednisolone monotherapy was successful in achieving full remission in 20/20 affected dogs, with an in protocol relapse rate of 20% (4/20 dogs) suggests relapse has a propensity to occur on treatment and not after cessation of treatment the described therapy resulted in disease free post treatment interval of at least 6 months limitations: small population size cases are from a single referral centre; this population may not be directly comparable with other populations i.e. those seen in first opinion practice appraisal, application and reflection the available evidence was split between a retrospective case series and two prospective case series. a retrospective case series is low on the hierarchy of evidence and therefore taking a meaningful conclusion clinically from its results is difficult. case series studies also have a high likelihood of bias. all papers suffered from a small sample size and are focused on a population of animals attending a referral centre rather than general practice. there was standardisation across all papers regarding diagnosis of srma; all cases were diagnosed based on clinical and neurological examination, cbc and serum biochemistry as well as csf analysis. select cases underwent further ancillary testing such as eeg and emg (tipold & jaggy, 1994), and mri and infectious disease pcr (lowrie et al., 2009). there were confounding variables in cizinauskas et al. (2000); four dogs were pre-treated with steroids prior to inclusion in the study, there was no defined follow-up period for these cases, and only three dogs received steroid monotherapy. pretreatment with steroids was an exclusion criterion of lowrie et al. (2009). a standardised treatment protocol for both relapses and follow-up were defined in lowrie et al. (2009), however tipold & jaggy (1994) did not detail a treatment protocol for relapse. it appears from the available literature that a 6 month tapering steroid monotherapy protocol as per lowrie et al. (2009) is effective at controlling clinically confirmed srma and resulted in a 6-month disease free post-treatment interval. a similar standardised 6 month treatment protocol was suggested by tipold & jaggy (1994) which described a 4 year disease free period post-treatment, however details of how follow-up data was obtained is lacking. it is difficult to draw meaningful conclusions from cizinauskas et al. (2000) due to the retrospective nature, small sample size and confounding variables. both prospective studies were based on a small sample size from a referral population, and tipold & jaggy (1994) is a 23-year-old paper. the available evidence, however, is limited and would benefit from studies of a higher power i.e. prospective, randomised, blinded studies, before a definitive recommendation of treatment duration can be made. methodology section search strategy databases searched and dates covered: the search was applied to cab abstracts via the ovid platform, covering 1973 to 2018 week 40 medline via the ovid platform from 1946 to 2018 search terms: ((dog or dogs or canine* or canid* or bitch*) and (steroid responsive meningitis-arteritis or steroid responsive meningitis arteritis or srma)) dates searches performed: friday 11 october 2018 exclusion / inclusion criteria exclusion: single case reports, duplicate papers, book chapters, conference proceedings, articles where the full text was not available in english or able to be located, or articles not relevant to the pico question. inclusion: articles published between 1946 – present, articles in english and relevant to the pico, articles with more than one animal, articles that used steroids as the only immunosuppressive. search outcome database number of results excluded – not relevant to the pico excluded – single case report/book chapter/conference proceeding excluded – not available in english total relevant papers cab abstracts 74 51 16 4 3 medline 53 44 6 0 3 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflicts of interest. references tipold, a. and jaggy, a. (1994) ‘steroid responsive meningitisâ€�arteritis in dogs: longâ€�term study of 32 cases’, the journal of small animal practice. wiley/blackwell (10.1111), 35(6), pp. 311–316. doi: https://doi.org/10.1111/j.1748-5827.1994.tb03293.x cizinauskas, s., jaggy, a. and tipold, a. (2000) ‘long-term treatment of dogs with steroid-responsive meningitis-arteritis: clinical, laboratory and therapeutic results’, journal of small animal practice. wiley/blackwell (10.1111), 41(7), pp. 295–301. doi: https://doi.org/10.1111/j.1748-5827.2000.tb03205.x lowrie, m., penderis, j., mclaughlin, m., eckersall, p. d. and anderson, t. j. (2009) ‘steroid responsive meningitis-arteritis: a prospective study of potential disease markers, prednisolone treatment, and long-term outcome in 20 dogs (2006–2008)’, journal of veterinary internal medicine, 23(4), pp. 862–870. doi: https://doi.org/10.1111/j.1939-1676.2009.0337.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. does the use of intratesticular blocks in cats undergoing orchiectomies serve as an effective adjunctive analgesic? a knowledge summary by erik fausak mslis, ma, lvt, rlat 1 elizabeth rodriguez lvt, cvt 1 anna simle student 1* netwarat merman student, mba 1 dakota cook student 1 1bel-rea institute of animal technology, 1681 s. dayton st., denver, co 80247 *corresponding author (asimle@gmail.com) vol 3, issue 4 (2018) published: 19 oct 2018 reviewed by: dick white (bvetmed phd dsas dvr dipacvs dipecvs frcvs) and bruce smith (bvsc ms fanzcvs dacvs) next review date: 19 oct 2020 doi: 10.18849/ve.v3i4.160 pico question in cats undergoing orchiectomy, does the use of intratesticular lidocaine reduce the pain in patients compared to not using intratesticular lidocaine? clinical bottom line with a low grade of evidence, when compared to a pre-medication with pure-µ agonist opioids, intratesticular lidocaine does not appear to provide significant benefit.  however, based on our clinical scenario where pre-medication is with a partial-µ opioid like buprenorphine, there may be benefit in utilising intratesticular lidocaine. clinical scenario while animals don’t appear to show a great deal of pain on our pain scale in post orchiectomies, does the use of intratesticular lidocaine work as a good adjunctive analgesic compared to not using it, and are there many severe complications? the evidence two randomised control trials with varying degrees of blindness were examined. all studies included involved cats. all studies had a high degree of variation in premedication and analysis of effect (moldal et al., 2013; fernandez-parra et al., 2017). summary of the evidence fernandez-parra et al. (2017) population: client-owned cats with an average age of 8 mo and 3.8 kg presenting for castration. sample size: 49 (out of 54 where 7 were excluded due to fractious behavior – math does not add up) (2 didn't meet inclusion criteria and 5 lacked follow up due to unavailability). intervention details: all received as a premedication and induction agent for neuter – dexmedetomidine (15 µg/kg) and alfaxalone (3 mg/kg)    patients were divided into three groups (itl) intratesticular lidocaine (n=15) 0.05 ml of lidocaine 2% in both testicles. (scl) sacrococcygeal epidural lidocaine (n=15) 0.1 ml/kg of lidocaine 2% epidural placed. (ivm) intravenous methadone (n=19), 0.3 mg/kg iv.   all patients received atipamezole (dexmedetomidine reversal) at the end of surgery. fentanyl was administered perioperatively (2 µg/kg) during the procedure if two values were 30% above the baseline for that animal, and patients were also administered propofol when light. animals failing vas pain scale and unesp-botucatu multidimensional composite pain score post operatively were given rescue analgesics of buprenorphine (20 µg/kg).   all cats received 0.02 mg/kg buprenorphine sq and 0.2 mg/kg meloxicam po.   study was blinded where all animals had their backs shaved (but did not inject saline in all testicles – or didn't mention it).   patients were evaluated by pulse oximetry, mean blood pressure,  respiratory rate, and heart rate during the procedure and the amount of time from injection to sternal recumbency and from recumbency to activity.  patients were also assessed on pain at regular intervals (1 hr, 2 hr, and 3 hr). study design: randomised blinded control trial outcome studied: perioperatively: mean arterial pressure breaths/minute pulse oximetry hr during surgery post-operatively: unesp-botucatu composite pain scores vas pain score recovery times surgical time post-operative scores measured 4 times, at return of active interaction, and at 1,2, and 3 hours later. main findings (relevant to pico question): no significant or readily visible differences between all three groups using the mcps (unesp-botucatu multidimensional composite pain score).  significant differences were found with vas scores, methadone group had lower vas scores.  itl had lowest overall recovery times to active interaction. rescue analgesia (as fentanyl) was delivered perioperatively to 1/15 cats in the epidural group.      2/15 for intratesticular lidocaine, 3/15 for the epidural group received propofol, and 0/19 required propofol in the methadone group.   post-operatively rescue analgesia of buprenorphine was delivered to 4/15 in the intratesticular lidocaine group, 3/15 in the epidural group, and 1/19 in the methadone group.   methadone had better reduction in pain scores but longer recovery times compared to lidocaine groups. limitations: surgery time was longer than average. a little confused on inclusion/exclusion. 54 cats were examined, 7 excluded due to behavior and 49 cats were included which doesn't make sense as 54-7 = 47. not sure if the vas or unesp-botucatu pain scales have been previously validated. moldal et al. (2013) population: client owned cats 34 domestic short hair and domestic long hair cats, 5 pedigree. inclusion criteria included clinically healthy cats not on medications 6 months to 5 years old. no abnormalities of testicular anatomy. sample size: 39 cats intervention details: all animals were premedicated with: 0.25 mg/kg midazolam iv 2.5 mg/kg ketamine iv 1-4 mg/kg propofol iv 0.5 ml lidocaine for glottal application (for intubation) groups were randomised by lot.  control group (ga) n=19 no saline was given in the testicles. lidocaine testicular group (la) n=20 0.1 ml/kg lidocaine -1/3 lidocaine in each testicle and 1/3 subcutaneous. surgeon but not anesthetist was blinded to placement.   lidocaine was introduced craniodorsal in each testicle but approached caudoventral 25 g x 1”needle (this did not make a great deal of sense to the author).  post operatively all animals received 2µg/kg medetomidine iv, 15 µg/kg buprenorphine im, 2 mg/kg ketoprofen sq and sent home with 1mg/kg ketoprofen oral for three days. study design: randomised control trial outcome studied: heart rate, mean arterial pressure, heart rate variability (hrv). main findings (relevant to pico question): lidocaine group (la) on average had less significant heart rate increase in hrv.  pulse rate in general was less pronounced in the lidocaine group.  cats in the lidocaine group also had lower mean arterial pressure (statistically significant). limitations: besides ketamine, there was no analgesic in the premed, probably not consistent with most practices. description of intratesticular injection was extremely confusing. blinding was done for the surgeon, who was not recording the values for the study, and there was no attempt to blind control from experimental in terms of a saline placebo in each testicle. likewise, the testicles may have become swollen from injection and surgeons may have noticed.  they also don’t mention who actually recorded these values (most likely the anesthetist) who knew which patient was given lidocaine or not.  appraisal, application and reflection examination of the whole body of studies made the effect of intratesticular blocks extremely inconsistent.  however, when taking into account the type of premedication used in the studies, a clearer picture presented itself.  the most significant contribution to post-operative analgesia in routine castration of the cat seems to be the analgesic used in premedication or perioperatively.  in the study that used a pure µ opioid agonists, there was marked improvement of the pure µ group over intratesticular groups and epidural groups in pain scores(fernandez-parra et al., 2017).  all studies only used lidocaine as an intratesticular block.  none of the studies used had adequate blinding measures which could create a bias in interpretation of the results.  a further limitation of these results is in our pico, we were focusing on pain and the use of intratesticular lidocaine.  if this pico were modified to isoflurane, propofol, and rescue analgesic sparing effect, our conclusion may be different.   overall, lidocaine led to no significantly aversive events in any of the studies, it is relatively inexpensive, and fairly easy to administer.  in light of the low cost and minimal risk with inconsistent results, an argument could be made that it is still worthwhile to administer in most clinical scenarios.  methodology section search strategy databases searched and dates covered: pubmed (1963 – 07/2017) vetmed resource (cab)  (1973 – week 1 2017) cab abstracts on ovid platform (1973 – week 1 2017) search terms: orchiectomy and intratesticular and veterinary (pubmed 22 results and 9 relevant) , (dog or cat) and intratesticular (pubmed 46 results/5 relevant), lidocaine and castration and (dogs or cats) (pubmed 21/3 relevant), orchiectomy and intratesticular (vetmed resource and cab abstracts) 11 results/3 relevant dates searches performed: 17 july 2017 exclusion / inclusion criteria exclusion: anaesthetic injections versus local blocks inclusion: english, french, spanish, and thai articles on intratesticular injection of local anaesthetic to testicles. search outcome database number of results excluded – not involving lidocaine or bupivacaine intratesticular injection on cats excluded – duplicate excluded – not local anesthetic – lidocaine or bupivicaine total relevant papers pubmed 89 80 0 7 2 vetmed resource 11 3 3 0 0 cab abstracts 11 0 11 0 0 total relevant papers when duplicates removed 2 conflict of interest erik fausak is a member of the editorial board of veterinary evidence. this paper underwent a rigorous peer-review process as per our normal reviewing guidelines of inviting a minimum of two external reviewers. the identity of the associate editor handling the paper has not been disclosed to the author. the final decision to accept this paper rested with the editor-in-chief. all other authors declare no conflict of interest. references fernandez-parra, r. et al. (2017) ‘comparison of intratesticular lidocaine, sacrococcygeal epidural lidocaine and intravenous methadone in cats undergoing castration: a prospective, randomized, investigator-blind clinical trial’, veterinary anaesthesia and analgesia. doi: http://dx.doi.org/10.1016/j.vaa.2016.03.010 huuskonen, v. et al. (2013) ‘intratesticular lidocaine reduces the response to surgical castration in dogs’, veterinary anaesthesia and analgesia, 40(1), pp. 74–82. doi: http://dx.doi.org/10.1111/j.1467-2995.2012.00775.x mcmillan, m. w., seymour, c. j. and brearley, j. c. (2012) ‘effect of intratesticular lidocaine on isoflurane requirements in dogs undergoing routine castration’, journal of small animal practice, 53(7), pp. 393–397. doi: http://dx.doi.org/10.1111/j.1748-5827.2012.01233.x moldal, e. r. et al. (2013) ‘intratesticular and subcutaneous lidocaine alters the intraoperative haemodynamic responses and heart rate variability in male cats undergoing castration’, veterinary anaesthesia and analgesia, 40(1), pp. 63–73. doi: http://dx.doi.org/10.1111/j.1467-2995.2012.00773.x perez, t. e. et al. (2013) ‘effects of intratesticular injection of bupivacaine and epidural administration of morphine in dogs undergoing castration’, journal of the american veterinary medical association, 242(5), pp. 631–642. doi: http://dx.doi.org/10.2460/javma.242.5.631 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. age at first calving in dairy cows: which months do you aim for to maximise productivity? a knowledge summary by mike steele bsc(hons), bvsc, mrcvs 1* 1inspire cattle solutions, 10 granborough road, winslow, buckinghamshire, mk18 3bp *corresponding author (mike@dairyconsulting.vet) vol 5, issue 1 (2020) published: 19 mar 2020 reviewed by: alastair hayton (bvm&s, dchp, mrcvs) and claire weeks (bsc) next review date: 01 mar 2021 doi: 10.18849/ve.v5i1.248 pico question in dairy cattle, which months should producers target age at first calving in order to maximise milk yield, minimize risk of non-voluntary culling and optimize fertility?   clinical bottom line category of research question risk the number and type of study designs reviewed seventeen papers were critically reviewed: 15 sets of case series, one review of case series and cohort studies and one randomised control trial, summarising over 2.4 million individual cow records strength of evidence strong outcomes reported an optimum range of age at first calving (afc) on dairy farms appears to be 22–25 months inclusive. lower or higher than this figure can bring lower first lactation 305 day and lifetime milk yields, lower fertility and lower chances of surviving to a second lactation. achieving an afc of 22–25 months can bring the highest economic return to dairies conclusion age at first calving is a useful and key performance parameter to measure in dairy cattle. achieving a range of 22–25 months at first calving can help to optimise both long term milk yield, fertility and longevity within the herd   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.    clinical scenario the age at which a cow calves for the first time is a key indicator of the quality of youngstock management. rate of growth in the heifer until she is inseminated, conceives and subsequently calves 9 months later can be affected by many factors. nutrition quality and availability, disease risk (including parasitism), breed and insemination practices being only some of these influencing factors (adamczyk, 2017; bond, 2015; davis rincker, 2011 and macdonald, 2005). a recent review of uk dairy herd data showed that the average (mean) age at first calving (afc) was 29 months (median 28 months) (eastham, 2018). this seemed significantly greater than the target of 22–24 months that is often quoted in press. although there have been publications to summarise the performance effects of varying the afc, few have concentrated on yield and reproduction together, in the same article and included data from more than one country.   the evidence there are 17 articles recorded in this knowledge summary. they reflect a geographical range representative of holstein-friesian (bos taurus) dairy cows in europe, asia and north america. there is one review of case series articles, including 125 referenced articles from 1979–2014. there is one randomised control trial, focusing on growth rates and afc. the other 15 papers are case series, including data collected from dairy software on farms mostly involving dairy herd improvement (dhi) schemes. these include data from at least 2,645,158 cow records (one paper from iran does not publish the number of cows in the dataset but describes the data as originating from 12 large farms and defines large farms in iran to include roughly 7,000 cows per farm). correlations in data are largely indicated by linear regression and covariance analysis and the main findings reported have been stated when either significant or no significant difference was observed at p-values of <0.05.   summary of the evidence of the 17 articles discussed in this knowledge summary, the reported range of afc is from 18 months old to 42 months old. the mean average afc reported in each study differs by country, with iran and usa at 25.5 months and uk at 29 months (ettema j.f. 2004) (elahi torshizi m. 2016). papers from other european countries do not report mean average but describe a commonly recorded afc on farm, to be between 26 and 30 months (krpalkova, 2014 and pirlo, 2011). as mentioned in the methodology section, this knowledge summary has reflected the pico and is not focused on the influencing factors of afc but it is worth noting that major inputs to afc include diet (intensive rearing or less intensive, both preweaning and post-weaning) and insemination procedures. obviously, afc reflects the gestation length of cattle (9 months) and insemination depends on animals reaching puberty and cycling healthy, viable ova. wathes (2014) states that the onset of puberty can occur from 10 months and can be brought forwards by intensive rearing management and diets (chester-jones, 2017). chester-jones (2017) also notes that to maximise the occurrence of healthy ova, at least three cycles should be allowed before inseminaton should be practised.   optimum range of afc the optimum range of afc varies according to paper, outcome studied and geographical region but a consensus can be seen in overlapping months: 18–23 months (banos, 2007): this range is inclusive of all data from 18–23 months and not considering data from each month separately 22 months (eastham, 2018) 5–23.5 months (changee, 2013) 22–24 months (pirlo, 2011 and nilforooshan, 2004) 22–26 months (elahi torshizi, 2016) 23–25 months (ettema, 2004) <24 months (adamczyk, 2017) 5 months (krpalkova, 2014) 25–­26 months (storli, 2017) in summary, most papers agree that from their observations that the optimum afc falls between 22–25 months inclusive. beyond this in either direction, there appear to be detrimental consequences on one or more of the outcome effects reported below. the effects of varying afc have fallen mainly into 4 categories: milk yield (first lactation 305 day yield; lifetime yield) fertility (first service conception rate; calving interval, days open, inseminations per pregnancy) longevity (survival to second calving and overall survival length) economic return (return on rearing cost; loss/month compared to other afc groups) consequently, each will be reported as a separate effect below: milk yield milk yield (my) has been measured as the volume of milk harvested from the cow in the 305 day lactation following her first calving (taken by addition of test-day results, daily milk weights or predicted 305 day yield in papers where yield was recorded over less than 305 days). prediction of 305 day milk equivalent is a common parameter from dairy software recording systems that use equations linked to prediction of the lactation curve. cows at certain days in milk (dim) can have known monthly test day results to base a prediction figure from and calculate their predicted yield to the end of that lactation. another parameter reported has been in my from the cow over her total productive lifetime (either in total milk volume or average daily yield). in terms of volume, milk losses and gains can be regarded from the perspective of pre-22 months; 22–25 months and post 25 months afc. at an afc of less than 22 months, 590–800 kg losses in the first 305 day lactation have been reported by (elahi torshizi, 2016) and (pirlo, 2011). ettema (2004) included pre-23 months in his study and reports a 320 kg loss in the first lactation: the lower volume lost is most likely because the cows at 22–23 months were included in the calculation. only one study reports higher yields in 18–23 months, quoting 4.5% more milk from the first 305 day lactation (banos, 2007). cows with an afc of greater than 25 months are also reported to have lower milk yields. elahi torshizi (2016) and pirlo (2011) report a 170–600 kg loss in milk above 26 months. berry (2009) reported that first lactation 305 day yield decreases by 55.5 kg less per month, increasing from 22 months afc to 38 months. cows calving between 22–25 months have been found to produce 2.1–2.4 kg/day more milk than their counterparts calving outside this window of time (storli, 2017 and eastham, 2018). in summary, there appear to be lower milk yields of between 170 and 600 kg in the first lactation in cows with low afcs (18–21 months) and 590–800 kg less yield in cows with high afcs (>26 months). fertility there is less clarity over fertility effects of varying age at first calving, mainly due to the parameters that researchers have measured on performance of reproduction. this is discussed in the appraisal section below. first service conception rate was reported by ettema (2004) to be highest in afc of <23, then 23–25, then >25 months (75%, 64%, 45%). conversely, days open and calving interval have been reported as improving in older afc groups (>26 months) compared to afcs of <26 months (eastham, 2018) and (krpalkova, 2014). banos, (2007) suggested that fertility would be compromised in younger afc cattle by reporting 7% more inseminations per pregnancy and 7.5% higher return rate in afc between 18–23 months. in summary, although more papers suggest higher fertility rates in older afc cattle, one key paper reflects that aiming for lower afc does not compromise first service conception rate targets (ettema, 2004). longevity there has been no significant, direct effect of afc on the survival length of cattle reported nilforooshan (2004 and wathes (2014). however, it must be noted that longevity of cattle is strongly linked to productivity and less productive cattle are more likely to be culled. therefore, links can be made between afc and survivability: eastham (2018) suggests that cows calving between 22–26 months old are more likely to survive to calve a second time but this is not a reflection of the afc itself but rather the management of transition and early lactation as a whole. profitability whether or not afc affects the profitability of a dairy is a difficult and highly variable parameter to calculate, as so many factors in the management of both heifer rearing and lactation affect dairy profit. however, five of the reviewed papers have attempted to associate afc with profitability. the longer it takes for a heifer to enter the milking herd, the more feed and management costs are involved in rearing her. ettema (2004) observed that an afc of 22–24 months was us$98–138 preferable per heifer than other afcs. pirlo (2011) calculated that an afc of 22–26 months improved income per heifer by us$24–41 over other afcs and changee (2013) reported that an afc of 22.5 months gave up to us$727 higher lifetime returns compared to an afc of 32 months. krpalkova (2014) suggests that between 24–26 months of afc returns the highest profitability but does not state the amount: the statement is based on higher milk returns and fertility parameters. wathes (2014) simply reviews the above papers. in summary, it seems that an afc of between 22–26 months produces the highest returns compared to lower or higher afcs.   acronyms adwg = average daily weight gain afc = age at first calving bcs = body condition score bw = body weight cp = crude protein ecm = energy corrected milk dhi = dairy herd improvement dim = days in milk dm = dry matter hol/fr = holstein-friesian my = milk yield scc = somatic cell count scs = somatic cell score sd = standard deviation   eastham et al. (2018) united kingdom population: primiparous, mainly hol/fr dairy cows sample size: 396,534 cows from 6,985 herds in uk. national milk record database data from 2006–2008 intervention details: varying afc and production parameters study design: case series outcome studied: first lactation my lifetime my first lactation milk fat and protein yield first lactation scc likelihood to calve a second time main findings (relevant to pico question): mean afc was 29 months and median 28 months. range 18–42 months 3% calved <24 months; 40.9% calved ≥30 months lowest predicted first 305 day yield was <21 months afc (6,617 kg) highest predicted first 305 day yield was >34 months afc (7,774 kg) animals with afc of 21 months had an scc of 72,765 and those with an afc of 36 months had an scc of 86,648 animals with an afc of 41 months had a modelled increase in calving interval (416 days) compared with afc of 23 months (401 days) animals with an afc of 22 months had a mean daily lifetime yield of 15.24 kg and those of 36 months had a mean daily lifetime yield of 12.83 kg predicted probability of calving for a second time was much greater in animals with an afc of 21–25 months (0.817–0.837) compared with those greater than 30 months (0.649–0.782) limitations: data is historical compared to publishing date. calving interval is dependent on pregnancy results and is a comparatively historical evaluation of reproductive performance. it is skewed by animals with very long days open or cull cows. storli et al. (2017) norway population: norwegian red dairy cow data from national norwegian herd records 2010–2012 sample size: 350 cows after exclusions to investigate the outcomes. only first lactation animals with single calves and within at least 275 and 575 days of calving were included. intervention details: growth rate, variance in afc and first lactation yield study design: case series outcome studied: heart girth measurement, afc and test-day my from 0–305 dim main findings (relevant to pico question): an optimal adwg of 0.830 kg/day is associated with the best first lactation yields first lactation yield is improved by 2.5 and 2.1 kg/day respectively at afc of 25 and 26 months compared with 23 or less or greater than 26 months limitations: many animals were excluded from the original dataset (started with 3,110). breed is not representative of most dairy herds globally. as sample population decreases, the chances of other herd factors influencing the afc and yield as well as just growth are increased (such as season of calving, heat stress, etc.). chester-jones et al. (2017) united states of america population: holstein dairy cows sample size: 2,880 holstein cows from three commercial dairy farms intervention details: starter intake, protein intake, milk replacer intake and birth season of calves to 195 days old and afc study design: case series outcome studied: first lactation 305 day yield main findings (relevant to pico question): mean afc was 23.5 months (46 days sd) but had no significant effect on first lactation yield mean first lactation 305 day yield was 10,959 kg mean adwg was 0.62 kg/day at 8 weeks old every 1 kg of 6 week adwg was associated with 544 kg more first-lactation 305 day milk and every 1 kg of 8 week adwg yielded 579 kg more first-lactation 305 day milk but there was great variation around the mean, so bw was more associated with first lactation yield than adwg. this is true, due to bw being more related to birth weight and this is strongly correlated to first lactation yield starter pellet intake had a significant effect on first lactation yields, with each 1 kg increase in intake resulting in 8.21 kg more 305 day milk (but variations were high). milk replacer intake had no effect on first lactation yield season of birth: summer calves had a slightly greater first lactation yield, probably due to photoperiod on intakes limitations: small number of farms in the sample population, so other herd management factors could have influenced differences between the three herds. there was no association with afc and 305 day yield but the variation between the three farms was small (715, 702 and 725 days). adamczyk et al. (2017) poland population: black and white and red and white dairy hol-fr cows in poland sample size: 135,496 cows, including 131,526 of the black and white breed, and 3970 of the red and white breed. data from the national dairy database of poland intervention details: association of herd size, breed and afc on lifetime yield ecm and longevity study design: case series outcome studied: culling and afc main findings (relevant to pico question): afc of <24 months was associated with 727 kg more lifetime yield (lifetime value of energy corrected milk 25,184 kg) than 24–31 months (lifetime value of energy corrected milk 24,387 kg) and 4,401 kg more lifetime yield than >31 months (lifetime value of energy corrected milk 20,783 kg) there was no significant difference between daily milk yield (over lifetime: lifetime range was 5.4 to 5.9 years, these being least square mean values) and afc up to 31 months but these were 1 kg/day higher than over 31 months there was no significant difference between afc and age at culling in all groups limitations: limited to dairy software recorded herds, which may not be representative of the general dairy population. no information on other milk constituents such as milk fat and protein. elahi torshizi (2016) iran population: primiparous hol-fr dairy cows sample size: 72,946 cows from 724 herds intervention details: effect of afc and season on the characteristics of the lactation curve study design: case series outcome studied: shape and area under the curve of first 305 day lactation curve main findings (relevant to pico question): seasonal effect was significant on the shape of the lactation curve. spring and winter showed the highest peak values (33 kg/day) and summer/autumn showed lower peaks (32 kg/day). autumn showed greater persistency in late lactation (by 0.5 kg/day over the last 200 to 305 dim) highest yields (8,000 kg) were associated with afc between 22–26 months. beyond this, they reduced considerably (by 600–800 kg up to 32 months) for every month increase in afc between 18–26 months there was an increase in 138 kg of 305 day yield limitations: more emphasis was placed on season effects on the lactation curvethan afc. a very good study overall on retrospective data. data sources not mentioned in the paper. krpalkova et al. (2014) czech republic population: commercial dairy cows from 33 farms. 18 farms were hol-fr and eight of fleckvieh. seven of mixed hol/fr and fleckvieh mixed sample size: 23,008 cows and 18,139 heifers (41,147 animals in total) intervention details: afc, adwg and milk yield effects on reproduction and profitability study design: case series outcome studied: first service conception risk conception rate days open calving interval number of completed lactations depreciation costs per cow my culling rate main findings (relevant to pico question): herds with more intensive rearing periods (adwg>0.8 kg/day) had lower conception rates among heifers at first and overall services the differences in conception rates between the group with the greatest adwg (≥0.8 kg/day) and the group with the least adwg (≤0.699 kg/day) were approximately 10 percentage points in favour of the least adwg conception at first and overall services (cows) was greatest in herds with afc ≥26 months the shortest days open (105 days) and calving interval (396 days) were found in the afc group of 24.5–26 months the highest number of completed lactations (2.67) was observed in the group with longest afc (≥26 months)the earliest afc group (≤24 months) was characterised by the highest depreciation costs per cow at 8,275 czech crowns (us$414), and the highest culling rate for cows of 41% the most profitable rearing approach was reflected in the afc groups of 24.5 months to 26 months and adwg groups of 0.799 to 0.700 kg the highest my (≥8,500 kg) occurred with the earlier afcs of <26 months higher my displayed lower conception rates in cows, but the highest my group also had the shortest days open (106 days) and a calving interval of 386 days limitations: used many parameters to measure reproduction when first service conception rate was the most relevant to the associations and outcomes studied. calving interval and days open would have included non-pregnant cows in the population and skewed the results towards healthier animals (pregnant cows are removed from the calculation for days open and calving interval includes chronically non-pregnant animals beyond those eligible for the group). herds using dairy software may not be representative of all herds. it is unclear what proportion of animals were of which breed: we know how many farms had animals of which breed and the average number of cows per farm of each breed but not the numbers of cows of each breed. wathes et al. (2014) united kingdom population: primiparous dairy and beef cows sample size: review of 125 articles from 1979–2014 intervention details: influences on afc and effects of varying afc study design: review of case series and cohort studies outcome studied: adwg effects on afc nutritional effects on adwg hormonal effects on puberty afc effects on longevity; fertility; my main findings (relevant to pico question): average afc ranges from 26 months (usa) to 31 (kenya) through 29 and 31 (uk and china respectively) timing of puberty obviously affects afc and this is influenced by both nutrition (adwg of 0.82 kg/day can bring on puberty to <10 months) breed and bw are influencers of timing of puberty conception rates are higher at third season from onset of puberty, so leave 2 months before timed artificial insemination from onset of puberty it is more beneficial to reach target growth rates preweaning as this influences time to onset of puberty beyond adwg after weaning afc of <23 months and >30 months results in lower my afc of > 25 months gives a greater calving interval (no data less than 21 months) there is no significant difference in first service conception rate from 23–30 months but overall fertility has been reported to decline from >26 months as afc increases above 22 months, survival tends to decrease but this is associated with production rather than the afc limitations: there was little mention of genetic influence on bw at birth and its consequent influence on first lactation yield but sufficient explanation was given regarding the small influence on heritability on afc. sadeghi-sefidmazgi et al. (2012) iran population: primiparous holstein dairy cows sample size: number of animals contributing to the dataset are not published. data comes from 10 “large farms”, which are described as >7,000 cows, from three regions in iran but it is not clear exactly how many. intervention details: using dairy software data to determine economic weight (in value) study design: case series outcome studied: economic value (us$) of: milk, fat and protein yield longevity afc scs mature bw stillbirth calving interval calving difficulty non-return rate main findings (relevant to pico question): economic value of each: milk/kg $0.15 fat % $1.36 protein % -$1.02 longevity/month $10.30 mature bw/kg -$1.58 scs -$105.67 calving difficulty/% rate -$2.60 calving interval -$0.72 afc/day -$1.73. afc mean = 25.0 months (sd 0.7), ranging from 24.0 to 26.6 months non-return rate $0.91 limitations: no sample population number published. all prices are modeled statistical calculations rather than direct measurements. data only from farms where dairy software is used, mentioned as representative of 12.5% of the dairy population of iran. davis rincker et al. (2011) united states of america population: primiparous holstein dairy cows sample size: 80 heifers n=40 in two intervention groups intervention details: intensive and non-intensive diets in preweaning details in paper on breakdown of diet but overview below: intensive: 1.12 kg dm/day milk replacer consisting of 30.6% cp and 16.1% fat/kg dm. non-intensive: 0.58 kg dm/day milk replacer consisting of 21.5% cp and 21.5% fat/kg dm. study design: randomised control trial outcome studied: conception age afc adwg bcs at mating economic return main findings (relevant to pico question): adwg was 0.2 kg/day greater preweaning on the intensive diet (0.64 vs 0.44 kg/day) adwg post-weaning was not significantly different age at conception and afc was 15 days sooner in the intensive diet group milk yield (to 150 dim and predicted 305 day yield) was not significantly different from each group bcs at mating was not significantly different economic return was marginally in favour of intensive feeding but return could be positive or negative based on milk prices limitations: out of the n=40 heifers in each group, 38 (out of 80 total) were excluded (not known exactly how many from each group were excluded) for reasons of disease, late attainment of pregnancy, failure to conceive after three services, abortion, low my and lameness. afc was found to have no effect on yield but there were only 15 days between each group so differences were not significant. haworth et al. (2008) australia population: primiparous dairy cows sample size: 442 cows from one farm intervention details: effects of varying afc study design: case series outcome studied: first lactation my lifetime my longevity main findings (relevant to pico question): afc varied from 700–1200 days (22–29 months) with most calving at 22–32 months there was no significant difference in the influence of afc on first lactation my, subsequent lactation yields and lifetime yield or on longevity cows giving <30 litres/day had greater longevity and cows giving >30 litres/day had higher yields and lower longevity limitations: very small sample number to make conclusions over effects of afc on lifetime parameters: this is why yield in the first lactation had more effect on outcomes than afc. one farm had huge variation in afc: this implies that there may have been many other factors in heifer management that could have influenced the yield result later in life. ruiz-sanchez et al. (2007) united states of america population: dhi contributing herds to national us dairy program sample size: 248,230 cow records from 3,042 herds in dhi program intervention details: retrospective analysis of data from us dairy program database. study design: case series: linking association of yield, afc and genetic heritability traits on herd data in “low” and “high” environment herds. high and low environment herds were classified by upper and lower quartile respectively of herd-year season combination of mean and sd for my. outcome studied: first lactation my afc genetic associations of afc and yield using breeding values and sire heritability traits lifetime my longevity main findings (relevant to pico question): afc had a mean of 28.4 months (sd 3.4) in lower quartile herds and 25.8 months (sd 2.9) in higher quartile herds first lactation my in lower quartile herds was 8,450 kg (sd 1,448) and 10,821 kg (sd 1,946) in higher quartile herds genetic associations of afc and my were negative regardless of herd “level”, suggesting a genetic by environment interaction but the author states that this should be interpreted with caution as genetic relationships are dynamic within herds, especially in situations of population selection. lower quartile environment herds had genetic correlation of -0.31 and higher herds had one of -0.51 for both afc and my limitations: limited to herds contributing to the dhi us dataset and therefore may be better managed herds. historical dataset (1987–1994) and over multiple years, where many other factors may have influenced the dataset (especially in improvement programs). linking genetic heritability to environmental factors and using afc as an outcome measurement is very risky: afc is influenced by every management factor in youngstock rearing, so linking genetics to this is extremely challenging. this is recognised by the authors as a limitation also. banos et al. (2007) united kingdom population: dairy cows sample size: 228,229 records from data from the uk national fertility database 1997–2005 intervention details: afc, age at second calving and bcs of dam in gestation study design: case series outcome studied: calving interval days between calving and first service number of inseminations per conception non-return to oestrus 56 days after first insemination my at third test day (3 months into lactation) main findings (relevant to pico question): afc of 18 to 23 months of age, produced 4.5% more ï¬�rst lactation daily milk, had 7% higher bcs, and had their ï¬�rst service 3 days earlier than cows whose dams calved late (30 to 36 months) afc of 18–23 months had 7% more inseminations and had a 7.5% higher rate of return to oestrus limitations: it is assumed that many of the cows included would have been holstein breed but it is not specifically stated in the paper. historical dataset (1987–1994) and over multiple years, where many other factors may have influenced the dataset (especially in improvement programs such as the fertility database). bcs is subjective and variable in recording. calving interval is historical and not considered a useful parameter in 2019 dairies. ettema & santos (2004) united states of america population: primiparous holstein dairy cows sample size: 1,905 heifers in three groups of afc: afc of <700 days, n=514 (low) afc of 701-750 days, n=917 (medium) afc of >750 days, n=474 (high) intervention details: varying afc and its effects on productivity study design: case series outcome studied: my conception rates disease rates after birth economic income main findings (relevant to pico question): mean group conception rates at first artificial insemination in low, middle and high groups were 76.9%, 64.4% and 44.9% respectfully my in first lactation per group: low (33.4 ± 0.23 kg/d); medium (34.4 ± 0.18 kg/d); high (34.7 ± 0.24 kg/d) and the low group tended to give 310 kg less milk in first lactation heifers in the middle afc group had economic income of between us$138.33 and us$98.81 compared with those in the low and high groups afc had no influence on post-partum diseases limitations: it is mentioned by the authors that afc can be confounded with bw, as this is recognised to influence first lactation yields. nilforooshan & edriss (2004) iran population: primiparous holstein dairy cows sample size: 12,082 cow records from 42 herds. data from 1991–2001 intervention details: varying afc effects on production and longevity study design: case series outcome studied: first lactation yield first lactation fat yield longevity main findings (relevant to pico question): afc was optimal between 22–24 months for first lactation yield, peaking at 7,000 kg (ranging 5,700 kg at 21 months to 6,100 kg at 34 months). this is true also for fat yield (190 kg for 22–24 months versus 170 kg for <22 months and 175 kg at 34 months) afc <22 months was detrimental for first lactation yield by up to 800 kg afc was not seen to directly influence longevity but productivity over lifetime positively influenced longevity. heritability of afc was very low (0.082) limitations: data collected over a long period of time and many other factors could influence outcomes, especially if the herds are in improvement programs. data from software recorded herds may be from better managed herds and therefore not be representative of the country population. pirlo et al. (2011) italy population: primiparous holstein dairy cows sample size: 1,048,942 cow records from italy between 1992 and 1997 intervention details: retrospective on-farm data analysis of afc effects on first lactation yield and economic return study design: case series outcome studied: first lactation yield and economic return main findings (relevant to pico question): optimum afc was between 22–24 months. cows calving with an afc of 36 to 29 months gave an average of 170.2 kg less milk over the first lactation. cows calving with an afc of 29–24 months gave a mean average of 254.9 kg less milk in the first lactation. cows calving with an afc of < 20 months gave a mean average of 589.8 kg less milk in the first lactation. reducing afc between 26–22 months increased the economic return by us$41.5 and us$24/heifer. delaying afc beyond 26 months reduced returns due to an increase in rearing costs. limitations: historical data and collected over several years, so other factors could have influenced results, such as improvement programs and environmental factors. berry & cromie (2009) republic of ireland population: primiparous holstein-friesian seasonal grazing dairy cows sample size: 196,120 cow records from herds of over 30 cows in the irish cattle breeding federation from 2000–2006 intervention details: varying effects of afc study design: case series outcome studied: first lactation my fertility survival main findings (relevant to pico question): afc ranged from 660–1156 days with peaks at 24 and 36 months afc decreased linearly, associated with first lactation yield of milk, fat and protein by 55.5 kg, 0.6 kg and 2.3 kg respectively for each month from 20 months afc was associated with survival to second, third, fourth and fifth parity animals with an afc of 24 months had greatest odds of survival in the first lactation (odds ratio of around 1.0), decreasing to an odds ratio of around 0.7 for afcs from 28–38 months there was no association found with afc and survival above the first parity limitations: collection of data over 6 years and other factors could influence the outcomes studied such as herd improvement programs and environment. herds specified as seasonal grazing herds but not specified whether spring or autumn calving. this may affect yield from grazing herds in ireland as well as heat effects in spring calving herds (even in ireland it can reach over 24 °c). very large range of afc. numbers of animals in distribution graphs peaked at 24 and 36 months (very far apart): this indicates a great variety of management factors that are influencing heifer growth, which may also affect the outcomes measured. changee et al. (2013) korea population: holstein dairy cows sample size: 276,573 cow records: data from 1998–2004 intervention details: varying afc on production effects study design: case series outcome studied: first two calving intervals days in milk for lifetime lifespan milk income lifetime profit main findings (relevant to pico question): profit increased by us$3.45 per day of lifetime increase afc had very few heritability traits (<0.14 on all outcomes studied) lifetime profit increased by us$727.30 by reducing afc from 32–22 months optimum afc for lifetime profit was between 22.5–23.5 months limitations: collection of data over 6 years and other factors could influence the outcomes studied such as herd improvement programs and environment. lifetime profit had a very large residual spread over 3000 days (6 lactations) which could skew some of the conclusions on profitability for later lactations. appraisal, application and reflection appraisal of papers this knowledge summary includes 17 papers from 10 countries: four from usa; three from iran; three from uk and one each from korea, ireland, italy, poland, czech republic, norway and australia. together, they include over 2,645,158 cow records in 15 case series, one randomised control trial and one review. they cover scientific literature published from 1979–2018 (pre-2000 references coming from wathes et al. (2014). case series mostly include data taken from large farms with computerised dairy records. many of these include farms on dhi programs (elahi torshizi,  2016 and ettema & santos, 2004) and cover data spreading over 2–5 years (berry & cromie, 2009; eastham et al., 2018 and nilforooshan & edriss, 2004). although this technique gives large sample population numbers, it may also create confounding factors: farms that use computer records and that participate in herd improvement schemes may not be representative of all dairy farms and are already skewing data towards the more advanced farm management systems. therefore the afcs recorded as the range within the country may be lower than the real picture. also, if data from farms on improvement programs cover several years, it may be likely that the afc and yields (and diets, disease management, heat abatement, etc.) may improve anyway, also confounding results. outcomes of afc generally, my data is well recorded on farms, as it represents the main form of income to the businesses. only one of the reviewed papers mention the confounding effect of bw at calving on first lactation 305 day yield (ettema & santos, 2004). as afc also influences first lactation 305 day yield, further research including this parameter would be preferable in future to attempt to separate these effects. in contrast, fertility data is not so clear. some papers use calving interval (the mean average between calvings in days); some use days open (the average number of days from calving to confirmed pregnancy) and others use first service conception rate (percentage of cows pregnant to the first service after voluntary waiting period). unfortunately, calving interval is a very historical parameter: it generally represents cows that got pregnant at least 9 months to 1 year previous to the date it is recorded. therefore, when measuring afc effects in calving interval, the records may not be representative of the afc group from the year studied, or include the confounding effect of culling in calculating calving intervals. similarly, days open requires at least 85–120 days from calving to calculate a figure, so to be representative of the sample population, it must be recorded over at least a year. again, this means that the afc recorded may not be the same group of those providing the days open result. also, when assessing improvements in days open, one must consider that it will go up before it goes down: only non-pregnant cows are included in the calculation: when a cow gets pregnant, she is removed from the “pool” of animals contributing to the data. therefore, if more cows get pregnant, the pool of non-pregnant animals is skewed to a larger figure as it is more influenced by chronically non-pregnant cows. when these leave the population, the days open figure will finally go down but this may be a long time from the afc figure recorded from the farm. so the more representative figure for testing afc is the first service conception rate used in ettema & santos (2004) compared to calving interval and days open used in krpalkova (2014) and eastham et al. (2018). two papers showed an influence on longevity from afc, with those calving in the 24 month window having a high odds ratio of surviving their first lactation of 0.8–1.0 and those calving later, beyond 28 months having an odds ratio of <0.72 (eastham et al. 2018 and berry & cromie, 2009). others found no significant, direct effect. survival in dairy cows is strongly influenced by productivity: whether this is from low yields, low fertility or presence of disease. afc is linked to lower yields in ranges outside of 22–26 months, which could influence a culling decision but this decision may be more likely to be made from one of the other factors first. as far as profitability is concerned, in order to calculate the effect of afc on yield and fertility, a considerable amount of modelling is required. there is a lot of potential here for different researchers to include different parameters into their model: feed prices change by country and over time, as does economy in general, therefore the conclusion of one paper may not be comparable with another. as the effects of afc (yield, fertility and culling) are influenced by so many other factors, the model is required to have many inputs, from labour, feed price, veterinary costs, rent, energy costs, disease rates, etc. when this is calculated, it is easy for some groups to miss some inputs and also, without considerable detail, avoid double-counting. for this reason, it is not advisable to take a value published from these papers and directly translate that to the reader’s situation. application and reflection the clinical bottom line has far-reaching consequences for advisors on dairy farms. afc is a key performance indicator of heifer management, including diet quality and availability, disease risk, insemination techniques and preweaning growth. a knowledge of the evidence that sets a target window of 22–26 months is a crucial tool in youngstock management advice. not reaching these goals can be detrimental to both fertility and milk income, so hitting these targets gives both foundation and drive to improvement projects throughout the industry. further research in the interaction of body weight at birth and afc on first lactation yield would provide more clarity on the individual effects of both on production.   methodology section three databases were used to search this pico. the author has chosen to exclude papers before 2000, as dairy records before this date were limited and the management/genetics of dairy cows since this date have changed considerably in many countries through improvement schemes. one review wathes et al. (2014) mentions papers back to 1979 and is a comprehensive work summarising much of the intervening period, so as it is included in this review, it was felt by the author to be a sufficient summary of the evidence pre-2000. the pico focused on effects rather than inputs to afc so articles were excluded that concentrated on influences on afc rather than consequences of varying afc. there have been publications linking afc to genetic heritability traits, as this is an attractive theme to offer from genetic improvement (semen) companies. however, it has been evident from the literature that heritability of afc is very low and not a significant factor (ruiz-sanchez et al. 2007): many other publications also make this conclusion. for this reason, the author has excluded genetic heritability papers from the knowledge summary. search strategy databases searched and dates covered: pubmed (ncbi) february 28th 2019; cab abstracts march 1st 2019; google scholar march 1st 2019). filtered from 2000 to 2019 search strategy: using advanced search keywords on words based only in the pico topic pubmed: ((((((bovi* or cattle or cow$ or heifer))) and (([age at first calving] or afc or [calving age])))) and milk) and ((yield or volume or weight)) and ("2000/01/01"[pdat] : "2019/12/31"[pdat]) cab abstracts: (cattle or cow$ or heifer or bovi*) and ([age at first calving] or afc ) and ( yield or production or lactation) and (reproduc* or fertility) limiters: scholarly (peer reviewed) journals; date of publication: 20000101-20191231 google scholar: (cattle or cow$ or heifer or bovi*) and ([age at first calving] or afc) and (yield or production or lactation) and (reproduc* or fertility). date of publication: last 10 years dates searches performed: date search performed 28/02/2019 and 01/03/2019 exclusion / inclusion criteria exclusion: pre-2000. heifer management and breeds of holstein dairy cattle have changed significantly since 2000 as dairies across the world increasingly use computer software and targeted strategies. bos taurus only papers concentrating on growth rates in youngstock and afc papers concentrating on nutritional protocols in youngstock and afc inclusion: associations between afc and yield or reproduction in bos taurus dairy cattle assessments of factors affecting afc and performance any breed reported (not restricted to holstein-friesian) but mentioned in the population studied sections peer-reviewed papers only search outcome database number of results excluded – pre 2000 excluded – non-relevance to pico excluded – related to factors before calving rather than afc total relevant papers pubmed 472 91 362 4 15 cab abstracts 677 296 359 14 8 google scholar 201 76 118 3 4 total relevant papers when duplicates removed 17 conflict of interest the author declares no conflicts of interest. references adamczyk, k., makulska, j., jagusiak, w. & wä™glarz, a. 2017. associations between strain, herd size, age at first calving, culling reason and lifetime 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fertility and carry over consequences for life time production in dairy and beef cattle. animal 8 (1): 91–104. doi: http://dx.doi.org/10.1017/s1751731114000755 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. integrating veterinary subject expertise with information literacy expertise to teach and assess the student skills in evidence-based veterinary medicine heather moberly (msls, ahip, afhea)1* 1texas a&m university, 400 bizzell st, college station, tx 77843, usa *corresponding author (hmoberly@library.tamu.edu) vol 2, issue 2 (2017) published: 24 may 2017 doi: 10.18849/ve.v2i2.121 in this talk heather will discuss how they successfully integrate asking a clinical question, searching the literature, appraising the literature, and applying evidence to the clinical question to make a clinical recommendation in a pre-clinical, 2nd year, course (pharmacology) and two 4th year clinical rotations (small animal dermatology and food animal). find out more about heather. view presentation slides comments: comparing rest alone to bandaging and rest in horses with superficial digital flexor tendinopathy a knowledge summary by rafael alzola bvms, msc, cert avp (ep, esst, eso, vdi) mrcvs 1* sarah l. freeman bvetmed, phd, certva, certvr, certes, dipecvs, fhea, frcvs 2 1oakham veterinary hospital, nottingham university, ashwell road, oakham, rutland, le15 7qh 2school of veterinary medicine and science, university of nottingham, sutton bonington campus, leicestershire, le12 5rd *corresponding author (rafael.alzola@oakhamvethospital.co.uk) vol 4, issue 3 (2019) published: 06 aug 2019 reviewed by: matthew stewart (mvetclinstud, phd, facvs) and peter clegg (ma vet, mb, phd, certeo, dipecvs, mrcvs) next review date: 11 sep 2020 doi: 10.18849/ve.v4i3.234 pico question in horses with superficial digital flexor tendonitis is bandaging and rest compared to rest alone more effective at promoting healing? clinical bottom line there is currently a lack of scientific evidence to suggest that bandaging promotes effective tendon healing following injury. however, rigid bandages significantly limit lesion propagation in equine superficial digital flexor (sdf) tendinopathies. the result of this pico question suggests that a short period (ten days) of cast immobilisation during the initial inflammatory phase of the injury improves prognosis by limiting lesion propagation. the level of confidence in the outcomes from the body of evidence in the four studies identified is moderate. clinical scenario an 8-year-old thoroughbred gelding used for national hunt racing presents with a recent history of swelling of the right forelimb (rf) flexor tendons (bowed tendon) following morning training. the horse is only slightly rf lame in straight line on hard ground but he resents palpation of the superficial digital flexor tendon (sdft). ultrasonographic examination revealed a sdf tendinitis with a core lesion affecting 4 zones (2a–3b); the maximal injury zone (miz) is located at 2b. the lesion at the miz is anechoic (score 1), affected <25% of the cross-sectional area (score 1) and between ≧50–75% of the longitudinal pattern (score 3) of the tendon (alzola et al., 2017). you discuss all treatment options, including medical and surgical options, with the owner and trainer. however, the horse raced only in low price claiming races and the trainer is not very fond of him. the decision is made to either treat the injury conservatively and cheaply or retire the horse from racing. what evidence is there to inform the owner and the trainer that bandaging and rest compared to rest alone is more effective in cases with sdf tendinopathy? the evidence there is no evidence within the literature to support that any type of bandaging enhances tendon healing during the resting period following a tendon injury. however, bandaging (cast bandage) has a significant effect limiting lesion propagation during the initial inflammatory phase in sdf tendinopathies. the quality of the evidence comparing rigid versus nonrigid bandages to limit lesion propagation is of moderate quality and reliability. in different randomised controlled trials lesion propagation was significantly reduced using a short period (10 days) of cast immobilisation compared to a two layer robert jones bandage or no bandage. however, the studies only included either surgically or collagenase-induced lesions and need validating in naturally occurring injuries. potential short or long-term detrimental effects of immobilisation (cast) were not investigated in these studies. summary of the evidence david (2011) population: six mature standardbred horses with an average age of 52 ± 13 months (mean ± s.d.) and weight of 489 ± 28 kg. including only horses that were free of lameness and absence of any current or previous sdft injuries was confirmed ultrasonographically sample size: 12 forelimbs with surgically induced core lesions in the sdft intervention details: core lesions in both front sdfts were surgically created mimicking clinical lesions through a stab incision into the sdft for a length of 6 cm using an arthroscopic obturator (diameter 3.5 mm) and burr (diameter 4 mm) with horses under general anaesthesia. one randomly chosen forelimb per horse (n=6) was immobilised with a half-limb cast while the opposite limb was placed in a two layer robert jones bandage (control; robert jones bandages were changed every third day): six cast and six control forelimbs. 10 days post surgery the cast, robert jones bandage and skin sutures were removed and a stable bandage (single layer inelastic bandage with padding) was placed on each forelimb for 5 days. horses were box rested until day 28 post surgery, followed by daily hand walking (10 minutes) until the end of the study (day 42) when they were euthanised. study design: prospective experimental study outcome studied: objective assessment variables measured: computerised ultrasonographic tissue characterisation (utc) was used with a standardised protocol on days, 0, 10, 15, 21, 28, 35 and 42 post surgery to evaluate the lesions: sonographic visualisation: lesion length (cm) stability of the echo pattern: lesion width (%) macroscopic digital photographs of the transverse slices of the tendons obtained on day 42 were used to calculate the macro length of the lesion for each forelimb. main findings (relevant to pico question): lesions were 19% shorter (length) and 57% smaller (width) in cast compared to the control (robert jones bandage) forelimbs (p≤0.04): utc findings (mean ±e.): lesion length (cm): cast (6.13 ± 12) control (7.30 ± 0.21) lesion width (%): cast (6.90 ±64) control (10.85 ± 1.22) macroscopic evaluation (mean ±e.): lesion length (cm): cast (7.00 ± 0.36) control (8.33 ± 0.33) limitations: core lesions in sdfts were created surgically and might not correspond to naturally occurring injuries or behave in the same way. extra load on the controlled limbs due to the cast on the opposite limbs was not calculated and its effect was not investigated. potential short or long-term detrimental effects of immobilisation (cast) were not investigated. although robert jones bandages were changed every third day, confirmation that desired pressure was achieved and maintained with the bandage was not performed (pressure sensors). bosch (2010) population: 12 mature dutch warmblood horses with mean age 9.3 years (range 7–14 years) and weight of 600 kg (range 550–650 kg) that were euthanised for reasons not related to tendon disorders. absence of tendon disorders was confirmed by physical palpation and postmortem ultrasonography sample size: 22 forelimbs with either surgical or collagenase-induced core lesions in the sdft intervention details: forelimbs were divided in three experiments: collagenase-induced tendon lesions: control group to study the propagation of lesion (unloaded conditions): n = 6 limbs.limbs were left without loading 8 h. loaded group to study the effect of cyclical loading and the effect of immobilisation: six pairs of limbs (12 limbs). limbs were subjected to 5000 unload load cycles over 8 h period using a pneumatic limb loading device (1800 n, 600 n/s): n = 6 limbs cast; 6 limbs uncast. lesions were created injecting bacterial collagenase type i (1500 u) (ultrasound guided) into the core of the sdft: surgically-induced tendon lesions: to study the propagation of lesions under cyclical loading: n = 4 limbs (no control group, all limbs were loaded). lesions were created through a stab incision into the sdft over a length of 7–8 cm (marked) using an arthroscopic burr (diameter 3.5 mm). all limbs were subjected to 5000 unload load cycles over 48 h period using a pneumatic limb loading device (1800 n, 600 n/s). study design: prospective experimental study outcome studied: objective assessment  variables measured: collagenase-induced lesions: ultrasonographic evaluation of the lesions on all limbs. macroscopic evaluation: average values of the length (cm) and width (%) of the lesions. force at rupture (n) between uncast and cast limbs (loaded group only.) surgically induced lesions: macroscopic evaluation: no difference in length (cm) of the lesions before and after cyclic loading. no further investigation performed. main findings (relevant to pico question): in surgically induced lesions in dead limbs where there is no enzymatic stimulation (only mechanical stimulation) there is no propagation. therefore, lesion propagation is caused by the combination of enzymatic and mechanical stimulation. in this ex vivo model casting appeared effective to reduce the enlargement of the original collagenase-induced tendon lesions after cyclical loading (2.85 ± 0.59 cm) compared to uncast limbs (4.33 ± 0.63 cm) but did not affect ultimate tendon strength. limitations: this is an ex vivo model that does not replicate the in vivo lesion. sdft lesions were created surgically or enzymatically and do not correspond to naturally occurring injuries or behave in the same way. loading regimen used in this experiment is low (1800 n) compared with the loading applied at walk (3600 n). relationship between type of lesion (surgical or collagenase-induced) and force at rupture was not investigated. potential detrimental effects of immobilisation (cast) were not investigated. smith (2002) population: postmortem equine forelimbs from thoroughbred type horses with no signs of distal limb injury sample size: seven postmortem equine forelimbs intervention details: forelimbs were loaded in a pneumohydraulic loading machine (hydraulic test rig):  force acting on the limb was recorded through plate and shear beam load cell (tw560) mounted under the hoof. metacarpophalangeal (mcp) joint angle was recorded with a goniometer. force and angle data were amplified via strain gauge amplifiers. data were captured and stored for analysis using a personal computer. forelimbs were initially loaded to a peak force of 5 kn over 5 seconds and then unloaded at the same rate. two further loading cycles were then applied during which forelimb force and mcp joint angle were recorded. five support methods (gamgee, neoprene, dalmar support system [settings 1, 2 and 3] and three layered bandage with and without splint) were applied in the same sequence for each forelimb. each forelimb was loaded twice for each support method, only the second loading cycle was used in the analysis. a control loading (bare forelimb) was recorded in between support methods. study design: prospective experimental study outcome studied: objective assessment  forelimb force (kn) at specific mcp joint angles (215°, 220°, 225°, 230°, 235°, 240°, 245°, 250°) main findings (relevant to pico question): three layered bandage with or without (only at high mcp joint angles ≧245°) a palmar splint, and the dalmar tendon support boot both provide significant resistance to mcp joint extension. this will reduce the strain experienced by the sdft, deep digital flexor tendon (ddft) and suspensory ligament allowing tendon/ligament healing. in addition, the dalmar tendon support boot can be used in exercising horses (mechanical protection). forelimb force mcp joint angle relationship for all the different support techniques compared to an isolated forelimb (ex vivo): neoprene boot or a simple gamgee bandage have no significant effect on the forelimb force mcp joint angle relationship. three layered bandage: without palmar splint has a significant effect only at high mcp joint extension angles ≧245°. with palmar splint has a significant effect at mcp joint extension angles ≧230°. dalmar tendon support boot: setting 1 and 2 have a significant support at high mcp joint extension angles ≧245°. setting 3 provides significant support at mcp joint extension angles ≧225°. limitations: this is an ex vivo model that does not replicate what occurs in live animals. further research (in vivo model) is required to confirm that some support methods (three layered bandage with or without palmar splint and dalmar tendon support boot) are useful to manage tendon/ligament injury throughout healing and rehabilitation. absence of any current or previous tendon injuries in the investigated limbs was not confirmed with palpation and ultrasonography. loading force in study was 10 n/kg body mass but it would have been more appropriate to use the peak mcp joint angle during stance (216° at walk, 232° at trot, 228° at lead canter, 238° at non lead canter and 250° at gallop (mcguigan, 2001)). long-term consequences of reduction of mcp joint extension vs. fibre alignment during the healing process in injured horses was not investigated. kicker (2004) population: mature warmblood horses (seven mares, two stallions, 17 geldings) were included with average age of 11 ± years (mean ± s.d.) and weight of 533 ± 53 kg. sample size: 26 mature warmblood horses intervention details: kinematics (six camera video system with a sampling frequency of 120 hz) of the forelimb fetlock joint angle at walk and trot on a treadmill when each horse was wearing three different support boots (sport medicine boots, eskadron and tsm aed rehaand sport bandages), one protective boot (streifamasche, predefined tension 50 n) and without boots (control group): constant speed for each horse (walk: 1.6 ±1 m/sec; trot: 3.3 ± 0.2 m/sec; mean ± s.d.) recorded: 30 seconds of walk and trot at walk: minimum of 20 cycles at trot: minimum of 30 cycles study design: prospective experimental study outcome studied: objective assessment variables measured: maximum extension of the fetlock joint: minimal virtual dorsal fetlock joint angle (°) moment at which maximum extension occurred in the stride cycle: occurrence time of minimal virtual dorsal fetlock joint angle (% of the stride cycle) main findings (relevant to pico question): support boots reduce maximum extension of the fetlock, which can be assumed to reduce tension in the suspensory apparatus and sdft. delay of the moment of maximal extension may be relevant in reducing dynamic forces. more specifically: at walk: two of the support boots reduced the maximum extension angle by 0.8° (eskadron) and 0.9° (tsm aed rehaand sportsbandages) (p<0.05) and one type of boot (tsm aed rehaand sportsbandages) also delayed the occurrence of maximal extension within the stride cycle (theorical reduction of the dynamic load of the sdft; no clinical significance). minimal virtual dorsal fetlock joint angle for the control group (unprotected) at walk: 136.26° ± 6.44° (mean ± s.d.) at trot: all support/protective boots reduced the maximum extension angle by 0.56°–44° (p<0.05) and none delayed significantly the occurence of maximal extension within the stride cycle. minimal virtual dorsal fetlock joint angle for the control group (unprotected) at trot: 122.73° ± 6.3° (mean ± s.d.) limitations: absence of any current or previous tendon injuries or lameness in the investigated limbs was not confirmed with palpation and ultrasonography. treadmill speed was not standardised for all horses which could have affected the results. a further group including horses recovering from a tendon injury would have provided useful information for this study. appraisal, application and reflection this pico question focuses on the benefits of bandaging and rest versus rest alone for treating superficial digital tendonitis in equids. the four relevant studies found to fit the pico criteria were prospective experimental studies and the evidence gained from them is reported above. this represents evidence of moderate quality and reliability as only one of the two in vivo studies, contrary to the in vitro, mimic the naturally occurring injuries. superficial digital flexor (sdf) tendinopathy is a common injury in equine athletes, following undefined periods of accumulation of exercise and age related microdamage without any preceding clinical signs. complete tendon healing is a long process, re-injury rates are high, and these injuries are potentially career ending for the most severe cases. lesion size is directly linked to prognosis, with poorer prognosis for larger sdft injuries (alzola et al., 2018). therefore, tendinopathy is a significant health and welfare concern in horses. in clinical situations, sdf tendinopathies have a tendency to propagate (length and width) significantly during the first few weeks after initial injury due to the combination of enzymatic and biomechanical stimulation (bosch et al., 2010). the tendon healing process follows the general pattern of wound healing with overlapping phases: inflammatory, proliferative and maturation phase. lesion propagation occurs during the initial inflammatory phase (approx. 10–21 days) when the disrupted tendon fibres are digested by proteolytic enzymes like metalloproteinases and then removed by phagocytosis ( leadbetter, 1992 and palmer et al., 1994). biomechanical loading, even at very low levels, induces propagation but only in conjunction with the activity of proteolytic enzymes (bosch et al., 2010). therefore, results from ex vivo cadaveric studies should be interpreted with caution as inflammation cannot be reproduced. there is no evidence within the literature to support that any type of bandaging promotes tendon healing during the resting period. however, bandaging has a significant effect on limiting lesion propagation. ex vivo (bosch et al., 2010) and in vivo (david et al., 2012) studies have proven that motion restriction of the lower limb with a rigid bandage (cast bandage) significantly reduces lesion propagation during the acute phase improving prognosis. nonsteroidal anti-inflammatory drugs (nsaids) also influence lesion propagation by inhibiting inflammation and concomitantly proteolytic enzyme activity (mehallo et al., 2006), but review of this evidence is beyond the scope of this knowledge summary. flexor tendons (sdft and ddft) and the suspensory ligament remain loaded for as long as the limb is weight-bearing, even in box rested horses. biomechanical loading on the sdft is maximal during hyperextension of the metacarpophalangeal (mcp) joint. in the standing horse, resistance to extension of the mcp joint is a passive process; an increase in mcp joint angle will result in an increase strain in the tendons and ligaments (bartel et al., 1978 and shoemaker et al., 1991). multiple external support techniques (rigid/nonrigid) have been used to resist overextension of the mcp joint to reduce potentially damaging peak loads and strains to the sdft after injury or to reduce re-injury risk. contrary to rigid bandages, in an ex vivo study, nonrigid support systems (conventional bandages) did not provide significant resistance to mcp joint extension during the stance phase or walk (smith et al., 2002). reducing mcp joint extension is essential in the box rest period for tendon healing. controversially in an in vivo study, support boots did reduce significantly mcp joint extension during walk and trot (kicker et al., 2004). using ultrasonography in an ex vivo equine model of acute sdft injury (collagenase-induced model), lesion length was significantly greater (p<0.05) in the repetitively loaded forelimbs compared to the cast (half forelimb cast) or unloaded forelimbs that were almost identical (bosch et al., 2010). in this study, there was no difference in lesion width or in the force at rupture (f failure) between uncast and cast limbs. in a more recent in vivo study using computerised ultrasonographic tissue characterisation to evaluate surgically induced sdft lesions, limb casting reduced significantly lesion size (length and width) compared to bandaging with a 2-layer robert jones bandage (p≤0.04). these findings were also corroborated during macroscopic evaluation of the lesions. in this study, cast immobilisation for ten days during the early phase of tendon healing effectively reduced lesion propagation compared to bandaging (david et al., 2012). although there is no evidence in equids regarding the optimal immobilisation time during the rest period, ten day cast immobilisation is in accordance with the human literature that recommends casting only during the acute phase of tendon injuries for about 5–7 days (buckwalter, 1995). cast immobilisation during the acute inflammatory phase provides constant counter-pressure to longitudinal, transverse and rotational forces and avoids mcp hyperextension (smith et al., 2002) avoiding lengthening of injured structures and slowing down the “pump” phenomenon at the tendon level (cribb & scott, 1995), hence preventing lesion propagation. in addition, cast immobilisation will also limit secondary sdft injuries (kannus et al., 2003). some human studies have shown that stress deprivation of the sdf tendon induced by long-term cast immobilisation could negatively affect tendon biochemical and biomechanic properties, as well as tendon repair (yasuda & hayashi, 1999 and aspenberg, 2007). however, the former effects are time dependent and, therefore, reversible with remobilisation. short term immobilisation does not result in significant reduction of physiological properties in healthy tendons (christensen et al., 2008). likewise, half limb casting does not seem to produce a complete stress shielding effect in equids, providing some degree of mechanical stimulation (david et al., 2012), which is known to avoid tendon degeneration (nabeshima et al., 1996). an early and gradual increase in physical load improves healing by enhancing synthesis of collagen during the proliferation phase and alignment of collagen fibres in the remodelling phase (dowling et al., 2000 and aspenberg, 2007). after cast removal, the support provided to the mcp joint should be reduced gradually using less rigid support systems: modified robert jones distal limb bandage with a contoured palmar splint, dalmar tendon support boot (smith et al., 2010) or some support boots (eskadron or tsm aed rehaand sportsbandages) (kicker et al., 2004). this will avoid sudden increase in tissue loading throughout healing tissues. unfortunately, not all of these systems will be practical to use in exercising horses during rehabilitation. lesion length and lesion width is bound to increase after support removal in both cast and bandage, although these changes were significantly shorter and smaller in casted lesions (david et al., 2012). after cast removal, rest should be continued until the initial inflammatory response subsides (approx. 4–6 weeks in total) and followed by a well designed exercise programme to achieve optimal alignment of collagen fibres (kicker et al., 2004). in conclusion, bandaging does not enhance tendon healing during the rest period (acute inflammatory phase) but a short period (ten days) of cast immobilisation improves prognosis for sdf tendinopathies by preventing lesion propagation with minimal negative effects to the tendon. cast immobilisation period must be followed by early functional therapy to enhance tendon healing using support systems to reduce extension mcp joint and subsequently tension in the sdft. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform (1973–2018 week 35) pubmed via the ncbi website (1910–september 2018) search terms: cab abstracts: (equine or equines or horse or horses or equus or equid or equids or mare or mares or broodmare or broodmares or pony or ponies or filly or fillies or colt or colts or yearling or yearlings or stallion or stallions or thoroughbred or thoroughbreds or standardbred or standardbreds or racehorse or racehorses or race horse or race horses).mp. or exp horses/ or exp equus/ or exp equidae/ or exp mares/ or exp colts/ or exp foals/ or exp stallions/ or exp thoroughbred/ or exp racehorses/. ("superficial digital flexor tendon" or "superficial digital flexor tendons" or "digital flexor tendon" or "digital flexor tendons" or "superficial digital flexor tendonitis" or "superficial digital flexor tendinitis" or "superficial digital flexor tendinopathy" or sdft or "superficial digital tendon" or "superficial digital tendonitis" or "superficial digital tendinitis" or "superficial digital tendinopathy" or sdf or tendonitis or tendinitis). (bandages or bandaging or bandaged or bandage or binding or bind or bound or binds or dresses or dressing or dressed or dressings or cast or casting).mp. or exp bandages/. (rest or resting or rested or rests). 1 and 2 and (3 or 4). pubmed  equine or equines or horse or horses or equus or equid or equids or mare or mares or broodmare or broodmares or pony or ponies or filly or fillies or colt or colts or yearling or yearlings or stallion or stallions or thoroughbred or thoroughbreds or standardbred or standardbreds or racehorse or racehorses or race horse or race horses. ‘superficial digital flexor tendon’ or ‘superficial digital flexor tendons’ or ‘digital flexor tendon’ or ‘digital flexor tendons’ or ‘superficial digital flexor tendonitis’ or ‘superficial digital flexor tendinitis’ or ‘superficial digital flexor tendinopathy’ or sdft or ‘superficial digital tendon’ or ‘superficial digital tendonitis’ or ‘superficial digital tendinitis’ or ‘superficial digital tendinopathy’ or sdf or tendonitis or tendinitis bandages or bandaging or bandaged or bandage or binding or bind or bound or binds or dresses or dressing or dressed or dressings or cast or casting. rest or resting or rested or rests. 1 and 2 and (3 or 4) dates searches performed: 11th september 2018 exclusion / inclusion criteria exclusion: non english or spanish language publications or articles not relevant to the pico. no study was excluded based on the study type. inclusion: studies available in english or spanish relevant to the pico search outcome database number of results excluded – not in english or spanish lan-guage excluded – did not address the pico question excluded – duplication total relevant papers cab abstracts 77 16 58 0 3 pubmed 32 1 28 2 1 total relevant papers when duplicates removed 4 conflict of interest the authors declare no conflicts of interest. the authors extend their thanks to myai du for doing the abstract search to answer this pico question. references alzola, r., riggs, c.m., gardner, d.s., and freeman, s.l. (2017). “ultrasonographic scoring system for superficial digital flexor tendon injuries in horses: intraand interrater variability”. vet rec 181(24): 1– doi: http://dx.doi.org/10.1136/vr.104233 alzola, r., easter, c., riggs, c.m., gardner, d.s., and freeman, s.l. (2018). "ultrasonographic-based predictive factors influencing successful return to racing after superficial digital flexor tendon injuries in flat racehorses: a retrospective cohort study in 469 thoroughbred racehorses in hong kong." equine vet j 50(5): 602– doi: 10.1111/evj.12810 aspenberg, p. (2007). "stimulation of tendon repair: mechanical loading, gdfs and platelets. a mini-review." int orthop 31(6): 783– doi: 10.1007/s00264-007-0398-6 bartel, d.l., schryver, h.f., lowe, j.e., and parker, r.a. (1978). "locomotion in the horse: a procedure for computing the internal forces in the digit." am j vet res 39(11): 1721– bosch, g., lameris, m.c., van den belt, a.j., barneveld, a., and van weeren, p.r. (2010). 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"cell-matrix response in tendon injury." clin sports med 11(3): 533– mehallo, c.j., drezner, j.a., and bytomski, j.r. (2006). "practical management: nonsteroidal antiinflammatory drug (nsaid) use in athletic injuries." clin j sport med 16(2): 170– doi: 10.1097/00042752-200603000-00015 nabeshima, y., grood, e.s., sakurai, a., and herman, j.h. (1996). "uniaxial tension inhibits tendon collagen degradation by collagenase in vitro." j orthop res 14(1): 123– doi: https://doi.org/10.1002/jor.1100140120 palmer, s.e., genovese, r., longo, k.l., goodman, n., and dyson, s. (1994). "practical management of superficial digital flexor tendinitis in the performance horse." vet clin north am equine pract 10(2): 425– doi: https://doi.org/10.1016/s0749-0739(17)30363-2 shoemaker, r.s., bertone, a.l., mohammad, l.n., and arms, s.w. (1991). 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"changes in biomechanical properties of tendons and ligaments from joint disuse." osteoarthritis cartilage 7(1): 122– doi: 10.1053/joca.1998.0167 acknowledgement rcvs knowledge was supported in producing this knowledge summary by an educational grant from petplan charitable trust. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in cats infected with feline herpesvirus type-1 (fhv-1) does treatment with famciclovir result in a reduction of respiratory and ocular clinical signs? a knowledge summary by jacqueline cole bsc, bvetmed, mrcvs 1* 1university of bristol, senate house, tyndall ave, bristol bs8 1th *corresponding author (jc16689@my.bristol.ac.uk) vol 2, issue 3 (2017) published: 03 jul 2017 reviewed by: myra forster-van hyfte (certvr, certsam, dipecvim-ca, frcvs) and eva spada (dvm, phd) next review date: 03 jul 2019 doi: 10.18849/ve.v2i3.105 clinical bottom line based on the current available evidence, famciclovir may have a positive effect on reducing respiratory and ocular clinical signs of feline herpesvirus type-1 (fhv-1) disease, however further research is needed before famciclovir can be routinely recommended as part of a treatment protocol for this disease. question in cats infected with feline herpesvirus type-1 (fhv-1), does treatment with famciclovir result in a reduction of respiratory and ocular clinical signs? clinical scenario you are presented with a 3 year old male neutered domestic shorthair that has non-resolving rhinitis, previously treated with two different antibiotics. you have taken an oropharyngeal swab, which has come back positive for fhv-1. a colleague recommends trying the antiviral drug famciclovir. as the drug can be expensive you are unsure whether it is worth trying. summary of the evidence malik (2009) population: client owned cats split between australia (5), europe (1), and usa (4). four had ocular disease, two had rhinosinusitis and four had fhv-1 associated dermatitis sample size: n=10 intervention details: 4 cats with primary ocular disease were treated with 62.5mg famciclovir once daily for 7 days, then changing to twice daily except one cat who appeared to only be given a once daily dose. treatment length varied, with the 1st cat being treated for 35 days, the 2nd cat was treated for 43 days, the 3rd cat had no treatment length reported, and the 4th cat was treated for 14 days. 2cats were diagnosed with presumptive fhv-1 associated rhinosinusitis. one was treated with 62.5mg of famciclovir once daily for 4 months, the 2nd was treated with 62.5mg of famciclovir once daily for 7 days then twice daily for a total of 5 weeks. 5 cats had confirmed fhv-1 associated dermatitis, 4 were treated with 125mg of famciclovir three times daily for 2-6 weeks  and 1 was treated with an acyclovir cream that was applied to the lesions three to four times daily for an unconfirmed length of time. study design: case series outcome studied: whether famciclovir would be effective in reducing clinical signs in ocular, respiratory and dermatological diseases caused by presumptive fhv-1 infection main findings (relevant to pico question): in cats with presumptive fhv-1 ocular disease, famciclovir treatment reduced conjunctivitis, blepharospasm, epiphora, and increased re-epithelisation of the cornea. corneal sequesta detached in 2 out of 3 cats treated in 2 cases of presumptive fhv-1 associated rhinitis, famciclovir showed a clinical improvement, especially when combined with antibiotics. in 4 cases of confirmed (via viral inclusion bodies in skin biopsies) of fhv-1 associated dermatitis, all showed improvement with treatment, with 3 relapsing when antiviral therapy was stopped. whether famciclovir would be effective in reducing clinical signs in ocular, respiratory and dermatological diseases caused by presumptive fhv-1 infection limitations: being case reports, treatment differed between the patients, and was subjective as it was not blinded, and clinical data and follow-up was limited cats presented with different clinical signs and the majority were diagnosed presumptively with fhv-1. three likely had confirmed fhv-1 via inclusion bodies noted on skin biopsy samples, the rest having no definitive diagnosis confirmed via laboratory assessment. dose given and frequency differed between the cats one of the cats was not treated with famciclovir, but another anti-viral agent due to sourcing issues some cats were on adjunctive medications during their course of treatment that included antibiotics, immunosuppressives, and l-lysine as the cats were from different countries, there was possible differences in formulation sourcing of famciclovir no negative control group was included thomasy (2011) population: non-vaccinated specific pathogen-free cats sample size: n=16 intervention details: cats were inoculated with fhv-1 and then administered either 90kg/kg of famciclovir or a similar volume of lactose (the placebo) three times daily for 21 days.  treatment was given at the time of inoculation of the fhv-1 (day 0) cats were examined prior to, and after inoculation and treatment twice daily, with a full clinical and ophthalmic exam. a complete blood count and biochemistry was performed on each cat before and after inoculation and treatment course. biopsies were taken from the conjunctival fornix of each cat immediately before inoculation, and on days 7, 14 and 21. severity of clinical signs of ocular and non-ocular disease were scored separately by 1 or 2 trained blinded evaluators. ocular discharge was scored from 0 (none) to 3 (mucopurulent), conjunctivitis was scored from 0 (none) – 3( severe) and blepharspam was scored from 0 (none) to 4 (eye completely closed). non-ocular signs of sneezing were graded from 0 (not sneezing) to 1 (sneezing) and nasal discharge graded from 0 (none) to 3(marked mucopurulent discharge). total clinical disease score was defined as the sum of all of the ocular and non-ocular scores. fhv-1 was verified in all cats via serologic testing of blood and by cytology samples taken inferior conjunctival sac for qpcr analysis. study design: randomised controlled trial outcome studied: to assess the impact of treatment with famciclovir on the clinical signs and course of disease of cats experimentally infected with fhv-1 main findings (relevant to pico question): famciclovir treated cats had significantly lower median total disease score and histologic conjunctivitis score than cats treated with the placebo there was a significant reduction in serum anti-fhv-1 dna titer, serum globulin concentration, and fhv-1 dna and rna viral load from conjunctival samples. famciclovir treated cats also had an increased goblet cell density histological conjunctivitis score rate was increased significantly in famciclovir, versus placebo famciclovir cats had a significant increase in body weight versus placebo fhv-1 dna was shed less frequently in famciclovir treated cats (90% in treated versus 98% in placebo) and fhv-1 dna was detected significantly less in treated cats, than placebo cats limitations: only 16 cats in the study, resulting in lower study power food intake was not measured when assessing changes in body weight, presumptively assuming that weight change was due to clinical disease of fhv-1 thomasy (2016) population: client owned cats seen at the university of california davis veterinary medical teaching hospital between june 1st 2006 and may 30th 2013 sample size: n=59 intervention details: cats were divided into two groups, 33 cats had been given famciclovir at a dose of approx. 40mg/kg three times daily, and the other group of 26 cats were given a dose of approx. 90mg/kg three times daily. length of treatment varied and was at the discretion of the attending clinician dosage was approximated due to the narrow range of commercially available tablets, which led to body-weight-dependent variations from targeted doses. retrospective disease severity scoring was performed by one ophthalmologist to assess clinical improvement post-treatment. a score of 1 (mild), 2(moderate), 3 (severe) was subjectively assigned for the most severely affected tissue (i.e. conjunctiva) at the initial physical exam and reassessments using the records of the attending clinician. the median duration of clinical signs and treatment course length  was calculated for only cats that showed a documented clinical improvement the timeframe was from the time the first dose of famciclovir was given to the first recheck, that varied, that showed an improvement. owners were also surveyed regarding satisfaction with treatment and observations of improvement using a semi-quantitative scales (1 mild-10 severe) to rat the severity of their cat’s illness before and after the treatment study design: retrospective case series outcome studied: to assess whether famciclovir given at 90mg/kg three times daily or 40mg/kg three times daily resulted in a reduction of clinical signs of naturally occurring feline herpesvirus (fhv-1) in client owned cats. as well as to assess variables contributing to owner satisfaction of each treatment plan. main findings (relevant to pico question): clinical improvement was observed via the disease severity scoring in 50 of 59 cats in both the 40mg/kg and 90mg/kg cohorts. in the owner’s assessed disease severity score there was a significant (p <0.001) improvement clinical signs the median duration of improvement in clinical signs was 14 days for the low dose group, and 7 days for the high dose group. the treatment course length was 36 days for the low dose group, and 14 days for the high dose group. there was a significant difference in improvement (p=0.025) in clinical signs and significantly shorter period (p<0.001) of initiation of treatment to improvement for cats in the 90mg/kg cohort versus the 40mg/kg group number of treatment courses did not differ significantly between the two treatment groups results of the survey reported that 70% of owners found that clinical signs were improved with treatment of both the 90mg/kg and 40mg/kg groups and that famciclovir was rated first of second in effectiveness  compared to various other treatments given. prior treatments varied per cat, with only 9 cats receiving no other medications prior to the study. the treatments used prior included antibiotics, antivirals, both oral and topical, immunosuppressant’s and nutraceuticals. limitations: as a retrospective study the dose of famciclovir given was not masked, and improvements in clinical signs was rated by different clinicians. prior to study, 50 of thecats from both groups were receiving one or more topical or systemic medication as sole agents or in combination. these drugs included antibiotics, antivirals (including famciclovir) and anti-inflammatory/immunosuppressive (prednisone and megestrol acetate). it is possible that some of the improvements noted to famciclovir were confounded by these other medications a median of 3 additional medications were prescribed along with famciclovir at the time of the study pcr for fhv-1 dna was performed in 10/59 cats presenting for ophthalmological signs with only 6 of the 10 being positive. 4 cats who did not have ophthalmological signs were not tested the manufacturer of the famciclovir was identified for only 59% of cases, with other sources being unidentified. this could have affected the differences noted between the high dose and low dose cohorts the course length of treatment  and follow up time differed between the cats and as some cats had chronic signs before being included in the study, their improvement may have been because of the natural course of the disease process as famciclovir was more costly, owners may have been more bias on whether their cats improved on it appraisal, application and reflection the available evidence studied varied between retrospective cases series, to case reports, to randomised controlled studies. each of these differed in what they were assessing, whether ocular, respiratory or dermatological disease and treatment design and length of treatment courses varied. there was also a range of famciclovir dosing regimens used in cats, demonstrating the knowledge gap in ascertaining the most appropriate dose for treatment fhv-1 in cats. there was confounding variables in some of the studies that may have impacted on clinical improvements attributed to famciclovir treatment.  one was that many of the cats had been treated with or were on other medications before and during some of the studies such as in thomasy et al (2016) and malik et al (2009). another was that in some of the studies, the full history of the previous treatments given were unknown or incomplete as some were case reports from multiple sources as in malik et al (2009). apart from thomasy et al (2011), in the majority of the cats in the studies evaluated, fhv-1 was the presumptive cause of clinical signs and was not confirmed via laboratory testing. also in thomasy et al (2011) the first dose of famciclovir was given at the same time of inoculation with the virus. this leaves to question whether famciclovir is useful when given after the infection becomes clinically apparent. thus, more research would be needed on timing of when treatment is started. despite these shortcomings, the cats in the studies that had confirmed fhv-1 infection, treatment with famciclovir did appear to have a significant positive effect in reducing respiratory and ocular clinical signs, in a similar pattern to the ones given a presumptive diagnosis. ideally more studies like thomasy et al (2011), would need to be performed, with a confirmed diagnosis, and set treatment protocols to provide a stronger evidence base, as well as a basis for better treatment guidelines for the use of famciclovir in general and referral practice. methodology section search strategy databases searched and dates covered: the following search terms were applied to the cab abstracts database (1973-2016) via the ovid platform and the medline database accessed via the ncbi website (1946-2016) search terms: cab abstracts search terms: cats/ or (cat or cats or feline or felis or felid) and felid herpesviruses/ or felid herpesvirus 1/ or herpes/ or (herpesviruses or fhv or fhv-1 or herpesvirus or herpes) and famciclovir/ or (famcycovir or famciclovir) medline search terms cats/ or (cat or cats or feline or felis or felid) and herpesviridae/ or (herpesviruses or fhv or fhv-1 or herpesvirus or herpes) and (famcycovir or famciclovir or famvir) dates searches performed: 24 november 2016 exclusion / inclusion criteria exclusion: in vitro studies, conference proceedings, review articles, book chapters, articles not relevant to the pico inclusion: in vivo studies, articles relevant to the pico, articles that had more than one animal. studies that only used oral famciclovir as the antiviral. search outcome database number of results excluded – in vitro studies excluded – single case report/book chapter/conference proceeding/review articles excluded – not relevant to the pico total relevant papers cab abstracts 15 2 6 5 2 ncbi pubmed 14 3 1 6 4 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflict of interest. assisted with medline and cab search by mrs. emma place bsc ma subject librarian at the university of bristol. references malik, r. lessels, et al (2009) treatment of feline herpesvirus-1 associated disease in cats with famciclovir and related drugs. journal of feline medicine and surgery, 11 (1), pp. 40-48. http://dx.doi.org/10.1016/j.jfms.2008.11.012 thomasy, s.m. et al (2011) evaluation of orally administered famciclovir in cats experimentally infected with feline herpesvirus type-1. american journal of veterinary research, 72 (1), pp. 85-95. http://dx.doi.org/10.2460/ajvr.72.1.85 thomasy, s.m. (2016) oral administration of famciclovir for treatment of spontaneous ocular, respiratory, or dermatologic disease attributed to feline herpesvirus type 1: 59 cases (2006-2013). journal of the american veterinary medical association, 249 (5), pp. 526-538. http://dx.doi.org/10.2460/javma.249.5.526 intellectual property rights knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. is robenacoxib superior to meloxicam in improving patient comfort in dog diagnosed with a degenerative joint process? a knowledge summary by adam swallow bvsc mrcvs 1* 1university of bristol *corresponding author (adam.swallow@bristol.ac.uk) vol 1, issue 1 (2016) published: 25 jan 2016 next review date: 18 jan 2018 doi: 10.18849/ve.v1i1.17 clinical bottom line at normal clinical doses, there is no evidence that robenacoxib would provide superior patient comfort compared to meloxicam. question in dogs diagnosed with chronic degenerative joint disease, is robenacoxib superior to meloxicam in improving patient comfort? clinical scenario you are presented with a 9 year old, male neutered labrador with a 2 month history of stiffness after rest and a strange gait at exercise. on clinical examination you note pain on extension of both hind limbs. the dog is moderately overweight (bcs 7/9) with no other significant abnormalities detected. haematology and routine biochemistry are unremarkable. you take pelvic radiographs which confirm your suspicion of bi-lateral hip dysplasia with secondary osteoarthritis. you wish to prescribe a non-steroidal anti-inflammatory for the dog, which the client is happy for you to do. however, your practice has recently added a new anti-inflammatory, robenacoxib, to the pharmacy following a recent ‘lunch and learn’ with the local drug rep. normally, you would have just used memloxicam but now you are unsure as to which would provide the best clinical outcome for this patient. summary of the evidence schmid et al. (2009) population: clinically healthy beagle dogs with experimentally induced acute synovitis of one stifle. sample size: eight dogs; four of each gender (n=8). intervention details: all dogs were subjected to each intervention in a cross-over design. each dog was assessed before inducing synovitis using uric acid in either the left or right stifle and then re-assessed once clinical signs developed. the investigators alternated between the left and right stifle with each round of testing. the doses used were: placebo, meloxicam 0.2mg/kg sub-cutaneously (sc), robenacoxib 0.25mg/kg sc, 0.5mg/kg sc, 1mg/kg sc, 2mg/kg sc, 4mg/kg sc. study design: randomised cross-over experimental trial outcome studied: to establish a dose-response and a blood concentration-response relationship for both the analgesic and anti-inflammatory effects of robenacoxib. to compare the efficacy of robenacoxib compared to meloxicam in acute, induced synovitis in the dogs. main findings (relevant to pico question): on forceplate analysis looking at the vertical peak force generated there was no significant difference between meloxicam and either 0.5mg/kg, 1mg/kg or 2mg/kg robenacoxib sc. both products were significantly more effective than placebo.  (3)the duration of onset was similar for meloxicam (1hr) and robenacoxib (1.5hrs for 1mg/kg sc, 1hr for 2mg/kg sc). a higher dose led to a more rapid onset of robenacoxib. on examination, there was no significant difference in pain on palpation of the joint and the degree of reduction joint swelling was similar in the period 0-6hr, but robenacoxib provided swelling reduction in the period 0-12hr too. this effect however was not marked. limitations: only eight dogs took part in this study. no power calculation was performed meaning the significance of the results is not fully known. the study assessed the effects on an experimentally induced synovitis which may differ from the disease process seen in naturally occurring joint diseases. the duration of efficacy was not fully assessed as both products are thought to be effective for 24 hours per dose. inflammation due to the uric acid is thought to resolve after approximately 12-16 hours. this study was funded by novartis, who commercially produce and sell robenacoxib for use in dogs. appraisal, application and reflection whilst only a single relevant paper was available for review, the study did directly compare the two drugs under identical conditions allowing a good assessment of clinical efficacy to be made between them. however, whilst the study did look at and compare many variables relating to meloxicam and robenacoxib no power calculation was demonstrated. one cannot help but be wary of the advanced statistics presented in this study given there were only eight dogs in the study. also, this study was conducted by authors working for novartis; the company producing the commercial brand of robenacoxib (onsior). finally, whilst experimental conditions were well matched, only efficacy in the acute stages of a joint inflammation were assessed. the study does not asses efficacy in naturally occurring disease and so there could be other factors (such as central sensitisation and patient physical abnormalities such as joint incongruity) affecting the perceived efficacy of the different products in the “real world”which were not considered here. overall however this study would be useful when considered in the general practice situation as the two products have been compared directly and useful efficacy data has come from it. this usefulness would likely be reduced though should similar studies using patients with naturally occurring disease be available for review. when searching the literature, papers in which meloxicam and robenacoxib were not directly compared were excluded. whilst these studies provided evidence of efficacy for both meloxicam and robenacoxib individually, they did not provide evidence for which drug would be more effective in the clinical setting and so would not suitably address the clinical question. ideally larger studies are needed with power calculations to validate these results in patients with naturally occurring disease. should sufficient data be available, a meta-analysis may also provide valuable data with regards to the clinical question posed. given the prevalence of degenerative disease seen in practice, there would certainly be an appetite for such research. methodology section search strategy databases searched and dates covered: the following search terms were applied to the pub med database, accessed via the ncbi website (1910-2015), and cab abstracts database (1973-2015), accessed on the ovid platform. search terms: (dog or dogs or canine or bitch or bitches) and (onsior or robenacoxib) and (meloxicam or metacam or inflacam or loxicom or meloxidyl) and (joint* or arthrit* or osteoarthrit* or arthros* or hip* or stifle* or elbow*) dates searches performed: 18 january 2016 exclusion / inclusion criteria exclusion: articles not written in the english language, papers that did not directly compare the efficacy of the two products, conference proceedings or book chapters. inclusion: original research articles which directly compared the efficacy of robenacoxib and meloxicam with regards to musculoskeletal pain. search outcome database number of results excluded – nonenglish language publication excluded – did not answer pico question total relevant papers ncbi pubmed 2 0 1 1 cab abstracts 3 1 1 1 total relevant papers when duplicates removed 1 references schmid, v.b. et al. (2009) analgesic and anti-inflammatory actions of robenacoxib in acute joint inflammation in dog. journal of veterinary pharmacology and therapeutics, 33 (2), pp. 118-131. http://dx.doi.org/10.1111/j.1365-2885.2009.01117.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. evidence synthesis of diagnostics: grade and how it can be used for veterinary evidence mariska leeflang phd1* 1university of amsterdam, amsterdam, department of clinical epidemiology and biostatistics *corresponding author (m.m.leeflang@amc.uva.nl) vol 2, issue 4 (2017) published: 04 oct 2017 doi: 10.18849/ve.v%25vi%25i.151 while textbooks on evidence-based medicine still mainly focus on accuracy studies as most appropriate level of evidence for diagnostic questions, the guideline developers have moved forward to patient important outcomes. in other words, a perfect test may still be useless if it does not change clinical decisionsand outcomes for patients. what is the current state of evidence-based diagnostics and how can this be translated to different veterinary situations? find out more about mariska. view presentation slides comments: in bitches diagnosed with pyometra, is medical therapy using antibiosis alone as effective as combining ovariohysterectomy with antibiosis in reducing morbidity and mortality? a knowledge summary by adam swallow bvsc mrcvs1* 1university of bristol *corresponding author (adam.swallow@bristol.ac.uk) vol 1, issue 1 (2016) published: 15 feb 2016 next review date: 18 jan 2018 doi: 10.18849/ve.v1i1.16 clinical bottom line ovariohysterectomy combined with antibiosis is more effective in achieving clinical cure than systemic antibiosis alone. systemic antibiosis may be associated with recrudescence of the pyometra and the evidence base is weaker for this approach. question in canine bitches diagnosed with pyometra, is systemic antibiotic therapy alone as effective as surgical ovariohysterectomy with systemic antibiosis in achieving clinical cure? clinical scenario you are presented with a 10 year old female entire staffordshire bull terrier during afternoon consultations. her owner has noticed that she has been drinking more than usual for around a week now and has also is displaying signs of being in season again, despite her last season being only 6 weeks ago. based on your clinical examination and a brief ultrasound examination an open pyometra is diagnosed. the owner is keen to do what she can for the dog however finances are limited and would like to know if there is an alternative to surgery. one of the options you consider is the use of systemic antibiosis alone. summary of the evidence adamovich-pippe et al (2013) population: entire bitches with pyometra. sample size: n=12 intervention details: dogs with confirmed pyometra underwent laparscopic ovariohysterectomy as a treatment. study design: case-controlled study outcome studied: was laparoscopic surgery curative? main findings (relevant to pico question): laparascopic ovariohysterectomy is a valid treatment option for canine pyometra. careful case selection is required; iatrogenic organ rupture is a potential complication. limitations: small population studied no long term follow-up on the animals. no control group used. bartoskova et al. (2007) population: bitches with pyometra undergoing ovariohysterectomy. sample size: n=13 intervention details: bitches undergoing treatment for pyometra had blood samples taken immediately before and 7days after ovariohysterectomy study design: case controlled study outcome studied: whether haematological parameters and immune function normalised after ovariohysterectomy. main findings (relevant to pico question): haematological parameters and immune function normalised within 7days of ovariohysterectomy. further immunostimulation was not necessary. limitations: all animals underwent same procedure; could not clarify whether was immunostimulation or if derragements were secondary to systemic inflammation. no population justification noted. de cramer (2010) population: entire bitches with pyometra. sample size: n=8 intervention details: dogs with confirmed pyometra were given supportive fluid therapies and antibiosis (gentamicin and potentiated amoxicillin). they then underwent trans-cervical uterine lavage using 5% povidone-iodine in saline solution, combined with direct visualisation of the uterus. study design: case control study outcome studied: whether surgical lavage of the uterus produced more reliable and faster outcomes. main findings (relevant to pico question): e. coli was the most common organism isolated. vaginal discharge was scant following the procedure, becoming absent by day4 in all except 1 dog, which resolved after 12days. all dogs subsequently returned to cyclicity and conceived. limitations: no set exclusion criteria; any dog presenting with pyometra was accepted. no case controls used. treatment is not licensed and small population means further studies needed before this method could be justified routinely. likely expensive as a treatment; benefit over medical therapy uncertain. gupta et al (2015) population: dogs with pyometra managed with ovariohysterectomy sample size: n=9 intervention details: all dogs underwent ovariohysterectomy. uterine pathology findings and surgical success rates are reported. study design: descriptive case series. outcome studied: the pathological findings in the uterus and ovaries, alongside the success of surgical ovariohysterectomy. main findings (relevant to pico question): all dogs survived surgery with no reported complications. the authors stated that their success was similar to that previously reported in well known text books, but did not quote any figures. the use of medical management in particularly ill/ toxaemic animas prior to surgery was thought to be beneficial. limitations: no statistics used in this study. no figures are directly quoted; the outcomes of surgery here are very vague and that paper better describes the pathological changes (gross and histological) associated with canine pyometra. there is no control group to compare the findings too. jitpean et al (2014) population: bitches diagnosed with pyometra sample size: n=356 intervention details: bitches presenting to a swedish hospital with pyometra between 2006-07, study design: retrospective case controlled clinical audit. outcome studied: complications arising from therapy for pyometra. main findings (relevant to pico question): 356 dogs in total; 315 treated surgically, 9 medically and 32 were euthansased on presentation. post operative mortality 1% (4/315). 12.4% (40/356) developed peritonitis, 5.3% (19/356) developed urinary tract infection, 2.2% (8/356) developed wound infections. 1.7% (6/356) developed uveitis and 1.4% (5/356) developed arrythmias. poorer clinical condition at admission associated with prolonged hospitalisation. leucopaenia and abnormal temperature associated with increased risk pyometra. antibiosis given pre-admission 21% dogs (65/356) and post-operatively in 35% dogs (124/356). didn’t seem significant as to when antibiotics were given. overall complication rate 25%. limitations: cases were not controlled at the time of admission; therefore therapeutic protocol not necessarily standardised between animals. included animals not receiving surgery in certain statistical calculations; artificially lowers scores. most animals received ovariohysterectomy; cannot reliably compare outcomes to medical therapy. sen et al (2001) population: female entire dogs with open pyometra sample size: n=22 or n=14 unclear intervention details: all dogs received daily vaginal douching with 50150ml 2.5% povidone iodine followed by intra-uterine infusion of intamox (amoxicillin and dicloxacillin; 20mg/kg). this was performed for 57 days.  all dogs received gynomeena liquid, 24 teaspoons a day depending on bodyweight, orally, for 14 days. some dogs received 5% dextrose in normal saline, systemic antibiosis and anti-emetics for toxaemia study design: descriptive case series outcome studied: resolution of the clinical signs of open pyometra. main findings (relevant to pico question): all dogs achieved clinical cure in this study, with no recurrence during a one year period. within 57 days then palpable uterine diameter reduced significantly. no vulval discharge was observed after 12 days. 4 out of 22 dogs conceived after subsequent mating. the authors concluded that this treatment regime can be adopted with great success. limitations: the study is not clear with regards to the population numbers; it says 22 initially and then 14 and does not clarify this point. it is a case series study; no control group and no statistics are performed. unknown number of dogs received systemic fluid therapy, antibiosis and anti-emetic therapy. there is a very limited literature review in this paper, with a textbook being referenced too. singh et al (2010) population: dogs diagnosed with pyometra sample size: n=5 intervention details: all dogs received intramuscular injection of ceftriaxone sodium and tazobactum sodium for 46 days. vitamin b injections and meloxicam was also used for supportive treatment. study design: case series outcome studied: clinical resolution of the pyometra. main findings (relevant to pico question): all dogs achieved clinical cure in this study; 3 dogs after 4 days treatment and a further 2 dogs after 6 days of treatment. no dogs experienced recurrence of the pyometra. the authors recommend that ovariohysterectomy be the choice treatment. the authors discussed that this medical management was effective only in the “earlier” stages of pyometra. limitations: this is a case series, so whilst treatment was successful there is no control group to compare the findings too. being a case series, no statistical analysis of the results was performed. only 5 dogs took part in this study, therefore the significance of the findings should be interpreted with caution. the paper mentions a lack of recurrence of pyometra, but follow up times are not quoted. medications given were mentioned in the study but other supportive measures, such as the need for intravenous fluid therapy, was not mentioned. dosages of other medications used was not mentioned. long term follow up is not available wallace et al.(2015) population: dogs diagnosed with open or closed pyometra, or mucometra with a uterine body of less than 5cm in diameter. sample size: n=7 intervention details: all dogs underwent laparascopic ovariohysterectomy, with diagnosis subsequently beign confirmed with either uterine culture or histopathology. study design: case series outcome studied: was laprascopic assisted overiohysterectomy a viable technique in the management of canine pyometra or mucometra? main findings (relevant to pico question): 1 dog had conversion to an open approach following the discovery of uterine rupture at the start of surgery. all dogs survived (100%). 6 dogs were discharged 1 day later. follow-up period ranged from 7421 days, with no complications reported. median uterine body diameter 2.2cm mean age at surgery 68months (range 19-151) 1 dog was subsequently diagnosed with a macro-follicular granulose cell tumour alongside pyometra (incision extended) 1 dog required a second port to exteriorise uterus. 1 dog experienced intra-operative loss of pneumoperitoneum. mean surgery time was 85 minutes (range 40-110 minutes). limitations: case series; not a prospective clinical trial so no comparison of different techniques. no statistics were used in this descriptive study. only 7 dogs form the case series, 1 of which required conversion to an open approach so less frequent complications may not have been encountered. wide range of follow-up means not all complications may have been noticed. use of concurrent antibiosis not recorded. wheaton et al (1989) population: entire female dogs diagnosed with pyometra who were managed surgically with ovariohysterectomy. sample size: n=73 intervention details: medical records were analysed for all dogs diagnosed with pyometra and treated surgically between january 1976 and april 1987. the diagnosis was confirmed surgically. some dogs had the diagnosis further confirmed histologically but these observations were not included. study design: retrospective descriptive study based on case records outcome studied: to discuss the outcome of dogs with pyometra when managed surgically with ovariohysterectomy. it also aims to discuss three particular complications associated with such management. main findings (relevant to pico question): mean age of affected dogs was 7.9 years. 6/8 dogs aged <3years had received estradiol cyprionate or megestrol acetate within 6 months of presentation, and one 10yr old bitch. the mean time since the last observed season was 8 weeks. the most common bacteria isolated was e. coli (66% cases). 3 dogs developed post-operative complications related to embolization of septic foci. all dogs survived, but one dog suffered intermittent recurrence of clinical signs which were antibiotic responsive over the next 3 years. 4 dogs (5%) died either during surgery or in the immediate post-operative period. age did not appear to affect outcome in this study. limitations: retrospective case study; no control groups. diagnosis confirmed based on visual assessment only; early cases or cases with less gross pathological change may have been inadvertently excluded no statistical analysis was performed in any of these groups and so associations cannot be clarified long term follow up data is lacking. the paper does not specify that all complications are mentioned; overall data on complication rates is difficult to state here. appraisal, application and reflection overall, there seemed to be much better quality evidence to support the use of ovariohysterectomy compared to antibiosis alone. that said however, there were no studies which directly compared the two methods. whilst potentially very useful, such studies would need careful case selection and safeguards given the potential for a detrimental clinical effect. once available however, a review of the new evidence alongside existing evidence would allow a more definitive comparison of the two protocols to be made. the quality of the current published papers reviewed also means that a bias towards ovariohysterectomy may have been made owing to the increased level of detail that the ovariohysterectomy protocols contained, and the fact that such papers were written more recently. in the studies themselves, inclusion criteria were often well defined; exclusion criteria were rarely defined though. a substantial number of papers were rejected for review because they focused on different protocols, such as comparing the efficacy of dopamine agonists versus an anti-progestin. such protocols will be evaluated separately. unfortunately, several other papers were rejected as they were single case reports. such reports were not deemed sufficient evidence to support the use of certain treatment protocols. whilst systemic antibiosis was advocated in all studies reviewed, there were no studies in which antibiosis alone was evaluated and compared to a control group.  it would also be interesting to see studies in which ovariohysterectomy was utilized in non-septic patients and no antibiosis used, which may prove beneficial from the perspective of antibiotic resistance. ovariohysterectomy appeared to yield good results clinically, with the large majority of cases achieving resolution of the clinical signs. statistical analysis was not commonly utilized in the studies evaluated here; primarily because they tended to be case series rather than controlled clinical trials. no studies seemed to include a phrase justifying their sample size either; with many clinical studies involving relatively small study populations. study recruitment issues may have been factors here. however, many of the studies did agree on anamnestic factors such as age of presentation. the most frequently isolated organisms were similar where culture and sensitivity was performed (with e. coli being most frequently isolated). methodology section search strategy databases searched and dates covered: the following search terms were applied to the pubmed database, accessed via the ncbi website (1910-2015) and the cab abstracts database (1973-2015) accessed on the ovid platform search terms: (dog or dogs or canine or bitch or bitches) and (antibio* or amoxicillin or sulphona* or sulfona* or genta or ceftriaxone) and (ovariohysterect* or ovariehysterect* or hysterect* or spey or spay* or neuter*) and (pyometra) and (treat* or manag*) dates searches performed: 18 january 2016 exclusion / inclusion criteria exclusion: articles not available in english, single case reports, book chapters and conference proceedings, articles which were not relevant to the pico. inclusion: articles available in english which were relevant to the pico. articles had to involve more than one animal and had to describe the protocol used search outcome database number of results excluded – study design excluded – nonenglish language publication excluded – did not answer pico question total relevant papers cab abstracts 126 2 0 115 9 pubmed 4 0 0 3 1 total relevant papers when duplicates removed 9 references adamovich-pippe, k.n. et al. (2013) evaluation of laparscopic-assissted ovariohysterectomy for treatment of canine pyometra veterinary surgery, 42 (5), pp. 572-578http://dx.doi.org/10.1111/j.1532-950x.2013.12012.x bartoskova, a. et al. (2007) hysterectomy leads to fast improvement of haematological and immunological parameters in bitches with pyometra journal of small animal practice, 48 (10), pp. 564-568. http://dx.doi.org/10.1111/j.1748-5827.2007.00345.x de cramer, k.g.m. (2010) surgical uterine drainage and lavage as treatment for canine pyometra journal of the south african veterinary association, 81 (3), pp. 172-177.http://dx.doi.org/10.4102/jsava.v81i3.143 gupta, a. k. et al. (2015) gross, histopathological, microbiological and management studies of pyometra in bitches intas pharmaceuticals ltd. 16 (1), pp. 153158. jitpean, s. et al. (2014) outcome of pyometra in female dogs and predictors of peritonitis and prolonged postoperative hospitalization in surgically treated cases bmc veterinary research,10 (6), pp. 1-20. http://dx.doi.org/10.1186/1746-6148-10-6 sen, t. b., nandi, s. k. and halder, s. (2001) efficacy of intamox in open cervix pyometra in canines intas polivet, 2 (1), pp. 67-68. singh, k.p. et al. (2010) diagnostic and therepeutic management of pyometra in bitchesnintas polivet 11 (1), pp. 86-87. wallace, m. l. et al. (2015) single incision, laparoscopicassisted ovariohysterectomy for mucometra and pyometra in dogs veterinary surgery 2015. 44 (s1), pp. 66-70.http://dx.doi.org/10.1111/vsu.12344 wheaton, l. g. et al. (1989) results and complications of surgical treatment of pyometra: a review of 80 cases journal of the american animal hospital association. 25 (5), pp. 563-568. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. comparison of epidural morphine and buprenorphine for hindlimb orthopaedic surgery in dogs a knowledge summary by thomas towers ma vetmb certavp(va) mrcvs 1* 1swayne & partners ltd., the veterinary surgery, 84 hamlet road, haverhill, suffolk, cb9 8qq *corresponding author (tom.towers@cantab.net) vol 5, issue 2 (2020) published: 09 jun 2020 reviewed by: andy morris (bsc(hons) bvsc certavp(gsas) mrcvs) and tristan merlin (dvm msc mvetmed) next review date: 14 jul 2021 doi: 10.18849/ve.v5i2.291 pico question in dogs undergoing hindlimb orthopaedic surgery does epidural with local anaesthetic and buprenorphine provide equivalent intraand postoperative analgesia as epidural with local anaesthetic and morphine?   clinical bottom line category of research question treatment the number and type of study designs reviewed one double-blinded randomised controlled trial strength of evidence weak outcomes reported epidural analgesia with buprenorphine and bupivacaine may provide equivalent analgesia to more traditional morphine and bupivacaine epidural injection conclusion there is weak evidence that buprenorphine may provide equivalent analgesia to morphine when combined with bupivacaine epidurally. the reduced regulatory requirements imposed on buprenorphine may sway some clinicians to utilise buprenorphine but further, higher powered, controlled trials are necessary to confirm equivalency   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario bessie is an adult female border collie with a complete rupture to the right cranial cruciate ligament. you are considering a tibial plateau leveling osteotomy (tplo) to manage this injury and routinely use preservative-free morphine and bupivacaine epidurally as part of your analgesic management. morphine is not licensed for use in dogs and is a controlled drug (schedule 2) requiring strict record keeping and storage due to its abuse potential. buprenorphine is available preservative-free in the uk and is licensed for use in dogs (although not via the epidural route), with a reduced abuse potential meaning, although it is controlled under schedule 3 it is subject to less stringent controls on record keeping. you wonder whether buprenorphine would be an appropriate substitution, in terms of its analgesic efficacy, duration of action and adverse effects, for morphine in the epidural. the evidence the only study identified that was relevant to the pico question was a randomised controlled trial by smith & yu (2001) that directly compares the use of sole agent buprenorphine against morphine for epidural administration during surgical correction of cranial cruciate ligament rupture. other papers identified compared various nerve block techniques to morphine or morphine-bupivacaine epidural and, as such, were not relevant to the question posed here. smith & yu (2001) performed epidural injections on 20 client-owned dogs from an unknown population, splitting them equally by an undisclosed method between receiving either 0.1 mg kg-1 morphine or 4 µg kg-1 buprenorphine diluted in saline (0.2 ml kg-1) to equal the volume of morphine. cranial cruciate rupture was confirmed with radiography at least 16 hours prior to surgery under sedation with acepromazine 0.05 mg kg-1 and butorphanol 0.2 mg kg-1. on the day of surgery, premedication was achieved with acepromazine 0.1 mg kg-1 followed by induction with propofol to effect (4–6 mg kg -1) and maintenance with halothane in oxygen via an endotracheal tube. the surgical technique employed for stabilisation of the cruciate ligament was lateral imbrication with monofilament suture. intraoperative monitoring included end-tidal halothane concentrations, heart rate, respiratory rate, non-invasive oscillometric blood pressure and end-tidal carbon dioxide measurement. postoperatively non-validated objective and subjective pain scores were utilised to determine when rescue analgesia may be required (intramuscular morphine, 1 mg kg-1) and if this was required the dog was considered a treatment failure and removed from further analysis. the authors found no statistically significant difference between either group and concluded that buprenorphine epidural is as effective as morphine for analgesia during surgery to stabilise the cranial cruciate ligament, although the level of statistical significance utilised is not stated. the authors note that no adverse effects could be attributed to either epidural protocol. however, the findings of this study must be interpreted in the light of the low post-hoc power calculation suggesting a high risk of type ii statistical error, with a less than 10% chance of detecting statistically significant differences to a level of p = 0.05. this study could be strengthened by formal assessment of the quality of anaesthesia (for example physiological indicators of nociception). although ethical considerations limit the application, a control group of saline epidural medication would help to determine if buprenorphine is truly equivalent to morphine. summary of the evidence smith & yu (2001) population: client-owned dogs with naturally occurring cranial cruciate ligament rupture admitted for surgical repair sample size: 20 dogs intervention details: premedication with acepromazine (0.1 mg kg-1) 20 minutes prior to induction of anaesthesia with 4–6 mg kg-1 propofol and controlled or spontaneous ventilation. random allocation equally between two epidural protocols, each diluted with sterile saline to a total volume of 0.2 ml kg-1, administered immediately after induction of anaesthesia: 4 µg kg-1 buprenorphine, or 1 mg kg-1 morphine. stabilisation of the cranial cruciate ligament by extracapsular imbrication using monofilament suture. study design: double-blinded randomised controlled trial outcome studied: subjective measurement of postoperative pain using a non-validated behavioural clinical instrument. objective postoperative pain assessment with a non-validated physiological clinical instrument (heart rate, respiratory rate, blood pressure). main findings (relevant to pico question): no statistically significant difference in objective or subjective pain scores. epidural buprenorphine at 4 µg kg -1 appears to provide equivalent postoperative analgesia to epidural morphine at 0.1 mg kg-1. there appears to be no adverse effects to either medication protocol. limitations: small sample size and post-hoc power calculation reveals a low probability of detecting a true difference between the two treatment arms. the level of statistical significance utilised is not stated. there is no control group (although ethical considerations limit application). intraoperative effects of the protocols are not formally measured. where attempts are made there are significant issues with the data: end-tidal co2 analysis is confounded by a subset of dogs in each study arm being mechanically ventilated. ventilation should reduce the difference between groups. end-tidal halothane tension is >1 %, higher than previously determined minimum alveolar concentrations (mac) which is surprising when used in combination with acepromazine and epidural morphine, which have been shown to be mac-sparing. dose of buprenorphine chosen is based on human data, canine data is seemingly lacking, and significantly lower than the licensed parenteral dose in the uk. the extent of systemic absorption of buprenorphine by the epidural route is not known in dogs and this study did not make provisions to account for this possibility. not comparable to normal clinical practice as most orthopaedic procedures will receive analgesic premedicants (such as full µ agonist opioids). the pain scales used have not been validated (although it is likely none were available in 2001). this is an old study from 2001, anaesthetic and surgical practices may have changed since. halothane is not commonly used in the uk at this time. acp is rarely used as a sole premedicant and is therefore often given at doses much less than 0.1 mg kg-1. extracapsular prostheses are not commonly employed for large dogs in the uk, with osteotomies preferred. appraisal, application and reflection there is a dearth of high-quality evidence to compare the treatments in this pico. although the paper by smith & yu (2001) is a randomised controlled trial, sitting high in the hierarchy of evidence, it has some flaws that mean application to day-to-day clinical practice may be challenging. most significantly, the paper presented has a low power; post-hoc power calculations suggest that to give a 20 % chance of detecting a statistically significant difference in pain scores over the first 2 hours, to p = 0.05, a sample size of 69 dogs per group is required – much larger than the 10 dogs per group utilised in the study. ideally, such sample size calculations should have been performed prior to commencement, or after a brief pilot study. the pain score used during the study is not validated, although the current validated pain scoring systems (such as the glasgow composite measure pain scale – short form (reid et al., 2007)) were not available in 2001. as the systems are not validated, they may not be best designed for the detection of pain or may demonstrate observer bias and reduce the reproducibility of this study; further, the effect size (significant difference in scores) chosen of 0.5 pain score units may not reflect a clinically significant difference in analgesia and the authors do not address the confounding sedation due to acepromazine dosing. a further flaw is the lack of knowledge of the extent of systemic absorption of epidural buprenorphine; smith & yu (2001) provide a brief literature review in this regard and summarise good evidence for the lack of absorption for morphine but limited data for buprenorphine in dogs. the author of this knowledge summary was also unable to find published studies on the bioavailability of epidural buprenorphine in dogs. therefore, it cannot be ruled out that the treatment effect seen for buprenorphine is attributable to a systemic effect. should this be the case, the higher risk of epidural drug administration would preclude this route of administration in patients in favour of other parenteral routes. although an attempt is made to compare the end-tidal co2 tensions between groups, the methodology states that an unspecified proportion of dogs in each study arm were mechanically ventilated. ventilation would be expected to reduce differences between groups so must be taken into account when interpreting this data. the requirement for ventilation may be due to blunting of physiological ventilatory responses caused by halothane, which in this study is seen at mean ± sd end-tidal concentrations (%) of 1.04 ± 0.26 (buprenorphine) and 1.06 ± 0.18 (morphine). these end-tidal halothane tensions are higher than previously reported minimum alveolar concentrations (mac) for halothane with 0.1 mg kg-1 epidural morphine (as in (smith & yu, 2001)) of 0.6 ± 0.017 (valverde et al., 1989) and despite the use of large doses of acepromazine as a premedicant, which has been shown to be mac sparing, producing end-tidal concentrations of 0.58 ± 0.044 with acepromazine doses of 0.1 mg kg-1 in one study (heard et al., 1986). additional to these clinical concerns regarding end-tidal co2 and halothane tensions, the statistical handling of both variables is unclear. the data sets for each variable would consist of a series of numbers for every dog in both study arms but the anova analysis applied requires one data point from each dog; the authors do not elaborate on the methodology used to derive that number. as anaesthetic and ventilatory requirements may be expected to vary over time in response to surgical stimulus, this statistical approach is unlikely to be appropriate for these data. in terms of application to clinical practice, there are some deviations that may be significant. no analgesic medication was administered to these patients other than the treatments being studied, which contrasts current anaesthetic practice where systemic opioid analgesics are often employed (epstein et al., 2015). the 50% requirement for rescue analgesia in both trial arms may reflect inadequate perioperative analgesia. current surgical preferences may lie towards more invasive osteotomy techniques (such as tibial tuberosity transposition or tplo) rather than extracapsular imbrication (bergh et al., 2014) so it is feasible that the analgesic requirements of different surgical techniques will differ. unfortunately, the only paper obtained from the literature search did not utilise local anaesthetic in the epidural protocols tested and is therefore not completely relevant to the pico question posed. therefore, it is not possible to make a recommendation to utilise buprenorphine epidurally in hindlimb orthopaedic surgery in dogs over morphine, although the reduced abuse potential and regulatory burden may make this attractive to individual practitioners. further randomised controlled trials are needed to answer this pico question. methodology section search strategy databases searched and dates covered: cab abstracts on vcab direct 1973 to july 12, 2019 (week 28 2019) medline 1946 to july 12, 2019 via ovid (week 28 2019) search strategy: cab abstracts and medline: (dog or dogs or canis or canine or canid*) and (stifle or joint or joints or limb or limbs or “hind limb” or hind-limb or hindlimb or tarsus or tarsal or hock or hocks or ankle* or patella* or knee* or phalanx or phalanges or orthopaedic* or orthopedic* or fracture*) and (morphine or buprenorphine) and (epidural* or extradural* or “extra dural*” or extra-dural* or extrathecal* or “extra thecal*” or extra-thecal* or “conduction anaesthesia” or “conduction anesthesia”) dates searches performed: 14/07/2019 exclusion / inclusion criteria exclusion: irrelevant to pico, review articles, not available in english, book chapters or sections, other non-peer reviewed material, articles not available for review, duplicated articles inclusion: peer-reviewed material including case series, observational or interventional studies and systematic reviews relating to the use of buprenorphine or morphine epidurally in dogs undergoing hindlimb orthopaedic surgery search outcome database number of results excluded – irrelevant to the pico question excluded – review article excluded – book chapters or sections, other non-peer reviewed material total relevant papers cab abstracts 36 33 0 2 1 medline 28 26 1 0 1 total relevant papers when duplicates removed 1 conflict of interest the author declares no conflicts of interest. this knowledge summary was originally prepared as submission to the university of liverpool’s evidence based veterinary medicine postgraduate certificate module and thanks must go to the assessors, whose feedback has been immensely helpful in preparing this paper. dr gavin jarvis of the department of physiology, development and neuroscience at the university of cambridge provided very useful advice on the review of this paper and i am grateful for his assistance. references bergh, m. s., sullivan, c., ferrell, c.l., troy, j. & budsberg, s.c. (2014). ‘systematic review of surgical treatments for cranial cruciate ligament disease in dogs’, journal of the american animal hospital association, 50(5), pp. 315–321. doi: https://doi.org/10.5326/jaaha-ms-6356 epstein, m. e., rodan, i., griffenhagen, g., kadrlik, j., petty, m.c., robertson, s.a. & simpson, w. (2015). ‘2015 aaha/aafp pain management guidelines for dogs and cats.’, journal of feline medicine and surgery. sage publications, 17(3), pp. 251–272. doi: https://doi.org/10.1177/1098612x15572062 heard, d. j., webb, a. i. & daniels, r. t. (1986). ‘effect of acepromazine on the anesthetic requirement of halothane in the dog’, american journal of veterinary research, 47(10), pp. 2113–2115. reid, j., nolan, a.m., hughes, j.m.l., lascelles, d., pawson, p. & scott, e.m. (2007). ‘development of the short-form glasgow composite measure pain scale (cmps-sf) and derivation of an analgesic intervention score’, animal welfare. universities federation for animal welfare, 16(suppl.), pp. 97–104. smith, l. j. & yu, j. k. a. (2001). ‘a comparison of epidural buprenorphine with epidural morphine for postoperative analgesia following stifle surgery in dogs’, veterinary anaesthesia and analgesia, 28(2), pp. 87–96. doi: https://doi.org/10.1046/j.1467-2987.2000.00038.x valverde, a., dyson, d. h. & mcdonell, w. n. (1989). ‘epidural morphine reduces halothane mac in the dog’, canadian journal of anaesthesia. springer, 36(6), pp. 629–632. doi: https://doi.org/10.1007/bf03005412 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in dogs with traumatic elbow luxation, does treatment using closed reduction and conservative management have a better prognosis than those treated with open reduction and surgery? a knowledge summary by barnaby dean bvsc, mrcvs 1* 1langford vets small animal hospital/university of bristol, langford, bristol, bs40 5du *corresponding author (barneydean@gmail.com) vol 2, issue 4 (2017) published: 28 nov 2017 reviewed by: nina kieves (dvm, dacvs-sa, dacvsmr, ccrt) and stephen jones (mvb, ms, dacvs) next review date: 28 nov 2017 doi: 10.18849/ve.v2i4.128 clinical bottom line in the available literature, cases of traumatic elbow luxation managed by closed reduction appear to have a better long-term prognosis  than cases managed by open reduction and surgical stabilisation. that being said, it is important to consider that the poorer outcome in surgically-managed cases could reflect the severity or chronicity of the injury rather than the treatment method itself, or indeed could reflect a combination of the two. closed reduction of traumatic canine elbow luxation should be attempted in all cases as soon as possible as this is associated with a better prognosis. should closed reduction not be possible, or should the elbow remain unstable or reluxate following closed reduction, surgical intervention is indicated. joint immobilisation is recommended with either a robert jones bandage or splinted bandage for two-to-four weeks following treatment. question in dogs with traumatic elbow luxation, does treatment using closed reduction and conservative management have a better prognosis than those treated with open reduction and surgery? clinical scenario a five-year-old, male, neutered labrador retriever presents to you with acute onset non-weight bearing left forelimb lameness following a road traffic accident. the left forelimb distal to the elbow is positioned laterally and is supinated. palpation of the left elbow is moderately resented, and reveals severely disrupted skeletal anatomy. no other abnormalities are detected on clinical examination. radiography of the left elbow reveals lateral elbow luxation and moderate soft tissue swelling. no other radiographic abnormalities are detected. should closed reduction be attempted, or is surgical intervention indicated? summary of the evidence billings (1992) population: dogs and cats that suffered traumatic elbow luxation that were referred to either the veterinary medical teaching hospital, university of california, davis, or to the contra costa veterinary hospital between january 1st 1985 and april 30th 1990. sample size: nine dogs and one cat. intervention details: closed reduction was attempted and achieved in all canine cases. six out of nine (67%) reduced canine elbows were palpably unstable following closed reduction, and open reduction and surgical stabilisation was performed. a medial or lateral approach to the elbow was made, and collateral ligaments and muscle attachments were repaired by primary repair or with bone anchor screws and figure-of-eight wire. the annular ligament was repaired in two cases. all cases had capsulorrhaphy performed. of the surgically managed canine cases, three (3/9, 33%) were placed in a spica splint for 14 days following surgery, and three had kirschner-ehmer external fixators applied for seven to ten days following surgery. the three non-surgically managed canine cases were maintained in spica splints for between seven and ten days, and had exercise restricted. study design: retrospective multi-centre (two) case series. outcome studied: follow-up veterinary examination was performed at the relevant referral centres between six and 53 months following treatment (all assessed subjectively): lameness: either yes or no, at walk or trot. muscle atrophy compared to contralateral limb: either yes or no. instability compared to contralateral limb: either yes or no. range of motion: either abnormal or normal. pain on palpation: either yes or no. joint thickening: either yes or no. crepitation: either yes or no. radiographic evidence of osteoarthritis: described briefly for each case in the results. results of client questionnaire at the time of follow-up (all assessed subjectively): return to work: either yes, no, or not applicable. lameness after exercise: either yes or no. regular use of analgesics: yes or no. overall pleased with results: either definitely, somewhat, or displeased. main findings (relevant to pico question): closed reduction cases (three): one was a companion animal which appeared clinically normal, one was a working dog that returned to active hunting, experiencing mild lameness after activity. both had mild-to-moderate radiographic evidence of osteoarthritis, and clients were satisfied with the outcome in both cases. the third case had severe radiographic evidence of osteoarthritis, continued lameness, moderate muscle atrophy, required regular analgesia, and the client was unsatisfied with the outcome. open reduction cases (six): in 5/6 (83%) cases, lameness was mild and intermittent, usually apparent after vigorous exercise, degree of radiographic evidence of osteoarthritis was variable (no further information provided); 1/6 (17%) had extensive soft tissue damage at the time of treatment, and showed evidence of severe degenerative joint disease and required regular analgesia at follow-up (53 months following treatment). the authors considered the results from both groups to be subjectively comparable, and postulate that severity of initial injury, chronicity of luxation, patient size, and patient activity level are important factors that contribute to outcome. limitations: it is a retrospective case series, which sits low on the hierarchy of evidence. cases are from 1985 to 1990, meaning techniques and medications may have changed during the study period and since publication. cases are provided from two centres, which may result in less standardisation of treatment protocols. there is a small number of cases. all outcome measures in both open and closed reduction groups are subjective. there is no description of techniques used to determine outcome measures i.e. degree of lameness, degree of radiographic evidence of osteoarthritis. time to follow-up is highly variable (between six and 53 months) between cases, which may have influenced outcome measures. cases had all been referred from primary care veterinary clinics, meaning an unrepresentative sample of more complicated and difficult to manage cases may be included. some outcome measures are listed on a two-point scale (e.g. presence of lameness on a yes or no scale), when it may be appropriate to record the outcome being measured on a multi-point scale. some outcome measures are based on client reports, not veterinary examination. guzel (2006) population: dogs and cats brought to istanbul university between 1998 and 2004 for management of traumatic elbow luxation. sample size: seventeen dogs and five cats. intervention details: seven canine cases managed by closed reduction followed by coaptation with a robert jones bandage for one week, and exercise restriction for four weeks. all seven cases were treated within seven days of the causative injury. ten canine cases managed by open reduction, augmented with primary ligament repair, cortical screw bone anchors and cerclage wire, and/or joint capsule repair as necessary (the number of cases requiring each of these procedures is not stated), followed by coaptation with a robert jones bandage for one week, and exercise restriction for four weeks. all cases treated by open reduction were considered ‘chronic luxations’; no further explanation is provided. study design: retrospective single-centre case series. outcome studied: follow-up veterinary examination was performed at the referral centre where surgery was performed between one month and two years following surgery: joint stability; subjectively determined to be either stable or unstable. severity of radiographic osteoarthritis at follow-up examination (one month to two years following surgery); subjectively determined to be mild, moderate, or severe. clinical outcome (lameness) at follow-up examination; subjectively determined to be excellent, good, fair, or poor. main findings (relevant to pico question): in the closed reduction group at follow-up examination, joint stability was achieved in 6/7 (86%) cases; severity of radiographic osteoarthritis was mild in 5/7 (71%), moderate in 1/7 (14%), and severe in 1/7 cases; clinical outcome was excellent in 4/7 (57%), good in 1/7 (14%), fair in 1/7, and poor in 1/7 cases. in the open reduction group at follow-up examination, joint stability was achieved in 9/10 (90%) cases; severity of radiographic osteoarthritis was mild in 3/10 (30%), moderate in 1/10 (10%), and severe in 6/10 (60%) cases; clinical outcome was excellent in 1/10 (10%), good in 2/10 (20%), fair in 1/10, and poor in 6/10 (60%) cases. limitations: it is a retrospective case series, which sits low on the hierarchy of evidence. cases are from 1998 to 2004, meaning techniques and medications may have changed since publication. cases are only provided from a single centre. there is a small number of cases. outcomes studied are measured subjectively, which may introduce bias. insufficient detail is provided to enable accurate replication of the study (e.g. the methods used to determine joint stability, degree of radiographic osteoarthritis, and clinical outcome). time to follow-up is not specified for each case, and varies wildly (one month to two years), which alone may have affected outcome. insufficient information on patient group selection is provided – the reader is only told that the groups consist of patients presenting within the first week following injury, or are ‘chronic’. mccartney (2010) population: dogs that underwent surgical stabilisation of traumatic elbow luxation following closed reduction between 2003 and 2009. sample size: ten dogs. intervention details: all dogs were referred because the referring veterinary surgeon could not reduce the elbow or could not maintain elbow in reduction. all dogs that presented following acute elbow luxation and were found to have any degree of instability (defined as a range of movement beyond 45 degrees for medial rotations, and 70 degrees for lateral rotation) underwent open stabilisation within four days of the causative injury. all elbows were repaired using cortical screw bone anchors and cerclage wire, with primary lateral collateral ligament repair as necessary. a support bandage was applied for three days following surgery in all cases. study design: retrospective single-centre case series. outcome studied: at follow-up client communication between six and 60 months following surgery: owner satisfaction; subjectively determined by client questionnaire as very satisfied, satisfied, or not satisfied. outcome; subjectively determined by unspecified authors based on a combination of client questionnaire results to assess long-term functional outcome and interpretation of clinical notes (including follow-up examination and radiography between four and six weeks following surgery) as either excellent (never stiff or lame), good (intermittent stiffness or lameness), or poor (frequently stiff or lame). main findings (relevant to pico question): veterinary surgeon-assessed outcome was considered excellent in 2/10 (20%), good in 5/10 (50%), and poor in 3/10 (30%) cases. owners reported that they were very satisfied with long-term outcome in 6/10 (60%), and satisfied in 4/10 (40%) cases. the authors suggest that elbow stability should be reassessed 48 hours following closed reduction to determine if surgical stabilisation is required. the authors state that bone anchor screws with figure-of-eight wire, and primary ligament repair with nylon suture is an effective means of surgical stabilisation of elbow luxation. the authors state that, in general, traumatic elbow luxation results in the majority of dogs suffering from clinically significant stiffness or lameness. limitations: it is a retrospective case series, which sits low on the hierarchy of evidence. cases are from 2003 to 2009, meaning techniques and medications may have changed since publication. cases are only provided from a single centre. there is a small number of cases. cases had all been referred from primary care veterinary clinics, meaning an unrepresentative sample of more complicated and difficult to manage cases may be included. the study only reports on a single patient group (those who underwent surgical stabilisation following closed reduction), so a comparison between treatment groups cannot be made. outcomes studied are measured subjectively using non-validated metrology instruments, which may introduce bias. long-term outcome is determined based on client feedback rather than veterinary assessment. time to follow-up is highly variable (six to 60 months) between cases, which may have influenced outcome, and there is no attempt to correlate time-to-follow up and outcome despite cases presenting four-to-six weeks following surgery for re-examination, findings are not reported for this. mitchell (2011) population: dogs and cats that presented to the pet emergency room or queensland veterinary specialists for treatment of traumatic elbow luxation between 1999 and 2009. sample size: fourteen dogs and 11 cats. intervention details: closed reduction was attempted in all patients within three days of the causative injury. the elbows of three dogs whose elbows were severely unstable after closed reduction re-luxated within 24 hours of closed reduction and underwent open reduction. this was achieved either via a medial approach to the elbow to repair the medial collateral ligament using cortical screw bone anchors and a figure-of-eight wire loop (in two dogs), or via a medial and lateral approach to repair a torn medial and avulsed lateral collateral ligament through primary ligament repair and by using a lag screw at the avulsion site, respectively (in one dog). external coaptation was employed in all cases, and was achieved using either a robert jones bandage (5/14, 36%), light bandage (2/14, 14%), or spica splint (7/14, 50%) for between one day and four weeks where recorded. study design: retrospective multi-centre (two) case series. outcome studied: at follow-up client communication between five months and nine years following treatment (clients only responded in 8/14, 57%, of canine cases): outcome; subjectively determined by client questionnaire as either excellent (no noticeable lameness), good (infrequent lameness), fair (persistent lameness), or poor (failure to use the limb). owner satisfaction; subjectively determined by client communication as either satisfied, or not satisfied. main findings (relevant to pico question): eight dog owners replied to the client questionnaire; six from the closed reduction group, two from the open reduction group. outcome was considered excellent in 4/6 (67%), good in 1/6 (17%), and fair in 1/6 closed reduction cases. outcome was considered fair in 2/2 (100%) of open reduction cases. owners considered themselves satisfied in all cases where questionnaires were completed (8/8). the authors consider joint stability following closed reduction to be a positive prognostic indicator, and suggest closed reduction should be attempted as soon as possible following injury. surgical management is advised in cases of persistent instability following closed reduction (time frame is not specified), or in the presence of avulsion fractures. limitations: it is a retrospective case series, which sits low on the hierarchy of evidence. cases are from 1999 and 2009, meaning techniques and medications may have changed during the study period and since publication. cases are provided from two centres, which may result in less standardisation of treatment protocols. there is a small number of cases. cases are all reported from a referral hospital which may select for more severe or difficult to treat cases (i.e. cases that underwent satisfactory closed reduction were not referred). outcomes studied are measured subjectively using non-validated metrology instruments, which may introduce bias. outcome is measured solely by client feedback rather than veterinary assessment. time to follow-up is highly variable (five months to nine years), which may have influenced outcome. there is significant variation in the duration of coaptation, which may have influenced outcome. o’brien (1992) population: dogs with traumatic luxation of the cubital joint diagnosed at angell memorial animal hospital and tufts university school of veterinary medicine, foster hospital for small animals from 1978 to 1988. sample size: forty-four dogs. intervention details: thirty-five (80%) dogs were treated with closed reduction, with two of these cases requiring surgical repair of the medial collateral ligament using a screw and spiked washer. nine (20%) dogs were treated with open reduction. additional surgical procedures performed at the time include: lateral collateral ligament repair using non-absorbable, monofilament suture (n=2); repair of the radial annular ligament using a stainless-steel wire prosthesis (n=1); transarticular pinning to maintain reduction for 14 days (n=3). external coaptation was employed in 43/44 (98%) dogs with a soft padded bandage (n=10), spica splint (n=7), cast (n=2), schroeder-thomas splint (n=1), or an unspecified bandage (n=23). duration of coaptation was known in 22 cases, and ranged from one day to six weeks (mean 14 days). study design: retrospective multi-centre (two centres) case series. outcome studied: follow-up client communication and/or veterinary assessment was performed between three and 137 months following treatment and involved: in all 44 dogs: result of treatment; determined subjectively by client telephone contact as either excellent (no detectable lameness), good (infrequent weight-bearing lameness, especially after exercise or inclement weather), fair (frequent episodes of lameness), and poor (marked non-weight bearing lameness with abnormal limb function). in all 44 dogs: client satisfaction; determined subjectively by client telephone contact as either satisfied or unsatisfied. in the 6/44 (14%) of dogs available for follow-up veterinary examination: gait evaluation, limb function and range of motion as determined by physical examination, and radiographic evidence of osteoarthritis, determined subjectively by veterinary assessment. main findings (relevant to pico question): closed reduction group: outcome was rated by clients as excellent in 27/35 (77.1%) cases, 4/35 (11.5%) good, 2/35 (5.7%) fair, 2/35 poor. 33/35 (94%) of clients were satisfied with the outcome. open reduction group: outcome was rated by clients as excellent in 1/9 (11.2%) cases, 4/9 (44%) good, 4/9 fair. 9/9 (100%) of clients were satisfied with the outcome. six dogs presented for veterinary assessment, four from the closed reduction and two from the open reduction group. closed reduction: 4/4 (100%) showed no detectable lameness andoutcome was rated excellent by the clients; 2/4 (50%) showed mild reduction in range of movement and mild radiographic osteoarthritic change, 50% showed no reduction in range of movement and no evidence of radiographic osteoarthritic change. open reduction: 2/2 (100%) were lame at walk and outcome was rated fair by the clients; range of movement was decreased in both cases, and there was evidence of severe radiographic osteoarthritic change in both cases. limitations: it is a retrospective case series, which sits low on the hierarchy of evidence. cases are from 1978 to 1988, meaning techniques and medications may have changed during the study period and since publication. cases are only provided from multiple centres, meaning there is likely to be reduced standardisation of care. there is a small number of cases. most outcomes studied are measured subjectively, which may introduce bias. time to follow-up is highly variable between and within patient groups making direct comparisons difficult. joint immobilisation method and duration is highly variable, and includes transarticular pinning as one of the options, which may affect outcome. pass (1971) population: dogs presented to ontario veterinary college with traumatic elbow luxation between 1966 and 1970 (12 cases identified, but only two cases reported) sample size: two dogs. intervention details: closed reduction was performed in both cases. an unspecified bandage was applied in both cases (for 12 days in case 1 and two days in case 2). exercise was restricted in case 2 for seven days. exercise restriction was not reported for case 1. study design: retrospective single-centre case series. outcome studied: clinical outcome; determined subjectively by veterinary assessment at unspecified times following closed reduction, and by client communication at either six weeks (case 1) or eight weeks (case 2) following closed reduction. main findings (relevant to pico question): case 1: the dog was weight-bearing lame on the affected limb after bandage removal, and the client reported intermittent lameness on the affected limb six-weeks following bandage removal. case 2: the dog underwent veterinary assessment at two unspecified times following discharge where no outcome is reported, and the client reported no evidence of lameness eight weeks following bandage removal. limitations: it is a retrospective case series, which sits low on the hierarchy of evidence. cases are from 1966 to 1970, meaning techniques and medications may have changed during the study period and since publication. cases are only provided from a single centre. there is a small number of cases, and there is no explanation or rationale provided for the selection criteria for the two presented cases out of 12 cases identified. follow up is described in extremely limited detail and reporting is not standardised between cases. outcome is measured subjectively, and is partly measured based on client reporting using non-validated reporting systems. management post closed reduction varies between cases, and no explanation is provided for this. sajik (2016) population: dogs referred to the queen mother hospital for animals at the royal veterinary college, small animal hospital at the university of glasgow, small animal specialist hospital in sydney, veterinary specialist centre sydney, and anderson moores veterinary specialists for management of traumatic elbow luxation between 2006 and 2013. sample size: thirty-seven dogs. intervention details: seventeen dogs were managed with closed reduction alone. twenty dogs underwent surgical management. indications for surgical management were inability to perform closed reduction, or persistent instability or reluxation following closed reduction. no case had open reduction without concurrent stabilisation. surgical stabilisation was grouped into the following categories: a) circumferential suture prosthesis through transcondylar bone tunnels (n=11), b) bone anchor screw placement with prosthetic ligament/orthopaedic wire placement (n=4), c) bone anchor screw placement with prosthetic ligament plus circumferential suture (n=1), d) bone anchor screw with prosthetic ligament plus transarticular pin (n=1), e) bone anchor screw placement with prosthetic ligament plus transarticular external skeletal fixator (n=1), f) open reduction plus transarticular external skeletal fixator (n=1), g) closed reduction plus transarticular external skeletal fixator (n=1). post-reduction, external coaptation or fixation was employed in 30 cases; spica splint in 20 cases (10 closed, 10 surgical), cast/bandage in seven cases (four closed, three surgical), transarticular external skeletal fixator in three cases (one closed, two surgical). duration of external coaptation is not listed. study design: retrospective multi-centre (five centres) case series. outcome studied: quality of life, limb pain, and limb function; assessed subjectively by clients using a validated metrology instrument (canine brief pain index questionnaire, brown et al 2008). this includes four questions that grade severity of the dog’s pain over the previous seven days (rated 0/no pain, to 10/extreme pain), six questions that evaluate limb function over the previous seven days (rated 0/no interference, to 10/extreme interference), and one question to assess overall quality of life (rated poor, fair, good, very good, or excellent). main findings (relevant to pico question): quality of life of patients at the time of follow-up client questionnaire (mean 961 days [+/-849 days]) following treatment: closed reduction: quality of life rated excellent in 4/9 (44%) of cases, very good in 4/9 cases, fair 1/9 (11%) cases; mean pain score is reported as 0.19/10 (range 0-1.25); mean limb function is reported as 0.80/10 (range 0-4.67). surgical intervention: quality of life rated excellent in 9/12 (75%) cases, very good in 2/12 (17%) cases, good in 1/9 (11%) cases; mean pain score is reported as 0.90/10 (range 0-3.75); mean limb function is reported as 0.96/10 (range 0-3.83). major post-operative complications occurred in 7/37 (19%) cases: reluxation (n=6) and infection required implant removal (n=1). five reluxations occurred following closed reduction; one was successfully managed with repeat closed reduction, three were surgically stabilised (and included in the surgical group), one was euthanased due to severity of disease. one reluxation occurred following surgical stabilisation with lateral screw and medial prosthetic ligament placement, revision surgery was performed successfully using the same technique. four of the six reluxations occurred in patients with dogs suffering from concurrent orthopaedic injuries in other limbs. limitations: it is a retrospective case series, which sits low on the hierarchy of evidence. cases are from 2006 and 2013, meaning techniques and medications may have changed during the study period and since publication. this is highlighted in the discussion, as a new surgical technique was described by farrell et al. (2009) that was employed later in the present study (data presentation prevents correlation of outcome with surgical method employed). cases are provided from five centres, which may result in less standardisation of treatment protocols. there is a small number of cases. cases are all reported from referral hospitals which may select for more severe or difficult to treat cases (i.e. cases that underwent satisfactory closed reduction were not included). outcomes studied are measured subjectively by clients rather than by veterinary assessment, which may introduce bias. the metrology instrument used is validated, however. there is no mention of duration of coaptation, but it is described as variable, which may have influenced outcome. time to follow-up is highly variable (961 +/849 days) between cases, which may have influenced outcome. there is variation in the surgical techniques used within the surgically managed group of patients, which may have influenced outcome. patients with concurrent orthopaedic injuries to other limbs were included in the study, which may have influenced outcome. the authors state that four out of the six reluxations occurred in these patients. schaeffer (1999) population: dogs with traumatic elbow luxation presented to utrecht university faculty of veterinary medicine between 1984 and 1996. sample size: thirty-one dogs. intervention details: nineteen dogs with acute lateral luxation were treated with closed reduction, and joint stability was assessed using campbell’s method. one collateral ligament (specific ligament not stated) was sutured following closed reduction in four of these dogs. joint immobilisation was achieved with application of a spica splint, lightweight bandage, or robert jones bandage for a mean of 25 days (range two to 42 days). exercise restriction was recommended for two weeks. one dog with acute bilateral luxation and two dogs with chronic elbow luxation were treated with open reduction. joint immobilisation was achieved with application of a spica splint or lightweight bandage for one to four weeks. five dogs had a monteggia fracture; these cases are excluded here as they are considered beyond the scope of this knowledge summary. three dogs with chronic (four weeks to one year) elbow subluxation received no treatment, and one dog had an acute lateral luxation and was euthanised at the owner’s request; these cases are excluded from this knowledge summary. study design: retrospective single-centre case series. outcome studied: follow-up reported subjectively from between four months and nine years (mean 35 +/22 months) following treatment in 24/31 (77%) of cases (three patients received no treatment; one was euthanised at presentation; three were lost to follow up – two from the closed reduction group, one from the open reduction group): owner’s opinion: reported as very satisfied, satisfied or unsatisfied. clinical results, determined based on: decrease in range of movement (none, slight, moderate, or severe); degree of osteoarthritis as assessed by the referring veterinary surgeon or by a member of the university’s veterinary radiology department (none, slight, moderate, or severe); activity after treatment (reported as normal, slightly decreased, or decreased); lameness (reported descriptively, with further quantification as none, mild, moderate, or severe). main findings (relevant to pico question): closed reduction had been attempted by the referring veterinary surgeon in nine cases, but this had failed in six cases, and resulted in severe subluxation in three cases. closed reduction (outcome available in 17 cases): clinical results are reported as excellent in five (29%) cases, good in three (18%) cases, fair in six (35%) of cases, and poor in three cases. the elbow was stable in 10 (59%) of these cases, and these were the only cases to achieve excellent or good outcome. moderate-to-severe osteoarthritic changes were identified in 10 (59%) of cases. clients are reported as very satisfied in 10 (59%) cases, satisfied in 5 (29%) cases, and unsatisfied in 2 (12%) cases. four (24%) cases were operated on later (nine days following closed reduction in one case, timing of surgery unspecified in two cases) to repair collateral ligaments or remove periarticular bone fragments, and outcome is only reported following surgery. the influence of joint instability after closed reduction on poor clinical result is considered significant (p>0.05). open reduction (outcome available in two cases / three elbows, one case suffered bilateral elbow luxation): clinical results are reported as good in 1 (33%) elbow, fair in 1 elbow, and poor in 1 elbow. the presence of an avulsion fracture did not seem to influence joint instability. indications for surgical management include chronic luxations, reluxation, and the necessity to remove bony fragments. limitations: it is a retrospective case series, which sits low on the hierarchy of evidence. cases are from 1984 to 1996, meaning techniques and medications may have changed during the study period and since publication. cases are only provided from a single centre. there is a small number of cases. outcomes are all reported subjectively, including client reporting using non-validated metrology instruments. time to follow-up is highly variable (four months to nine years), which may have influenced outcome. cases that had surgical stabilisation after closed reduction are considered part of the closed reduction group alongside those that did not undergo stabilisation surgery, meaning there is significant variation in treatment protocols in this patient group. cases are all reported from a referral hospital which may select for more severe or difficult to treat cases (i.e. cases that underwent satisfactory closed reduction were not included). the authors state that the necessity to remove bony fragments is an indication for surgical management, but do not explain the rationale of this statement, or the method of identifying these problematic fragments. the authors state that avulsion fractures do no always require surgical management, which may be considered contradictory to the previous statement. vedrine (2017) population: canine and feline patients treated at the veterinary clinic seinevet, rouen-boos, france, for traumatic elbow luxation or triceps muscle avulsion with elastic transarticular external fixator between may 2013 and december 2014. sample size: two dogs and two cats treated for elbow luxation, one dog treated for triceps tendon avulsion. intervention details: all patients underwent closed elbow reduction and had residual joint instability diagnosed using campbell’s test. all patients underwent the elastic transarticular external fixator technique. this involves surgical placement of a transverse pin in the distal quarter of the humerus, and another in the centre of the olecranon. the pins are connected by medially and laterally placed rigid connecting bars with the joint held at 140° for two days. after two days, the connecting bar is replaced with tight elastic bands on the medial and lateral aspects of the joint. the elastic transarticular external fixator was kept in place between 12 and 15 days in canine patients. exercise restriction was recommended in all cases, however the duration of this is not listed. study design: retrospective single-centre case series. outcome studied: outcome assessed subjectively by veterinary assessment and client reports. factors considered during assessment include: range of motion at time of implant removal (in case one and two), limb use (in case one only), and lameness (in case two only). main findings (relevant to pico question): case one was considered to have a poor outcome as at nearly two years following surgery, it is reported that the dog does not use its operated limb (it is reported as having suffered limb paralysis with loss of deep pain perception in the operated limb at the time of injury). range of motion was limited to 25° at the time of implant removal. case two was considered to have a good outcome. at implant removal, the patient was lame in the operated forelimb and in both hindlimbs (the patient suffered concurrent pelvic fractures at the time of injury), with a range of motion in the operated forelimb of 75° at the time of implant removal, and 90° (140° in contralateral limb) at six weeks following surgery. the patient was weight-bearing lame at six weeks following surgery, with the clients reporting increased lameness after exercise, but they were unable to localise the lameness. limitations: it is a retrospective case series, which sits low on the hierarchy of evidence. cases are only provided from a single centre. there is a small number of cases. outcomes are all reported subjectively, including client reporting. there is limited information on the outcome measures used, and how they were assessed. assessment method varies between patients. time to implant removal was variable, which may have influenced outcome. both dogs with elbow luxation in this study has significant concurrent injuries (limb paralysis with loss of deep pain perception in the operated limb caused at the time of injury, and pelvic fractures with associated lameness, respectively), making follow-up assessment of the outcome of management of the elbow luxation difficult. appraisal, application and reflection all relevant studies identified and reported above are retrospective case series, which sit low on the hierarchy of evidence. further to this, they all report on a small number of cases, ranging from just two to 44 (mean 13.8) cases; multiple single case reports were identified during the literature search, but were excluded. of the nine studies reported, only five have been published since 2000, and only two have been published in the last five years. since veterinary medicine and surgery is a rapidly developing branch of the medical industry, older studies are sometimes less relevant to the modern practitioner, however it appears that a lot of techniques used in the older reports are still employed today. five of the studies report cases that had presented as referrals from primary care veterinary surgeons (the remaining four studies do not state whether they are a referral hospital), which may introduce bias as, it appears, more difficult to manage cases (i.e. more severe injuries/comorbidities) that are inevitably over-represented at referral centres tend to require surgical management. because different presentations appear to require different management, it is difficult to compare the success of open reduction (with or without surgical stabilisation) and closed reduction. overall, the quality of evidence is poor. this limits the ability to generalise the results. however, trends in case management and a rough consensus among authors can be identified, allowing an evidence-based approach to be formulated. until higher quality evidence (i.e. randomised, controlled, blinded) is available, it is difficult to draw more definitive conclusions. in the available literature, cases of traumatic elbow luxation managed by closed reduction appear to have a better long-term prognosis than cases managed by open reduction and surgical stabilisation. that being said, it is important to consider that the poorer outcome in surgically-managed cases could reflect the severity or chronicity of the injury rather than the treatment method itself, or indeed could reflect a combination of the two. when considering all the studies listed above, there appears to be a step-by-step approach to management of traumatic canine elbow luxation, outlined most completely by sajik et al. (2016). closed reduction should be attempted in all cases as it seems that early, successful closed reduction provides the best long-term prognosis. stability of the elbow should then be assessed using campbell’s method – this should also help identify which collateral ligaments are injured. should closed reduction not be possible, or should the elbow continue to be unstable or reluxate after closed reduction, surgical management is indicated. there are multiple surgical techniques described, though the most commonly employed appears to be primary ligament repair with non-absorbable suture, with concurrent placement of bone anchor screws and a figure-of-eight wire on the injured aspect(s) of the elbow – a comparison of the efficacy of individual surgical methods was considered beyond the scope of this knowledge summary and further research in this area is warranted. joint immobilisation is widely recommended and commonly employed, however this is quite variable amongst studies with no clear consensus on the type or duration of immobilisation. in conclusion, in cases of traumatic canine elbow luxation, closed reduction should be attempted in all cases. surgical intervention is indicated in cases where closed reduction is not possible, or where reluxation or persistent joint instability follows closed reduction. a period of joint immobilisation should follow treatment. a significant proportion of cases in both treatment groups will suffer varying degrees of continued morbidity in the future. when cases can be treated successfully with early closed reduction, prognosis appears to be better than those cases requiring surgical management. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform 1973-present medline via the ovid platform 1946-present pubmed 1955-present search terms: [dog or dogs or canine or canines or bitch or bitches] and [elbow or elbows] and [luxation or luxate or luxated or dislocation or dislocate or dislocated] dates searches performed: search last performed on 26/10/17 exclusion / inclusion criteria exclusion: articles not available in english, single case reports, book chapters, conference proceedings, articles which were not relevant to the pico question. inclusion: articles available in english which were relevant to the pico. articles had to involve more than one animal. literature reviews were included. search outcome database number of results excluded – nonenglish language excluded – single case report excluded – book chapter excluded – conference proceedings excluded – irrelevant to pico total relevant papers cab abstracts 138 51 12 3 12 53 7 medline 40 3 5 0 0 27 5 pubmed 62 8 5 0 0 44 5 total relevant papers when duplicates removed 9 conflict of interest the author declares no conflicts of interest. references billings la, vasseur pb, todoroff rj, johnson w (1992). clinical results after reduction of traumatic elbow luxations in nine dogs and one cat. journal of the american animal hospital association; 28(2): pp137-142. guzel o, altunatmaz k, saroglu m, aksoy o (2006). traumatic luxations of the elbow in cats and dogs. veteriner fakultesi dergisi (istanbul); 32(2): pp31-43. mccartney w, kiss k, mcgovern f (2010). surgical stabilization as the primary treatment for traumatic luxation of the elbow joint in 10 dogs. international journal of applied research in veterinary medicine; 8(2): pp97-100. mitchell ke (2011). traumatic elbow luxation in 14 dogs and 11 cats. australian veterinary journal; 89(6): pp213-216. http://dx.doi.org/10.1111/j.1751-0813.2011.00718.x o’brien mg, boudrieau rj, clark gn (1992). traumatic luxation of the cubital joint (elbow) in dogs: 44 cases (1978-1988). journal of the american veterinary medical association; 201(11): pp1760-1765. pass ma, ferguson jg (1971). elbow dislocation in the dog. journal of small animal practice; 12(6): pp.327-332. http://dx.doi.org/10.1111/j.1748-5827.1971.tb06237.x sajik d, meeson rl, kulendra n, jordan c, james d, calvo i, farrell m (2016). multi-centre retrospective study of long-term outcomes following traumatic elbow luxation in 37 dogs. journal of small animal practice; 57(6): pp422-428. http://dx.doi.org/10.1111/jsap.12499 schaeffer igf, wolvekamp p, meij bp, theijse lfh, hazewinkel haw (1999). traumatic luxation of the elbow in 31 dogs. veterinary and comparative orthopaedics and traumatology; 12(1): pp33-39. vedrine b (2017). use of an elastic transarticular external fixator construct for immobilization of the elbow joint. canadian veterinary journal; 58(4): pp353-359. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. in solitary rabbits, does the presence or absence of a mirror affect stress, fear and anxiety? a knowledge summary by rebecca schofield rvn, bsc (hons)1* 1pdsa, veterinary client services, prospect house, north hylton road, sunderland, sr5 3ad *corresponding author (schofield.rebecca@pdsa.org.uk) there is an erratum to this paper published in veterinary evidence vol 4, issue 2 (2018): http://dx.doi.org/10.18849/ve.v4i2.262 vol 4, issue 2 (2019) published: 12 april 2019 reviewed by: laura dixon (phd bsc) and jackie belle (rvn certsan certfn certvnes dipcabt dipesm dip br dipendv ptlls bsc msc) next review date: 12 april 2021 doi: 10.18849/ve.v4i2.177 pico question in solitary rabbits, does the presence or absence of a mirror affect stress, fear and anxiety? clinical bottom line four studies were reviewed in this knowledge summary. despite the small number of papers available, the controlled trials and their methodologies provide strong evidence that the behavior of solitary laboratory rabbits is affected by the presence or absence of mirrors. this evidence also indicates an effect on their welfare. the studies suggest that the presence of mirrors provides environmental enrichment and have a positive effect on the subjects health and welfare. however, it is also suggested that mirrors may have some detrimental physical and psychological effects for some individuals. there are also many gaps in the available research and these need to be addressed to give better insight into the effect of mirrors on rabbits. because of the current level of knowledge, clinical recommendations cannot be made at present on the use of mirrors in solitary rabbits to improve their veterinary care whilst hospitalised. clinical scenario rabbits are social animals and require same species companionship in captivity. from recent rabbit cpd courses run by lagolearn and the rabbit welfare association & fund, the accepted gold standard of rabbit veterinary care is to also bring bonded companions into practice during periods of hospitalisation. mirrors have been successfully used and proven to reduce stress in other isolated social species; sheep (parrott et al., 1988); cattle (piller et al., 1999); horses (mcafee et al., 2002). could mirrors help reduce stress in rabbits? could the use of mirrors be advantageous for solitary housed rabbits in a veterinary practice, subsequently improving their recovery time, nursing care and welfare? the evidence the literature searches found four relevant papers (jones & phillips, 2005; dalle zotte et al., 2008; edgar & seaman, 2010; reddi et al., 2011) that directly compared whether presence or absence of mirrors influenced rabbit behaviour. none of these directly measured stress, fear or anxiety, however all assessed preference for mirrors by observing rabbit behaviour instead. the quality of evidence was strong due to the use of controlled trials in all research papers. all studies suggested that in laboratory rabbits, mirrors had some welfare advantages. no evidence was found on the use of mirrors in a domesticated or veterinary setting. summary of the evidence reddi et al. (2011) population: weaned new zealand white rabbits, weighing 450–500 g on a private rabbit farm in bangalore, india sample size: 10 rabbits split into two treatment groups: t1 (n = 5) t2 (n = 5) intervention details: experimental set up t1 rabbits were housed individually in cages without a mirror t2 rabbits were individually housed in cages with a mirror on one wall only further experimental detail all rabbits were provided with feeders and drinking cups rabbits had access to ad libitum green grasses and concentrate feed each day, fed at 0900h and 1400h respectively temperature was controlled at 24oc lighting was controlled, rabbits had 16 hours of light per day methodology rabbit bodyweights were recorded weekly on electronic weighing scales rabbits were observed for their behavioural activities. it is not clear from the research methodology how this outcome was measured data was analysed using a t-test (snedecor & cochran, 1968) experimental timeline study duration was 6 weeks study design: controlled trial outcome studied: the influence of presence or absence of a mirror on: growth performance including average daily and weekly bodyweight gains behaviour changes including; activities, performance, feeding preferences, comfort and other notable behaviours ex. scrabbling at the mirror main findings (relevant to pico question): growth performance t1 rabbits (without mirror) weighed 459 g and 844.2 g on average in the first and sixth week respectively mean weight for rabbits in t1 over the 6 week trial period was 638.07 g (p<0.05) t2 rabbits (with mirror) weighed 436 g and 1017 g on average in the first and sixth week respectively mean weight for rabbits in t2 over the 6 week trial period was 729.87 g (p<0.05) rabbits individually housed with a mirror in their cage had higher average weight gains throughout the trial period behaviour changes t2 rabbits were more active t2 rabbits tried to look at the mirror most of the time, including when feeding t2 rabbits consumed all feed without residues t2 rabbits preferred the cage side and to remain in comfortable positions limitations: small sample size only one breed of rabbit used increase in bodyweight may not mean better welfare for the rabbits. a barren experimental environment could mean that feeding is the only enrichment and stimulation received each day, so rabbits may have spent more time eating in general as that was the only activity available frequency of behaviour (activity, looking into the mirror whilst eating) for t2 rabbits housed individually with a mirror remained significant until decreasing after 2 weeks into the trial. this could be due to habituation to the mirror as the rabbit did not receive confirmatory cues that the image was a conspecific limited insight into methodology for behavioural measurement and assessment so unable to gain insight into how the data was acquired jones & phillips (2005) population: unrelated female rabbits aged between 7 and 12 months obtained from a breeder sample size: six rabbits of two breeds: dwarf lop (n = 3) lionhead (n = 3) four rabbits were split into four treatment groups (two of each breed): t1 isolated without mirrors (n = 1) t2 partially isolated without mirrors (n = 1) t3 isolated with mirrors (n = 1) t4 partially isolated with mirrors (n = 1) the other two rabbits were used as conspecific stimuli and were not observed intervention details: experimental set up all test rabbits had access to a cage with two sections, separated by a small door section 1 was approximately 1700 cm2 in size and had four solid sides, including a small door into section two section 2 in isolated rabbit treatment groups (t1 and t3) was 2400 cm2 with three solid sides and a wire mesh grill at the front section 2 in partially isolated rabbit treatment groups (t2 and t4) was the same size, had two solid sides, a wire mesh grill at the front but could also see another rabbit through a plastic mesh panel attached to a single cage. these rabbits will not be discussed in this knowledge summary as this is not relevant to the pico mirrors were attached to the walls of section 2 and did not run parallel to each other to avoid multiple reflections further experimental detail cage floors were covered in newspaper and straw rabbits had access to ad libitum hay and water provided in drinking bottles rabbits were offered a daily carrot at 0900h fresh hay and 30 g concentrate were offered at 1600h cages were weather proofed with roofing felt cages were outside but positioned facing a building for shelter ensuring rain could not enter methodology initial observations were done 1h after rabbits were placed in their test environment on day 1 at 1500h on day 7, rabbits were observed from 0800h to 1430h the duration and number of occurrences of all behaviours were recorded at the end of every 1 minute period behaviour was divided into two categories via a post hoc analysis; ‘long duration’ (lasted for more than a minute on more than 50% of occasions) and ‘short duration’ (all other behaviour) rabbits were randomly allocated to treatment groups using a balanced latin square (davis and hall, 1969) experimental timeline study duration was 1 week study design: randomised controlled trial outcome studied: the effects of provision or absence of mirrors on behaviour duration and frequency of behaviour exhibition over time. the time periods observed were: initial response response over time (comparison between day 1 and day 7) main findings (relevant to pico question): initial response rabbits housed with a mirror showed some alert behaviour, whereas rabbits without a mirror did not mirror presence doubled sniffing behaviour initially mirror presence did not affect sniffing of the wire mesh grill at the front of the cage more exploratory behaviour performed initially response over time (comparison between day 1 and day 7) mirror presence had a stronger effect in increasing sniffing of vertical surfaces than those without decreased the time rabbits spent looking out of their cage increased the time rabbits spent sitting increased the frequency of multiple behaviours observed over every 1 minute period limitations: females only so the results cannot be generalised to include all rabbits as males may have reacted differently a small sample size was used and there was only one rabbit in each treatment group it was not stated in the study how the observations were carried out edgar & seaman (2010) population: new zealand white rabbits aged between 15–16 weeks old sample size: 24 rabbits, both males and females who had been singly housed from weaning: males (n = 9) females (n = 15) intervention details: experimental set up rabbits were individually housed in standard metal laboratory cages in the top two rows of a standard three row rack of cages positioned facing a wall (1.5 m away)   further experimental design test rabbits were not in visual contact but had olfactory and auditory contact as all rabbits were housed in the same room ad libitum access to standard rabbit pellets and water controlled lighting; light hours were between 0530h and 2330h urine and faeces were removed twice weekly rabbits were also used for antibody production with blood being collected every week. they were not handled at any other time   methodology rabbits were split into three groups of 8 cages for filming. rabbits were continuously recorded using two cctv cameras to film four cages each observations were split into three sections: pre-trial observations (day 1–3) each rabbit acted as its own control to provide a baseline behavioural assessment. mirror trial observations (day 4–10) an acrylic mirror was attached to the inside of the cage at either the front (males n = 4; females n = 8) or back (males n = 5; females n = 7). this was randomly assigned on the left or right of the cage. post-trial observations (day 11–13) mirrors were removed and behaviour observed and recorded for a further three days. observation schedules and behavioural assessment was validated using a pilot study (2 day pre-trial, 13 day mirror trial, 7 day post-trial)   experimental timeline study duration was 13 days study design: randomised controlled trial outcome studied: gender percentage of time rabbits spent performing behaviours in each behavioural category; inactive, eating and drinking, body maintenance, mobility, stereotypy, investigatory behaviour, comfort behaviour, mirror related behaviour, time spent at the front and back of the cage main findings (relevant to pico question): gender female rabbits spent less time on body maintenance than males. there was a significant interaction between period and gender (p = 0.006) with females and body maintenance, showing a significant reduction in body maintenance at the end of the trial compared to at the start male and female rabbits spent on average 1.2% and 0.8% of time, respectively, engaged in stereotypic behaviour ex. bar biting and scratching at the floor of the cage females showed a more consistent level of stereotypic behaviour ex. bar biting and scratching at the floor of the cage males showed an initial increase in stereotypic behaviour in the pre-trial period. this decreased during the mirror period and subsequently increased again in the post-trial period (p = 0.042) males exhibited more investigatory behaviour than females, although this was similar in pattern across both genders. investigatory behaviour increased during day 1–2 and then subsequently declined over time females spent 0.21% of time sniffing, scratching and biting the mirror males spent 0.15% of time sniffing, scratching and biting the mirror females spent more time at the front of the cage in the mirror trial period [31%] than in the pre-trial period [25%] (p = 0.017)   behaviour performance all rabbits showed an increase in investigatory behaviour (p = 0.042) all rabbits showed an increase in inactive behaviour over time during the mirror-trial period (p = 0.014) limitations: investigatory behaviour declined over time. this could be due to habituation to the mirror and the rabbit not receiving confirmatory cues that the mirror image was another rabbit could not distinguish between grooming (body maintenance) and hair chewing (stress response/coping mechanism) different social strategies between males and females could have affected the results. for example, males showed increased investigatory behaviour at the start which was more so than females. this may have contributed to stress if the mirror image was perceived as a conspecific, and therefore did not positively influence male rabbit welfare it was not clear in the mirror trial period of the study if the mirror positioning at either the front or back of the cage had an effect on the rabbits behaviour dalle zotte et al. (2008) population: pannon white rabbits aged 5 weeks old [sic], housed in a closed, climatised rabbitry located in kaposvár university, hungary sample size: 56 [sic] rabbits split into two treatment groups: individually housed (n = 18) group housed (n = 2, 28 rabbits in total, 1 group of 12 and 1 group of 16) intervention details: experimental set up individual cages had a basic area of 0.24 m2 individual cages had a stocking density of four cages per m2 with one rabbit in each cage two group pens had an area of 1 m2 each both group pens and individual cages were split into two parts; one side was covered in mirrors and one side was covered in plastic panels each side of all pens were separated by a swinging door further experimental detail temperature was controlled at 18oc ad libitum commercial pellet diet and water provided controlled lighting; 16h light and 8h dark per day methodology each treatment group was used as its own control random assignment of rabbits to pens 24h video recording performed twice weekly using infrared cameras rabbits were not disturbed by human presence on the days of recording the number of rabbits in each pen was counted every 15 minutes, a total of 96 times per day rabbit preference was assessed using a chi-squared test experimental timeline study duration was 6 weeks the study assessed stocking density, age and the effect of the time of day on rabbits’ preference for cages with or without a mirror. only data from individually housed rabbits will be used in this knowledge summary as this is the only data relevant to the pico. study design: randomised controlled trial outcome studied: percentage of time spent in cages with mirrors including: by age by time (active [dark] vs. inactive [light] periods) overall (throughout the 6 week study duration) main findings (relevant to pico question): by age 74.2% of rabbits aged 5.5 weeks [sic] preferred the mirrored part of the cage (p<0.001) 67% of rabbits aged 11.5 weeks preferred the mirrored part of the cage (p<0.001) rabbits were attracted to their mirror reflection up to 11 weeks old mirror preference decreased slightly with age by time period during the active (dark) period, 70.9% (p<0.001) of rabbits were found to prefer the mirrored part of the cage during the inactive (light) period, 70.1% (p<0.001) of rabbits preferred the mirrored part of the cage overall 67% of individually housed rabbits showed a preference for the part of the cage enriched with mirrors (p<0.001) limitations: preference for mirrors decreased as the rabbits got older. however, this could be due to habituation to mirrors and becoming more familiar with them in the environment. they did not receive confirmatory cues that the mirror image was a conspecific so could have reduced interest sample was restricted as all rabbits were between 5 [sic] and 11.5 weeks old. this could be potentially useful for the hospitalisation of young rabbits, but would not be generalisable to all rabbits as there was no indication of mirror preference in older rabbits 6 weeks in duration which is a longer amount of time than a rabbit would generally be hospitalised for. although there may be some cases requiring longer hospitalisation depending on the aetiology minimal enrichment in cages, which would be similar to that of veterinary hospitalisation. did rabbits prefer the mirror because it was the only thing to interact with in the environment? was this down to curiosity instead of recognising the mirror image as a conspecific? the study involved pens which would be familiar to laboratory rabbits but not to pet rabbits. it is an unnatural, artificial environment and may therefore not be generalisable wholly to domesticated rabbits the information in this knowledge summary is taken directly from the paper, it is unclear whether the rabbits were aged 5 or 5.5 weeks at the start of the study and 11 or 11.5 weeks at the end respectively appraisal, application and reflection all four studies addressed the effects of introducing a mirror to a solitary rabbits environment. it is important to note however, that the experimental timeline of all studies was generally longer than the average rabbit would spend hospitalised in veterinary practice. stress, fear and anxiety, as outlined in the pico, were not directly measured although all four studies concluded that the presence of mirrors did in fact affect the subject rabbits behaviour. all studies measured behavioural responses, some of which could be indicative of a stressed, fearful or anxious rabbit. as an example, fearful or anxious behaviour could include, but is not limited to, banging hind feet, darting and tachypnoea. also, expression of stereotypies such as hair chewing has been suggested by previous studies to be indicative of stress due to social deprivation (gunn & morton, 1995). therefore, if a rabbit recognises a reflective mirror image of itself as another rabbit, this psychologically provides companionship. this was the case in female rabbits in edgar & seaman (2010) as a significant interaction was observed. female rabbits spent less time on body maintenance during the mirror trial. so, if addition of a mirror reduces social deprivation through provision of a conspecific image, this may lead to reduced exhibition of stress-related behaviour. combined, this can improve rabbit welfare for short term periods of hospitalisation in a veterinary practice. however, it is important to note that no differentiation between grooming (normal behaviour, generally considered positive) or hair chewing (stress-related behaviour) could be made during this study. body maintenance was previously considered to be at elevated levels as each rabbit was used as its own control. the quality of this research was good due to it being a controlled trial, however, it was unclear from the methodology as to what constituted as a ‘high level’ of body maintenance prior to commencing behavioural observations. regardless, body maintenance did significantly decrease after introduction of the mirror. this requires further investigation to be able to differentiate between normal and stress-related behaviour, grooming and hair chewing respectively. if both were previously at higher levels than normal, this could be indicative of stress anyway. therefore, in relation to the pico, presence of a mirror could reduce stress-induced over-grooming in female laboratory rabbits although further research is needed with a larger sample before this result can be applied to improving welfare and nursing care of hospitalised rabbits. taking this into consideration, both the variety of behaviour expressed and activity levels of rabbits housed with mirrors decreased over time also. jones & phillips (2005) found rabbits were initially attracted to mirrors placed in their cages and spent time scrabbling at it, although this behaviour was observed less often over time. this study was very limited however as breed and treatment were confounded. activity of rabbits also gradually decreased throughout the duration of the study in reddi et al. (2011). it was suggested in both studies that this was because test rabbits did not receive confirmatory cues that the mirror was a conspecific and became less interested over time. they then became habituated to the mirror. it could therefore be suggested that, short term, a mirror could be beneficial and provide welfare advantages through environmental enrichment. similarly, mirror preference was suggested to decrease as the rabbits got older in dalle zotte et al. (2008). it was shown that rabbits were attracted to the mirror up to 11 weeks of age and the strongest preference was at the start of the study when the test rabbits were 5.5 [sic] weeks old. it is therefore unclear if the contributing factor towards mirror preference was the age of the rabbits or time spent with the mirror. in this paper, the ages of the rabbits do not add up, however the data was taken directly from the published study. in relation to the pico, it is likely that younger rabbits show a stronger preference towards mirrors although all rabbits may be initially interested in them if introduced to their immediate environment. further research could control rabbit age and offer a better insight into this finding. on the other hand, edgar & seaman (2010) contradicts the idea of habituation. body maintenance continued to decrease over time. if this was stress-related behaviour, this strengthens the argument that mirrors have welfare advantages for rabbits, particularly those hospitalised short-term. however it was unclear from this study whether the position of the mirror within the cage also had an effect on rabbit behaviour. the fact stress-related body maintenance decreased significantly overall also suggests female test rabbits recognised the mirror image as a conspecific, subsequently improving welfare by psychological provision of companionship. another behaviour that decreased over time was investigatory behaviour, although some aspects of this may not be advantageous to welfare. for example, many of the studies above (jones & phillips, 2005; edgar & seaman, 2010; reddi et al., 2011) stated in the initial experimental periods that investigatory behaviour increased, including sniffing and scratching at not only the mirror but vertical surfaces. in relation to the pico, this strengthens the idea that a mirror could be considered a good and relatively cheap form of environmental enrichment in a veterinary setting for short term hospitalisation. however, before any clinical recommendations can be made, further research is needed into specific factors affecting this, particularly the initial response of male rabbits to mirrors. it was suggested mirrors could be detrimental to male rabbits as vigilance and alertness increased initially, and more dramatically than females when introduced to a mirror (edgar & seaman, 2010). the reasoning for this is not clear, however it is not unreasonable to suggest this could be due to competition for resources and territory with the mirrored image, especially being in a small and confined space. it is important to assess whether increased alertness also leads to increased levels of stress, fear and anxiety. it is important to investigate this before being able to recommend mirrors as nursing consideration for hospitalised male rabbits. social factors behind these results need to be identified and assessed to avoid negative effects on welfare. as well as reducing some behaviour, mirror presence has shown to be advantageous in improving some aspects of rabbit husbandry such as food consumption. reddi et al. (2011) found the presence of mirrors increased rabbit bodyweight, food consumption and feeding efficiency.  this was also found in jones & phillips (2005) although hay intake was lower initially in this study. in relation to the pico, it is important to consider these results could potentially be detrimental to rabbit welfare and increase stress, fear and anxiety. the presence of a mirror could increase food intake due to competition and resource rivalry with conspecific images. however, this does assume that rabbits are able to distinguish the mirror image from their own reflection and recognise it as another rabbit. it is assumed in all studies outlined above that rabbits are not capable of self-recognition. in a veterinary setting, mirrors could potentially aid inappetence in rabbits however further investigation into influencing factors, particularly in male rabbits, is needed before this can be recommended. considering all the above in relation to the pico, there have been some benefits to rabbit welfare through using a mirror as environmental enrichment when assessed using behavioural observations. however, there have also been some indications that mirrors may be detrimental to the welfare of some rabbits. it is important to note that rabbits in a hospitalised environment will most likely be unwell or injured. they may prefer to be alone opposed to being housed with an unfamiliar conspecific image. this highlights the need for further, well controlled research studying both healthy and unwell rabbits, as well as a variety of treatments. there is also a need for larger sample sizes in future studies as this would add more confidence to any results before any practical application can be taken from existing research. in conclusion, solitary rabbits are affected by the presence or absence of a mirror in their environment, but it is difficult to make definitive recommendations as there are large knowledge gaps currently in available published research. methodology section search strategy databases searched and dates covered: pubmed via the ncbi website (01/01/1973 – 31/12/2017) cab abstracts on the ovid interface (1973 – 2017 week 40) search terms: pubmed (rabbit or rabbits or lagomorph or lagomorphs or “oryctolagus cunniculus” or bunny or bunnies or hare or hares or buck or bucks or doe or does or kittens or kits or kitten) and (mirror or mirrors or “reflecting glass”) and (stress or stressed or anxiety or fear or anxious or fearful or worried or nervous or nervy or panic or panicked or fright or frightened or “tonic immobility” or ti or immobility or distressed or distress or scared or scary or afraid or behavioural or pressure or tension or alarm or alarmed or vigilant or vigilance or apprehension or apprehensive or activity or time or budget or “time budget” or nervousness or stressful or distress or pain or painful or “pain score” or “pain scoring”) cab abstracts (rabbit or rabbits or lapine or lagomorph or lagomorphs or bunny or bunnies or hare or hares or buck or bucks or doe or kittens or kits or kittens or oryctolagus).mp. or exp rabbits/ or exp oryctolagus cuniculus/ (mirror or mirrors or reflector or reflective or reflection or 'reflecting glass' or 'reflective glass') (stress or stressed or stressful or distressed or anxiety or anxious or fear or fearful or fearfulness or worried or nervous or nervy or nervousness or panic or panicked or fright or frightened or scared or scary or afraid or alarmed or alarm or apprehension or apprehensive or behaviour or behaviour).mp. or exp stress/ or exp fearfulness/ or exp anxiety/ 1 and 2 and 3 dates searches performed: 05/12/2017 16/10/2017 exclusion / inclusion criteria papers were screened by titles and abstracts initially upon whether they met the criteria to answer the knowledge summary question. upon meeting the inclusion criteria, the full text article was obtained and assessed exclusion: irrelevant to pico question paper subjects were not rabbits no use of mirrors non-english publications duplicates inclusion: primary research papers peer reviewed journals rabbit subjects comparison of presence or absence of mirrors relevant to pico question publications in english language search outcome database number of results excluded – not relevant to pico excluded – duplicates total relevant papers pubmed 106 106 0 0 cab abstracts 12 7 1* 4 total relevant papers when duplicates removed 4 *paper was first presented at proceedings of the 9th world rabbit congress, verona, italy, 10–13 june 2008 conflict of interest the author declares no conflict of interest. references dalle zotte, a., princz, z., matics, zs., gerencsér, zs., metzger, sz. & szendrö, zs. (2008) rabbits’ preference for cages and pens with or without mirror. 9th world rabbit congress, june 10–13, 2008 verona (italy), pp. 1165–1170. davis, a.w. & hall, w.b. 1969. cyclic change-over designs. biometrika 56 (2), pp. 283–293. https://doi.org/10.1093/biomet/56.2.283 edgar, j.l. & seaman, s.c. (2010) the effect of mirrors on the behaviour of singly housed male and female laboratory rabbits. animal welfare, 19 (4), 461–471. gunn, d. & morton, d.b. (1995) inventory of the behaviour of new zealand white rabbits in laboratory cages. applied animal behaviour science, 45 (3–4), pp. 277–292. https://doi.org/10.1016/0168-1591(95)00627-5 jones, s.e. & phillips, c.j.c. (2005) the effects of mirrors on the welfare of caged rabbits. animal welfare, 14 (3), pp. 195–202. mcafee, l.m. mills, d.s. & cooper, j.j. (2002) the use of mirrors for the control of stereotypic weaving behaviour in the stabled horse. applied animal behaviour science, 78, 159–173. http://dx.doi.org/10.1016/s0168-1591(02)00086-2 parrott, r.f. houpt, k.a. & misson, b.h. (1988) modification of the responses of sheep to isolation stress by the use of mirror panels. applied animal behaviour science, 19 (3–4), 331–338. https://doi.org/10.1016/0168-1591(88)90015-9 piller, c.a.k. stookey, j.m. & watts, j.m. (1999) effects of mirror-image exposure on heart rate and movement of isolated heifers. applied animal behaviour science, 63 (2), pp. 93–102. http://dx.doi.org/10.1016/s0168-1591(99)00010-6 reddi, a.k.g. gouri, m.d. raeshwari, y.b. & ningaraju, k. (2011) growth and performance changes in rabbits housed with or without a mirror. mysore journal of agricultural sciences, 45 (3), pp. 688–690. snedecor, g. & cochran, w.g. 1968. statistical methods. 6th edition. iowa state university press, iowa, usa. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in horses with chronic laminitis, do venograms compared to plain radiographs give greater diagnostic or prognostic information? a knowledge summary by claire elizabeth wylie bvm&s, msc, msc, phd, mrcvs 1* christopher c pollitt bvsc, phd 2 1rossdales equine hospital, cotton end road, exning, newmarket, suffolk cb8 7nn 2university of queensland, st lucia qld 4072, australia *corresponding author (claire.wylie@rossdales.com) vol 2, issue 3 (2017) published: 14 aug 2017 reviewed by: bruce bladon (bvm&s, cert ep, dests, dipl, ecvs, mrcvs) and james carmalt (ma, vetmb, mvetsc, frcvs) next review date: 14 aug 2019 doi: 10.18849/ve.v2i3.124 clinical bottom line there is no conclusive evidence available to guide recommendations as to whether venograms provide any greater diagnostic or prognostic information compared to the use of plain radiographs in horses with chronic laminitis. further evidence is needed to better answer this pico. question in horses with chronic laminitis, do venograms compared to plain radiographs give greater diagnostic or prognostic information? clinical scenario a 20-year old, obese shetland pony mare with a history of recurrent episodes of acute laminitis is presented with reluctance to move, resistance to attempts to lift either of her front feet and weight shifting. plain radiographs obtained on site reveal evidence of rotation of both the distal phalanges, consistent with a diagnosis of chronic laminitis. should you proceed with further diagnostic imaging using contrast venograms to further inform your diagnostic or prognostic advice? the evidence one publication was identified that compared concurrent findings of plain radiography and venograms to aid the diagnosis of chronic laminitis in a horse (rucker, 2010b). this was a review article published in the peer-review journal ‘journal of equine veterinary science’, within a special issue featuring the proceedings of the 2nd laminitis west conference, monterey, california in september 2010. as the data presented referred to only one horse, this publication is graded level 4 (case report) according to the 2011 oxford centre for evidence-based medicine (ocebm) levels of evidence[1]. whilst a number of other review articles were identified from literature search on the subject of venography in horses, these did not include empirical comparative data between plain radiographs, and screening of all referenced primary research, including conference proceedings, also failed to identify any relevant data. summary of the evidence rucker (2010b) population: 18-year old american saddlebred gelding with insulin-resistance. presented with a history of six-hour bilateral forelimb lameness and elevations in digital pulse pressure in all four limbs, subsequent to being ridden on trails one week earlier. bruising of the sole had been identified four days prior to presentation. sample size: 1 intervention details: plain lateral radiographs, and lateral and dorsopalmar venograms taken of both front feet at initial presentation. study design: review article containing a case series of three animals, one of which had laminitis (i.e. empirical data relevant to this knowledge summary presented on one case). outcome studied: objective diagnosis of laminitis on the basis of radiographic and venographic findings with descriptive, plain radiographic and venographic images provided. main findings (relevant to pico question): plain radiographs identified mild remodelling at the apex of the distal phalanx and narrow sole depth (7 mm in the most painful, right fore). the lateral venogram revealed reduced contrast in the circumflex vessels and corium of the sole, absence of sole papillae visible distal to the apex of the distal phalanx, distortion of the lamellar-circumflex junction around the apex of the distal phalanx, and alterations in the dorsal coronary vessels. the dorsopalmar venogram confirmed absence of contrast in the circumflex vessel and sole corium beneath the descended apex of the distal phalanx, with relatively normal medial and lateral sublamellar vascular beds. the authors concluded “the venogram helped confirm that the lameness was not because of solar bruising or shoeing, but was because of laminitis”. objective diagnosis of laminitis on the basis of radiographic and venographic findings with descriptive, plain radiographic and venographic images provided. limitations: unclear quality of peer-review for special issue of conference proceedings. single animal. whilst subsequent imaging was undertaken, plain radiographs and venograms were not reported to have been repeated simultaneously. sequential imaging of both modalities and their correlation with prognosis was not done. provides low level evidence of an improved diagnosis of chronic laminitis using venograms compared to plain radiography. appraisal, application and reflection equine laminitis is a highly debilitating, multifactorial disease of the foot that affects equidae worldwide (herthel and hood, 1999, hood, 1999a, wylie et al., 2011).  it remains a significant welfare concern due to the potential for debilitating and unrelenting pain (baxter, 1986, collins et al., 2010, cripps and eustace, 1999a, hunt, 1993, luthersson et al., 2017, menzies-gow et al., 2010). the common feature of all laminitis cases is the induction of pathological changes within the suspensory apparatus of the distal phalanx (sadp) (collins et al., 2010, hood, 1999b). ‘acute’ laminitis refers to the development of clinical signs associated with foot pain considered to represent pathological changes of the lamellar attachments, manifest as changes in the normal stance and gait of the animal (baxter, 1994, swanson, 1999, wylie et al., 2013, wylie et al., 2016). acute laminitic cases can either progress to complete recovery, persist in a subacute form, or develop to ‘chronic’ laminitis (hood, 1999b). the terminology used to describe  chronic laminitis is extremely variable (parks and mair, 2009), but is commonly considered to occur when there is dislocation of the distal phalanx, as failure of the sadp disrupts the normal suspension of the appendicular skeleton within the hoof capsule (collins et al., 2010, hood, 1999b, obel, 1948). diagnosis of chronic laminitis is often hampered by the variability of clinical presentation (wylie et al., 2013, wylie et al., 2016), influenced by the underlying aetiology, concurrent disorders, disease phase and number of feet involved (hunt and wharton, 2010). traditionally, the perceived ‘gold-standard’ diagnosis of chronic laminitis has included evidence of capsular and/or phalangeal rotation (‘founder’), distal displacement of the distal phalanx (‘sinker’), remodelling at the apex of the distal phalanx and the presence of gas lines, identified by standard, non-contrast (‘plain’) radiography (cripps and eustace, 1999a, cripps and eustace, 1999b, eustace, 2010, hunt and wharton, 2010). however, plain radiographs are unable to provide visualisation of the corresponding digital vasculature and soft tissue damage (baldwin and pollitt, 2010, eastman et al., 2012), and the lack of consensus regarding the evaluation of laminitic cases  (cripps and eustace, 1999b, hunt, 1993, stick et al., 1982), suggests the need for appraisal beyond clinical examination and plain radiographic findings. vascular perfusion casts have previously been identified to reveal macroscopic perfusion defects in the distal digit of chronic laminitis cases compared to controls (hood et al., 1994). the development of a digital venography technique in the early 1990s demonstrated retrograde filling of the digital veins following injection of radiopaque contrast fluid into the lateral digital vein and potential clinical application  in the standing horse using standard radiographic equipment and a tourniquet following injection into the digital palmar or plantar veins (baldwin and pollitt, 2010, d'arpe and bernardini, 2010, redden, 1993, redden, 2001, rucker, 2010a).  digital venography illustrates the major areas of interest including the bulbar vessels, circumflex vessels, coronary plexus, dorsal lamellar vessels and terminal arch (arthur and rucker, 2003, d'arpe and bernardini, 2010). in the healthy equine digit, venography reveals consistent digital vasculature without perfusion deficits, including filling of the venous vessels and retrograde arterial filling in some cases (arthur and rucker, 2003, d'arpe and bernardini, 2010, redden, 2001, rucker, 2003a, rucker, 2003b, rucker et al., 2006, rucker, 2010c).  in both experimentally-induced and naturally-occurring chronic laminitis it is reported that venography highlights notable perfusion deficits (arthur and rucker, 2003, baldwin and pollitt, 2010, d'arpe and bernardini, 2010, rucker, 2010a).  this knowledge summary sought to gather peer-reviewed comparative data regarding concurrent plain radiographic and venographic findings in laminitic cases to appraise the evidence for improved diagnostic or prognostic indications following the use of venograms. no prospective studies, designed to quantify the sensitivity and specificity of the diagnostic modalities were identified. only one conference proceeding identified by the search presented venographic data, yet presented no comparative plain radiographic data (d'arpe and bernardini, 2008). due to the limited success, all potentially relevant review articles were also sourced and screened to identify any empirical data contained within them. all bibliographies from the retrieved articles and review articles were hand-checked and potentially relevant articles sourced.  furthermore, the leading researchers in the field, in australia, europe and the united states, were contacted to obtain any other relevant grey literature evidence.  single case reports of venographic findings in laminitic horses were presented in eight conference proceedings (arthur and rucker, 2003, d'arpe, 2007, d'arpe, 2008, d'arpe and bernardini, 2008, lyle, 2002, pittman, 2016, rucker et al., 2006, redden, 2008), and in four review articles (baldwin and pollitt, 2010, d'arpe and bernardini, 2010, eastman et al., 2012, rucker, 2010c). none of these publications presented concurrent plain radiographic findings, yet many anecdotally discussed the merits of undertaking venograms in chronic laminitics, stating that venography can predict distal phalangeal displacement and the associated vascular changes in advance of their occurrence, even whilst the foot looks normal on plain radiographs (arthur and rucker, 2003, d'arpe and bernardini, 2008, d'arpe and bernardini, 2010, eastman et al., 2012, rucker, 2010c,).  the review article by baldwin and pollitt (2010) referred to data presented in a msc thesis publicly available through the university of queensland website (baldwin, 2012). this prospective clinical study investigated venographic changes in 10 standardbred horses with no known prior history of laminitis, no clinical lameness and normal foot conformation, in which laminitis was induced using the carbohydrate (oligofructose) overload model. although the data were not presented, as time progressed plain radiographs showed gradual dislocation of the distal phalanx within the hoof of the most severe of the six treated horses, whilst concurrent venography showed dramatic compression of dorsal venous compartments interpreted as progression of distorted hoof growth likely to contribute to pathological lysis of the distal phalanx. the authors stated that venographs allowed clinicians to detect and treat laminitis at a much earlier time point than relying on plain radiographs alone, enabling early diagnosis of irreversible changes that timely intervention could have prevented. a close correlation is also anecdotally reported to exist between prognosis, venographic findings, clinical and radiographic evidence of pathologic changes within the foot, in approximately 1000 laminitis cases (rucker et al., 2006), with venograms reportedly providing superior prognostic information (baldwin and pollitt, 2010, d'arpe and bernardini, 2010, pollitt, 2008, redden, 1993).  the only identified evidence related to the clinical scenario was, therefore, one review article published in the journal of equine veterinary science, as summarised in the summary of evidence (rucker, 2010b).  whilst this is a peer-reviewed journal, this was published as a special issue featuring the proceedings of the 2nd laminitis west conference, monterey, california in september 2010, and it is unclear whether such issues undergo the same degree of peer-review. this was a descriptive report which presented concurrent radiographic and venographic findings in a single horse with chronic laminitis. the authors stated that venography helped confirm a diagnosis of laminitis, providing low level evidence regarding the value of venograms compared to radiographs in the diagnosis of chronic laminitis.  in conclusion, this knowledge summary failed to find any evidence of any prospective, comparative clinical studies between the findings of plain radiography and venography and their association with the diagnosis or prognosis of chronic equine laminitis.  as this systematic scrutiny of the available evidence identified a knowledge gap, a strong justification for publication of original research is therefore apparent (lund et al., 2016). it was apparent from the data discussed in review articles and conference proceedings that a large number of venograms have been undertaken in clinical practice and these authors should be encouraged to provide an empirical evidence-base for the use of venograms as a diagnostic and prognostic modality for chronic laminitis. a simple retrospective case series providing descriptive data regarding both plain radiographic and venographic changes relative to diagnosis and outcome in clinical cases would provide a foundation for more robust observational and experimental studies. if indicated, future work should include prospective, comparative clinical studies designed to quantify the sensitivity and specificity of the diagnostic modalities. if data indicating a benefit of venography can be documented, then the effort and expense of undertaking venographic imaging in the chronic laminitic would become more justifiable than the current lack of evidence supports. methodology section search strategy databases searched and dates covered: (a) cab abstracts on the ovid interface (1973 to 2017 week 10) (b) pubmed database, accessed via the ncbi website (last 20 years 1997-), veterinary science filter applied. search terms: (a) (equine* or horse* or equus or colt* or pony or ponies or mares or filly or fillies or gelding* or stallion* or yearling* or thoroughbred or standardbred or warmblood).mp. or equidae/ or equus/ or horses/ or foals/ or colts/ or mares/ or stallions/ (laminitis or laminitic or founder).mp. or exp laminitis/ (venogram or venograms or venography or venographic or phlebography or phlebographic or phlebogram or phlebograms).mp. (radiograph or radiographs or radiography or radiographic).mp. or radiography/ 1 and 2 and (3 or 4) (170) (b) horse laminitis or founder radiography venogram or venography or phlebogram or phlebography 1 and 2 and (3 or 4) dates searches performed: 22-23/03/2017 exclusion / inclusion criteria papers were initially screened on title and abstract, and all potentially relevant articles were retrieved in full-text format. there were no pre-specified limitations regarding study design, study location or sample size. exclusion: non english-language publications inclusion: primary research papers conference proceedings review articles with empirical data horses or ponies with chronic laminitis (defined as displacement of the distal phalanx, irrespective of duration) both concurrent plain radiographic and venographic findings presented search outcome database number of results excluded – not related to pico excluded – not laminitis excluded – not radiography/venography excluded – review article with no empirical data excluded – unable to source total relevant papers cab abstracts 170 142 0 8 18 1 1 medline 174 167 0 0 7 0 0 hand-searching reference lists of all cab abstract and medline articles retrieved at screening stage for novel results 3 0 0 3 0 0 0 hand-searching all identified review articles for novel results 12 0 2 10 0 0 0 total relevant papers when duplicates removed 1 conflict of interest dr claire e wylie is funded by the margaret giffen charitable trust, and declares no conflicts of interest.  professor christopher c pollitt declares no conflicts of interest. references arthur, e. & rucker, a. 2003. the use of digital venography for assessment of perfusion deficits in laminitis. proceedings of the 2nd international equine conference on laminitis and diseases of the foot, november 10-11th 2003, florida, usa, p319. baldwin, g. i. 2012. venography and histopathology of the equine foot following oligofructose induced laminitis. mphil, the university of queensland. baldwin, g. i. & pollitt, c. c. 2010. progression of venographic changes after experimentally induced laminitis. veterinary clinics of north america: equine practice, 26(1), p135-140. http://dx.doi.org/10.1016/j.cveq.2009.12.005 baxter, g. m. 1986. equine laminitis caused by distal displacement of the distal phalanx: 12 cases (1976-1985). journal of the american veterinary medical association, 189(3), p326-329. baxter, g.m. 1994. acute laminitis. veterinary clinics of north america: equine practice, 10(3), p627-642. http://dx.doi.org/10.1016/s0749-0739(17)30351-6 collins, s. n., pollitt, c., wylie, c. e. & matiasek, k. 2010. laminitic pain: parallels with pain states in humans and other species. veterinary clinics of north america: equine practice, 26(3), p643-671. http://dx.doi.org/10.1016/j.cveq.2010.08.001 cripps, p. j. & eustace, r. a. 1999a. factors involved in the prognosis of equine laminitis in the uk. equine veterinary journal, 31(5), p433-442. http://dx.doi.org/10.1111/j.2042-3306.1999.tb03845.x cripps, p. j. & eustace, r. a. 1999b. radiological measurements from the feet of normal horses with relevance to laminitis. equine veterinary journal, 31(5), p427-432. http://dx.doi.org/10.1111/j.2042-3306.1999.tb03844.x d'arpe, l. 2007. case reviews high scale laminitic cases treated in france & italy. 18th bluegrass laminitis symposium, 25th-28th january 2007, kentucky, usa. d'arpe, l. 2008. case reviews of high risk scale laminitic cases treated in europe. proceedings of the international laminitis symposium, 2008, berlin, germany. p44-45. d'arpe, l. & bernardini, d. 2008. interpreting contrast venography in horses with controlateral laminitis. 14th european society of veterinary orthopaedics and traumatology, 10th-14th september 2008, munich, germany. p226-233. d'arpe, l. & bernardini, d. 2010. digital venography in horses and its clinical application in europe. veterinary clinics of north america: equine practice, 26(2), p339-359. http://dx.doi.org/10.1016/j.cveq.2010.06.006 eastman, s., redden, r. f. & williams, c. a. 2012. venograms for use in laminitis treatment. journal of equine veterinary science, 32(11), p757-759. http://dx.doi.org/10.1016/j.jevs.2012.02.020 eustace, r. a. 2010. clinical presentation, diagnosis, and prognosis of chronic laminitis in europe. veterinary clinics of north america: equine practice, 26(2), p391-405. http://dx.doi.org/10.1016/j.cveq.2010.06.005 herthel, d. & hood, d. m. 1999. clinical presentation, diagnosis, and prognosis of chronic laminitis. veterinary clinics of north america: equine practice, 15(2), p375-394, vii. http://dx.doi.org/10.1016/s0749-0739(17)30151-7 hood, d. m. 1999a. laminitis in the horse. veterinary clinics of north america: equine practice, 15(2), p287-294, v. http://dx.doi.org/10.1016/s0749-0739(17)30145-1 hood, d. m. 1999b. the mechanisms and consequences of structural failure of the foot. veterinary clinics of north america: equine practice, 15(2), p437-461. http://dx.doi.org/10.1016/s0749-0739(17)30154-2 hood, d. m., grosenbaugh, d. a. & slater, m. r. 1994. vascular perfusion in horses with chronic laminitis. equine veterinary journal, 26(3), p191-196. http://dx.doi.org/10.1111/j.2042-3306.1994.tb04368.x hunt, r. j. 1993. a retrospective evaluation of laminitis in horses. equine veterinary journal, 25(1), p61-64. http://dx.doi.org/10.1111/j.2042-3306.1993.tb02903.x hunt, r. j. & wharton, r. e. 2010. clinical presentation, diagnosis, and prognosis of chronic laminitis in north america. veterinary clinics of north america: equine practice, 26(1), p141-153. http://dx.doi.org/10.1016/j.cveq.2009.12.006 lund, h., brunnhuber, k., juhl, c., robinson, k., leenaars, m., dorch, b. f., jamtvedt, g., nortvedt, m. w., christensen, r. & chalmers, i. 2016. towards evidence based research. british medical journal, 355, i5440. http://dx.doi.org/10.1136/bmj.i5440 luthersson, n., mannfalk, m., parkin, t. d. h. & harris, p. 2017. laminitis: risk factors and outcome in a group of danish horses. journal of equine veterinary science, 53, p68-73. http://dx.doi.org/10.1016/j.jevs.2016.03.006 lyle, b. e. 2002. the digital venogram: interpretation and suggested implications for therapy in the laminitic horse. 15th annual bluegrass laminitis symposium 2002, kentucky, usa, p53-57. menzies-gow, n. j., stevens, k., barr, a., camm, i., pfeiffer, d. & marr, c. m. 2010. severity and outcome of equine pasture-associated laminitis managed in first opinion practice in the uk. veterinary record, 167(10), p364-369. http://dx.doi.org/10.1136/vr.c3206 obel, n. 1948. studies on the histopathology of acute laminitis. doctor of philosophy phd, sweden. parks, a.h. & mair, t.s. 2009. laminitis: a call for unified termiology. equine veterinary education, 21(2), p102-106. http://dx.doi.org/10.2746/095777309x403673 pittman, s. l. 2016. using venograms to guide your clinical approach to common foot problems. podiatry 7th annual symposium from our practice to yours northeast association of equine practitioners, 21st-24th september 2016, virginia, usa, p45-55. pollitt, c. c. 2008. chronic laminitis, the hidden danger. 14th european society of veterinary orthopaedics and traumatology, 10th-14th september 2008, munich, germany, p273-276. redden, r. f. 1993. the use of venograms as a diagnostic tool. proceedings of the 7th bluegrass laminitis symposium, 1993, kentucky, usa, p1-6. redden, r. f. 2001. a technique for performing digital venography in the standing horse. equine veterinary education, 13(3), p128-134. http://dx.doi.org/10.1111/j.2042-3292.2001.tb00077.x redden, r. f. 2008. hoof correction according to redden in the chronically laminitic horse. proceedings of the international laminitis symposium, 2008, berlin, germany, p194-209. rucker, a. 2003a. interpreting venograms: normal or abnormal and artifacts that may be misinterpreted. 16th bluegrass laminitis symposium, 2003, kentucky, usa, p97-101. rucker, a. 2003b. key points of the digital venogram. 16th bluegrass laminitis symposium, 2003, kentucky, usa, p105-109. rucker, a. 2010a. chronic laminitis: strategic hoof wall resection. veterinary clinics of north america: equine practice, 26(1), p197-205. http://dx.doi.org/10.1016/j.cveq.2009.12.009 rucker, a. 2010b. clinical applications of digital venography. journal of equine veterinary science, 30(9), p491-503. http://dx.doi.org/10.1016/j.jevs.2010.07.016 rucker, a. 2010c. equine venography and its clinical application in north america. veterinary clinics of north america: equine practice, 26(1), p167-77. http://dx.doi.org/10.1016/j.cveq.2009.12.008 rucker, a., redden, r. f., arthur, e. g., reed, s. k., hill, b. w., dziuban, e. m. & renfro, d. c. 2006. how to perform the digital venogram. 52nd annual convention of the american association of equine practitioners, 2006, texas, usa, p526-530. stick, j. a., jann, h. w., scott, e. a. & robinson, n. e. 1982. pedal bone rotation as a prognostic sign in laminitis of horses. journal of the american veterinary medical association, 180(3), p251-253. swanson, t.d. 1999. clinical presentation, diagnosis, and prognosis of acute laminitis. veterinary clinics of north america equine practice, 15(2), p311-319. http://dx.doi.org/10.1016/s0749-0739(17)30147-5 wylie, c. e., collins, s. n., verheyen, k. l. & newton, j.r. 2011. frequency of equine laminitis: a systematic review with quality appraisal of published evidence. the veterinary journal, 189(3), p248-256. http://dx.doi.org/10.1016/j.tvjl.2011.04.014 wylie, c. e., collins, s. n., verheyen, k. l. & newton, j. r. 2013. a cohort study of equine laminitis in great britain 2009-2011: estimation of disease frequency and description of clinical signs in 577 cases. equine veterinary journal, 45(6), p681-687. http://dx.doi.org/10.1111/evj.12047 wylie, c. e., shaw, d. j., verheyen, k. l. & newton, j. r. 2016. decision-tree analysis of clinical data to aid diagnostic reasoning for equine laminitis: a cross-sectional study. veterinary record, 178(17), p420. http://dx.doi.org/10.1136/vr.103588 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. building a multi-centre clinical research facilitation network: the arc experience ian nicholson bvsc, cert, sas, dipecvs, mrcvs1* 1southern counties veterinary specialists, unit 6, forest corner farm, hangersley, ringwood, hampshire bh24 3jw *corresponding author (inicholsonvet@gmail.com) vol 2, issue 2 (2017) published: 07 jun 2017 doi: 10.18849/ve.v2i2.122 in this talk ian will discuss how the association for veterinary soft tissue surgery (avsts), an affiliate group with the british small animal veterinary association (bsava), created a role for itself in facilitating the production (by its members) of multi-centre clinical research of relevance to its members to further ebvm. find out more about ian. comments: in adult horses with septic peritonitis, does peritoneal lavage combined with antibiotic therapy compared to antibiotic therapy alone improve survival rates? a knowledge summary by sarah scott smith ma, vetmb, mvetmed, dipacvim, mrcvs, rcvs 1* 1equine referral hospital, langford veterinary services, langford, bs40 5du *corresponding author (sarah1.smith@bristol.ac.uk) vol 2, issue 4 (2017) published: 13 nov 2017 reviewed by: kate mcgovern (bvetmed, certem(int.med), ms, dacvim, dipeceim, mrcvs) and cathy mcgowan (bvsc, macvs, deim, dip eceim, phd, fhea, mrcvs) next review date: 13 nov 2019 doi: 10.18849/ve.v2i4.135 clinical bottom line the quality of evidence in equids is insufficient to direct clinical practice aside from the following: the use of antiseptic solution to lavage the abdomen causes inflammation and is detrimental to the patient. for peritonitis caused by actinobacillus equuli, treatment with antibiotics alone may be sufficient. a variety of antibiotics were used in the two reported studies. question in adult horses with septic peritonitis, does peritoneal lavage combined with antibiotic therapy compared to antibiotic therapy alone improve survival rates? the evidence there is a small quantity of evidence and the quality of the evidence is low, with comparison of the two treatment modalities in equids only performed in case series. there is a single study which performed the most robust analysis possible of a retrospective case series by using multivariate analysis to examine the effect of multiple variables on survival (nogradi et al., 2011). inherent to case series is the risk that case selection will have introduced significant bias into the results; peritoneal lavage maybe used more commonly in more severely affected cases or where the abdomen has been contaminated with intestinal or uterine contents. there have been no randomised trials to compare the efficacy of the treatment options discussed. when examining the method of peritoneal lavage chosen there is a single experimental, randomised control trial comparing the use of sterile saline, saline containing potassium penicillin and neomycin, 3% or 10% povidone iodine solution for abdominal lavage in horses. the quality of evidence describing types of antibiotics used is low (case series) and there is no direct comparison of antibiotics used. summary of the evidence golland (1994) population: horses with peritonitis attributed to actinobacillus equuli at one australian equine hospital 1982-1992 excluded: post-operative peritonitis peritonitis: not defined sample size: 15 intervention details: antibiotics: n=15 (procaine penicillin and neomycin [n=12], procaine penicillin and gentamicin [n=1], trimethoprim sulfadiazine [n=1], oxytetracycline then trimethoprim sulphadiazine [n=1]) abdominal lavage: 1/15 (3l balanced polyionic solution + 3g benzyl penicillin q 12h) study design: case series outcome studied: clinical improvement after 48h of treatment survival rate main findings (relevant to pico question): there was a rapid response to antibiotic treatment and high survival rate of peritonitis caused by a. equuli infection clinical improvement after 48h: 15/15 return to previous activity: 11/15 (7 ridden, 4 breeding) information not available for 3/15, euthanised for unrelated condition 1/15 limitations: small sample size abdominal lavage was only performed in one case and there was no comparison of treatment protocols survival information was not available for 3/15 cases neomycin is rarely used in current clinical practice hawkins (1993) population: horses with peritonitis at a single equine hospital 1985-1990 peritonitis: peritoneal fluid total nucleated cell count > 10 x 10-9 cells/l sample size: 67 peritonitis due to: intestinal rupture [n=14] after abdominal surgery [n=25] no intestinal rupture or abdominal surgery [n=28] intervention details: antibiotics only: penicillin (22000iu/kg q6-12h) [n=38] gentamicin (2.2-3.3mg/kg q8-12h) [n=44] metronidazole (15-25mg/kg q6-12h) [n=13]peritoneal lavage (no further details) [n=9] study design: case series outcome studied: survival to discharge from the hospital main findings (relevant to pico question): there is a high mortality with septic peritonitis after abdominal surgery survival to discharge from hospital: 27/67 (40.3%) survival of cases undergoing peritoneal lavage: 6 out of9 (60%) limitations: no details of substance, volume, frequency of peritoneal lavage very limited details of other treatments given no statistical comparison of interventions no follow-up of survival after discharge from the hospital the dosing regime of gentamicin is not consistent with that used in current clinical practice henderson (2008) population: horses with peritonitis at two uk equine hospitals over 12 years. peritonitis: peritoneal fluid total nucleated cell count > 5 x 10-9 cells/l excluded: post-laparotomy/ laparoscopy cases gastrointestinal rupture sample size: 65 the effect of treatment was compared for 50 horses with idiopathic peritonitis. 15 horses with identified causes of peritonitis were excluded from treatment comparison. intervention details: broad-spectrum antibiotics (no further details provided) [n=56], with anthelmintics [n=7] peritoneal lavage [n=9] via exploratory laparotomy [n=5] or standing drain placement [n=4] study design: case series outcome studied: survival development of complications main findings (relevant to pico question): 84% of cases survived to 12 months. there was no association of treatment method with outcome or complication rate. limitations: few details of treatment methods including type of antimicrobials and solution used/ frequency of abdominal lavage. it is not described within the 50 horses with idiopathic peritonitis how many horses there were in each treatment group or the outcome of each treatment group javsicas (2010) population: post-partum mares (within 7 days of foaling) with peritonitis or a confirmed uterine tear treated at two equine hospitals 1990-2007 peritonitis: peritoneal fluid total nucleated cell count > 10 x 10-9 cells/l, total protein concentration > 2.5g/dl, predominance of degenerative neutrophils +/intracellular bacteria on cytological examination excluded: vaginal laceration, gastrointestinal rupture, death on day of admission sample size: 49 intervention details: medical [n=15]; antibiotic therapy surgical [n=34]; ventral midline coeliotomy abdominal lavage was performed in both groups and frequency of abdominal lavage was not different between the treatment groups study design: case series outcome studied: survival to discharge main findings (relevant to pico question): overall survival to discharge: 76% survival was not different between medically (11 out 15 survived) and surgically treated (26 out of 34 survived) cases. use of peritoneal lavage was not different between survivors and non-survivors limitations: no definitive diagnosis of uterine tear in 7/11 surviving medically treated cases no details of peritoneal lavage treatment or antibiotics used no follow up information beyond discharge matthews (2001) population: horses with peritonitis attributed to actinobacillus equuli seen at one australian equine hospital 1993-1999 peritonitis: not defined sample size: 51 intervention details: antibiotic treatment (procaine penicillin 20mg/kg iv bid [n=31], procaine penicillin andgentamicin sulphate 6.6mg/kg iv sid [n=20] for 5-14d, followed by trimethoprim sulphonamide 5mg/kg for 2 weeks [n=6]) abdominal drain [n=2] study design: case series outcome studied: clinical improvement survival to discharge main findings (relevant to pico question): all horses survived to discharge and were clinically normal at the time of discharge limitations: no description of use of abdominal drain; it is unclear whether the abdomen was lavaged or a drain placed without lavage.no comparison of interventions no follow up beyond discharge from the hospital nieto (2003) population: horses at a single equine hospital treated with a closed negative suction drainage system 1989-1996 patients included had abdominal surgery [n=54], reproductive abnormalities [n=7] or peritonitis (peritoneal fluid total nucleated cell count > 10 x 10-9 cells/l) [n=6] sample size: 67 intervention details: abdominal lavage [n=66] with lactated ringer’s solution or saline containing; heparin [n=39], potassium penicillin g [n=7] or aminoglycosides [n=16] or 0.1% povidone iodine [n=2]. no lavage [n=1] closed negative suction drain system [n=67] systemic antibiotic therapy (combination of beta-lactam antibiotic and aminoglycoside in 60% cases, the remainder were given an additional antibiotic) study design: case series outcome studied: volume of fluid retrieved complications survival to discharge from the hospital and long-term main findings (relevant to pico question): on average 83% of lavage fluid was retrieved complications reported in 49% included obstruction of drain, leakage of fluid/omental migration through the abdominal wall after drain removal, pain, structural damage to drain, haematoma formation around drain. incisional suppuration occurred in 32% of surgical cases and 5 developed an incisional hernia. survival to discharge from the hospital: 93% long-term survival: 78% survived >7 months. death was due to colic (n=4), laminitis (n=3), adhesions (n=3), peritonitis (n=1) limitations: no comparator group no description of treatment allocation between different disease states several different disease states were included making comparison of treatment outcomes difficult 0.1% povidone iodine solution was used for lavage. 3% and 10% povidone iodine solution has previously been shown to cause inflammation (schneider et al., 1988) nogradi (2011) population: horses with peritonitis 2004-2007 peritonitis: peritoneal fluid total nucleated cell count > 10 x 10-9 cells/l or total protein concentration > 25g/l. sample size: 55 intervention details: non-surgical: abdominal lavage [n=21]; 1-4x/ daily with polyionic crystalloid solution by gravity flow for 1-12 days.antibiotic therapy surgical: exploratory laparotomy [n=26] study design: case series outcome studied: survival rate factors associated with survival main findings (relevant to pico question): survival rate: total 43/55 (78%) non-surgical 27/29 (93.1%)abdominal lavage 17/21 (80.9%) surgical: abdominal surgery within 2 weeks of diagnosis 11/18 (61%) factors associated with survival (multivariate model) packed cell volume on presentation coeliotomy treatment with antibiotics vs antibioticsand peritoneal lavage was not associated with survival limitations: duration of survival was not defined limited details of antibiotic treatment protocols are described the statistical details of the comparison of antibiotics vs antibiotics and peritoneal lavage is not provided. schneider (1988) population: healthy, adult ponies sample size: 24 intervention details: peritoneal lavage performed once with 20l of: sterile saline (0.9% nacl) [n=6] sterile saline containing 5 x 106 u of potassium penicillin and 3g neomycin [n=6] povidone-iodine diluted to 3% with sterile saline [n=6] povidone-iodine diluted to 10% with sterile saline [n=3] control population: lavage catheter placed, no fluid instilled [n=3] study design: randomised controlled trial outcome studied: clinical response (pain) peritoneal fluid nucleated cell count, cytology, protein concentration peritoneal cavity at necropsy survival to 96h, at which time all ponies were euthanised for post mortem examination main findings (relevant to pico question): all ponies undergoing abdominal lavage showed signs of discomfort lavage with 10% povidone-iodine [n=3]: all ponies treated showed severe abdominal pain, tachycardia and pyrexia. 1 pony died after 30h and another was euthanised after 36h 1 pony survived to 96h no further ponies were lavaged with 10% povidone-iodine diffuse, fibrinous peritonitis lavage with 3% povidone iodine diffuse peritonitis lavage with sterile saline/ sterile saline & antibiotics no significant difference to controls at post mortem examination povidone-iodine solution (3% and 10%) caused irritation to peritoneal surfaces and should not be used to lavage the peritoneal cavity limitations: randomisation process not described more dilute povidone-iodine solution was not trialled only a single lavage procedure was performed these were healthy ponies without pre-existing abdominal inflammation or infection appraisal, application and reflection only low-quality evidence is available comparing the use of antibiotics with the combined use of antibiotics and peritoneal lavage to treat horses with peritonitis. there are many likely confounding factors in the case series reported which are inherent to use of case series. this includes unblinded treatment selection; it is likely that more severely affected cases or those where the abdomen is contaminated with gastrointestinal or uterine contents are treated with peritoneal lavage and antibiotics whereas those thought to be less severely affected are treated with antibiotics alone. there is also significant variation in the treatments used between cases within studies and between studies, including the use of treatment protocols which are now outdated, in particular, aminoglycoside choice, dose and frequency, (golland et al., 1994, hawkins et al., 1993). there is variation in the class of antibiotics, doses and frequency used and duration of treatment for cases within and between studies. a single study (nieto et al., 1993) included patients in which abdominal lavage was performed using povidone-iodine solution, which has been shown to cause peritoneal inflammation (schneider et al., 1988) and several studies do not describe the fluid used for lavage the abdomen (hawkins et al., 1993, henderson et al., 2008, javsicas et al., 2010, matthews et al., 2001). financial constraints may have influenced the choice of treatment and the survival of patients reported. patients in all the case series studies described received additional treatments including intravenous fluid therapy, non-steroidal anti-inflammatory medication, gastroprotectants, anti-endotoxic medication and prokinetics. the impact of these treatments was not analysed in most studies and is not described in this summary. conclusion: there is no evidence in equids that there is a difference in survival when the use of antibiotics is compared to the use of antibiotics combined with peritoneal lavage. however, the quality of data available is insufficient to direct clinical practice apart from two areas; in peritonitis caused by actinobacillus equuli, treatment with antibiotics alone is sufficient, and the use of antiseptic solutions such as povidone iodine to lavage the abdomen causes inflammation and is detrimental to the patient. more definitive conclusions cannot be drawn until higher quality evidence on this topic is available. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform 1973week 17 2017 pubmed accessed via the ncbi website 1973week 17 2017 search terms: (equine or horse or equus or colt or equid) and peritonitis) (antibiotic or antimicrobial or antibacterial or anti-microbial) (lavage or surgery or exploratory laparotomy or laparotomy or coeliotomy or celiotomy)  1 and (2 or 3) dates searches performed: 11th may 2017 exclusion / inclusion criteria exclusion: non-english language papers single case reports book chapters and literature reviews without novel information not relevant to the question inclusion: papers comparing the use of antimicrobials with the combination of antimicrobials and peritoneal lavage were included. due to the very limited available literature papers describing the use of antimicrobials or antimicrobials and peritoneal lavage or peritoneal lavage were included even when there was not a direct comparison of treatment modalities. search outcome database number of results excluded – non-english language excluded – case report excluded – narrative review/ opinion pieces excluded – not relevant to pico total relevant papers cab abstracts 195 44 15 7 121 8 ncbi pubmed 134 3 6 3 115 7 total relevant papers when duplicates removed 8 conflict of interest the author declares no conflicts of interest. references golland, l.c., hodgson, d.r., hodgson, j.l. et al., (1994) peritonitis associated with actinobacillus equuli in horses: 15 cases (1982-1992). journal of the american veterinary medical association, 205(2), 340-343. doi: 1111/j.1751-0813.2001.tb10741.x http://europepmc.org/abstract/med/7928617 hawkins j.f., bowman k.f., roberts m.c., cowen p (1993) peritonitis in horses: 67 cases (1985-1990). journal of the american veterinary association, 203 (2) 284-289. http://europepmc.org/abstract/med/8407492 henderson i.s.f, mair t.s., keen j.a. et al., (2008) study of the shortand long-term outcomes of 65 horses with peritonitis. the veterinary record, 163, 293-297. doi:1136/vr.163.10.293 https://www.researchgate.net/publication/23242144_study_of_the_short-_and_long-term_outcomes_of_65_horses_with_peritonitis javsicas, l.h., giguere, s., freeman, d.e., et al., (2010) comparison of surgical and medical treatment of 49 postpartum mares with presumptive or confirmed uterine tears. veterinary surgery, 39(2) 254-260. doi: 1111/j.1532-950x.2010.00645.x http://onlinelibrary.wiley.com/doi/10.1111/j.1532-950x.2010.00645.x/full matthews, s., dart, a.j., dowling, b.a. et al., (2001) peritonitis associated with actinobacillus equuli in horses: 51 cases. australian veterinary journal, 79(8), 536-539. doi: 1111/j.1751-0813.2001.tb10741.x http://onlinelibrary.wiley.com/doi/10.1111/j.1751-0813.2001.tb10741.x/full nieto, j.e., snyder, j.r., vatistas, n.j. et al., (2003) use of an active intraâ€�abdominal drain in 67 horses. veterinary surgery, 32(1) 1-7. doi: 1053/jvet.2003.50013 http://onlinelibrary.wiley.com/doi/10.1053/jvet.2003.50013/full nógrádi, n., tóth, b. and macgillivray, k. (2011) peritonitis in horses: 55 cases (2004–2007). acta veterinaria hungarica, 59(2), 181-193. doi: 1053/jvet.2003.50013  http://akademiai.com/doi/abs/10.1556/avet.2011.011 qadan, m., dajani, d., dickinson, a. and polk jr, h. c. (2010), meta-analysis of the effect of peritoneal lavage on survival in experimental peritonitis. british journal of surgery, 97: 151–159. doi:10.1002/bjs.6906 http://onlinelibrary.wiley.com/doi/10.1002/bjs.6906/full schneider, r.k., meyer, d.j., embertson, r.m. et al., (1988) response of pony peritoneum to four peritoneal lavage solutions. american journal of veterinary research, 49(6), 889-894. http://europepmc.org/abstract/med/3400925 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. two watercolours by edward mayhew mrcvs managing editor vol 1, issue 1 (2016) published: 22 jan 2016 two watercolours by edward mayhew mrcvs, from around 1864. they are part of a collection of almost 400 illustrations acquired by the rcvs trust in 1990. this collection will be catalogued, digitised and made available online, along with many other historic and valuable papers, as part of the rcvs archives project. for more information visit here: https://knowledge.rcvs.org.uk/support-us/rcvs-archives-project/ click for full size        are adult cats fed on wet maintenance diets less at risk of developing chronic kidney disease compared to adult cats fed on dry maintenance diets? a knowledge summary by catherine anne mcleonard bvetmed msc mres mrcvs 1* 1university of liverpool, leahurst campus, chester high road, neston, cheshire, ch64 7te *corresponding author (hlcmccar@liv.ac.uk) vol 2, issue 4 (2017) published: 18 oct 2017 reviewed by: nicola ackerman (bsc(hons), rvn, certsan, certvnecc, vts(nutr), a1 v1 mbvna) and jacqueline cole (bsc, bvetmed, mrcvs) next review date: 18 oct 2019 doi: 10.18849/ve.v2i4.130 clinical bottom line a comprehensive search of the available veterinary literature found three studies which assess whether feeding wet or dry maintenance diets place cats at an increased risk of chronic kidney disease (ckd) diagnosis. none of the three studies found any significant benefit of feeding either diet in reducing the risk of ckd. however, the criteria used to diagnose ckd was not standardised across any of the three studies. there is currently insufficient evidence that feeding a wet maintenance diet will help to reduce the risk of ckd but further studies are needed to assess whether diet can play some role in reducing the risk of ckd diagnosis. question are adult cats fed on wet maintenance diets less at risk of developing chronic kidney disease (ckd) compared to adult cats fed on dry maintenance diets? clinical scenario you diagnose chronic kidney disease (ckd) in a 12-year-old cat. the owner asks whether they can do anything to help to reduce the risk of their younger, 6-year-old cat getting ckd in the future. they are particularly interested in whether different types of food might help to reduce the risk of the disease. the evidence the literature searches returned three papers which directly answered our pico question. two papers (hughes et al., 2002; greene et al., 2014) were case-control studies and one (lefebvre, 2013) was a cross-sectional study. none of the three studies found any significant difference in the prevalence of feeding wet, dry or a combination of wet and dry food to cats with ckd compared to healthy cats. summary of the evidence hughes (2002) population: pet cats seen in five private practices or one university teaching hospital in texas, usa whose owners were willing to participate in a telephone questionnaire. cats were divided into cases or controls. cases were cats diagnosed with ckd between december 1994 and december 1995. ckd was diagnosed based on the presence of at least two of the following criteria: blood urea nitrogen (bun) > 35 mg/dl and/or serum creatinine > 1.9 mg/dl urine specific gravity (usg) < 1.035 palpation, radiography or ultrasound findings of kidneys which were smaller than normal, larger than normal or irregular/lumpy. control cats were those aged 7-years or above and free from renal disease, classified as the presence of at least two of the following criteria: bun ≤ 35 mg/dl and/or serum creatinine ≤ 1.9 mg/dl usg ≥ 1.035 normal kidneys on palpation exclusion criteria for all cats were: died within 2 weeks of first visit to the veterinary clinic diagnosed with lower urinary tract disease, renal cancer/calculi/other serious organ-system malfunction sample size: 38 cases and 56 control cats were included in the study intervention details: owners were contacted for a telephone interview between june 1995 and july 1997. a variety of questions were asked including previous activity levels; indoor/outdoor access; diet; and previous health problems. all data were collected for the 3 years prior to diagnosis. study design: retrospective case-control study outcome studied: significant lifestyle risk factors were compared between cases and controls using logistic regression modelling. nutritional information was collected in high-detail including type, frequency and volume of food and treats fed, together with specific nutritional values (metabolisable energy, protein, fat, fiber, ash, calcium, phosphorus, potassium, sodium and magnesium in food ). factor analysis was performed to determine relevant differences between variables whilst allowing for potential interaction terms. main findings (relevant to pico question): a questionnaire was used to record the type of food fed to each cat. owners could select several options if more than one type of food was fed. dry food was fed to 95% of cases and 96% controls. semi-moist food was fed to 8% cases and 4% controls and canned food was fed to 47% cases and 52% controls. there was no significant difference between feeding dry, semi-moist or canned food between cases and controls in the univariable analysis (p ≥ 0.25). a detailed list of possible foods were discussed during the interview questionnaire. nutritional content from the food was then calculated using a software program (animal nutritionist, version 2.5, n-squared incorporated & durango software, silverton, or). the following nutritional values within food was found to be significant from the multivariable logistic regression: increasing fibre content had a protective effect, with an odds ratio (or) of 0.8 (p=0.03 or 0.02 depending on the model) ad libitum feeding increased the odds of ckd development (or 4.1, p=0.02 in one model; or 5.5, p=0.02 in a second model) a new variable from the factor analysis, termed “factor-2” also had a protective effect with an or of 0.4 (p=0.045). this factor was a composition of the fibre, magnesium, protein, sodium and ash content of the diet. metabolisable energy (kcal), fat, calcium, phosphorus and potassium content of the diet were not significant risk factors limitations: the criteria used to diagnose ckd in the case cats within this study does not fit with current iris guidelines (international renal interest society, 2013). only 26 cats met the criteria for both (1) bun > 35 mg/dl and/or serum creatinine > 1.9 mg/dl; and (2) usg < 1.035. 12 cats were included as cases with only one of these two criteria plus gross irregularity on the kidney on either palpation or diagnostic imaging. current iris guidelines are dependent upon creatinine and usg results rather than bun or kidney irregularities. futhermore, these guidelines provide a lower creatinine cutoff value of 1.6 mg/dl. there is a large potential for misclassification bias between cases and controls in this study and is one of the greatest limitations to this study. the owner questionnaires asked information such as diet and activity levels from the cat’s previous 3-year history prior to diagnosis. there was a median time from diagnosis to interview of 7 months (range 0.9-25) for controls and 5 months (range 1-24) for cases. this is a potential relapsed time of between 3 and 5 years (3 year history prior to diagnosis plus timeframe from diagnosis to interview of 1 month or 25 months respectively). the reliability of owner recall from such a historical timeframe has to be questioned, especially when considering the complexity of some of the questions.  owners were asked to list all food that the cats had eaten, which could then be listed as “dry food”, “canned food”, “semi-moist food”, “treats”, “cooked meat” or “milk”. the authors haven’t clarified what type of food was counted within the “semi-moist” category but it could be assumed that the “canned” food is equivalent to wet food. owners could also list several different types of food, therefore statistical interpretation was overly complex. finally, the selection of cats from veterinary practices with a large feline bias and the prerequisite for owners to be available and compliant for telephone interviews, could have created a selection bias amongst the cats which were available to participate in the study. lefebvre (2013) population: any canine or feline patient within 815 banfield pet hospitals in the united states which was first diagnosed as having ckd in 2011 or 2012. prior to inclusion in the study, participants needed to have visited one of the study hospitals on at least one other occasion. there was no information provided on the criteria used for ckd diagnosis. sample size: 11,752 cats and 7,293 dogs were included. intervention details: clinical records were analysed to collect information on the patients: age, bodyweight, sex, reproductive status and breed size for dogs biochemistry values, usg and evidence of concurrent diseases was noted from the visit closest to the ckd diagnosis type of diet fed (wet, dry, mixed). the reproductive status, breed size, and diet types in the ckd patients were compared to the general population of cats and dogs which attended any banfield pet hospital over the same timeframe. study design: cross-sectional study outcome studied: the authors compared the demographical and clinicopathological features from the clinical records of patients diagnosed with ckd. main findings (relevant to pico question): there was no difference in the type of food consumed (wet, dry, mixed) between cats and dogs with ckd and the general pet population which attended the banfield pet hospitals. no further details on how many animals were fed wet or dry food were provided. we also have no details on the age or breed of the general pet population, or how these animals were selected for inclusion in the study. therefore, this cannot be considered as a true control group for this study.  the presence of periodontal disease, cystitis, hyperthyroidism, diabetes mellitus and hypertension were all significantly (p<0.01) higher in cats and dogs with ckd than in the general population. limitations: the study results are presented in a short-communication format rather than a traditional journal article. as such, there is a substantial lack of information provided. of relevance to our pico question, we are not provided with the following information: the criteria used to diagnose ckd duration of feeding the dry or wet food statistical results for type of food fed greene (2014) population: cats brought to any banfield pet hospital in the united states from 1st january 2010 to 31st december 2010. all cats must have visited a banfield pet hospital at least once prior to their inclusion in the study. cats were divided into cases and controls. inclusion criteria for cases: known age, breed and reproductive status serum creatinine concentration > 1.6 mg/dl (measured within 30 days of ckd diagnosis) usg < 1.035 (measured within 30 days of ckd diagnosis) diagnosis of ckd first made in 2010 inclusion criteria for controls: known age, breed and reproductive status no previous ckd diagnosis serum creatinine concentration < 2.2 mg/dl (measured within 30 days of ckd diagnosis) usg > 1.035 (measured within 30 days of ckd diagnosis) controls were randomly selected to match the case cats by age at study entry (± 6 months) in a 1:1 ratio. the authors state that at the time of writing, the banfield pet hospital network included 755 primary care veterinary hospitals in 43 states in the usa. sample size: 6,747 cats were diagnosed with ckd during the study period but only 1,230 (18.2%) met the criteria for inclusion as a case. the authors state that typical reasons for exclusion were errors in reporting birth date, breed or unspecified reproductive status. case cats: 408/1,230 cats (diet information was available from 408 cases) control cats: 424/1,230 cats (diet information was available from 424 controls) intervention details: medical records were retrospectively collected from all cats included in the study. of relevance to our pico question, data was analysed on: type of diet fed within 1 year prior to study entry (as either wet, dry or wet and dry food) when available clinical signs of ckd at study entry and in the latest visit 6-12 months prior to study entry. diagnosis of predisposing or concurrent diseases (for example, arthritis, diabetes mellitus, hyperthyroidism, periodontal disease etc).  study design: retrospective case-control study outcome studied: the outcome measure was a diagnosis of ckd based on serum creatinine concentration and usg values at one-point in time. logistic regression was used to investigate which factors make a diagnosis of ckd more likely amongst cats that present to a veterinary clinic. main findings (relevant to pico question): dry food was fed to 64.0% of cases (n=261/408) and 66.0% of controls (n=280/424). wet food was fed to 4.7% cases (n=19) and 4.5% controls (n=19) whereas a mixture of wet and dry food was fed to 31.4% cases (n=128) and 29.5% controls (n=125). there was no significant effect in the univariate logistic regression analysis between type of diet fed at the 95% confidence level. the following concurrent diseases/interventions were all significantly associated with the odds of being diagnosed with ckd: anaesthetic within the previous year (or 1.78, 95% ci 1.35 – 2.35); prior diagnosis of diabetes mellitus (or 0.48, 95% ci 0.28 – 0.84); prior diagnosis of periodontal disease (or 1.77, 95% ci 1.42 – 2.20) and prior diagnosis of cystitis (or 3.50, 95% ci 2.62 – 4.67). the authors did not examine potential interactions between the type of diet fed and the significant concurrent diseases/interventions. limitations: one major limitation of this study is the disparity in inclusion criteria between cases and controls. the case cats needed to have a creatinine concentration above 1.6 mg/dl which is in accordance with current iris guidelines for classification of stage 2 ckd (defined as those cats with mild renal azotemia). however, the control cats could have a creatinine concentration up to the upper reference limit from the laboratory of 2.2 mg/dl. we are not provided with average creatinine or usg values for the controls and so have no information on how the controls would be classified within the updated iris guidelines. without this information, there could be a potential misclassification of the controls creating biased results. although a reasonably large number of cats were included in this study, the number of cases included (n=1,230) is only 18.2% of the 6,747 cats diagnosed with ckd during the study period. the authors explain the reasons for this which include noncompliance with inclusion criteria, particularly an absence of birth date, breed and reproductive status. this seems to be a strict criteria precluding many cases from being included. the authors fail to explain whether the case cats were representative of the ckd population which was not included in the study. furthermore, there are potential interaction terms with respect to our pico question if for example, there was an association between unknown birth date (for example in a feral cat) and the feeding of dry food. of particular relevance to our pico question, we are not able to understand the relevance of diet on the significant concurrent diseases which are risk factors for ckd diagnosis. for example, one typical post-periodontal disease management would be to encourage the feeding of dry food to minimise further plaque development. conversely, the feeding of wet food is often recommended after a cystitis diagnosis. the authors have not evaluated whether diet fed is either an interaction term or confounder for ckd development with concurrent diseases. appraisal, application and reflection the feeding of dry food to cats has been hypothesised by some authors to cause ckd due to a low water content within the food (see for example, greene et al., 2014). from the three relevant papers found within this literature search, only hughes et al. (2002) comprehensively examined the effect of nutritional parameters within food whereas the other two papers examined clinical records for descriptions of food given, as noted by the owners. unfortunately, the small sample size and potential misclassification bias (by not abiding by current iris guidelines to diagnose ckd)  within hughes et al. (2002) reduces its reliability. ultimately, none of these three papers provided conclusive evidence to answer the pico question. for the general practitioner, it is encouraging to find evidence that certain nutritional parameters may be beneficial in delaying the onset of ckd diagnosis. hughes et al. (2002) found that an increased fibre content in the diet and the ambiguous “factor-2” were both protective in delaying ckd development whereas ad-libitum feeding was detrimental. whilst performing the literature search, a small number of additional papers were uncovered which appeared to suggest that diet could help to reduce the risk of ckd development (dibartola et al., 1993; frantz et al., 2007; lane et al., 2012; geddes et al., 2016), although these were all excluded from the current pico question as they did not look at the difference between wet and dry food. further research, including a broader literature search, is needed in this area. there was a significant association between ckd diagnosis and a history of previous anaesthetics, periodontal disease, hyperthyroidism, hypertension, cystitis and diabetes mellitus. this is perhaps unsurprising since some cats may be more likely to present for more acute problems such as urinary tract infections than chronic conditions such as ckd. moreover, a previous, acute illness such as cystitis, or chronic condition like hyperthyroidism, may facilitate more careful veterinary monitoring by both owners and vets. however, none of these studies analysed whether diet fed was a significant interaction term with the comorbidity. this is a frustrating omission given the frequency of veterinary advice recommending a diet change after for example, lower urinary tract conditions or periodontal disease. another interesting knowledge summary could be developed to look at the usefulness of wet food on preventing further episodes of feline lower urinary tract disease. this pico question has an underlying assumption that all wet maintenance diets, and all dry maintenance diets, can be treated equally with regards to water content and nutritional value. to the author’s knowledge, there have been no studies performed which confirm this assumption. arguably, the plethora of commercial diets available for cats makes this an unrealistic assumption. furthermore, the proportion of cat owners amongst the general cat-owning population who change diets or feed a mixture of wet and dry food is unknown. therefore, it seems unlikely that any retrospective study into this pico question would yield sufficient power to answer this question with certainty. furthermore, it should be acknowledged that these studies have looked at risk factors for ckd diagnosis, not the onset of kidney damage. it is possible that cats which obtain an increased water content, by for example, eating a wet diet, are diagnosed later in the disease process due to a relative compensation for kidney damage. alternatively, it is theoretically possible that a risk factor may create such severe kidney disease that cats are never presented to veterinary practices. therefore, the potential biases of using the veterinary-presenting population of cats should be considered when considering the risk factors for ckd. ultimately, a prospective randomised control trial (rct) would provide greatest evidence on whether the feeding of wet or dry diets can reduce the risk of kidney damage. further research into this area is needed to ensure that vets aren’t inadvertently placing cats at an increased risk of ckd when suggesting a diet change after being diagnosed with periodontal disease, cystitis or several other comorbidities. methodology section search strategy databases searched and dates covered: cab abstracts on ovid interface (1973 – week 06 2017); pubmed (1973 – week 13 2017) search terms: cab abstracts: (cat or cats or feline or felines or queen or tom) and (chronic renal failure or chronic renal disease or chronic renal insufficiency or chronic kidney insufficiency or chronic kidney failure or chronic kidney disease) and (diet or food or maintenance diet or maintenance diets) limited to english language ncbi pubmed: (cat or cats or feline or felines) and (chronic renal failure or chronic renal disease or chronic renal insufficiency or chronic kidney insufficiency or chronic kidney failure or chronic kidney disease or renal failure or kidney disease) and (diet or maintenance diet or maintenance diets) limited to english language; species: other animals; subjects: veterinary science dates searches performed: cab abstracts 21/02/2017; pubmed 28/03/2017 exclusion / inclusion criteria inclusion and exclusion criteria were determined prior to performing the search. filters were added after a preliminary search returned a large number of irrelevant results. the suitability of articles was initially assessed through examination of the title and abstract. full-text articles were then retrieved and examined. exclusion: human literature was excluded as this was deemed irrelevant to our pico question. review papers aside from systematic reviews inclusion: any relevant primary veterinary research or systematic review which examined the association between feeding dry maintenance food or wet maintenance food and the development of chronic kidney disease. search outcome database number of results excluded – duplicates excluded – did not answer pico question excluded – diet as treatment not prevention excluded – no assessment of wet or dry food total relevant papers cab abstracts 117 0 59 51 5 2 ncbi pubmed 124 18 61 38 6 1 total relevant papers when duplicates removed 3 conflict of interest the authors declare no conflicts of interest. i would like to thank clare boulton for assistance in running the searches and finding complete copies of the papers and bridget sheppard for assistance throughout the process. references dibartola, s. p., buffington, c. a., chew, d. j., et al., (1993) development of chronic renal disease in cats fed a commercial diet. journal of the american veterinary medical association, 202 (5), 744–751 frantz, n. z., yamka, r. m. and friesen, k. g. (2007) the effect of diet and lysine:calorie ratio on body composition and kidney health in geriatric cats. international journal of applied research in veterinary medicine, 5 (1), 25–36 geddes, r. f., biourge, v., chang, et al., (2016) the effect of moderate dietary protein and phosphate restriction on calcium-phosphate homeostasis in healthy older cats. journal of veterinary internal medicine, 30 (5), 1690–1702. doi: http://dx.doi.org/10.1111/jvim.14563 greene, j. p., lefebvre, s. l., wang, m., et al., (2014) risk factors associated with the development of chronic kidney disease in cats evaluated at primary care veterinary hospitals. journal of the american veterinary medical association, 244 (3), 320–327. doi: http://dx.doi.org/10.2460/javma.244.3.320 hughes, k. l., slater, m. r., geller, s., et al., (2002) diet and lifestyle variables as risk factors for chronic renal failure in pet cats. preventive veterinary medicine, 55 (1), 1-15 doi: http://dx.doi.org/10.1016/s0167-5877(02)00088-0 international renal interest society (2013) iris staging of ckd ( modified 2013 ), novartis animal health, 1–8. lane, e. p., miller, s., lobetti, r., et al., (2012) effect of diet on the incidence of and mortality owing to gastritis and renal disease in captive cheetahs (acinonyx jubatus) in south africa. zoo biology, 31 (6), 669–682. doi: http://dx.doi.org/10.1002/zoo.20431 lefebvre, s. (2013) clinical findings in cats and dogs with chronic kidney disease. veterinary focus, 23 (3), 26–27 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. surgery in epilepsy – how advances in human neurology can benefit veterinary patients m. charalambous dvm gpcert(neuro) rsci mrsb mrcvs 1 * 1ucl institute of neurology *corresponding author (marios.charalambous.15@ucl.ac.uk) vol 1, issue 1 (year) published: 09 feb 2016 doi: 10.18849/ve.v1i1.19 section index:    aim of epilepsy surgery in humans | pre-surgical evaluation of epileptic human patients | electroencephalography (eeg) magnetoencephalograpy (meg) functional magnetic resonance imaging (fmri) | the current evidence behind epilepsy surgery in veterinary medicine | references | supplementary files aim of epilepsy surgery in humans epilepsy in humans is a common neurological disorder, following stroke, with a prevalence of 0.5% in the global population (de boer et al., 2008). approximately 30% of epileptic individuals do not adequately respond to antiepileptic drugs (drug-resistant epilepsy) (engel, 1996) and continue to manifest seizure activity. drug-resistant epilepsy dramatically lowers quality of life to the point that surgical resection is a viable option. the aim of epilepsy surgery is to completely remove the epileptogenic area while avoiding neurological deficits (zhang et al., 2014). post-operative results have showed that seizure freedom has reached rates as high as 60% to 90% and 40% to 60 % in individuals with temporal and extra-temporal lobe epilepsy, respectively (tellez-zenteno, 2005). a recent systematic review (hader et al., 2013) showed that there was a mortality of 0.4% and 1.2% in epileptic individuals with temporal and extra-temporal lobe surgical resection, respectively. the same study reported severe neurological complications, mainly visual field defects, related to surgery in 4.7% of the patients. however, several studies have shown that epileptic patients who constantly manifest seizures (e.g., in drug-resistant epilepsy) have mortality rates three times higher compared to average population (neligan et al., 2010, sillanpaa and shinnar, 2010). epilepsy surgery might be considered as an inevitable treatment option in these cases. pre-surgical evaluation of epileptic human patients pre-surgical assessment has the most important role in the epilepsy surgery and is offered to patients with drug-resistant epilepsy or persistence of seizures despite administration of two anti-epileptic drugs in sufficiently high dosages (kwan et al., 2010). total resection or functional disconnection of the epileptogenic zone (ez) which is area of cortex responsible for the generation of epileptic seizures, for achieving seizure-freedom while preserving vital cortex areas responsible for sensory processing and avoiding post-operative neurological deficits is the ideal outcome of surgery (rosenow and luders, 2001, tellez-zenteno, 2005). in order to succeed this outcome, precise localization of the ez during the pre-surgical assessment is quite important. however, it still remains a challenge, mainly for extra-temporal lobe epilepsy (tellez-zenteno, 2005, knowlton et al., 2008a, knowlton et al., 2008b, thomas et al., 2002, papanicolaou et al., 2005). however, the ez is considered to be a hypothetical region as, currently, there is no diagnostic tool to locate it. one should indirectly detect it by locating other relevant zones, which are involved in generating the epileptic disorder or relevant electrographical and clinical symptoms, such as the irritative zone (iz). the latter refers to the cortex responsible for generating interictal epileptiform discharges and it often provides an accurate definition of the ez, although the ez might cover a more or less extensive cortex area in some patients (hunyadi et al., 2015, rosenow and luders, 2001, knake et al., 2006, schneider et al., 2012, krishnan et al., 2015). detection of the iz is relatively accurate for locating the actual ez, but the precise link between the two zones still remains vague (badier et al., 2015). the iz can be evaluated by interictal non-invasive neuroimaging techniques such as scalp electroencephalography (eeg), magnetoencephalography (meg) and functional magnetic resonance imaging (fmri) or combination of them as well as invasive intracranial electroencephalography (iceeg); the latter has high sensitivity and specificity (blount et al., 2008, vulliemoz et al., 2011) and is considered as the “gold standard” for defining the epileptogenic area (blount et al., 2008). despite its diagnostic benefits, it is considered invasive, sample-limited, costly and risky (hematomas, acute bleeding or infections; blount et al., 2008, zhang et al., 2014). the non-invasive neuroimaging techniques have improved the pre-surgical evaluation, surgical outcome and decision-making and managed to include a more extended number of patients who might not have been ideal candidates for pre-surgical evaluation in the past (whiting et al., 2006). although neuroimaging could not replace iceeg as far as the localization properties are concerned, a considerable amount of studies have shown that non-invasive neuroimaging could greatly reduce the need for iceeg (knowlton et al., 2006, zhang et al., 2014). electroencephalography (eeg) scalp eeg is routinely used to record the electrical signals of the brain and is considered an effective method for defining the iz (rosenow and luders, 2001) in approximately 70% of patients (foldvary et al., 2001). eeg can be used either as a sole technique or combined with other ones. eeg source imaging (esi), which involves combined results of eeg and mri and computerized 3d analysis of the eeg source, has been used over the last years to localize the iz with very promising results (park et al., 2015, plummer et al., 2008, michel et al., 2004). simultaneously recorded eeg/fmri provides high spatial and temporal resolution data for the iz, mainly by overcoming a few of the limitations of eeg with regards to sensitivity, and improved localization in challenging cases (hunyadi et al., 2015). the eeg/fmri technique is used to map haemodynamic epileptogenic-related networks in the brain, and, as a result it provides further valuable data for iz localization (van graan et al., 2015). despite the promising results of the eeg/fmri technique, in approximately 40%-70% of the cases, it could not adequately detect the iz. main reasons include the lack of interictal discharges in the eeg, lack of significant blood oxygen level dependent (bold) signal changes in relation to their timing and presence of artifacts (grouiller et al., 2011, zhang et al., 2015). magnetoencephalograpy (meg) meg detects the magnetic signals of the brain and has also shown very promising results as a pre-surgical evaluation method (knowlton et al., 1997, stefan et al., 2000). meg has an increased temporal resolution that makes it effective in localizing the iz (tellez-zenteno, 2005). compared to the electric signals recorded by scalp eeg, the magnetic signals are only minimally distorted from intervening tissues (i.e., skull and dura), resulting in an improved spatial resolution and sensitivity compared to scalp eeg that can be quite useful in guiding surgery (ebersole and ebersole, ray and bowyer, kakisaka et al., 2012). in addition, a technique involving both meg and eeg can detect neuronal activity at different orientation levels and therefore many studies reported the increased diagnostic value of the combined meg/eeg in pre-surgical evaluation (ebersole and ebersole, 2010, paulini et al., 2007, zhang et al., 2015). finally, meg might be a predictive factor for a good surgical outcome in temporal lobe epilepsy (assaf et al., 2004, iwasaki et al., 2002). localization accuracy of meg has been considered to be close to that of the iceeg (papanicolaou et al., 2005, knowlton et al., 2006), although meg is generally less available and needs more interictal spikes (knowlton et al., 1997, zhang et al., 2014). in on study (papanicolaou et al., 2005), results from interictal meg and ictal and interictal invasive video-recording eeg were compared in 41 surgical candidates (29 patients with temporal lobe epilepsy and 12 with extra-temporal lobe epilepsy). the study found that the overall localization accuracy of the iz was 54% and 56% in iceeg and meg, respectively (temporal lobe epilepsy: iceeg 55.2% versus meg 65.5%; extra-temporal lobe epilepsy: iceeg 50.0% versus meg 33.3%). the authors concluded that meg might be as accurate as iceeg. in another study (knowlton et al., 2006), meg and iceeg were evaluated in 49 patients with partial epilepsy. they showed that meg and iceeg could localize the iz at sub-lobar level in 65.3% and 69.4% of the patients, respectively. however, in another study (knowlton et al., 2008a, knowlton et al., 2008b) in which meg was compared to iceeg in 77 epileptic patients (39 with temporal lobe epilepsy, 33 with extra-temporal lobe epilepsy and 5 with non-localized epilepsy), it was found that meg and iceeg localized the seizure focus in 61% and 70.1% cases, respectively. the same study found that meg and iceeg failed to detect the seizure activity in 20.8% and 6.5% cases, respectively (knowlton et al., 2008a). these results indicated that meg might not be an ideal replacement of iceeg as far as the localization ability is concerned. functional magnetic resonance imaging (fmri) using fmri in the pre-surgical evaluation of epileptic focus has shown promising results. its current use involves identification of the eloquent cortex affecting visual, oral and motor functions that need to remain intact during surgery (thornton et al., 2009) and it is commonly combined with simultaneous scalp eeg (liu and he, 2008, liu et al., 2006, he and liu, 2008). simultaneous eeg/fmri correlates the epileptiform activity found on eeg with hemodynamic changes in bold in order to map the area of the brain responsible for the epilepsy (hamandi et al., 2004, he and liu, 2008, gotman et al., 2006, laufs and duncan, 2007, lopes et al., 2012). during standard eeg/fmri method, identification of the timing of interictal spikes is performed on eeg and then each one of these impulses is combined with the hemodynamic response function in order to obtain a general linear model. the latter is then linked to the fmri data using statistical methods to reach on an activation map (lemieux et al., 2001). however, this technique has a few limitations, for example eeg artifacts during fmri scan (jacobs et al., 2009). all in all, non-invasive functional neuroimaging techniques such as meg, eeg, fmri alone or in combination still might not be as efficient in localizing the ez/iz as iceeg, especially in extra-temporal lobe idiopathic epilepsy. however non-invasive neuroimaging could reduce the need for invasive pre-surgical monitoring in certain cases. the current evidence shows that multimodal approach (i.e. combination of techniques) might be the most accurate diagnostic method, followed by meg, eeg, eeg/fmri and fmri (figure 1); however results should be interpreted with caution until further studies with low overall risk of bias contribute to the current evidence. figure 1: a proposed diagram of hierarchy for the diagnostic accuracy of non-invasive neuroimaging techniques to localize the interictal epileptiform activity during pre-surgical evaluation, with multimodal neuroimaging to be at the top of the scale. eeg, electroencephalography; fmri, functional magnetic resonance imaging; meg, magnetoencephalography the current evidence behind epilepsy surgery in veterinary medicine epilepsy in dogs has been found to be the most common chronic neurological disorder, with a reported prevalence of 0.5% 5% in non-referral populations (ekenstedt and oberbauer, 2013, podell et al., 1995). in uk, this prevalence was estimated to be 0.62% (kearsley-fleet et al., 2013). drug-resistant canine epilepsy has been previously reported to affect as high as 30% of all dogs with idiopathic epilepsy (lane and bunch, 1990). despite the fact that drug-resistant epilepsy can commonly occur in dogs, there is no or limited evidence behind surgical treatment options. there is one report in which experimental corpus callosotomy (i.e. surgical division of corpus callosum) in a very small number dogs with drug-resistant epilepsy was performed and showed encouraging initial short-term results (bagley et al., 1996). however, the long-term outcome in these canine patients was not evaluated and further details related to the study design were not widely accessible. due to this fact and the several limitations of the study, the overall risk of bias might be considered high. therefore, surgical epilepsy has been inadequately described in dogs. the reason is mainly due to the fact that the ez and/or iz have not been extensively defined or described in animals and the lack of application of advanced functional neuroimaging techniques (e.g., eeg, meg, fmri). the latter are highly important in order to map and successfully localize the epileptogenic area. eeg has been used though in veterinary medicine to detect abnormal discharges in various diseases in dogs (chandler, 2006) as well as interictal spikes in epileptic anaesthetized dogs (jaggy and bernardini, 1998, srenk and jaggy, 1996). the introduction of eeg in veterinary medicine as a routine diagnostic technique in the near future might change the current state and form the base of epilepsy surgery in animals. references assaf, b.a. et al (2004) magnetoencephalography source localization and surgical outcome in temporal lobe epilepsy clinical neurophysiology 115 (9) pp 2066-2076 http://dx.doi.org/10.1016/j.clinph.2004.04.020 badier, j. m. et al (2016) ictal magnetic source imaging in presurgical assessment brain topography 29 (1) pp182-192 http://dx.doi.org/10.1007/s10548-015-0445-3 bagley, r. s., harrington, m. l. & moore, m. p. (1996) surgical treatments for seizures: adaptability for dogs. veterinary clinics of north america: small animal practice 26 (4) pp 827-842. http://dx.doi.org/10.1016/s0195-5616(96)50107-5 blount, j. p. et al (2008) advances in intracranial monitoring. neurosurgical focus 25 (3) pe18. http://dx.doi.org/10.3171/foc/2008/25/9/e18 chandler, k. (2006) canine epilepsy: what can we learn from human seizure disorders? veterinary journal 172 (2) pp 207-217  http://dx.doi.org/10.1016/j.tvjl.2005.07.001 de boer, h. m., mula, m. & sander, j. w. (2008) the global burden and stigma of epilepsy. epilepsy & behaviour 12 (4) pp 540-546.  http://dx.doi.org/10.1016/j.yebeh.2007.12.019 ebersole, j. s. & ebersole, s. m. (2010) combining meg and eeg source modeling in epilepsy evaluations. journal of clinical neurophysiology 27 (6) pp 360-371 http://dx.doi.org/10.1097/wnp.0b013e318201ffc4 ekenstedt, k. j. & oberbauer, a. m. (2013) inherited epilepsy in dogs. topics in companion animal medicine 28 (2) pp 51-8.  http://dx.doi.org/10.1053/j.tcam.2013.07.001 engel, j. jr. (1996). surgery for seizures. new england journal of medicine 334  pp 647-652. http://dx.doi.org/10.1056/nejm199603073341008 foldvary, n. et al (2001) the localizing value of ictal eeg in focal epilepsy. neurology 57 (11) pp 2022-2028.  http://dx.doi.org/10.1212/wnl.57.11.2022 gotman, j., et al. 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http://dx.doi.org/10.1016/j.clinph.2014.04.011 zhang, j. et al (2014). multimodal neuroimaging in presurgical evaluation of drug-resistant epilepsy. neuroimage: clinical, 4 pp 35-44. http://dx.doi.org/10.1016/j.nicl.2013.10.017 supplementary files, images & tables all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form,and will in return retain certain rights as detailed on the form. tenoscopic debridement or surgical repair for longitudinal tears of the equine deep digital flexor tendon within the digital flexor tendon sheath? a knowledge summary by daniel castillo mv mrcvs 1* neal ashton bvet med cert ep cert es (soft tissue) mrcvs 2 1pierson stewart & partners, brooksden veterinary hospital, high street, cranbrook, kent, tn17 3dt 2oakham veterinary hospital, ashwell road, oakham, rutland, le15 7qh *corresponding author (d.castillocastagneto@gmail.com) vol 3, issue 2 (2018) published: 07 june 2018 reviewed by: sushmitha durgam (bvsc, phd, dacvs) and james carmalt (ma, vetmb, mvetsc, frcvs) next review date: 30 may 2019 doi: 10.18849/ve.v3i2.164 pico question in horses with longitudinal tears of the deep digital flexor tendon within the digital flexor tendon sheath, is surgical repair as effective as tenoscopic debridement alone for returning to previous level of performance? clinical bottom line current literature on the efficacy of surgical repair or tenoscopic debridement is limited. criteria to define and evaluate performance outcomes is not uniform and confounded with multiple variables, merely representing low quality evidence that is difficult to draw meaningful conclusions from. however, the literature suggests tenoscopic debridement alone has been associated with improved outcomes. a more definitive conclusion cannot be made until higher quality evidence is made available on this topic. the evidence the quality of the evidence comparing both treatment modalities is low and insufficient. primarily, two authors provided data on performance outcomes for both treatment modalities, highlighting surgical repair as an inferior technique associated with reduced performance. other authors solely assessed tenoscopic debridement alone, or may have included a very limited number (n=2) of surgical repair cases that were unresponsive to previous tenoscopic surgery. case selection may have introduced significant bias into these results as tenoscopic debridement alone is the preferred surgical technique, whilst surgical repair has been reserved for more extensive tears, or tears unresponsive to tenoscopic debridement. no randomised controlled trials are available to compare the efficacy of these treatment modalities. summary of the evidence arensburg (2011) population: horses with non-septic tenosynovitis of the digital flexor tendon sheath sample size: n=130 intervention details: all horses were examined tenoscopically under general anaesthesia between 1999 and 2009. palmar annular ligament desmotomy was performed on cases with evidence of chronicity or obvious thickening of the ligament. before 2003, desmotomy was performed in all cases. torn tendon fibrils and granulomata were resected using a motorised synovial resector and suction punch ronguers. in some cases further debridement and smoothing of the fibrillated edge was achieved using a coblation probe on a low energy setting and in no contact mode. in other cases manual debridement rather than mechanical debridement was selected using an arthroscopic punch and ferris-smith rongeurs. study design: case series outcome studied: semi-objective to evaluate the effect of different treatment modalities, post-operative distension and duration of clinical signs prior to presentation on the final functional outcome. main findings (relevant to pico question): of 130 horses with chronic tenosynovitis of the digital flexor tendon sheath (dfts) that had tenoscopic surgery, 101 horses were diagnosed with 115 longitudinal tears (lts) affecting a digital flexor tendon in 104 digital flexor tendon sheaths. palmar-plantar annular ligament (pal) desmotomy was performed in 71/104 dfts (68%). follow-up on 98 horses revealed that 37 horses (38%) returned to a previous level of work or higher. 27 horses (27%) returned to a lower level of work and 34 horses (35%) remained lame. coblation was associated with a lower level of performance and cosmetic outcome (increased distension). manual debridement of lts (no resector or coblation) was associated with a better functional outcome. limitations: retrospective case-series study. multiple confounding variables affecting final functional outcome. poorly defined outcome assessment. wilderjans (2003) population: warmblood horses with chronic tenosynovitis and annular ligament constriction syndrome. sample size: n=25 intervention details: all horses were examined tenoscopically under general anaesthesia between 1999-2000. desmotomy of the palmar annular ligament was performed in all horses with a hook knife. in all cases, the torn fibres were resected using a motorised synovial resector. study design: case series outcome studied: semi-objective to evaluate the incidence of longitudinal tears as the underlying cause of chronic tenosynovitis and annular ligament constriction syndrome in warmblood horses. to evaluate the final outcome after tenoscopic debridement and palmar annular ligament desmotomy. postoperative distension, ultrasonographic findings and level of performance were assessed. main findings (relevant to pico question): of 25 horses, 17 were diagnosed with a longitudinal tear. after 12-24 months, 10 horses (59%) were sound and resumed their previous level of work. four horses (24%) returned to their previous level of work but needed intrasynovial treatment of the dfts and reduced competition frequency to remain sound. three horses (18%) remained lame. limitations: retrospective case-series study. ambiguous definition of previous level of performance. surgical repair was not considered by the author because the tear edges were always in close apposition. the author states suture repair requires a large open approach which are prone to a greater risk of post-operative complications, such as partial wound dehiscence and leakage from the tendon sheath, although no references are provided to support this. wilderjans (2006) population: horses with non-infected tenosynovitis of the dfts. sample size: n=108 intervention details: all horses had diagnostic tenoscopy under general anaesthesia between 1999 and 2005. desmotomy of the pal was performed from 1999 to 2003 using a hook meniscectomy knife. from 2003, pal desmotomies were performed only if there was an obvious thickening of the pal. longitudinal tears were debrided with a motorised synovial resector, followed by further microdebridement in some cases using coblation wands. arthroscopic ferris-smith rongeurs were used to remove the larger masses of torn tendon fibres, fibrin, and to remove synovial adhesions. fibrillation of the palmar/plantar surface of the superficial digital flexor tendon (sdft was smoothened with coblation. study design: case series outcome studied: semi-objective to evaluate the final functional outcome and performance of horses suffering from longitudinal tears in one or more flexor tendons. to evaluate the relation between final outcome and treatment with synovial resector, coblation, pal resection, length of the tear, presence of post-operative distension and duration of clinical signs. main findings (relevant to pico question): 71 horses were diagnosed with lts in 73 dftss examined tenoscopically. follow-up on 69 horses (71 dfts) revealed that 26 horses (38%) returned to their previous level of work or higher. 26 horses (38%) returned to a lower level of work, and 17 horses (25%) remained lame. surgical repair was performed on 2 cases with lts of the lateral edge of the ddft unresponsive to tenoscopic debridement. one horse returned to previous level of work and the other one to a lower level of work. desmotomy of the pal and the use of coblation do not seem to affect the final outcome. limitations: retrospective case-series study. limited statistical analysis. insufficient analysis and discussion of the outcome studied. multiple confounding variables affecting final functional outcome. smith (2006) population: horses with non-infected tenosynovitis of the digital fts. sample size: n=76 intervention details: all horses were evaluated tenoscopically under general anaesthesia between 1st january 1996 and 31st december 2003. 65 horses underwent treatment with tenoscopic techniques only. large masses of torn tendon tissue and granulomata were dissected free with arthroscopic scissors or meniscectomy knives before removal with ferris-smith arthroscopic rongeurs. tendinous defects were also debrided with a motorised synovial resector in an oscillating mode with suction applied. pal desmotomy was performed in 2 horses using an endoscopically assisted ‘freehand’ technique using a curved meniscectomy knife. partial tears of the manica flexoria (mf) were debrided (n=5) and the mf was removed in its entirety when one margin was disrupted completely (n=18). the opposite, intact margin was divided from the sdft using arthroscopic scissors and/or meniscectomy knives. 11 horses underwent open surgery for repair or removal of lesions identified at tenoscopy. repair of torn ddft, sdft and mf was performed with simple continuous sutures of 2 or 3 metric polyglactin 910 (vicryl). incision closure involved repair of sectioned mf, pals and sheath walls with simple continuous sutures of 3 metric polyglactin 910. this was followed by a subcuticular layer of the same material and by stainless steel staples in the skin. a total of 7 cases with lts of the ddft were repaired via open surgical approach. tenoscopy skin portals were closed with simple interrupted sutures of monofilament polyamide. study design: case series outcome studied: semi-objective to evaluate the clinical features, diagnoses, treatment and outcomes of a series of horses with non-infected tenosynovitis of the dfts. to identify significant associations between the 3 dependent variables (lameness; performance; distension) and the clinical variables. main findings (relevant to pico question): 46 longitudinal tears of the ddft were identified in 44 horses. tears of the ddft occurred in combination with tears of the mf (n=5) and sdft (n=1). two further cases had thickening of the pal. adhesions were present between the torn surface of the ddft and the dfts wall in 4 cases. follow-up information (>6 months) post-surgery was available for 61 horses. follow-up on 33 horses with longitudinal tears of the ddft revealed that 14 horses (42%) returned to their previous level of performance. lts of the ddft and open surgical repair of the ddft lesions were associated with reduced post-operative  performance. limitations: retrospective case series study. selection bias represented in some cases with severe lesions of the ddft having surgical repair. multiple factors confounding treatment outcomes. wright (1999) population: horses with tenosynovitis associated with longitudinal tears of the ddft. sample size: n=20 intervention details: all horses were evaluated surgically under general anaesthesia. diagnosis was established by tenoscopy in 9 horses. 2 horses evaluated tenoscopically subsequently had an open surgical approach to the dfts. in 7 horses torn tendon fibrils were removed tenoscopically with a motorised synovial resector. in 13 horses, 14 dftss were explored surgically. identification of the proximal extent of the deep digital flexor tendon lesions necessitated section of the enclosing manica flexoria in 9 limbs. torn tendon fibrils were removed by sharp dissection. where present, granulomata and adhesions were also excised. 11 horses had surgical repair of ddft lesions in 12 limbs. in 10 limbs the repair was performed with simple continuous sutures of 2 or 3 metric polyglactin 910 (vicryl) and in 2 horses simple interrupted sutures of 1.5 metric polydioxanone (pds). torn (n=2) or sectioned manica flexoria were repaired by simple continuous sutures of 2 metric polyglactin 910. the tendon sheaths and palmar/plantar annular ligaments were closed with simple continuous sutures of 3 metric polyglactin 910. this was followed by a subcuticular layer of similar material and stainless steel staples in the skin. tenoscopic portals were closed with simple interrupted sutures of monofilament polyamide. study design: case series outcome studied: semi-objective to evaluate clinical characteristics of horses with tenosynovitis associated with longitudinal tears and ability to return to work. main findings (relevant to pico question): 19 tears of the ddft and 2 tears the manica flexoria were identified in 20 horses. follow-up information was obtained by telephone from owners and, or, trainers. five horses were re-examined post-operatively; 3 at 4 months, 1 at 7 months and 1 at 10 months after surgery. 3 of these were sound and 2 were lame. of 7 horses with ddft lesions treated tenoscopically, 4 were sound and in work, 3 were in controlled exercise programmes. of 11 horses with surgical repair of ddft lesions, 5 were sound and in work, 1 was sound and in controlled exercise, 5 were lame. the prognosis for horses with tears of the ddft which are treated by tenoscopic removal of torn tendon fibrils is better than that for animals treated by subsequent repair of the defect. the repaired tears in the ddft were, on the whole, considered to be more extensive. it is not yet possible to determine whether the apparently inferior prognosis results from the extent of the lesion, the surgical technique used or the repair process. limitations: retrospective case-series study. selection bias for surgical repair of ddft lesions. subjective outcome assessment used to determine post-operative performance. multiple factors confounding treatment outcomes. appraisal, application and reflection the five relevant identified studies discussing the outcome of tenoscopic debridement alone, versus surgical repair of lts, are retrospective case series. this represents evidence of low quality and reliability. cases within and between studies have been managed using different treatment modalities. diagnostic tenoscopy is often performed to assess the severity and extent of the lesions affecting the border of the ddft. criteria for treatment selection is poorly defined and primarily based on the surgeon’s experience and preference. torn tendon fibrils and granulomata are resected using a motorised synovial resector, or by manual debridement with an arthroscopic punch, ferris-smith rongeurs, and in some cases arthroscopic scissors or meniscectomy knives. further debridement was pursued in several cases with the use of coblation. surgical repair has been reported using an open approach subsequent to initial tenoscopic debridement to gain complete access to the longitudinal tear (smith et al., 2006; wright et al., 1999). in some cases, this necessitated sectioning of the manica flexoria to gain access to the proximal extent of the tear. tear repairs were performed with a simple continuous suture of 2 or 3 metric polyglactin 910 or polydioxanone. less frequently, repairs have been performed with simple interrupted sutures of 1.5 metric polydioxanone. incision closure involves repair of sectioned manica flexoria, palmar or plantar annular ligaments and sheath walls with simple continuous sutures of 2 or 3 metric polyglactin 910, followed by a subcuticular layer of the same material and stainless steel staples in the skin. current evidence from published literature, suggests that tenoscopic debridement, without repair of longitudinal tears, is the preferred treatment method. open surgical repair of ddft lesions have been associated with reduced post-operative performance. although tenoscopic debridement has been associated with improved functional outcomes, animals treated by surgical repair were considered to have more extensive ddft tears, or tears unresponsive to tenoscopic debridement. case selection inherently added significant bias to the results, which is identified in more than one study. since the repaired longitudinal tears were, on the whole, considered to be more extensive, it is not yet possible to determine whether the inferior prognosis results from the extent of the lesion, the surgical technique used or the repair process (wright et al., 1999). some cases with severe lesions were repaired based on the observation that intrinsic tendon repair mechanisms, derived primarily from the epitenon, promoted tendon healing following surgical repair in experimental conditions (gelberman et al., 1983, cited in smith et al., 2006). another study also reported that surgical repair was only performed on 2 cases with lts of the lateral border of the ddft unresponsive to tenoscopic debridement (wilderjans et al., 2006). although outcomes following surgical repair were less successful than tenoscopic debridement, there are likely many confounding factors in these case series which need consideration. some of these include prior medical or surgical treatment, duration of clinical signs prior to presentation, severity and extent of the tear, concomitant pathology, treatment modality and technique, rehabilitation, intrinsic mechanisms of repair, and outcome assessment. until randomised controlled trials directly comparing tenoscopic debridement and surgical repair are made available, drawing meaningful conclusions from the current literature is limited. methodology section search strategy databases searched and dates covered: cab abstracts on the ovid platform; 1973 to 05/2017 pubmed via the ncbi website; 1910 to 05/2017 search terms: cab abstracts: (equine* or horse* or equus or thoroughbred*) or equus/ or horses/ or thoroughbred/ ((tear* or laceration* or ‘longitudinal tear*' or 'marginal tear*' or lt or lts or defect) and ('deep digital flexor tendon' or 'ddft' or 'flexor tendon' or 'tendon' or 'digital flexor tendon sheath' or dfts or 'tendon sheath' or sheath*)) 1 and 2 ('suture repair' or 'surgical repair' or sutur* or repair* or surgery) ((tenoscop* or 'tenoscopic surger*' or 'diagnostic tenoscopy' or 'tenoscopic exam*' or 'tenoscopic technique*') and ('mechanical debrid*' or debrid* or 'motorised shaver*' or shaver* or 'motorised synovial resector*' or 'motorised resector*' or 'synovial resector*' or resector* or 'radiofrequency device*' or 'radiofrequency energy device*' or 'coblation wand*' or coblation or 'coblation treatment*' or coblation-treat* or 'monopolar radiofrequency device*' or 'monopolar radiofrequency energy device*' or 'monopolar device*' or 'manual debrid*' or manual or 'synovial resector*' or resector*)) 3 and (4 or 5) pubmed: ((((equine or horse or thoroughbred) and ((tear or longitudinal tear or marginal tear or lt or lts or defect) and (deep digital flexor tendon or ddft or flexor tendon or tendon or digital flexor tendon sheath or dfts or tendon sheath or sheath)))) ((tenoscopy or tenoscopic or debridement) or (suture repair or surgical repair or suture or repair or surgery)) 1 and 2 dates searches performed: 30/5/2017 exclusion / inclusion criteria exclusion: non-english language publications, studies performed in other species, articles not relevant to the pico. inclusion: studies available in english relevant to the pico search outcome database number of results excluded – studies in other species excluded – non-english articles excluded – not relevant to pico excluded – duplicates total relevant papers cab abstracts 72 0 13 54 0 5 pubmed 46 3 1 38 4 0 total relevant papers when duplicates removed 5 conflict of interest the authors declare no conflicts of interest. references arensburg, l., wilderjans, h., simon, o., et al., (2011) nonseptic tenosynovitis of the digital flexor tendon sheath caused by longitudinal tears in the digital flexor tendons: a retrospective study of 135 tenoscopic procedures. equine vet. j. 43 (6) 660-668. doi: http://dx.doi.org/10.1111/j.2042-3306.2010.00341.x smith, m.r.w., wright, i.m. (2006) noninfected tenosynovitis of the digital flexor tendon sheath: a retrospective analysis of 76 cases. equine vet. j. 38, 134-141. doi: http://dx.doi.org/10.2746/042516406776563350 wilderjans, h., boussauw, b., madder, k., et al., (2003) tenosynovitis of the digital flexor tendon sheath and annular ligament constriction syndrome caused by longitudinal tears in the deep digital flexor tendon: a clinical and surgical report of 17 cases in warmblood horses. equine vet. j. 35, 270-275. doi: http://dx.doi.org/10.2746/042516403776148183 wilderjans, h., boussauw, b. (2006) deep digital flexor tendon lesions in the fetlock region: a retrospective study of 108 tenoscopies of digital flexor tendon sheaths suspected of deep digital flexor tendon laceration. management of lameness causes and sport horses: muscle, tendon, joint and bone disorders. conference on equine sports medicine and science. cambridge, uk. 21-23 july 2006: 15-25. wright, i.m., mcmahon, p.j. (1999) tenosynovitis associated with longitudinal tears of the digital flexor tendons in horses: a report of 20 cases. equine vet. j. 31, 12-18. doi: http://dx.doi.org/10.1111/j.2042-3306.1999.tb03785.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. does intra-articular injection of antimicrobials alongside corticosteroids or other medications reduce the risk of synovial sepsis? a knowledge summary by helen braid bsc (hons) bvetmed certavp fhea mrcvs 1* 1university of liverpool, institute of veterinary science, liverpool, l69 3gh *corresponding author (h.braid@liverpool.ac.uk) vol 4, issue 4 (2019) published: 30 oct 2019 reviewed by: ellen singer (ba, dvm, dvsc) and lynn martin (dvm, mph, dacvim (laim)) next review date: 26 feb 2021 doi: 10.18849/ve.v4i4.194 pico question in horses, does treatment with intra-articular antimicrobials concurrently with intra-articular corticosteroids reduce the risk of iatrogenic synovial sepsis compared to intra-articular corticosteroids alone? clinical bottom line from the current literature, there is no evidence showing that intra-articular injection of antibiotics in conjunction with corticosteroids reduces the risk of synovial sepsis. however, the intra-articular injection of polysulphated glycosaminoglycans (psgags) in combination with corticosteroids was noted as a risk factor for developing iatrogenic synovial sepsis and therefore concurrent antibiotic injection when administering psgags may be warranted. the reported frequency of infection following intra-articular injections was very low (0.02–0.08%).  an overall prevalence of iatrogenic synovial sepsis following all intra-articular injections based on data from all included studies was calculated as 0.02% (ci 0.02–0.03%). however, due to the paucity of literature on the topic, further studies are required in this field to determine more accurate clinical recommendations. clinical scenario antimicrobials such as amikacin sulphate or gentamicin sulphate are often added to corticosteroid preparations when performing intra-articular injections in horses. this summary aims to determine whether the risk of iatrogenic synovial sepsis increases in the absence of these antimicrobials and to consider whether injecting them concurrently with intra-articular corticosteroids is necessary. the evidence of the three studies examined, only two studies directly evaluated the prevalence of iatrogenic synovial sepsis following intra-articular injection. two out of the three studies were retrospective analyses of medical records (smith et al., 2018 and steel et al., 2013) and one was a survey based study with retrospective analyses of medical records submitted by questionnaire respondents (gillespie et al., 2016). the searches also revealed an abstract by smith et al. (2013) which was later published as a full study (smith et al., 2018) and for the purposes of avoiding data replication, only the full study has been included. the scientific literature surrounding this topic was sparse and of inconsistent quality. there were no randomised controlled trials evaluating the risk of iatrogenic synovial sepsis following corticosteroid administration. most studies comprised retrospective analyses of medical records, which are considered mid-level in the hierarchy of evidence-based medicine (murad et al., 2016). the number of cases of iatrogenic synovial sepsis was very low in all included studies; therefore evaluating risk factors using multivariable models may have been biased by a low number of events per variable. all included studies were likely to have insufficient statistical power to identify a true difference in incidence between different treatments (peduzzi et al., 1996). summary of the evidence where prevalence and 95% confidence intervals (ci) were not provided in the publication, the author performed calculations where published data permitted using epitools epidemiological calculators (ausvet pty ltd., 2019). (italics denote author calculations). steel, c.m., pannirselvam, r.r., & anderson, g.a. (2013) population: 16,624 intra-articular injections performed in 1103 thoroughbred racehorses. sample size: 16,624 injections in 1103 horses. intervention details: cases included 16,624 joints injected in 1103 horses over a 45 month period from 31 march 2002 to 31 december 2005. 15,934 of these injections included corticosteroids. control group included all horses given intra-articular medication (iam) on the same day, day before or the day after septic cases (224 control horses with 13 infected joint cases – no specific data was provided on injections for each case). standardised aseptic preparation procedure was used. hair was not clipped and was scrubbed with 4% chlorhexidine for a minimum of 2 minutes, then 70% alcohol wipes. injections included corticosteroid (triamcinolone, betamethasone, dexamethasone or methylprednisolone) with or without amikacin sulphate, plus other unspecified medications. doses were not recorded. non-sterile dressing applied to all except stifle and shoulder joints, where no dressing was applied. study design: retrospective and prospective descriptive study, with nested matched case-control. outcome studied: diagnosis of septic arthritis within 1–19 days following intra-articular injection and identification of any risk factors for this complication. septic arthritis was diagnosed if synovial fluid bacterial culture was positive or if synovial fluid analysis revealed elevated total leucocyte count (>5.0 x 109/l) with a predominance of neutrophils (>80%) and increased total protein (>25 g/l). main findings (relevant to pico question): of 16,624 joints injected in 1103 horses, septic arthritis occurred in only 13 joints (13 horses). the risk of septic arthritis following intra-articular injection was one case per 1279 injections or 7.8 per 10,000 joints (prevalence 0.08% [ci 0.05–0.13%]). of the 13 septic cases, 12 horses were injected with a corticosteroid plus or minus sodium hyaluronate (individual case details unspecified) and one was injected with a homeopathic anti-inflammatory product. risk factors identified were veterinary surgeon and type of corticosteroid. betamethasone had a lower risk of septic arthritis than dexamethasone. when data for each joint location was compared there was no significant difference in the number of cases. none of the 824 joints injected with amikacin developed septic arthritis. of the 15,800 joints not injected with amikacin, 13 developed iatrogenic synovial sepsis. there was no statistically significant association between the absence of amikacin and development of synovial sepsis (fisher’s exact test p > 0.99). limitations: the effect of the individual performing skin preparation was not studied because information was unavailable for seven of the 13 septic cases and for 50% of the nonseptic cases. study did not clarify whether veterinary surgeon or assistant performed skin preparation. due to certain veterinary surgeons having an apparently higher rate of septic cases than others, this would have been useful information in order to determine if there were differences in aseptic technique despite a standardised procedure being in place. nonsterile dressing applied to all except stifle and shoulder joints, where no dressing was applied. medication doses were not recorded so association between corticosteroid dose and septic cases could not be evaluated. statistical validity of results is limited by a large number of injections with relatively low number of septic cases for comparison (resulting in a low number of events per variable for analysis of risk factors). gillespie, c.c., adams, s.b., & moore, g.e. (2016) population: equine veterinarians who were members of the american association of equine practitioners (aaep) in 2014. sample size: 241 surveys were returned containing details of 319,760 intra-articular injections. intervention details: a link to an online survey was distributed to all members of the aaep via email a total of three times between 17 march and 9 may 2014. the survey consisted primarily of multiple choice questions about intra-articular injection site preparation methods, injection methods, types of medication used and aftercare. several open questions and written responses were also included. guidelines were provided for determining joint sepsis. medical records for septic cases were requested and analysed. study design: retrospective survey based cross-sectional study. outcome studied: reported rate of joint sepsis following intra-articular injection. guidelines for diagnosing sepsis included one or more of: increased lameness score attributed to the injected joint, periarticular swelling, joint effusion, cloudy or turbid synovial fluid, elevated total protein of the synovial fluid and elevated nucleated cell count of synovial fluid. main findings (relevant to pico question): only 26.6% of respondents (64/241 surveys) provided data regarding joint sepsis. 67/319,760 injected joints became septic following injection; 2.10 septic joints per 10,000 intra-articular injections (prevalence 0.02% [ci 0.02–0.03%]). no significant reduction in joint sepsis was noted with the concurrent intra-articular injection of antimicrobials. infection rates were significantly lower when: veterinary surgeons prepared their own injection sites veterinary surgeons had fewer than 20 years of practice experience. infection rates were significantly higher when: hair was removed at the injection site. some findings were significant on the univariable analysis but were not retained in the final multivariable model. these included: lower infection rates when the intra-articular injection site was prepared for longer than 7 minutes lower infection rates when surgeons wore sterile or non-sterile gloves when performing the injection higher infection rates when veterinary surgeons used the same needle to draw up medications and perform the injection. limitations: horses with septic joints diagnosed by one veterinary surgeon but injected by another (i.e. second opinions) were not included in the study. this could have falsely lowered the apparent infection rate, as approximately 60% of respondents reported treating infections in horses that were injected by other veterinary surgeons. risk of misclassification bias – the method of diagnosing synovial sepsis was recommended in the study, though the true method of diagnosis may have varied between veterinary respondents. study was questionnaire based and thus open to non-response, response and recall bias. response rate was low with only 241 respondents, which equates to a response rate of around 2.5% (241 responses from around 9600 veterinarians receiving the survey), with only 26.6% of respondents (64/241) providing data on joint infections. statistical validity of results is limited by a large number of injections with relatively low number of septic cases for comparison (resulting in a low number of events per variable for analysis of risk factors). exact numbers of corticosteroid injections and how many of these were septic were not provided, limiting the reliability of interpretation of these results in direct relevance to the pico question. smith, l., wylie, c.e., palmer, l. & ramzan, p.h.l. (2018) population: case records for every horse that received intra-synovial medications performed by 10 ambulatory clinicians in one uk equine hospital between 1 january 2006 and 31 december 2011. sample size: 9456 intra-synovial injections in 1732 horses over 4331 sessions. intervention details: 1732 horses receiving therapeutic intra-synovial injections using standardised aseptic technique. records were cross-referenced against admissions of synovial sepsis cases to the hospital and against cytology submissions. post-medication sepsis was considered if the horse developed two or more of four signs of synovial sepsis within 8 weeks of medication (listed below) and failed to respond to conservative therapy. study design: retrospective analysis of medical records. outcome studied: prevalence of iatrogenic synovial sepsis following intra-synovial injections. synovial sepsis was defined as any horse developing two or more of four signs, including lameness, joint distension, synovial white blood cell count >10 x 109/l, or synovial total protein >25 g/l within 8 weeks of intra-synovial medication of the same joint. cases that resolved with conservative therapy (short courses of non-steroidal anti-inflammatory drugs and antimicrobials) were not diagnosed as septic. main findings (relevant to pico question): frequency of iatrogenic synovial sepsis was very low (0.04%, 4/9456). 3% of injections (3869/4331) included corticosteroids; 93.4% included amikacin (4044/4331). dosages were not recorded. four horses developed iatrogenic synovial sepsis – two following injection of psgags, one following triamcinolone acetonide combined with amikacin sulphate and one following triamcinolone acetonide alone. administration of intra-synovial psgags was associated with an increased risk of iatrogenic synovial sepsis, though the 95% confidence intervals cross 0, therefore this finding was not statistically significant. concurrent injection of amikacin sulphate with any other intra-synovial medication was associated with a low risk of developing iatrogenic synovial sepsis (attributable risk -1.02%, [ci -2.21–0.16]), though the confidence interval crosses 0, therefore this finding was not statistically significant. limitations: 4% of injections (4044/4331) included a prophylactic antibiotic (amikacin sulphate) so true risk of sepsis without concurrent antimicrobial administration is difficult to quantify. dosages of medications were not recorded. high proportion of racehorses within study population may limit external validity. case definition of synovial sepsis in relation to descriptive clinical parameters (lameness, joint swelling) was open to interpretation and may vary between veterinary surgeons. data analysed in sessions rather than per individual injection; there were 9456 injections performed in total, though data is analysed over 4331 sessions. statistical validity of results is limited by a large number of injections with relatively low number of septic cases for comparison (resulting in a low number of events per variable for analysis of risk factors). appraisal, application and reflection the current literature suggests that the frequency of infection following all intra-articular injections (including corticosteroids, antimicrobials, anaesthetic agents, psgags, combinations of the above and any other unspecified or unlisted medication included in the studies reviewed) is very low and equates to roughly one case per 1000 or 2364 injections, according to steel et al. (2013) and smith et al. (2018) respectively. these figures equate to a prevalence of iatrogenic sepsis of 0.02–0.08%. the overall prevalence of synovial sepsis following all intra-articular injections based on data from all included studies was calculated as 0.02% [ci 0.02–0.03%]. the prevalence of synovial sepsis following corticosteroid injections across three studies which provided the necessary data (smith et al., 2018 and steel et al., 2013) was 0.07% [ci 0.04–0.012%].   table 1: prevalence estimates for synovial sepsis for all intra-articular injections across all studies (as calculated by author of this knowledge summary).   study injections septic cases prevalence (%) ci (%) steel et al. (2013) 16,624 13 0.08 0.05–0.13 gillespie et al. (2016) 319,760 67 0.02 0.02–-0.03 smith et al. (2018) 9456 4 0.04 0.02–-0.11 all 345,840 84 0.02 0.02–0.03   table 2: prevalence estimates for iatrogenic synovial sepsis following corticosteroid injections in the only two included studies which provided the necessary data (as calculated by the author of this knowledge summary).   study corticosteroid injections septic cases prevalence (%) ci (%) steel et al. (2013) 15,934 12 0.08 0.04–0.13 smith et al. (2018) 3,871 2 0.05 0.01–0.19 all 19,805 14 0.07 0.04–0.12   from the studies examined, there is no evidence that injecting antibiotics in conjunction with corticosteroids reduces the frequency of synovial sepsis following intra-articular injection. there is some evidence indicating that the risk of iatrogenic synovial sepsis following intra-articular medication may be increased by a number of factors, including: the veterinary surgeon not performing the skin preparation herself/himself the veterinary surgeon being qualified for over 20 years clipping the injection site skin preparation with chlorhexidine for fewer than 7 minutes* not wearing gloves* using the same needle to draw up medications and to inject the joint* (* denotes factors that were statistically significant on univariable analysis though not on multivariable analysis (gillespie et al., 2016)) one of the included studies provided weak evidence of an increased risk of synovial sepsis following the injection of psgags. smith et al. (2018) reported that injection of psgags was positively associated with iatrogenic synovial sepsis, though this finding was not statistically significant. in an abstract found in the literature search (though not included in the knowledge summary as it was an unpublished proceedings expanded abstract), bohlin et al. (2014) also reported that injection of psgags in combination with corticosteroids appeared to increase the risk of infection. although not included in the summarised evidence due to it not meeting the inclusion criteria, a paper by gustafson et al. (1989) reported that psgags potentiate the risk of iatrogenic infection. gustafson found that intra-articular injection of 125 mg amikacin immediately after inoculating the joint with staphylococcus aureus significantly decreased the potentiation of infection by the psgag. from this data, it can be concluded that concurrent injection with antimicrobials when injecting psgags may be warranted. further studies with larger sample sizes would be required to confirm whether concurrent antibiotic administration when injecting psgags is necessary. responsible use of antimicrobials is of paramount importance across all health sectors, and making appropriate, evidence-based choices is crucial to preventing the development of antimicrobial resistance. therefore, the following recommendations can be made: sterile skin preparation should be performed for a minimum of 7 minutes when using chlorhexidine, ideally by the veterinary surgeon performing the intra-articular injection. gloves should be worn for skin preparation as well as for intra-articular injection. needles should be changed after drawing up medications and before intra-articular injection. veterinary surgeons should consider not clipping the injection site, though this will depend on the length of hair, visibility of landmarks and gross contamination of the surrounding hair and skin. intra-articular injection of antimicrobials is unlikely to be necessary, though may be warranted if psgags are being injected. although some of the above factors were only statistically significant on univariable analysis rather than on multivariable analysis, they have been included in the clinical recommendations for performing intra-articular injections as they are factors that may be implemented with ease in a clinical setting. a systematic review of aseptic skin preparation procedures for intra-articular injections in horses would be of benefit to equine practitioners, with particular attention on clipping and the substance used for disinfection (e.g. chlorhexidine or iodine). an investigation of skin preparation protocols in relation to septic arthritis rates would also be of great benefit to equine practitioners. the quality of the evidence included in this summary is mixed. only three studies were found and one of those three did not provide enough information regarding exact medications injected (corticosteroids vs others) to accurately interpret the results with direct relevance to the pico question (gillespie et al., 2016). none of the studies rank highly in the hierarchy of research and evidence-based medicine (arlt & heuwieser, 2016 and murad et al., 2016). the poor quality and heterogeneity of the studies precluded meta-analysis of their results. in answer to the pico question, it can be concluded that injecting antibiotics in conjunction with corticosteroids is likely to be unnecessary. however, there is a paucity of strong, evidence based research on the subject. although the available studies provide useful data, they have limited external validity and insufficient statistical power. further studies are required in this area to reach a definitive conclusion for this particular pico question. given the very low frequency of iatrogenic synovial sepsis following intra-articular injection reported in the included studies, a randomised controlled trial is unlikely to be feasible and a multicenter case control study would likely be required in order to recruit an adequate number of cases to achieve sufficient statistical power. methodology section search strategy databases searched and dates covered: cab abstracts – 1973 to 26 february 2019. pubmed via the ncbi website; 1910 to 26 february 2019 science direct – elsevier – unknown to 26 february 2019 scopus – unknown to 26 february 2019 wiley online library – unknown to 26 february 2019 search terms: the search terms used for cab abstracts, pubmed, wiley online library and scopus were: search 1: “(intra-articular or intraarticular or intra-synovial or joint or synovial or articular) and (injection or medication or administration ) and (corticosteroid or cortico-steroid or steroid or corticoid or betamethasone or triamcinolone or methylprednisolone or dexamethasone) and (risk or risks or infection or sepsis or complication or complications) and (antibiotic or antimicrobial or antibacterial or amikacin or gentamicin or antibiosis or anti-microbial or antibiotics or antimicrobials) and (horse or horses or equine)”.   search 2: “(intra-articular or intraarticular or joint or synovial or articular) and (injection or medication) and (corticosteroid or cortico-steroid or steroid or corticoid or betamethasone or triamcinolone or methylprednisolone or dexamethasone) and (risk or risks or infection or sepsis or complication or complications) and (horse or horses or equine)”.   search 3: “(intra-articular or intraarticular or joint or synovial or articular) and (injection or medication) and (antibiotic or antimicrobial or antibacterial or amikacin or gentamicin or antibiotics or anti-microbial) and (horse or horses or equine)”.   the search terms for science direct (which does not support searches of more than eight boolean connectors per field), as well as all of the databases mentioned above were: search 4: “(intra-articular or intraarticular or joint or synovial or articular) and (injection or medication) and (infection or sepsis) and (horse or horses or equine)”.   reference lists and bibliographies of discovered articles were also examined to identify other relevant publications, none of which were found.   the wiley online library search yielded 1344 results with search 1, necessitating subject refinement to veterinary medicine, medical science and equine science. dates searches performed: 26 february 2019 exclusion / inclusion criteria exclusion: studies not related to the pico question studies performed in other species non-english language publications abstract and full text unavailable inclusion: studies relevant to the pico question in the english language. search outcome database number of results excluded – not related to pico excluded – studies in other species excluded – non-english language excluded – abstract and full text unavailable total relevant papers cab abstracts 129 124 0 1 1 3 pubmed 115 112 0 0 1 2 science direct 275 2 272 1 0 0 scopus 51 46 1 0 1 3 wiley online library 1344 209 1129 1 2 3 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflicts of interest. references arlt, s.p., & heuwieser, w. (2016). ‘the staircase of evidence–a new metaphor displaying the core principles of evidence-based veterinary medicine’. veterinary evidence, 1(1). doi: 10.18849/ve.v1i1.18 ausvet pty ltd. (2019). ‘epitools epidemiological calculators’.  bohlin, a.m., kristoffersen, m., & toft, n. (2014). ‘infectious arthritis following intra-articular injection in horses not receiving prophylactic antibiotics: a retrospective cohort study of 2833 medical records’. in proceedings of the 60th annual convention of the american association of equine practitioners, salt lake city, utah, usa, december 6-10 2014 (pp. 255–256). american association of equine practitioners (aaep). gillespie, c.c., adams, s.b., & moore, g.e. (2016). ‘methods and variables associated with the risk of septic arthritis following intraâ€â�articular injections in horses: a survey of veterinarians’. veterinary surgery, 45(8), pp. 1071–1076. doi: https://doi.org/10.1111/vsu.12563 gustafson, s.b., mcilwraith, c.w., jones, r.l., & dixon-white, h.e. (1989). ‘further investigations into the potentiation of infection by intra-articular injection of polysulfated glycosaminoglycan and the effect of filtration and intra-articular injection of amikacin’. american journal of veterinary research, 50(12), pp. 2018–2022. murad, m.h., asi, n., alsawas, m., & alahdab, f. (2016). ‘new evidence pyramid’. bmj evidence-based medicine, 21(4), pp. 125–127. doi: http://dx.doi.org/10.1136/ebmed-2016-110401 peduzzi, p., concato, j., kemper, e., holford, t.r., & feinstein, a.r. (1996). ‘a simulation study of the number of events per variable in logistic regression analysis’. journal of clinical epidemiology, 49(12), pp. 1373–1379. doi: https://doi.org/10.1016/s0895-4356(96)00236-3 smith, l., palmer, l., shepherd, m., steven, w.n., dallas, r., baldwin, g., sommerville, g., hawthorne, t. and ramzan, p. (2013). ‘risks of synovial sepsis following intra-synovial medication in ambulatory practice, 2006–2011: 9456 intra-synovial injections’. in: clinical research abstracts of the british equine veterinary association congress 2013, equine veterinary journal, 45, pp. 6–6. doi: https://doi.org/10.1111/evj.12145_13 smith, l.c.r., wylie, c.e., palmer, l., & ramzan, p.h.l. (2018). ‘synovial sepsis is rare following intra-synovial medication in equine ambulatory practice’. equine veterinary journal. doi: https://doi.org/10.1111/evj.13063 steel, c.m., pannirselvam, r.r., & anderson, g a. (2013). ‘risk of septic arthritis after intraâ€â�articular medication: a study of 16,624 injections in thoroughbred racehorses’. australian veterinary journal, 91(7), pp. 268–273. doi: https://doi.org/10.1111/avj.12073 acknowledgement rcvs knowledge was supported in producing this knowledge summary by an educational grant from petplan charitable trust. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. a guide for students and staff (thinking of) doing systematic reviews nieky van veggel msc, cbiol, fhea1* 1school of sport, equine and animal science, writtle university college, lordship road, chelmsford, essex, cm1 3rr, united kingdom * (nieky.vanveggel@writtle.ac.uk) vol 3, issue 1 (2018) published: 03 jan 2018 title of book: doing a systematic review – a student’s guide (2nd edition) doi: 10.18849/ve.v3i1.161 section index:    book review | conflict of interest | references book review more and more students on a variety of higher education courses are performing systematic reviews as part of their independent research, and it is becoming more common for research students to undertake a systematic review as part of their thesis or dissertation. although plenty of guidance is available in the form of books, paper collections and online advice, the majority of currently available sources are aimed at health care practitioners and researchers rather than students in general. writing for students requires a clear narrative and a more accessible writing style, this gap was addressed by the first edition of this book published in 2014. however, systematic review as a method of research has evolved rapidly, and expanded into more and more fields. the publication of a second edition, with a new student-friendly 10-step roadmap, more comprehensive coverage of qualitative systematic reviews and a chapter on disseminating review findings was justified. in addition, in line with many other student-focussed textbooks, the new edition is now supported by online resources which aid in understanding the systematic review process. starting with an introduction to carrying out a systematic review as a student, the authors cover the whole process from planning and defining the question, to data synthesis and writing a discussion. in addition, chapters on specific aspects of reviewing qualitative and economic evidence and guidance on the dissemination of reviews makes this a well-rounded textbook. the strongest feature of this book is its use of clear examples supported by “frequently asked questions” sections. the combination of these approaches allows for a very unthreatening journey that is the production of a systematic review. most, if not all, common questions received by supervisors from students undertaking systematic review projects have been addressed, which will make students more confident when discussing their work with supervisors. furthermore, the student-friendly language of this book makes for engaging reading. the authors have chosen to address the reader throughout the book, rather than opting for a more neutral writing style. keeping in mind the target audience and the aim of the book, this style helps maintain the reader’s interest (treagust and harrison, 1999). a possible improvement to this book would be a more thorough introduction to realist reviews. where in many cases systematic reviews are the most appropriate way forward for knowledge synthesis, the complex areas of evidence-based policy making and social interventions calls for a more “realist approach” to evaluation (pawson et al., 2005). however, as realist synthesis warrants a book in its own right, and is possibly not appropriate for master’s level research, this gap is forgivable and does not diminish the contribution that doing a systematic review makes to student systematic review research and learning. to conclude, doing a systematic review is the book of choice for all students and early career researchers who are considering or undertaking systematic review research, and makes a valuable teaching resource for all academic staff in areas of evidence-based practice. conflict of interest nieky van veggel received a copy of this book as a free inspection copy as per standard academic practice, but reports no other conflicting interests and was not involved in the conception of this book or its previous edition. references boland, a., cherry, m.g. and dickson, r. (eds.) (2017) doing a systematic review – a student’s guide (2nd edition), london: sage. pp.275. pawson, r., greenhalgh, t., harvey, g., walshe, k. (2005) realist review a new method of systematic review designed for complex policy interventions. journal of health services research & policy. 10 (1_suppl), 21–34. http://dx.doi.org/10.1258/1355819054308530 treagust, d., harrison, a. (1999) the genesis of effective scientific explanations in the classroom. in j. loughran, ed. researching teaching: methodologies and practices for understanding pedagogy. abingdon: routledge, pp. 28–43. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. does adding transdermal nitroglycerine to other therapies used for management of left-sided congestive heart failure in dogs speed the resolution of clinical signs? a knowledge summary by jenefer r stillion dvm, dacvecc 1 søren r boysen dvm, davecc 2* 1western veterinary specialist and emergency centre, calgary, canada 2department of veterinary clinical and diagnostic sciences, faculty of veterinary medicine, university of calgary, calgary, canada *corresponding author (srboysen@ucalgary.ca) there is an erratum to this paper published in veterinary evidence vol 3, issue 1 (2018): http://dx.doi.org/10.18849/ve.v3i1.168 vol 2, issue 4 (2017) published: 12 dec 2017 updated: 01 feb 2018 reviewed by: myra forster-van hijfte (certvr certsam dipecvim-ca frcvs) and william chandler (bvetmed, mrcvs) next review date: 02 jan 2019 doi: 10.18849/ve.v2i4.115 clinical bottom line there is very weak veterinary clinical and experimental evidence based upon a limited number of studies to indicate that adding transdermal nitroglycerine to other therapies used for management of left-sided congestive heart failure in dogs speeds the resolution of clinical signs. question does adding transdermal nitroglycerine to other therapies used for management of left-sided congestive heart failure in dogs speed the resolution of clinical signs? clinical scenario transdermal nitroglycerin is frequently recommended as an adjunct therapy in many canine treatment protocols for left-sided congestive heart failure due to its preload and afterload reducing effects. does adding transdermal nitroglycerin to other therapies used for management of left-sided congestive heart failure in dogs speed the resolution of clinical signs? the evidence there is no evidence in the literature to suggest transdermal nitroglycerin speeds resolution of clinical signs in dogs with pulmonary oedema secondary to left-sided congestive heart failure. there is equivocal to weak evidence that transdermal nitroglycerin reduces systolic and/or mean arterial blood pressure in dogs. there is no evidence that transdermal nitroglycerin has any effect on resolution of any clinical signs of left-sided congestive heart failure. although there are no reports of adverse harm associated with transdermal nitroglycerin, there are insufficient clinical studies to be able to state nitroglycerin does not have any adverse affects in dogs. summary of the evidence nakayama (2007) population: mixed breed dogs with seller’s grades 2+ or 3+ mitral regurgitation sample size: 9 dogs intervention details: mitral regurgitation was produced by surgical disruption of the mitral valves.  five months after production of mitral regurgitation, left atrial dimension and ventricular function were measured using echocardiography/doppler and left ventricular micromanometry.  nine mixed breed dogs weighing 21-32 kg were administered butorphanol (0.05 mg/kg im) prior to the start of each study.  enalaprilat, nitroglycerin, ouabain, milrinone or placebo (iv saline, there was a one-week washout period between arms of the study to ensure at least 10 half-lives between exposures. recordings were obtained, along with an ecg, during baseline and 30 minutes after dogs received iv (in random sequence) 0.3 mg/kg enalaprilat, 20mg/kg ouabain, or  100mg/kg  of  milrinonel;  or  2  inches  of  2% nitroglycerin paste applied to the skin of the inner thigh over an area of 16 cm2. all dogs also were given an iv (saline) and   a   transdermal   placebo  (vaseline). dogs were studied 1 hour and 2 hours after application. study design: randomised controlled clinical trial outcome studied: the effect of 4 different cardioactive drugs on left ventricular function in dogs with mitral regurgitation of 5 months duration. parameters studied included intracardiac dimension, peak aortic flow, left atrial diastolic and systolic function. main findings (relevant to pico question): when compared to placebo (vaseline), transdermal nitroglycerin failed to produce an effect on any of the parameters studied. limitations: small sample size. surgically induced mitral regurgitation may not accurately reflect clinical mitral endocardiosis. no animals had clinical signs of congestive heart failure.  kanda (1995) population: healthy beagle dogs sample size: 5 dogs in each group intervention details: there were 3 groups; nitroglycerin tape at 2.5 mg/kg (nt-l, 5 mg nitroglycerin per 5 x 10 cm2) with placebo capsule, nifedipine given orally (3mg/kg) with placebo tape, and a control group that received a placebo (blank) capsule orally and pacebo tape. placebo and nitroglycerine tape were applied to a clipped area of skin on the chest of healthy beagle dogs. study design: prospective study (non-randomised, non-blinded) outcome studied: the effect of nitroglycerin tape compared to placebo tape on blood pressure (systolic and diastolic), heart rate and coronary blood flow in healthy beagle dogs. baseline values recorded for 1 hour before drug administration and then at 30 min, 1 hour and every hour until 9 hours. parameters were measured again 1 hours following removal of tape. main findings (relevant to pico question): systolic blood pressure was decreased by 10-15%, compared to baseline, with application of nitroglycerin tape in awake healthy instrumented beagle dogs. the decrease was noted 1 hour after application, persisted for the duration of the study and returned to baseline values within 1 hour of removing the tape. calculated (not directly measured) mean arterial pressure decreased 4-5 %. diastolic blood pressure and heart rate were not affected. changes were noted 30 minutes after the application of nitroglycerin tape and remained constant for 8h. no changes from baseline parameters were noted in the control group. limitations: small sample size may have failed to detect true differences that existed between groups or within groups. decrease in blood pressure provides indirect evidence of the efficacy of nitroglycerin which does not equate to clinical improvement. dogs were healthy and did not have any clinical signs of congestive heart failure. mckie (2014) population: male mongrel dogs with induced mild left ventricular dysfunction. sample size: three study groups with 7 dogs in each group (intravenous m-anp, nitroglycerin, and vehicle 0.9% normal saline) intervention details: mild left ventricular dysfunction was induced via right ventricular pacing at 180 beats per minute for 10 days in male mixed mongrel dogs. rv pacing was terminated the day of the study and dogs were anesthetized with pentobarbital sodium (15mg/kg iv), intubated and ventilated. hypertension was induced in instrumented dogs via iv administration of angiotensin ii (40 mg/kg/1min). dogs were then administered either m-anp (30 pmol/kg/min), nitroglycerin (10 ug/kg iv) or 0.9% normal saline at a rate of 1ml/min. study design: prospective experimental study under anaesthesia (non-randomised, non-blinded) outcome studied: blood pressure, pcwp, systemic vascular resistance, left ventricular filling pressures, heart rate, cardiac output. main findings (relevant to pico question): nitroglycerin significantly decreased mean arterial blood pressure, pcwp, systemic vascular resistance and left ventricular filling pressures. no effect on heart rate or cardiac output. limitations: nitroglycerin was administered iv, not topically. sample size was small. study was not blinded or randomised. experimentally induced heart failure was studied, not naturally occurring heart failure. evidence provided that iv nitroglycerin reduced preload and afterload but this does not equate to improvement in clinical signs. parameswaran (1999) population: healthy anaesthetised dogs sample size: 15 dogs intervention details: sonomicrometer crystals were applied to the spleen in each dog and a pressure-measuring catheter was inserted into a splenic vein. a 2.5cm strip of transdermal 2% nitroglycerin ointment was applied to the inner surface of the pinna in 10 dogs and 5 additional dogs (control group) were given only petrolatum. study design: non-randomised clinical trial outcome studied: splenic dilatation in healthy dogs anaesthetised with alpha chloralose after transdermal application of nitroglycerin. splenic dimension and venous pressure were measured for 10 minutes before application and time from application of transdermal nitroglycerin to the initial change in dimension and to the maximal change in dimension (measured to the nearest second). main findings (relevant to pico question): splenic dimension increased significantly from baseline in all 10 dogs receiving transdermal nitroglycerin. splenic enlargement was noted within 482 ± 652 seconds after application of transdermal nitroglycerin with maximal dilatation at 861 ± 632 seconds. splenic venous pressure did not change significantly in dogs receiving transdermal nitroglycerin or in control dogs. limitations: animals were healthy and anaesthetised with alpha chloralose, whose physiologic effects are not well characterized in the literature for any species. results of the present study may not translate to un-anaesthetised dogs with left-sided congestive heart failure. appraisal, application and reflection given studies are lacking with regards to the efficacy of transdermal nitroglycerin when included as an adjunct treatment to other therapies in dogs with left-sided congestive heart failure, it’s use cannot be recommended in the management of these cases at this time. future clinical studies are needed to evaluate the safety, efficacy and ideal dosage of transdermal nitroglycerin in the treatment of dogs with left-sided congestive heart failure.  methodology section search strategy databases searched and dates covered: pubmed platform 1973week 1 2017], cab abstracts <1973 to 2016 week 51> search terms: pubmed search ((((glyceryl trinitrat*) or glyceryltrinitrat*) or trinitrat glycerin*) or nitro glycerin*) or nitroglycerin* 16518 search ((((((((heart) or cardiac) or chf) or cardio*) or left ventricular) or left ventricle*) or lv) or heart diseases) or cardiovascular diseases 2866548 search (((((dog) or dogs) or canine) or bitch*) or canis) or bitches 351249 search ((transdermal) or cutaneous) or ointment 185703 cab abstracts: ("glyceryl trinitrat*" or glyceryltrinitrat* or "trinitro glycerin*" or trinitroglycerin* or "nitro glycerin*" or nitroglycerin*).mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (374) (heart or cardiac or chf or cardio* or "left ventricular" or "left ventricle*" or "left ventrical*" or "lv").mp. or heart diseases/ or cardiovascular diseases/ [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (151135) (dog or dogs or canine or bitch*).mp. or dogs/ or canis/ or bitches/ (192085) 1 and 2 and 3 (16) dates searches performed: 22/12/2016 (cab) 02/01/2017 (pubmed) exclusion / inclusion criteria exclusion: study design did not involve dogs and/or was not relevant to the research questions asked inclusion: any relevant primary veterinary research or systematic review which compared transdermal nitroglycerine to other therapies to answer the following question; “does adding transdermal nitroglycerine to other therapies used for management of left-sided congestive heart failure in dogs speed the resolution of clinical signs?” search outcome database number of results excluded – did not address the pico excluded – proceedings and review articles with no evidence excluded – given iv, did not compare groups, and did not address clinical question excluded – single case report with no evidence to the question excluded – duplicate results total relevant papers ncbi pubmed 10 6 0 0 0 0 4 cab abstracts 16 0 6 6 2 2 0 total relevant papers when duplicates removed 4 conflict of interest the authors declare no conflicts of interest. references kanda a, yoshida m, kanou m, et al. (1995). cardiovascular effects of nt-1, a new patch form of nitroglycerin, alone and in combination with nifedipine in conscious dogs. journal of pharmacy pharmacology. 47(12a): pp. 1021-1024. doi: http://dx.doi.org/10.1111/j.2042-7158.1995.tb03289.x mckie pm, cataliotti a, ichiki t, et al. (2014). m-atrial natriuretic peptide and nitroglycerin in a canine model of experimental acute hypertensive heart failure: differential actions of 2 cgmp activating therapeutics. journal of the american heart association, 3(1):e000206. doi: http://dx.doi.org/10.1161/jaha.113.000206 nakayama, t. nishijima, y.  miyamoto, et al. (2007). effects of 4 classes of cardiovascular drugs on ventricular function in dogs with mitral regurgitation.   journal of veterinary internal medicine, 21(3), pp. 445-450. pmid: 17552449 doi: http://dx.doi.org/10.1111/j.1939-1676.2007.tb02988.x parameswaran, n. hamlin, r. l.  nakayama, t.  rao, s. s. (1999). increased splenic capacity in response to transdermal application of nitroglycerin in the dog.   journal of veterinary internal medicine, 13(1), pp. 44-46. pmid: 10052063 doi: 1111/j.1939-1676.1999.tb02164.x sellers r, levy m, amplatz k, lillehei cw. left retrograde cardioangiography in  acquired  cardiac  disease:  technic,  indications  and  interpretations  in  700    am j  cardiol  1964;14: 437–447 doi: http://dx.doi.org/10.1016/0002-9149(64)90027-x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. in dogs diagnosed with osteoarthritis, is meloxicam superior to carprofen for reducing patient discomfort? a knowledge summary by lesca monica sofyan dvm student 1* 1sydney school of veterinary science, the university of sydney, head office jd steward building university of sydney, nsw, 2006, australia *corresponding author (lesca.sofyan.xx@hotmail.com) vol 5, issue 3 (2020) published: 29 jul 2020 reviewed by: andy morris (bsc(hons) bvsc certavp(gsas) mrcvs) and robert pettitt (bvsc pgcertlthe dsas (orth) sfhea frcvs) next review date:28 aug 2021 doi: 10.18849/ve.v5i3.288 pico question in dogs diagnosed with osteoarthritis, is meloxicam superior to carprofen for reducing patient discomfort?   clinical bottom line category of research question treatment the number and type of study designs reviewed only two papers have compared the efficacy between meloxicam and carprofen in the treatment of dogs diagnosed with osteoarthritis. both of the papers were clinical, prospective and randomised trials. strength of evidence weak outcomes reported one randomised controlled clinical trial compared the level of efficacy between meloxicam and carprofen in reducing pain and discomfort in dogs diagnosed with osteoarthritis1. orthopaedic surgeons found dogs treated with either meloxicam or carprofen showed significant improvement in ground reaction forces (grf). the study emphasised that dogs treated with meloxicam had grf values that returned to normal baseline values, with owners also commenting on gait improvement. this study however, had a low sample size, did not use a validated metrology instrument for assessment by owners and the data used to assess grf was not conclusive on all parameters to favour meloxicam. an additional study was evaluated but this also had very small case numbers, no control group and gave no detailed statistical analysis2. the paper descriptively suggests meloxicam to show a better response than carprofen but there was no scientific analysis or evidence to statistically support and validate this. conclusion both meloxicam and carprofen are validated as effective treatments for canine osteoarthritis but it cannot be suggested that meloxicam is superior to carprofen as the available evidence is weak. to accurately assess this, a future clinical study using validated metrology instruments, adequate sample sizes and proper statistical analysis is required.   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision-making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a 10-year-old rottweiler cross has been diagnosed with canine osteoarthritis, specifically affecting the hip joints. his owner asks what the patient can be treated with to reduce discomfort and pain, particularly during walks. you recommend non-steroidal anti-inflammatory drugs (nsaids). you present the different types of nsaids available in your clinic, which are meloxicam and carprofen. the owner asks if one is superior to the other and whichever one that is, he will purchase. ensuring that you are providing gold standard treatment, you want to ensure that you are providing an nsaid that has proven to be the most effective. the evidence only one randomised controlled clinical trial compared the level of efficacy between meloxicam and carprofen in reducing pain and discomfort in dogs diagnosed with osteoarthritis. an additional study was evaluated but this had very small case numbers, no control group and gave no detailed statistical analysis. both articles directly compared meloxicam and carprofen along with another treatment (either a nutraceutical or another nsaid) in reducing pain and discomfort for dogs diagnosed with osteoarthritis. summary of the evidence mariana et al. (2013) population: recruitment osteoarthritis registered cases were retrieved from two private veterinary hospitals and faculty of veterinary medicine iasi registered patients individually underwent a thorough clinical examination and a paraclinical test   criteria for eligibility and inclusion patients were eligible and deemed to be appropriately diagnosed with osteoarthritis if they were found to experience the following osteoarticular inflammatory processes: intense pain during movement limping sensitivity to pain when applied pressure muscular rigidity paravertebral tone decreased impairment   criteria for exclusion and rejection recent operations (date and time range not stated) limb or spinal fractures females in gestation diagnosed with a hepatic, renal or cardiac disorder diseases or disorders that may interfere with the efficiency and safety of the treatment ages ranged from 3–15 years weight ranged from 6 to 15 kg 21 males and nine females (n=30) sample size: 30 dogs (n=30) intervention details: random allocation into treatment groups each dog was randomly assigned to either a meloxicam, carprofen or ketoprofen treatment group meloxicam treatment group = 10 subjects (n=10) carprofen treatment group = 10 subjects (n=10) ketoprofen treatment group = 10 subjects (n=10)   administration of treatment owners were instructed to provide treatment once a day (sid) in the morning after breakfast for 21 days   dosage of treatment meloxicam at 0.3 mg/kg per body weight carprofen at 2.5 mg/kg per body weight ketoprofen at 2 mg/kg per body weight   collection of faeces on days 1 and days 21 faeces were collected for haemoccult tests study design: clinical, randomised, blind study outcome studied: therapeutic efficiency of the nsaid treatment parameters of dogs assessed: inflammation pain intensity any deformities or modifications functional depreciation and limitations general state modification local hyperaemia   numeric and visual analogic scale: owners were required to examine and score the parameters of the dog daily based numeric scale ranked from 0 to 3: 0 = absence of pain; 1= moderate pain; 2= increased pain with general state modification; and 3 = intense pain, immobilised and general state modification the visual analogic scale assisted with evaluating the intensity of pain and inflammation   clinician’s assessment: on days 5, 10, 15 and 21, clinicians also evaluated the parameters of the dog according to the numeric and visual analogic scale   appearance of side effects and tolerability degree of nsaid treatment information on symptoms associated with gastrointestinal localisation, sensitivity to abdominal palpation, weight loss, queasiness, inappetence, hypersensitivity, oedema, sleeping disorders, high haemorrhagic risk, renal and hepatic disorders were recorded haemoccult tests were carried out to detect haemoglobin and haemoglobin-haptoglobin in faeces collected from day 1 and day 21 the haemoccult tests screened for potential digestive haemorrhage that may occur in intoxications or long-term therapy (7–10 days) with nsaids main findings (relevant to pico question): at day 21, approximately 93% of the total subjects displayed total remission of pain and inflammation associated with osteoarticular disorders since administered to a treatment group meloxicam treatment group had the highest positive response to diminished pain and inflammation (90%) followed by ketoprofen (75%) and carprofen (68%). this finding was not significant limitations: small sample size subjective assessment by owners no power analysis or statistical analysis was mentioned or performed to obtain a p-value. the authors do comment there was no statistical difference between treatment groups but give no details of the statistics performed poor inclusion criteria and eligibility – no radiographic evaluation alongside orthopaedic examination by a board registered specialist treatment doses were not in line with current recommendations moreau et al. (2003) population: recruitment medical files of the université de montréal teaching hospital newspaper advertisement   criteria for eligibility and inclusion canines over 18-months-old and weighed over 20 kg provided radiographic evidence of osteoarthritis in one or two elbows, one or two hips or one or two stifle joints osteoarthritis pathology caused by lameness determined by complete orthopaedic examination canines with a rupture due to cranial cruciate ligament that had been surgically repaired over a year or diagnosed over a year without surgical correction   criteria for rejection and exclusion canines with abnormalities in both the forelimb and hindlimb canines on concurrent treatment for osteoarthritis pregnant bitches as reports have highlighted hypersensitivity reactions to nsaids canines with a neurological or musculoskeletal pathology other than osteoarthritis that had undergone orthopaedic surgery within the same year   control group normal and breed-matched dogs determined by orthopaedic, radiographical and neurological examination sample size: 71 dogs diagnosed with osteoarthritis (n=71) intervention details: subjective owner assessment at the first visit (day 0), owners were to complete a subjective owner assessment that produced a cumulative score related to the activity and signs of pain their dog exhibited the same scoring system would be used on the second (30 days) and third visit (60 days)   gait analysis by analysis of grf grf with a biomechanical force plate was used to objectively measure the gait of the dog dogs were trotted over a force plate between 1.9 to 2.2 m per second   radiographic score elbows, hips and stifle joints of the dogs were radiographed a criteria provided a scoring system to assess the evidence of osteoarthritis   allocation of treatment groups computer-generated random list assigned each eligible dog to one of the following four treatment groups   treatment 1 – nutraceutical group: dogs weighing between 20–45 kg received two nutraceutical capsules two times a day (bid) for 30 days and then sid every 12 hours for the next 30 days 19 subjects in total (n=19) treatment 2 – carprofen group: dog were provided 2.3 mg/kg carprofen by oral administration every 12 hours for 60 days 17 subjects in total (n=17) on day 0 but resulted in 16 subjects by day 30 (n=16) treatment 3 – meloxicam group: dogs received 0.2 mg/kg meloxicam post-orally on the first day dogs received 0.1 mg/kg meloxicam for the following 59 days 17 subjects in total (n=17) on day 0 but resulted in 16 subjects by day 30 (n=16) treatment 4 – placebo group: dogs received the same volume of meloxicam as those in treatment 3 only administered for 30 days for ethical reasons 18 subjects in total (n=18) on day 0 but resulted in 17 subjects by day 30 (n=17)   subjective clinical evaluation by a veterinary orthopaedic surgeon on day 0, 30 and 60 one of two veterinary orthopaedic surgeons visually examined the gait of the patients if osteoarthritis was present in more than one joint, only the most affected was clinically evaluated the two veterinary orthopaedic surgeons were not aware of the grf or the treatment assigned to the dogs   blood and faecal analysis blood samples from each patient were sampled to provide haematology and biochemical results as a general pre-health check screen prior to continuation in the study haematology and biochemistry values were repeated on days 30 and 60 to ensure no adverse reactions or side effects were encountered   verification that treatment was provided on days 30 and 60 post-treatment, owners were to bring the unused/unnamed product to verify the dogs indeed received the treatment study design: clinical, prospective, randomised double-blind study outcome studied: on the first day of the study followed by 30 days and 60 days post-treatment, the following were analysed: subjective evaluation provided by owners of the patient subjective clinical evaluation by a veterinary orthopaedic surgeon objective gait analysis of dogs using a gfr main findings (relevant to pico question): only owners of the dogs in the meloxicam group claimed there had been improvement, appearing to alleviate the arthritic lameness of the dog and allow it to resume to normal daily activities subjective orthopaedic assessments revealed both carprofen and meloxicam improved the mobility of patients by day 30 and day 60 gait profiles/grf values compared by the wilcoxon rank-sum test at a significance level of 5% 2 grf improved in response to meloxicam and carprofen treatment (p < 0.017) on days 60, dogs treated with meloxicam had craniocaudal grf considered to be of normal value (p < 0.05) whilst those treated with carprofen had steady, declining grf (p > 0.05) treatment with meloxicam was found to be the most appropriate and improved for canines with a severe and inflammatory process, efficacy in improving the dog’s gait to resume to normal life and have an absence of side effects limitations: small sample size daily mobility level and activity of the dogs were not described which may have influenced the progression of the treatment subjective assessment by owners and veterinary orthopaedic surgeons validated metrology instruments for measuring response to osteoarthritis treatments/assessment of chronic pain not available at time of publication appraisal, application and reflection both studies obtained observational evaluations from owners regarding their dog’s mobility and gait during treatment although, this qualitative approach was more predominant in the study by mariana et al. (2013). whilst this is beneficial in providing primary insight on owner’s experiences, it does possess weaknesses. qualitative evaluations are not narrowly focused on a specific question3. the observations made by owners are not controlled in a clinical setting and thus, selective bias may be introduced into the study as an owner may favour one nsaid over another (e.g. meloxicam over carprofen). furthermore, participants may misinterpret criteria and guidelines and thus deliver incorrect or vague answers. metrology instrument testing for canine osteoarthritis are now available and have been clinically validated to effectively assess the quality of life and locomotive function in dogs with orthopaedic related disorders4.  one of the instruments that may have been useful for mariana et al. (2013) and for future related studies is the canine orthopaedic index (coi)4. the coi assesses the following four domains – stiffness, function, gait and quality of life for patients diagnosed with osteoarthritis or related orthopaedic disorders. the outcome provides a quantifiable assessment that clinicians and researchers can use to assess the efficacy of treatment provided. the sample sizes in both studies were considerably small. both studies did not provide details on how sample size was determined for it to be considered appropriate and adequate for clinical research. in validated scientific research and clinical trials, sample size should be determined from a power analysis. appropriate sample sizes are essential in providing a true representation of an underlying population and ensuring that the clinical question proposed allows for a valid statistical analysis5. inadequate sized studies are underpowered and may lead to statistical error and invalid conclusions. blinding is an important and distinct feature in randomised controlled trials to reduce selection bias from affecting results, which both studies did1,2,6,7. patients and evaluators assigned to a treatment with knowledge and no concealment may deliberately select to disapprove or approve a treatment based on personal beliefs and influential factors6,7. clinically, it is common for practitioners to favour a particular therapeutic drug over another for certain procedures. the lack of a control group in the mariana et al. (2013) study also meant there was no baseline to compare and assess the efficacy of the intervention (i.e. meloxicam or carprofen) that is essential in clinical trials 5,6. statistical analysis is a crucial foundation in evidence-based clinical practice and should be implemented in all clinical trials and research8. the small sample size, lack of statistical analysis and poor eligibility criteria in the study by mariana et al. (2013) may have meant that the results retrieved from the study were largely due to chance, thus limiting valid conclusions to be drawn. the application of statistical analysis (e.g. use of p-values and confidence intervals) aids in building a solid and sound evidence to ensure that the clinical courses and treatments tested are most likely to follow and have the same result8. moreau et al.’s (2003) application of analysing gfr strengthened the findings of the study. analysis of gfr is a non-invasive method and objective measurement of gait evaluation9,10. it accurately assesses between normal and abnormal gait, identifying characteristic features in gait abnormalities9. the findings of the gfr in moreau et al.’s study (2003) was accompanied with the owner’s assessment of their dog’s mobility, representing a quantitative and qualitative approach to the study and orthopaedic surgeon assessment. the combined use of a quantitative and qualitative approach as used in moreau et al.’s (2003) study is advocated in clinical trials as it neutralises flaws that may be present in one methodology and strengthens and validates results9,10,11. the results of the gfr can be corresponded to the owner’s assessment in regard to treatment response. consistency was adhered to in both methodological approaches where there was no note on potential external interferences (e.g. weight loss, hydrotherapy, physiotherapy, chondroitin sulphate injections) that may have potentially skewed the results of the studies. an additional finding in the moreau et al. (2003) study worth noting was a case whereby a patient was diagnosed with toxic idiosyncratic hepatitis to the carprofen treatment group. side effects from the use of long-term nsaids are a significant concern amongst owners and small animal practitioners. mariana et al. (2013) claimed meloxicam was better tolerated than carprofen due to the differing pathogenesis of the two treatments, as meloxicam is a cox-2 inhibitor and carprofen is a cox-1 inhibitor2. however, this is questionable as current evidence recognises carprofen preferentially inhibiting the cox-2 enzyme pathway9.  despite the finding in moreau et al. (2013) study, all dosages must be adjusted or lowered to the safest level when treating any case of osteoarticular inflammation. the dose range of 0.3 mg/kg for meloxicam used in the mariana et al. (2013) study is actually higher than what is recommended9. the recommended meloxicam initial dose is 0.2 mg/kg followed by a maintenance dose of 0.1 mg/kg post-orally (po) every 24 hours9. in monteir-steagall et al.’s (2013) systematic review of the drug induced adverse effects found variable results on the number of common adverse effects encountered from carprofen and meloxicam13. across the high strength of evidence, both meloxicam and carprofen induced adverse side effects including vomiting and diarrhoea as the two most common, as well as anorexia, lethargy, diarrhoea and melena13. meloxicam is available in both tablet and liquid formulation whilst carprofen is available only in tablet form. dogs that do not tolerate well with tablet administration may be provided the alternative of the meloxicam liquid formulation, but this may be limited if unwanted side effects have been experienced with dogs on meloxicam. therefore, whether practitioners and clients choose to prescribe carprofen and meloxicam for managing osteoarthritis, the health parameters and status of the patient on the treatment should be independently and regularly monitored to detect early unwanted side effects. both studies found patients diagnosed with osteoarthritis treated with either meloxicam or carprofen indeed improved articular motility. however, the absence of validated metrology instruments, poor eligibility and inclusion criteria, lack of statistical analysis and poor sample sizes does mean the studies are not universally and scientifically valid to conclude that the benefits of meloxicam are superior to carprofen. the two studies are nonetheless good foundations for a much wider and future study, such as a prospective randomised controlled trial with adequate population sizes, proper statistical analysis and validated metrology instruments to potentially assess the superiority of one nsaid to another. meloxicam or carprofen evidently improve patients with osteoarthritis but the evidence to scientifically conclude that meloxicam is superior to carprofen is weak. the selection of an nsaid by small animal practitioners for patients diagnosed with osteoarthritis should thus be selected on other variables such as suitability for the patient signalment (e.g. dosage levels, history of side effects if previously medicated on an nsaid), owner’s satisfaction (e.g. tablet vs liquid form, cost) and veterinarian’s discretion. methodology section search strategy databases searched and dates covered: pubmed database accessed via the ncbi platform (1910–2019) cab abstracts database via web of science (1973–2019) search strategy: ((((osteoarthritis or arthritis or oa or osteo-arthritis)) and (canine or canines or dogs or dogs)) and (meloxicam or metacam or loxicom or loxioral or melonex or meloxidy or mobic or mobicox or orocam)) and (carprofen or rimadyl or novox) dates searches performed: 28 aug 2019 exclusion / inclusion criteria exclusion: articles not written in english articles not associated with the efficacy of meloxicam and carprofen for canine osteoarthritis case reports case studies book chapters conferences systematic reviews inclusion: meta-analysis randomised controlled study search outcome database number of results excluded – systematic reviews excluded – did not relate directly to the factors of pico excluded – case reports and studies excluded – book chapters excluded – not written in english excluded – conferences total relevant papers pubmed 9 3 5 0 0 0 0 1 cab abstracts 19 1 13 0 0 1 2 2 total relevant papers when duplicates removed 2 conflict of interest the author declares no conflicts of interest. however, the author would like to greatly thank bridget sheppard and jennifer morris for their assistance and guidance in this publication, the reviewers (clare boulton, andy morris and robert pettitt) and the team of the journal for providing this opportunity. lastly but not least, the author would like to dedicate this paper to matt fotheringham and in memory of sefton fotheringham for inspiring the clinical question to hopefully aid future clients and patients alike. references moreau, m., dupuis, j., bonneau, n. h. & desnoyers, m. (2003). clinical evaluation of a nutraceutical, carprofen and meloxicam for the treatment of dogs with osteoarthritis. veterinary record, 152(11): 323–329. doi: http://dx.doi.org/10.1136/vr.152.11.323 mariana, g., valentin, n., raluca, m. & hritcu, d-l. (2013). comparative evaluation on the efficiency and tolerability of three nsaids used in locomotive osteoarticular inflammations in dog. scholars journals of agriculture and veterinary sciences. 56: 274–282. choy, l. t. (2014). the strengths and weaknesses of research methodology: comparison and complimentary between qualitative and quantitative approaches. journal of humanities and social science, 19(4): 99–104. doi: http://dx.doi.org/9790/0837-194399104 cook, j. (2014). canine orthopedic outcome measures program: where are we now? veterinary surgery, 43(3): 229–231. doi: https://doi.org/10.1111/j.1532-950x.2014.12167.x suresh, k. p. & chandrashekara, s. (2012). sample size estimation and power analysis for clinical research studies. journal of human reproductive science, 5(1): 7–13. doi: https://doi.org/4103/0974-1208.97779 bang, h., ni, l. & clarence, e. d. (2004). assessment of blinding in clinical trials. controlled clinical trials, 25(2): 143–156. doi: https://doi.org/10.1016/j.cct.2003.10.016 juni, p., altman, d.g. & egger, m. (2001). assessing the quality of controlled clinical trials. bmj, 323: 42–46. doi: https://doi.org/10.1136/bmj.323.7303.42 barkan, h. (2015). statistics in clinical research: important considerations. annals of cardiac anaesthesia, 18(1): 74–82. doi: http://dx.doi.org/10.4103/0971-9784.148325 ramsey, i. (2017). small animal formulary 9th edition – part a: canine and feline. 59. anderson, m. a. & mann, f. a. (1994). force plate analysis: a non-invasive tool for gait evaluation. compendium on continuing education for the practicing veterinarian, 16: 857-866. mclaughlin, r. m. (2001). kinetic and kinematic gait analysis in dogs. veterinary clinics of north america: small animal practice, 31(1): 193–201. doi: https://doi.org/10,.1016/s0195-5616(01)50045-5 hussein, a. (2009). the use of triangulation in social sciences research: can qualitative and quantitative methods be combined? journal of social work practice, 01–12. monteiro-steagall, b. p., steagall p. m. v. & lascelles, b. d. x. (2013). systemic review of nonsteroidal anti-inflammatory drug-induced adverse effects in dogs. journal of veterinary internal medicine, 27(5): 1011–1019. doi: http://doi.org/10.1111/jvim.12127 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in dogs does feeding raw dietary treats reduce or prevent periodontal disease? a knowledge summary by nieky van veggel msc, cbiol, fhea 1* james oxley mres 2 1writtle university college, lordship road, chelmsford, essex, cm1 3rr 2independent researcher, 102 bosworth road, measham, swadlincote, de12 7lq *corresponding author (nieky.vanveggel@writtle.ac.uk) vol 3, issue 3 (2018) published: 17 aug 2018 reviewed by: simone kirby (mrcvs, dipl.evdc) and louise buckley (bsc (hons), ba (hons), pg cert (tlhep), pgdip, phd, rvn) and kit sturgess (ma, vetmb, phd, certvr, dsam, certvc, mrcvs) next review date: 07 jun 2019 doi: 10.18849/ve.v3i3.153 pico question in dogs does feeding raw dietary treats reduce or prevent periodontal disease? clinical bottom line considering the weak evidence on raw bones and lack of evidence on other types of raw treats, veterinarians and veterinary nurses should be cautious when recommending raw treats to support periodontal health in dogs. additionally, they should advise clients accordingly by relying on their clinical experience rather than the literature until more and better quality evidence is generated. clinical scenario you are asked by a client for advice on improving the dental health of their dog after they read on the internet that periodontal disease negatively affects their dog’s wellbeing. they read that feeding raw treats helps improve the dental health of their dog and are now asking you if there is evidence to support this. the evidence the research question effectively contains sub-questions addressing four topics: (1) preventive effects of raw treats vs. non-raw treats, (2) curative effects of raw treats vs. non-raw treats, (3) preventive effects of raw treats vs. no treats, and (4) curative effects of raw treats vs. no treats. there is currently no evidence directly comparing curative or preventive effects of raw dietary treats to non-raw treats (sub-questions 1 and 2) or for preventive effects of raw dietary treats compared to no treats at all (sub-question 3). evidence for sub-question 4 was found in a paper by marx et al. (2016), who described the use of two different raw bovine bone treats to reduce dental calculus. however, as this paper is a quasi-experimental non-randomised within-group comparison over time containing confounding variables, the risk of bias is judged as serious using the robins-i tool (sterne et al., 2016). furthermore, the reporting of this paper did not adhere to guidelines for reporting non-randomised studies (reeves and gaus, 2004), which made a full critical appraisal difficult. summary of the evidence marx (2016) population: experiment 1: healthy adult (3 ± 0.5 years) laboratory housed beagle dogs who had never undergone dental cleaning and had never received regular dental prophylaxis. experiment 2: the same group of laboratory housed beagle dogs, 7 months after experiment 1 finished. no dental prophylaxis was administered in-between experiments. sample size: one group of 8 (4 male, 4 female) intervention details: at the start of the study (day 0) dental calculus assessment was conducted and compared to experiments 1 & 2. dogs in each study were provided with a bone for 12 and 20 days respectively.  experiment 1: one piece of cortical bone (incl. marrow, raw bovine femur, approx. 4 cm long, weighing 122 ± 17 g) daily for a period of 12 days. experiment 2: seven months after experiment 1, one piece of epiphyseal bone (incl. marrow, raw bovine femoral epiphysis, approx. 5 cm long, weighing 235 ± 27 g) was given to dogs daily for a period of 20 days. in both studies, the previous days bone was removed before administering a new bone. bones were obtained from a commercial slaughterhouse, cut using a band saw then stored at -18 °c and thawed before use. throughout both experiments dogs were kept in individual cages and fed twice daily with a non-dental dry extruded complete commercial diet that met approximate daily maintenance energy requirements. water was provided ad libitum. study design: both experiments: quasi-experimental non-randomised within-group baseline-to-intervention comparison over time. outcome studied: outcome 1. experiment 1: reduction (%) of tooth area covered with dental calculus over time (1, 3, 7, 9, 12 days) compared to baseline day 0. outcome 2, experiment 2: reduction (%) of tooth area covered with dental calculus over time (1, 3, 7, 9, 12, 14, 17, 20 days) compared to baseline day 0. both experiments: discrete measurements made on lateral view photographs of the canines, premolars 1-4 and molars 1-2 of all arcades using image-pro plus image analysis software. outcome 3. comparison of calculus reduction between the two experiments were compared over the twelve day period. main findings (relevant to pico question): outcome 1. experiment 1: at day 0 mean dental calculus coverage was 42% of total surface of dental arcade. after 12 days a 70.6% reduction was observed to 12.3% of surface area (p<0.05). outcome 2. experiment 2: at day 0 mean dental calculus coverage was 38.6% of total surface of dental arcade. after 12 days an 81.6% reduction was observed to 7.1% (p<0.05) and after 20 days an 84% reduction to 4.7%. outcome 3. no difference (p=0.09) was found when comparing dental calculus reduction at day 12 during experiment 1 and day 12 of experiment 2. but a significant (p<0.05) reduction after day 3 was seen and was lower in experiment 1 than in experiment 2 (35.5% and 56.5% respectively). limitations: this paper describes a non-randomised study with within group comparisons over time. a reason for not using a randomised between-group comparison design was not provided, even though it appears a more straightforward option. the comparison between the two treatments is confounded by the fact that for cortical bone, dogs had received no dental prophylaxis for three years, whereas for epiphyseal bone they received no prophylactic treatment for 7 months. having said this, it is important to highlight the similarities between the calculus build up on the first days in the first (42% calculus coverage of dental arcades) and second study (38.6% calculus coverage of dental arcades). this could explain the reduced calculus coverage at the start of experiment 2 and/or the limited long term effect of prophylactic treatment over a 7 month period. the sample size is very small, with a narrow age range. the reason for this is not provided. the dogs used in this study are unlikely to be representative of pet dogs, which makes extrapolating findings troublesome. data in the results section did not show exact data from all days of experiments. mean reduction was only shown in a percentage without including indicators variance. only the p value was provided for statistics. extrapolations regarding efficacy compared results to other calculus reducing methods were made using the literature, even though no direct comparisons have been performed. this paper does not adhere to guidelines for reporting non-randomised studies (reeves and gaus, 2004). for example, it does not explain why an rct was not possible or reports on precautions to reduce bias, nor does it provide information on other environmental enrichment provided to the dogs under investigation. appraisal, application and reflection raw feeding has become an increasingly popular concept in companion animals in recent years (schlesinger and joffe, 2011; freeman et al., 2013; fredriksson-ahomaa et al., 2017). recent research (morgan et al., 2017) highlighted that owners searching for information on raw diets are more reliant on online resources due to a lack of trust in the veterinary profession regarding this topic. this indicates the importance of veterinary practitioners having access to high quality evidence on raw feeding to educate owners during consultations. however, the evidence-base for raw feeding-related issues in dogs, and companion animals in general, is lacking with the majority of evidence being of an anecdotal nature. most research relating to raw feeding to date has focused on nutritional risk/benefit to the animal and public health and consumer safety (for example see finley et al., 2006; fredriksson-ahomaa et al., 2017; van bree et al., 2018). schlesinger and joffe (2011) argue that although some high-level evidence based on mainly north american studies is available regarding the latter, the evidence base for the former is weak. recent work by van veggel and armstrong (2017) found no evidence regarding effects of feeding raw complete diets on dental health in dogs. in the current study on raw complementary feeds, this lack of evidence is similar, with no evidence available for effects on dental health of any type of dietary raw treat other than raw bones. however, the evidence on raw bones (marx et al., 2016) is weak due to a serious risk of bias caused by limitations in the experimental design. furthermore, weaknesses in reporting meant this research was difficult to fully appraise. this knowledge summary specifically excluded research on rawhides and rawhide products. due to the industrial techniques used to manufacture these products, the authors do not consider them to be a raw feed in the true nature of the word. the evidence of potential effects of rawhide products on dental hygiene in dogs would merit appraisal in a separate knowledge summary. in all literature search strategies, the balance between sensitivity and precision of the literature search is key (o’connor et al., 2014). due to the nature of the evidence regarding raw feeding, similar to work by van veggel and armstrong (2017) and taylor and van veggel (2018), the search strategy for this paper was deliberately on the sensitive side so that no potential relevant papers would be missed. as a result, the authors believe the outcome of this paper to be representative of the lack of research on raw feeds and feeding, rather than it being related to the specificity of the literature search strategy. this knowledge summary clearly highlights a gap in the evidence, therefore a strong justification (lund et al., 2016) for further research is present. the authors therefore recommend original research in the form of a randomised controlled study into dental health and complementary raw feeding is undertaken while keeping risks to humans caused by feed hygiene issues (van bree et al). (2018) in mind. methodology section search strategy databases searched and dates covered: cab abstracts (1973 june 2017) pubmed (1950 june 2017) – veterinary science filter applied search terms: cab abstracts: ((dog or dogs or canine or canines or bitch or bitches).mp. or dogs/ or canis/ or bitches/) and ((periodontal disease or gingivitis or gingiva or tartar or plaque or stomatitis or periodontitis or 'gum disease' or 'dental disease' or calculus).mp. or periodontal diseases/ or gingivitis/ or dental plaque/) and ((feed* or diet* or food* or 'pet food').mp. or diet/ or food/ or exp pet foods/ or ('dental treats' or treats or snack or chew or bone or knuckle or biscuit or titbits).mp. or snacks/) pubmed: ((("dogs"[mesh terms] or "dogs"[all fields] or "dog"[all fields]) or "canine"[all fields]) or bitch[all fields] or bitches[all fields]) and (("periodontal diseases"[mesh terms] or ("periodontal"[all fields] and "diseases"[all fields]) or "periodontal diseases"[all fields] or ("periodontal"[all fields] and "disease"[all fields]) or "periodontal disease"[all fields]) or ("gingivitis"[mesh terms] or "gingivitis"[all fields]) or ("gingiva"[mesh terms] or "gingiva"[all fields]) or ("dental calculus"[mesh terms] or ("dental"[all fields] and "calculus"[all fields]) or "dental calculus"[all fields] or "tartar"[all fields]) or "dental plaque"[mesh terms] or ("dental"[all fields] and "plaque"[all fields]) or "dental plaque"[all fields]) or ("stomatitis"[mesh terms] or "stomatitis"[all fields]) or ("periodontitis"[mesh terms] or "periodontitis"[all fields]) or ("gingival diseases"[mesh terms] or ("gingival"[all fields] and "diseases"[all fields]) or "gingival diseases"[all fields] or ("gum"[all fields] and "disease"[all fields]) or "gum disease"[all fields]) or ("stomatognathic diseases"[mesh terms] or ("stomatognathic"[all fields] and "diseases"[all fields]) or "stomatognathic diseases"[all fields] or ("dental"[all fields] and "disease"[all fields]) or "dental disease"[all fields]) or ("calculi"[mesh terms] or "calculi"[all fields] or "calculus"[all fields]))) and (feed[all fields] or ("diet"[mesh terms] or "diet"[all fields]) or ("food"[mesh terms] or "food"[all fields]) or (pet[all fields] and ("food"[mesh terms] or "food"[all fields])) or (("dental health services"[mesh terms] or ("dental"[all fields]) and treats[all fields]) or treats[all fields] or ("snacks"[mesh terms] or "snacks"[all fields] or "snack"[all fields]) or ("chew"[all fields]) or ("bone and bones"[mesh terms] or ("bone"[all fields] and "bones"[all fields]) or "bone and bones"[all fields] or "bone"[all fields]) or "knuckle"[all fields]) or biscuit[all fields] or titbits[all fields]) dates searches performed: 19 june 2017 exclusion / inclusion criteria inclusion and exclusion criteria were determined in advance of the search phase. papers were screened by both authors independently by title and abstract and included for analysis if they met the inclusion criteria below. where there was doubt, papers were included. subsequently, full-text articles were obtained and a second inclusion/exclusion phase based on the criteria below was performed. where there was doubt about the suitability of a full text paper, an independent party was consulted and a majority vote applied. exclusion: not related to pico not addressing raw complementary feed review papers non-peer reviewed material inclusion: primary research papers or systematic reviews (sr) and dental hygiene using any types of complementary raw feeds search outcome database number of results excluded – not related to pico excluded – not peer reviewed excluded – not primary research excluded – not raw treat total relevant papers cab abstracts 368 338 5 9 15 1 ncbi pubmed 1368 1351 3 5 8 1 total relevant papers when duplicates removed 1 conflict of interest nieky van veggel is a member of the editorial board of veterinary evidence. this paper underwent a rigorous peer-review process as per our normal reviewing guidelines of inviting a minimum of two external reviewers. the identity of the associate editor handling the paper has not been disclosed to the author. the final decision to accept this paper rested with the editor-in-chief. the authors would like to gratefully acknowledge clare boulton (rcvs knowledge) for her help with finalising the search strategy and retrieving full-text papers. references bond, j. c. and lindburg, d. g. (1990) carcass feeding of captive cheetahs (acinonyx jubatus): the effects of a naturalistic feeding program on oral health and psychological well-being. applied animal behaviour science, 26 (4), pp. 373-382. doi: http://dx.doi.org/10.1016/0168-1591(90)90036-d fagan, d. a. (1980) diet consistency and periodontal disease in exotic carnivores. in: proceedings of the american association of zoo veterinarians, pp. 34–37. available at http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.462.6411 fredriksson-ahomaa, m., heikkilä, t., pernu, n., kovanen, s., hielm-björkman, a., kivistö, r. (2017) raw meat-based diets in dogs and cats. veterinary sciences. 4(3), 33. doi: http://dx.doi.org/10.3390/vetsci4030033 finley, r., reid-smith, r., weese, j.s. and angulo, f.j. (2006) human health implications of salmonella-contaminated natural pet treats and raw pet food. clinical infectious diseases, 42 (5), pp. 686-691. doi: http://dx.doi.org/10.1086/500211 freeman, l. m., chandler, m. l., hamper, b. a., et al. (2013) current knowledge about the risks and benefits of raw meat–based diets for dogs and cats. journal of the american veterinary medical association, 243 (11), pp. 1549-1558. doi: https://doi.org/10.2460/javma.243.11.1549 lund, h. brunnhuber, k. juhl, c. et al. (2016) towards evidence based research. british medical journal, 355, october, i5440. doi: http://dx.doi.org/10.1136/bmj.i5440 marx, f.r., machado, g.s., pezzali, j.g., marcolla, c.s., kessler, a.m., ahlstrom, o., trevizan, l. (2016) raw beef bones as chewing items to reduce dental calculus in beagle dogs. australian veterinary journal, 94 (1–2), pp. 18–23. doi: http://dx.doi.org/10.1111/avj.12394 morgan, s.k., willis, s., shepherd, m.l. (2017) survey of owner motivations and veterinary input of owners feeding diets containing raw animal products. peerj. 5, e3031. doi: http://dx.doi.org/10.7717/peerj.3031 o’connor, a. m. anderson, k. m. goodell, c. k. et al. (2014) conducting systematic reviews of intervention questions i: writing the review protocol, formulating the question and searching the literature. zoonoses and public health, 61, 28-38. doi: https://doi.org/10.1111/zph.12125 reeves, b.c., gaus, w. (2004) guidelines for reporting non-randomised studies. complementary medicine research. 11 suppl 1, pp. 46–52. doi: http://dx.doi.org/10.1159/000080576 schlesinger, d. p. and joffe, d. j. (2011) raw food diets in companion animals: a critical review. the canadian veterinary journal, 52 (1), pp. 50-54. available at https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3003575/ sterne, j.a., hernán, m.a., reeves, b.c., savoviä‡, j., berkman, n.d., viswanathan, m., henry, d., altman, d.g., ansari, m.t., boutron, i., carpenter, j.r., chan, a.-w., churchill, r., deeks, j.j., hróbjartsson, a., kirkham, j., jüni, p., loke, y.k., pigott, t.d., ramsay, c.r., regidor, d., rothstein, h.r., sandhu, l., santaguida, p.l., schünemann, h.j., shea, b., shrier, i., tugwell, p., turner, l., valentine, j.c., waddington, h., waters, e., wells, g.a., whiting, p.f., higgins, j.p. (2016) robins-i: a tool for assessing risk of bias in non-randomised studies of interventions. british medical journal. 355, i4919. doi: http://dx.doi.org/10.1136/bmj.i4919 taylor, e. and van veggel, n. (2018) in adult dogs, does feeding a raw food diet increase the risk of urinary calculi formation compared to feeding a complete dry kibble diet?. veterinary evidence. 3(2). doi: http://dx.doi.org/10.18849/ve.v3i2.155 van bree, f.p.j., bokken, g.c.a.m., mineur, r., franssen, f., opsteegh, m., van der giessen, j.w.b. van der, lipman, l.j.a., overgaauw, p.a.m., 2018. zoonotic bacteria and parasites found in raw meat-based diets for cats and dogs. veterinary record. doi: http://dx.doi.org/10.1136/vr.104535 van veggel, n. and armstrong, m. (2017) in dogs with periodontal disease is feeding a complete raw meat diet more effective than a complete kibble ‘dental’ diet at reducing periodontal disease? veterinary evidence. 2(2). doi: http://dx.doi.org/10.18849/ve.v2i2.88 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. should levetiracetam or imepitoin be used in preference as second-line treatment in pharmacoresistent epileptic cats? a knowledge summary by sophie elizabeth wyatt bvetmed(hons), mrvcs 1* 1queen mother hospital for animals, royal veterinary college, hawkshead lane, hatfield, hertfordshire, al9 7ta *corresponding author (swyatt@rvc.ac.uk) vol 4, issue 2 (2019) published: 28 jun 2019 reviewed by: jacqueline cole (bsc, bvetmed, mrcv) and myra forster-van hijfte (certvr, certsam, dipecvim-ca, frcvs) next review date: 25 jan 2021 doi: 10.18849/ve.v4i2.226 pico question in adult cats with idiopathic epilepsy, which is poorly controlled with phenobarbital monotherapy, should levetiracetam or imepitoin be used in preference as a second line treatment in order to reduce seizure frequency? clinical bottom line there is currently insufficient evidence to reliably determine whether levetiracetam or imepitoin should be used in preference as a second line treatment for the management of cats with refractory idiopathic epilepsy. there is weak evidence however to suggest clinical efficacy of levetiracetam and imepitoin in management of cats with idiopathic epilepsy. further studies which evaluate and directly compare the efficacy of second line anticonvulsants in feline epilepsy are needed. clinical scenario a five-year-old female neutered cat is presented to you for ongoing management of presumed idiopathic epilepsy. the cat has suffered generalised seizures since she was approximately 18 months of age, and despite long-term therapy with phenobarbital anticonvulsant medication, the cat’s seizure frequency has continued to increase with time. based on recent patient serum phenobarbital concentrations, the dose of phenobarbital cannot be safely increased further. the owner has consulted internet forums and suggests you try a new ‘wonder drug’ named imepitoin. after consulting a colleague however, they suggest levetiracetam is a better second line treatment in this case. of the two drugs, what is the next best option for successful pharmacological management of this cat’s seizure episodes? the evidence three studies of varying relevance to the pico were reviewed including one systematic review and two uncontrolled prospective clinical trials. although the studies provide evidence of the clinical efficacy of both levetiracetam and imepitoin, the strength of the evidence is low. only one study specifically evaluated efficacy of levetiracetam as an adjunct to phenobarbital, and no direct comparison to date has been made between efficacy of levetiracetam or imepitoin as a second line anticonvulsant. summary of the evidence charalambous et al. (2018) population: cats with confirmed or presumed idiopathic epilepsy, varying breeds sample size: 239 cats [systematic review of 40 studies] intervention details: studies were grouped based on the antiepileptic drugs evaluated and the overall quality of evidence. details of the drugs doses, treatment period, pre and post-treatment seizure frequency, and 95% confidence interval of the successfully treated study population were provided. study design: systematic review outcome studied: objective: individual studies were evaluated based on the quality of evidence (study design, size of study population, enrolment of study subjects, overall risk of bias) and outcome measures reported, including the proportion of cats with ≥ 50% reduction in seizure frequency. main findings (relevant to pico question): risk of bias was high in 2/5 studies relevant to the pico question. disease characterisation was variably defined in all studies relevant to the pico question. small (20–50 cats) or very small (< 10 cats) populations were included in 4/5 studies relevant to the pico question. there was weak evidence to support efficacy of levetiracetam and imepitoin in terms of seizure reduction in cats with idiopathic epilepsy. limitations: the limitations in this review are intrinsically derived from the studies included and evaluated. levetiracetam and imepitoin were evaluated in only five of the 40 studies included in the review (i.e. 51 cats) and only two of these studies considered levetiracetam in combination with phenobarbital. bailey et al. (2008) population: cats with presumed idiopathic epilepsy of varying breeds which continued to experience seizures despite phenobarbital therapy, suffered unacceptable side effects attributed to phenobarbital, or had unacceptably high serum phenobarbital levels. sample size: 12 cats intervention details: single treatment group (no control), levetiracetam therapy initiated at a dose of 20 mg/kg every 8 hours, in addition to existing phenobarbital anticonvulsant medication. treatment period: ≥ 3 months. study design: prospective uncontrolled clinical trial outcome studied: objective: seizure frequency was documented by owners with a log book both before and after initiation of levetiracetam treatment. cats were considered to have responded to therapy when ≥ 50% reduction in seizure frequency was recorded. main findings (relevant to pico question): accurate seizure logs were not maintained for two cats which were excluded from data regarding drug efficacy. a successful response was recorded in 7/10 cats treated with levetiracetam as an adjunct to phenobarbital; in three of these successful responders the seizures were completely abolished. despite this there was no significant difference in the number of seizures recorded 3 months before and after the initiation of levetiracetam treatment (p = 0.109); data on this was available in only seven cats. limitations: non-blinded, non-randomised and uncontrolled trial. small study population. precise doses of concurrent phenobarbital treatment and corresponding serum levels were not reported. outcome measure was recorded by lay personnel (i.e. owners) and therefore may not be entirely representative. variable inclusion criteria (i.e. 2/12 cats were included on basis they had unacceptable side effects attributed to phenobarbital or had unacceptably high serum phenobarbital levels), therefore not a completely homogenous study population. owners documented seizure frequency and thus were responsible for measuring outcome data; this is open to bias but realistically there are no other reliable and validated methods for recording seizures long-term in a home environment. engel et al. (2017) population: epileptic cats with ≥ 2 seizures within the preceding 2 weeks of study enrolment, ≥ 9 months of age. sample size: eight cats intervention details: single treatment group (no control), imepitoin monotherapy initiated at a dose of 30 mg/kg every 12 hours. treatment period: ≥ 8 weeks. study design: prospective uncontrolled clinical trial outcome studied: objective: animals with ≥ 8 weeks of seizure freedom reported as treatment success, ≥ 50% reduction in seizure frequency reported as partial success. seizures were recorded by owners in a patient diary. main findings (relevant to pico question): 4/8 cats (50%) experienced treatment success, 1/8 cats (12.5%) experienced partial success, 2/8 cats (25%) continued seizuring without success, and 1/8 cats was lost to follow-up. there was a significant reduction in number of seizures per month following initiation of imepitoin treatment (p = 0.0313). one of the two study cats which failed to respond received additional phenobarbital at a dose of 1 mg/kg every 12 hours and attained seizure freedom until the point of last recorded follow-up.  limitations: non-blinded, non-randomised and uncontrolled trial. small study population. one cat was diagnosed with seizures secondary to feline infectious peritonitis (fip), and therefore not idiopathic. owners documented seizure frequency and thus were responsible for measuring outcome data; this is open to bias but realistically there are no other reliable and validated methods for recording seizures long-term in a home environment. appraisal, application and reflection although the strength of evidence is greatest with systematic reviews or meta-analysis, only one such study was included in this knowledge summary.1 unfortunately however, the majority of findings from this particular study are not directly relevant to the pico as they concern efficacy and safety of other anticonvulsants in feline epilepsy. for those aspects of the systematic review which were applicable to the pico, the quality of evidence was low, risk of bias was frequently high, there was often incomplete outcome data, disease characterisation and study design, including drug dosages, were variable, and study group sizes were often small. in addition, two uncontrolled prospective clinical trials were evaluated. one study specifically investigated the efficacy of adjunct treatment with levetiracetam in addition to phenobarbital in cats refractory to treatment.2 the other study evaluated imepitoin monotherapy, although in one ‘non-responder’ additional therapy with phenobarbital was initiated.3 the strength of evidence is low as both studies were non-blinded, non-randomised and uncontrolled, with very small sample sizes. this limits the conclusions we can draw. the regulatory aspects of the prescribing cascade should be considered during selection of treatment options for management of feline epilepsy; there is currently no licensed veterinary product for feline epilepsy in the uk. phenobarbital and imepitoin is licensed in dogs only and levetiracetam is not licenced in cats or dogs. as per the prescribing cascade, authorised veterinary medicines where available should be used first. when unlicensed veterinary medicines are used, written consent should be obtained from the animal’s owner. therefore, the legal aspects of the cascade should be considered when prescribing drugs for management of feline epilepsy. although drug safety and tolerability were not specifically part of the pico, this should be considered during selection of treatment options for management of feline epilepsy. in the study by charalambous et al. (2018), the safety profile was regarded as strong for imepitoin, while the level of evidence for the safety profile of both phenobarbital and levetiracetam was weak. no study to date has specifically evaluated efficacy of either levetiracetam or imepitoin as a monotherapy or second line anticonvulsant with a strongly convincing clinical effect. such a study might utilise a randomised control trial design with clear inclusion criteria and objective outcome measures. more precisely, there are no studies which directly compare efficacy of levetiracetam or imepitoin. therefore, there is insufficient evidence to answer the current pico. methodology section search strategy databases searched and dates covered: pubmed database accessed via ncbi, and cab abstracts accessed via ovid platform search strategy: pubmed: (cat* or feline* or felid* or felis) and (epilepsy or seizure*) and (levetiracetam or imepitoin)   cab abstracts: (cat* or feline* or felid* or felis) and (epilepsy or seizure* or epileptic) and (levetiracetam or imepitoin) dates searches performed: 25/01/2019 exclusion / inclusion criteria exclusion: single case reports, duplicate articles, review articles, book chapters or sections, articles which did not directly evaluate the effect of levetiracetam or imepitoin on seizure frequency in cats, articles where the full text was not available in english language, articles which were unavailable for review. inclusion: original peer reviewed articles including case series, observational or interventional studies, and systematic reviews which evaluate the efficacy of imepitoin or levetiracetam in cats with idiopathic epilepsy. search outcome database number of results excluded – not relevant to the pico excluded – review article excluded – not available in english language or unavailable for review excluded – book chapters or sections total relevant papers pubmed 32 22 7 0 0 3 cab abstracts 42 25 8 2 4 3 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflicts of interest. references charalambous, m., pakozdy, a., bhatti, s.f.m., and volk, h.a. systematic review of antiepileptic drugs’ safety and effectiveness in feline epilepsy. bmc vet res. 2018; 14(1). doi: https://doi.org/10.1186/s12917-018-1386-3 bailey, k.s., dewey, c.w., boothe, d.m., barone, g., and kortz, g.d. levetiracetam as an adjunct to phenobarbital treatment in cats with suspected idiopathic epilepsy. j am vet med assoc. 2008; 232(6): 867–872. doi: https://doi.org/10.2460/javma.232.6.867 engel, o., van klopmann, t., maiolini, a., freundt-revilla, j., and tipold, a. imepitoin is well tolerated in healthy and epileptic cats. bmc vet res. 2017; 13(1). doi: https://doi.org/10.1186/s12917-017-1087-3 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. a survey of the non-clinical benefits of ebvm sarah hauser bsc (hons) mpa mpp1* elizabeth l. jackson bag (hons) mba phd sfhea1 1royal veterinary college, hawkshead lane, north mymms, hatfield, hertfordshire, al9 7ta, united kingdom *corresponding author (shauser@rvc.ac.uk) vol 2, issue 3 (2017) published: 03 aug 2017 reviewed by: nieky van veggel (msc, cbiol, fhea) and dr sebastian arlt doi: 10.18849/ve.v2i3.102 section index:    abstract | introduction | methods | results | discussion | footnotes | conflict of interest | references | supplementary files abstract objective: this study aims to add non-clinical benefits to the virtues for adopting evidence-based veterinary medicine (ebvm). the objective is to quantify the commercial benefits of ebvm through an online survey of veterinary professionals, giving clear indications of the key areas of non-clinical benefits of ebvm. further, the study aims to outline barriers to the wider implementation of ebvm and find preferred ways of overcoming those barriers. background: a pico-based literature review (hauser and jackson, 2016) found that while there are some papers suggesting a link between the practice of ebvm and better non-clinical benefits such as client satisfaction, a single study, focusing on the non-clinical benefits of ebvm, had yet to be conducted. this study builds on the findings of an exploratory study (jackson and hauser, 2017) outlining key areas of non-clinical benefits of ebvm: increased client satisfaction and retention, improved reputation, confidence, as well as employee engagement. evidentiary value: this online survey of veterinary professionals (n=407) provides evidence for practitioners, universities and other veterinary staff regarding the non-clinical benefits of ebvm, the barriers to a wider adoption of the practice and ways of overcoming those barriers. methods: the online survey of veterinary professionals was conducted during september – october 2016 and contained 23 questions. survey participation was voluntary and the data used for analysis were de-identified. results: the survey responses of 407 veterinary professionals provide quantitative evidence of how ebvm is put into practice, how ebvm is perceived to impact client behaviour and employee engagement, what the barriers are to practising ebvm and how these could be overcome. key findings are that veterinary professionals are more likely to practise ebvm if they have been taught how to do so at vet school. ebvm is a way to provide value to and build trust with clients. survey respondents who practise ebvm are more likely to find their workplace inspiring and to be an intellectual challenge and the main barriers to ebvm are: time and access to information. respondents, especially those who were employees suggested overcoming these barriers through attending journal clubs and other training opportunities. conclusion: the study provides the view of veterinary professionals on the non-clinical benefits of ebvm, the barriers to wider implementation and ways of overcoming those barriers. further research is needed to obtain the perspective of clients and more detailed cost effectiveness analyses could shed more light on specific practices of ebvm. application: findings are applicable to universities, veterinarians and vet nurses seeking to increase the practice of ebvm. the ultimate beneficiaries are those vets who seek additional non-clinical reasons for the adoption of ebvm in their practice. introduction it was revealed by a pico-based literature review (hauser and jackson, 2016) that little knowledge exists about the non-clinical benefits of ebvm. it concluded that while there is some literature suggesting a link between the practice of ebvm and better non-clinical benefits such as client satisfaction and client retention, a study, focusing primarily on the non-clinical benefits of ebvm, had not yet been conducted. in the first stage of a two-stage process jackson and hauser (2017) conducted an exploratory study that found four key themes that emerged from the existing knowledge: the definition of ebvm, the benefits of ebvm, the barriers to the adoption of ebvm and ideas for exploring the broader adoption of ebvm.  this study forms the second stage of a two-part, mixed-method research project. it combined the existing knowledge from the literature (hauser and jackson, 2016) and the key commercial benefits of ebvm identified by jackson and hauser (2017) and developed a subsequent confirmatory study: an online survey comprising of 23 questions, which provides a base-line of performance and demonstrates the non-clinical benefits of ebvm. the first stage of the project clearly showed that veterinary practitioners were definite in their descriptions of other types of non-clinical benefits: increased standard of care, client satisfaction, client retention, reputation and vets’ confidence. these issues were tested in the online survey as well as issues regarding the definition of ebvm, the barriers to the adoption of ebvm and the ideas practitioners have for increasing the adoption of ebvm. this paper discusses the non-clinical benefits of ebvm by 1) defining ebvm, 2) displaying what ebvm looks like in clinical practice, 3) outlining perceived benefits to client relationships, 4) outlining benefits to employee engagement, 5) discussing the main barriers of ebvm, and 6) suggesting ways of overcoming such barriers. it is important to note that the results represent the answers of veterinary professionals, thus questions about the behaviour of other people such as clients, represent the perceived benefits of the survey participants, rather than actual benefits. where survey participants answer for themselves, the study provides evidence of actual benefits to the veterinary profession. results the survey responses of 407 veterinary professionals [1] provided information on the definition of ebvm and how it is put into practice, how ebvm is perceived to impact client behaviour and employee engagement, what the barriers are to practising ebvm and how these could be overcome. characteristics of the 407 survey participants 59.0% were female, 39.8% male and 1.2% did not answer the question. respondents’ age ranged from 21 to 76 years. the average age was 41.3 years, with most participants (33.0%) being in the age group of 30 to 39 year olds. survey participants included veterinarians (86.5%), vet nurses (12.8%) and students pursuing a veterinary or vet nursing degree (0.7%). most respondents worked with small animals (77.8%), followed by those working in equine (8.1%), mixed animal (5.2%) and farm animal practices (3.7%), and other fields (5.2%), including academia, laboratories, exotics and practice management. the large proportion of respondents from the small animal field likely resulted due to the use of convenience sampling. most respondents (45.3%) stated to be working in a sub or semi urban area; this was followed by 33.5% of respondents who worked in a city and 21.2% of respondents who worked in a rural area.  the majority of respondents (80.2%) were in full time employment at the time of the survey, 17.3% were working part time, 2.0% were not employed and 0.5% preferred not to answer. respondents were asked what best describes their current role in veterinary practice, half of all respondents were employees (50.9%), the second largest group were owners or joint partners (39.0%), and 10.1% were in other working arrangements, such as locum, retired, self-employed or in academia. the veterinary professionals mainly worked in independent veterinary practice (57.9%), corporate veterinary practice (28.0%), academia (8.9%) and other, which included government (5.2%).  defining ebvm the following definitions of ebvm were given at the beginning of the survey: evidence based medicine was first discussed in the human healthcare literature in the 1990s, and was defined as: "the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. the practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research" (sackett et al., 1996, p. 71). more recently, rcvs knowledge has adapted this definition to the provision of veterinary medicine and defines evidence based veterinary medicine (ebvm) on its web site as: "...evidence-based decisions combine clinical expertise, the most relevant and best available scientific evidence, patient circumstances and owners’ values." with these definitions in mind, survey participants were asked if they practise evidence based veterinary medicine. the choices were ‘yes’, ‘no’ and ‘unsure’. out of 405 respondents, 282 (69.6%) said they practise ebvm, 16 people (4.0%) said they did not practise ebvm and 107 respondents (26.4%) were unsure.  for the statistical analysis respondents were divided into two groups, based on whether they actively practise ebvm or not. those who answered the question with “yes” were considered to be actively practising ebvm, those who answered “no” or “unsure” were considered not to be actively practising ebvm. in order to generate evidence on how ebvm is practised by veterinary professionals, respondents were asked a range of questions about their daily practice, including about their access to publications and time and frequency of scientific research (table 1). over half of all respondents (60.4%) have access to scientific publications via platforms such as pubmed, this is largely made up of those who actively practise ebvm compared to those who do not (pearson chi-square statistic, c2 = 32.383, and p < 0.05). the result does not tell us whether those respondents who can easily access scientific publications, are also more likely to use them or whether respondents wanting to access scientific information are more likely to ensure there to be access. overall participants are split almost evenly into participants who have (46.7%) and participants who have not (53.3%) actively contributed to scientific research. there is statistically significant evidence that those who are actively practising ebvm are also more likely to have contributed to scientific research than those who are not actively practising ebvm (pearson chi-square statistic, c2 = 9.734, and p < 0.05). 51.8% of those practising ebvm have also contributed to scientific research, in comparison to only 35% of respondents who are not practising ebvm. a majority of respondents (71.6%) do not attend journal clubs or discussion forums. however, those actively practising ebvm (36.9%) are more likely to attend such an event than those who do not actively practise ebvm (8.9%) (pearson chi-square statistic, c2 =32.874, and p < 0.05). most survey participants have not contributed to scientific research in the past 12 months (80.2%), however those respondents who actively practise ebvm are more likely to have contributed to scientific research in the past 12 months (23.9%) compared to those who do not actively practise ebvm (9.9%) (pearson chi-square statistic, c2 = 10.531, and p < 0.05). table 1: defining ebvm. 2 percentages were calculated of the total (o.t.) number of respondents. throughout the paper, any ‘apparent’ discrepancies in percentages are due to rounding to one percentage point. most participants (62.0%) stated that they performed the last literature search in order to influence clinical practice less than one month ago (table 2). those who practise ebvm were statistically more likely to have searched the literature more recently, than those who do not actively practise ebvm (pearson chi-square statistic, c2 = 44.987, and p < 0.05). a much greater number of people (26.8%) not actively practising ebvm did their last literature search to influence clinical decision making over a year ago, in comparison to only 5.3% out of those who actively practise ebvm. many research participants (44.3%) spend 2-5 hours researching the literature per month (table 2). there is statistically significant evidence that those actively practising ebvm are spending more time researching the literature, than those who are not (pearson chi-square statistic, c2 = 41.493, and p < 0.05). of the respondents who are practising ebvm, 32.2% of people spend six or more hours per month researching the literature, in comparison to those who do not practise ebvm, where only 14.9% spend 6 or more hours on literature research. table 2: last literature search and time spent on research 3. ebvm and clinical practice most survey participants agreed (52.0%) or strongly agreed (25.1%) with the statement: “i practise veterinary medicine in a way that is supported by published evidence” (table 3). [2] most respondents agreed (46.6%) or strongly agreed (13.6%) with the statement that clinical practice is based on current research. however, those respondents who do not actively practise ebvm are more likely to choose the middle ground, disagree or strongly disagree option, than those who do (pearson chi-square statistic, c2 =27.664, and p < 0.05). overall, a majority of veterinary professionals either agreed (41.2%) or strongly agreed (16.6%) with the statement: “being a veterinary professional, i actively seek out opportunities to learn about ebvm”. statistically significant evidence was found that those practising ebvm are also more likely to agree with the statement (pearson chi-square statistic, c2 = 39.063, and p < 0.05). a large number of respondents either strongly disagreed (21.7%) or disagreed (27.7%) with the statement: “i was taught how to practise ebvm at university”. the survey results provide statistically significant evidence that those who practise ebvm were also more likely to agree (22.7%) or strongly agree (15.5%) in comparison to those who did not (agree: 8.1%, strongly agree 4.1%) (pearson chi-square statistic, c2 = 31.456, and p < 0.05). this finding suggests that those who were taught how to practise ebvm at university are also more likely to practise ebvm in their careers than those who did not. overall those who practise ebvm are more likely to consult the literature when facing a difficult case, spend more time per month researching the literature, and are more likely to contribute to scientific literature and are more likely to have done so in the past 12 months. those who were taught how to practise ebvm at university were also more likely to practise ebvm, thus a direct link between university teaching and practising ebvm can be drawn. table 3: ebvm and clinical practice *as in the collected data there are more than 20% of the contingency table cells with expected cell frequencies less than 5, the chi-square approximation is not appropriate, thus the data cannot be analysed for statistically significant associations. 4. understanding the benefits of ebvm in the following section respondents were asked about their understanding of the benefits of ebvm. it was also tested if there is a significant association between those who do and those who do not actively practise ebvm and the responses given to the survey questions. the majority of survey participants agreed or strongly agreed (76.4%) with the statement: “clients are unaware of ebvm” (table 4). interestingly those who do not practise ebvm are significantly more likely to strongly agree (48.0%), than those who do practise ebvm (28.0%) (pearson chi-square statistic, c2 =21.791,and p < 0.05). those veterinary professionals who practise ebvm were more likely to agree or strongly agree with the statement: “ebvm helps overcome the unknown”, than those who did not (pearson chi-square statistic, c2 =10.212, and p < 0.05). interestingly even out of those not practising ebvm, a large number of people either agreed (52.8%) or strongly agreed (14.6%) with the statement. out of the same group, only 8.9% disagreed and 2.4% strongly disagreed with the statement. this finding suggests that also those not practising ebvm believe it to be a good practice to help overcome the unknown, however there are other barriers to implementation. many respondents either agreed (50.1%) or strongly agreed (23.8%) with the following statement: “clients appreciate when i put in extra work researching their specific case”. no significant difference in associations was found between the two groups. over 63.6% of all respondents agreed or strongly agreed with the statement that practising ebvm provides the best value to the customer. even of those not practising ebvm, only 8.4% of people disagree and 1.7 % strongly disagree with the statement. this further suggests that even though the non-clinical benefits of ebvm are perceived even by those who do not practice it, there are some barriers to the adoption of ebvm, that still outweigh those perceived benefits. there is a statistically significant difference in associations between the two groups significant (pearson chi-square statistic, c2 =30.283, and p < 0.05). table 4: perceived benefits to the client i. ** no significant difference in association was found between the groups as shown in table 5, the majority of respondents agreed (47.9%) or strongly agreed (14.4%) with the following statement: “practising ebvm builds trust with clients”. those who practise ebvm were statistically more likely to strongly agree with the statement in comparison to those who do not practise ebvm (pearson chi-square statistic, c2 =29.827, and p < 0.05). the findings also show that many respondents (40.7%) chose the middle ground on the question whether ebvm provides a competitive advantage over other practices. while the responses between the two groups do statistically differ (pearson chi-square statistic, c2 =28.027, and p < 0.05), the important finding is, that overall respondents are either choosing the middle ground (40.7%), agree (30.1%) or strongly agree (11.6%). while those who actively practise ebvm are more likely to agree or strongly agree with the statement, the interesting finding is here, that also those who do not actively practise ebvm believe there to be a competitive advantage. most respondents (42.4%) chose the middle ground option to the question: “clients appreciate an evidence based approach”. while survey participants who actively practise ebvm were more likely to agree or strongly agree with the statement than those who do not (pearson chi-square statistic, c2 =23.391, and p < 0.05), there does not seem to be a consensus about whether clients appreciate an evidence-based approach. table 5: perceived benefits to the client ii the study does not provide conclusive evidence on whether veterinary professionals believe that ebvm saves the client money (table 6). there was no significant difference in the responses between those who do and do not actively practise ebvm. most survey participants (44.6%) chose the middle ground on this answer. interestingly out of those respondents who do not practise ebvm about as many people disagreed (23.6%) with the statement as agreed (22.8%). this result is not surprising, as the practice of ebvm, does not necessarily always favour the cheapest option and is sometimes associated with spending more time and money on diagnostics. the study finds no conclusive evidence that clients are more invested in treatment choice through ebvm. many respondents (49.8%) chose the middle ground option, this could be based on the underlying assumption that clients are unaware of ebvm. there is statistically significant evidence that those survey participants practising ebvm were more likely to agree or strongly agree that clients are more invested in treatment choice through ebvm, than those who do not (pearson chi-square statistic, c2 =12.447, and p < 0.05). overall respondents either strongly disagree or disagree (37.6%), chose the middle ground (35.6%) or where slightly less likely to agree or strongly agree (26.7%) on the statement: “clients are less likely to seek out a different practice if they know a vet is practising ebvm”. survey participants who practise ebvm were more likely to agree or strongly agree that clients are less likely to go to a different practice than those who do not practise ebvm (pearson chi-square statistic, c2 =16.950, and p < 0.05). table 6: perceived benefits to the client iii. ** no significant difference in association was found between the groups 4.1 understanding ebvm and employee engagement participants were asked questions about ebvm and employee engagement, which included questions about the impact of ebvm on confidence in decision making and provision of best care for the patient. as shown in table 7, the clear majority of respondents either agreed (47.8%) or strongly agreed (40.6%) with the following statement: “practising ebvm makes me feel like i have provided the best medical care for my patient”[3]. most veterinary professionals either agree or strongly agree (83.4%) with the following statement: “ebvm gives me more confidence in clinical decision making”.[4] most respondents agree (48.3%) or strongly agree (31.9%) with the statement: “i frequently share research and clinical experience with colleagues”.[5] most respondents agree (43.5%) or strongly agree (25.8%) with the statement: “practising ebvm provides me with an inspiring, intellectual challenge to my job as a vet”. those practising ebvm are more likely to find ebvm an inspiring and intellectual challenge, than those who do not (pearson chi-square statistic, c2 =47.645, and p < 0.05). these are arguably the most important findings of this research as they suggest that the practice of ebvm can be viewed as a powerful tool for greater employee engagement, specifically when attracting early career veterinary professionals. further research could be conducted to measure the importance of being able to practice ebvm in comparison to other factors playing a role in a vet’s decision to choose a practice for satisfying employment. table 7: ebvm and employee engagement. *as in the collected data there are more than 20% of the contingency table cells with expected cell frequencies less than 5, the chi-square approximation is not appropriate, thus the data cannot be analysed for statistically significant associations. 5. the barriers to ebvm participants were asked to share their opinion on barriers to using ebvm. overall most survey participants agreed (43.7) or strongly agreed (23.8) that clinical practice is often based on anecdotal evidence (table 8). this suggests that there is scope to expand ebvm further. there was no significant association between the practice of ebvm and the answer to the question of whether clinical practice is based on anecdotal evidence. many respondents agreed (43.1%) or strongly agreed (17.0%) with the following statement: “there is not enough time to practise ebvm. those not practising ebvm tended to select the “strongly agree” more often (26.2%), than those who do (12.9%) (pearson chi-square statistic, c2 =17.607, and p < 0.05). only 17.9% of respondents disagreed with the statement that information is not freely available. no significant difference in associations was found between the groups. this finding thus suggests that availability of information is a key barrier to practising ebvm. table 8: the barriers to ebvm i. ** no significant difference in association was found between the groups as shown in table 9, most respondents chose the middle ground (30%) or agree (38.6%) option on the following question: “clients do not want lengthy, diagnosis laden treatment options.” statistically, those not practising ebvm are more likely to agree (40.7%) or strongly agree (23.6%) with the statement than those who do not (pearson chi-square statistic, c2 =18.937, and p < 0.05). the study provides no clear indication on the quality of evidence. those who practise ebvm are more likely to disagree (21.9%) or strongly disagree (1.4%) with the statement: “the evidence available is often of low quality” (pearson chi-square statistic, c2 =12.227, and p < 0.05). however, there were a large number of veterinary professionals who were undecided (32.2%), thus no clear statement can be made on the perceived quality of information available. over half (50.5%) of survey participants chose the middle ground on the question of whether eminence based veterinary medicine is taught at vet schools. this finding is likely to suggest that higher educational institutions provide a mix of eminence and evidence-based veterinary teaching, differing based individual courses and teaching staff. no significant difference in associations was found between the two groups. table 9: the barriers to ebvm ii. ** no significant difference in association was found between the groups table 10 shows that most respondents did not agree (48%) with the following statement: “application of ebvm ignores clinical experience.” this suggests that the perception of ebvm undermining a veterinarian’s clinical experience is only perceived as a barrier by a minority of vets. those who practise ebvm are more likely to disagree or strongly disagree than those who do not (pearson chi-square statistic, c2 =13.947, and p < 0.05). interestingly only 9.6% of respondents agreed or strongly agreed with the statement that ebvm is impractical. this suggests that impracticality is not perceived to be a barrier to practising ebvm by most survey respondents. as highlighted in table 10, those practising ebvm were more likely to disagree or disagree strongly than those who do not (pearson chi-square statistic, c2 =37.886, and p < 0.05). survey respondents disagreed (49.7%) or strongly disagreed (14.6%) with the statement that through ebvm their clinical autonomy is lost or reduced. those who practice ebvm were statistically more likely to disagree than those not practising ebvm (pearson chi-square statistic, c2 =17.988, and p < 0.05). table 10: the barriers to ebvm iii as outlined in table 11, most survey participants agreed (56.2%) or strongly agreed (12.7%) that they are confident in evaluating scientific evidence. those who practise ebvm, were more likely to agree than those who do not (pearson chi-square statistic, c2 =27.745, and p < 0.05). this finding suggests that the ability to evaluate scientific evidence is not considered to be a large barrier to practising ebvm by most respondents. overall 53.3% of respondents stated to have received sufficient training to find evidence and solve clinical problems. those who practise ebvm are more likely to have received sufficient training in finding evidence to solve clinical problems (pearson chi-square statistic, c2 =19.107, and p < 0.05). one option to improve the adaptation of ebvm is to involve vet nurses in the training process more. most respondents agreed (38.3%) or strongly agreed (15%) with the statement, with those practising ebvm being more in favour of a greater inclusion of vet nurses than those who do not. (pearson chi-square statistic, c2 =14.863, and p < 0.05). table 11: the ability to put ebvm into practice 6. overcoming the barriers respondents were asked to read each statement below (as listed in table 12) and rank the following methods of increasing adoption of ebvm from best to worst (please answer even if you are currently not practising ebvm/are unsure). 1 = most important/best and 5 = least importance/worst. as shown in table 5, on average, “training opportunities” received the best score (2.60), followed by “journal clubs” (2.97), “discussion forums” (3.05), “paid time for research” (3.16) and “encouragement from my line manager/employer” (3.22). table 12: methods of increasing the adoption of ebvm on average, for all respondents (n=349), “training opportunities” received the best scores (2.60) from survey participants, this was followed by “journal clubs” (2.97) and “discussion forums” (3.05). the two options to receive the lowest scores wore “paid time for research” (3.16) and “encouragement from my line manager/employer” (3.22). this ranking changed, when taking into account only the scores of employees (n=180), where training opportunities still received the best scores (2.74), but “paid time for research” now received the second highest scores (2.83). these findings suggest that opportunities need to be targeted depending on which group of veterinary professionals is being addressed. further to these findings, the distribution of responses shows that ‘training opportunities’ was mainly chosen in first, second or third place while “paid time for research” and “encouragement from my line manager/employer” was strongly favoured my some but also chosen as last option by other respondents (figure 1). this finding highlights the importance of targeting the right opportunities to the right group of professionals. future studies should further analyse the characteristics of those respondents, in order to effectively tailor programmes to increase ebvm to the right groups. figure 1: distribution of responses to the question of methods to increase the adoption of ebvm discussion the survey responses of 407 veterinary professionals provided evidence on how ebvm is practised, how ebvm impacts client behaviour and employee engagement, what the barriers are to practising ebvm and how these could be overcome. the vet futures initiative (http://www.vetfutures.org.uk/), a collaboration between the royal college of veterinary surgeons and the british veterinary association, has yielded much contemporary knowledge about how further work needs to be carried out on the veterinary workforce and its leadership, communicating veterinary fees and value, focusing on reflective practice and supporting the royal college of veterinary surgeons’ mind matters initiative (http://www.vetmindmatters.org/).  this research has particularly important implications for the latter. vnfutures (2016) cites research from the mind matters initiative that found increasing public expectations and professional isolation to be amongst some of the casual factors associated with stress in the veterinary and veterinary nursing professions. while our study does not reveal any indisputable relationships between ebvm and improved practice competitive advantage, creating savings for clients or reducing in-practice waste, we have been able to show that practicing ebvm does create a collegiate atmosphere amongst those who practice it and does provide clinicians with a feeling of confidence in their day-to-day activities.  the veterinary professions are dedicated to improving the work environments of people in practice and the results of this research go some way into supporting their efforts. this study provides clear evidence on what practising ebvm entails for veterinary professionals, with most respondents (62.0%) having performed a literature search in order to influence clinical practice less than one month ago and spending 2-5 hours per month researching the literature. most respondents (60.4%) have access to online research platforms such as pubmed and most veterinary professionals (60.0%) state they practise veterinary medicine that is based on current research. there is an almost even split in participants who have and have not contributed to scientific research, however a clear majority of participants (80.2%) have not contributed to scientific research in the last 12 months, which suggests the pool of the veterinary professionals surveyed does not only reflect the views of those in research and higher academic institutions.  interestingly most participants (71.6%) do not attend journal clubs or discussion forums regularly, despite that being one of the top priorities when looking at ways to overcome the barriers to ebvm. one of the key non-clinical benefits to come out of this study is the finding that practising ebvm has a very positive effect on employee engagement. most survey participants agreed with the statement that ebvm makes them feel like they have provided the best medical care for their patient (88.4%). most respondents agree or strongly agree (80.2%) with the statement: “i frequently share research and clinical experience with colleagues”. the majority of respondents either agree or strongly agree (83.4%) with the following statement: “ebvm gives me more confidence in clinical decision making”. those practising ebvm are more likely to find ebvm an inspiring and intellectual challenge, than those who do not. these findings suggest that ebvm could become an increasingly important topic when talking about attracting new employees and keeping these employees engaged. another important finding was that the majority of respondents stated that ebvm helps overcome the unknown (76.2%), even out of those not actively practising ebvm, many agreed. most respondents (63.6%) believe that ebvm provides the best value to the customer and more than half (62.3%) believe ebvm to be a method to build trust with clients. respondents were somewhat more likely to agree than disagree with the following statement: “clients are more invested in treatment choice through ebvm”. the majority of respondents either agreed (50.1%) or strongly agreed (23.8%) with the following statement: “clients appreciate when i put in extra work researching their specific case”. for this question, no significant difference in associations was found between the two groups. respondents are slightly more likely to think that clients appreciate an evidence-based approach, than not. there is however no clear evidence that practising ebvm provides a competitive advantage over other practices, and there is no conclusive evidence that ebvm saves the client money, which is likely due to the fact that ebvm in itself does not always take into account treatment cost and sometimes favours further diagnostics and longer treatment options. the veterinary professionals surveyed did not provide conclusive evidence if clients are less likely to seek out a different practice if a vet practises ebvm. interestingly most survey participants agreed or strongly agreed (76.4%) with the statement: “clients are unaware of ebvm”. those who do not practise ebvm are significantly more likely to strongly agree (48%), than those who do practise ebvm (28%). this provides an opportunity for further research, as the perspectives of the clients are key to verify this opinion held by veterinary professionals. the mixed responses on client engagement also provide an opportunity for greater education of clients on the practice of ebvm, and the clinical benefits it can yield. the two most clearly identified barriers to practising veterinary medicine were time and free information. most respondents (60.1%) state that there is not enough time to practise ebvm and that information is not freely available (59.0%). overall 67.5% of survey participants agreed or strongly agreed that clinical practice is often based on anecdotal evidence. this suggests that there is scope to expand the practice of ebvm further. on several other issues, further research is required to obtain conclusive evidence. for example, this study found no clear consensus on whether the evidence available is of low quality. no strong evidence was found that “clients do not want lengthy, diagnosis laden treatment options”. the survey delivered no clear finding on whether eminence based veterinary medicine is taught at vet schools or not. a positive finding was, that some of the barriers the researchers expected, were not perceived as such, by a large portion of the veterinary professionals surveyed. most respondents did not agree (48%) with the following statement: “application of ebvm ignores clinical experience.” this suggests, that the perception of ebvm undermining a veterinarians’ clinical experience is only perceived as a barrier by a minority of vets. interestingly only 9.6% of respondents agreed or strongly agreed with the statement that ebvm is impractical. this suggests that impracticality is not perceived to be a barrier to practising ebvm by most survey respondents. survey respondents largely disagreed (49.7%) or strongly disagreed (14.6%) with the statement that through ebvm their clinical autonomy is lost or reduced. overall 53.3% of respondents said they have received sufficient training to find evidence and solve clinical problems. most responses agreed (56.2%) or strongly agreed (12.7%) that they are confident in evaluating scientific evidence. one of the limitations of this study was the use of convenience sampling. through the use of this sampling technique, the survey results do not accurately represent the industry. due to the channels used to disseminate the survey, the study is likely to over-represent the small animal sector.  the majority of survey participants were veterinarians, thus the results are unlikely to be representative of the views of vet nurses and technicians. while this paper establishes that a greater involvement of vet nurses is viewed favourably my many participants, further research on how to integrate vet nurses in the practice of ebvm, is needed. further, participation in the study was voluntary. it is also important to note that this study addresses ebvm as a concept and while it aims to provide evidence on what ebvm looks like in practice, it does not cover specific practices. further analysis, including cost effectiveness analysis is needed to further detail the financial benefits of specific aspects of ebvm. as the results of this study portray the opinions of veterinary professionals, further research is needed to obtain the perspective of clients, to test whether clients are aware of ebvm and how the practice of ebvm is viewed by clients. to conclude, the results of this study suggest that the practice of ebvm is a virtue for supporting current initiatives aimed at improving the work environment of the uk veterinary professions.  there is no suggestion made herein that tangible, measurable business performance will be increased as a result of implementing ebvm.  we do, however, recommend encouraging the practice of ebvm as it closely aligns with the values of so many initiatives being undertaken in the professions, such as vet futures, vn futures and the mind matters initiative. methods a pico-based literature review was conducted by hauser and jackson (2016) to establish current knowledge about the non-clinical benefits of ebvm and yielded few answers to the research questions of this project.  with the limited knowledge generated from this activity, an interview guide containing broad, open-ended questions was developed to explore three key themes that emerged from the sparse existing knowledge: the definition of ebvm, the benefits of ebvm, the barriers to the adoption of ebvm and ideas for exploring the broader adoption of ebvm.  this interview guide, the information sheet about the project and the consent form to be signed by research participants was scrutinised and approved by the royal veterinary college’s clinical research ethical review board (approval #2015 1457). the results of the interviews were used to create an online survey that empirically tested the tacit knowledge documented in jackson and hauser (2017).  the survey, comprised of 23 questions, aimed through a range of questions to: define ebvm and get an insight into ebvm looks like in practice outline the non-clinical benefits of ebvm including: improving relationships with clients, achieving a sense of pride in one’s work and employee engagement outline the main barriers to wider implementation of ebvm: time and access suggest ways of overcoming those barriers including more training opportunities and access to journal clubs. the online survey was piloted on five uk vets and was not substantially altered beyond being released; the only major change that was strongly recommended by all pilot participants was that a definition of ebvm be included at the beginning of the survey. the survey ‘went live’ via survey monkey on 5 september, 2016 and was closed on 10 october, 2016.  the link to the survey was circulated on social media (facebook and twitter) by the rvc and rcvs knowledge.  rcvs knowledge and the rcvs also published the link to the survey in their respective e-newsletters.  the researchers’ networks were also utilised and the link to the survey was circulated within vets4pets, vets now, medi vet, goddard veterinary group and spvs.  we are grateful for the support of all of these organisations in helping to achieve a sample size of 407 usable responses. survey participation was voluntary and the data was analysed anonymously. all statistical analyses were performed using the spss statistical package. comparison between groups was performed using the pearson chi-square (c2) test. the significance level was set as α = 0.05. footnotes [1] not all questions had to be answered by all respondents [2] as in the collected data there are more than 20% of the contingency table cells with expected cell frequencies less than 5, the chi-square approximation is not appropriate, thus the data cannot be analysed for statistically significant associations. [3][4][5] as in the collected data there are more than 20% of the contingency table cells with expected cell frequencies less than 5, the chi-square approximation is not appropriate, thus the data cannot be analysed for statistically significant associations. conflict of interest acknowledgments: we would like to thank rcvs knowledge for its generous support of this project, our co-investigator: graham milligan mrcvs and all the interview and survey participants.  we are also sincerely grateful to everyone who completed the on-line survey and to the veterinary businesses which circulated the survey amongst their staff. funding: rcvs knowledge grants. competing interests: there are no areas of conflicting interest associated with this work. references hauser, s. and jackson, e.l. (2016) non-clinical benefits of evidence-based veterinary medicine.veterinary evidence, 1 (3), http://dx.doi.org/10.18849/ve.v1i3.34 jackson, e.l. and hauser, s. (2017) an exploratory study investigating the non-clinical benefits of evidence-based veterinary medicine. veterinary evidence, 2 (2), http://dx.doi.org/10.18849/ve.v2i2.97 sackett, l, david. et al. (1996) evidence based medicine: what it is and what it isn't. bmj, 312 (71), p. 71. http://dx.doi.org/10.1136/bmj.312.7023.71 vnfutures (2016). vnfutures – taking charge of our future together. [available at]: http://www.vetfutures.org.uk/resource/vn-futures-report-and-action-plan/ supplementary files, images & tables all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. a randomised non-inferiority trial on the effect of an antibiotic or non-antibiotic topical treatment protocol for digital dermatitis in dairy cattle a knowledge summary by amarins dotinga msc 1 ruurd jorritsma dvm phd msc 2* mirjam nielen dvm phd dipl. ecvph 2 1van stad tot wad dierenartsen, loppersum, the netherlands 2department of farm animal health, faculty of veterinary medicine, utrecht university, yalelaan 7, 3584 cl utrecht, the netherlands *corresponding author (r.jorritsma@uu.nl) vol 2, issue 4 (2017) published: 6 dec 2017 reviewed by: mike steele (bsc(hons), bvsc, mrcvs) and peter cockcroft (ba, ma, vet. mb, msc, dip. dat., dvm&s, dchp, fhea, dip. ecbhm, mba) doi: 10.18849/ve.v2i4.111 section index:    abstract | introduction | methods | results | discussion | footnotes | conflict of interest | references | supplementary files abstract objective: investigation of the therapeutic effect of a protocol using non-antibiotic intra epidine (ie) spray containing copper and zinc chelate on m2 digital dermatitis (dd) lesions compared to a treatment protocol using antibiotic chlortetracycline (ctc) spray for non-inferiority testing. background: digital dermatitis (dd) is an infection in dairy cattle which frequently results in lameness. a common individual treatment for dd in europe is a topical administration of antibiotic ctc spray. given the important objective to minimise antibiotic use in order to prevent selection for antibiotic resistance, there is a need for effective non-antibiotic treatments for common animal diseases. evidentiary value: this clinical trial on commercial farms with registered products is valuable for all veterinary practitioners interested in the quantitative curative effects of treatments fordd. methods: professional hoof trimmers trimmed hind legs of 944 cows from nine dairy herds. all legs with dd m2 lesions were included and randomly assigned to a treatment protocol with ie spray or ctc spray according to the label instructions from the manufacturers. at the end of the study 231 individual legs, one per cow, in seven herds were eligible for analysis. clinical improvement was defined as the transition of the clinical most relevant ulcerative m2 lesion to any other less severe lesion stage at 10 days after the start of the treatment. results: the overall individual leg clinical improvement rate of ie spray (86.8%) was higher compared to ctc spray (47.9%). the herd adjusted odds ratio for clinical improvement was 8.2 (95% ci 4.2 – 15.7) for ie spray versus ctc spray with an estimated relative risk of 1.9. conclusion: in conclusion, the ie treatment protocol was non-inferior but more effective than the ctc treatment protocol to clinically improve dd m2 lesions. introduction digital dermatitis (dd), also called mortellaro’s disease, is a superficial, painful, contagious inflammation of mainly the epidermis of the feet (schroeder et al., 2003; döpfer et al., 1997) that occurs worldwide (reviewed by refaai et al., 2013) and frequently results in lameness. it affects not only the welfare of the animals but also gives rise to significant economic losses (bruijnis et al., 2010; cha et al., 2010; enting et al., 1997). typically, the skin adjacent to the interdigital space at the plantar side of the hind claws is affected and may cause animals to walk on the toes (blowey, 1987; read and walker, 1998). the disease is observed in cattle of all ages. a wet and dirty environment is an important risk factor for dd as pathogens can survive easily and foot hygiene is generally poor (brizzi 1993; somers et al., 2005a). cows kept under drier circumstances therefore suffer less from dd (brizzi, 1993). other risk factors are floor type, access to pasture and hoof trimming interval (holzhauer et al., 2006; somers et al., 2005a; somers et al., 2005b). in the netherlands, about 21% of dairy cows were found to have one or more dd lesions, while within herd prevalence up to 83% were reported (holzhauer et al., 2006). there are five stages of dd, m0 to m4, described by döpfer et al. (1997). although recent investigations utilise a six-stage system for dd (berry et al., 2012), the five-stage system by döpfer et al. (1997) is generally applied in the netherlands and therefore was used during the trial. an m0 stage relates to normal skin where no dd lesion is visible; an m1 relates to an early stage lesion of up to 2 centimetres; an m2 relates to the ulcerative, ‘strawberry-like’ lesion of more than 2 centimetres which is usually very painful; an m3 relates to a healing stage when the lesion is covered by a scab and an m4 relates to the chronic stage with a proliferative lesion (döpfer et al., 1997). the aetiology of dd seems to be multifactorial, while spirochetes of the treponema genus seem to be involved frequently (döpfer et al., 1997; stamm et al., 2002; gomez et al., 2012; rasmussen et al., 2012). mumba et al. (1999) observed that the presence of spirochetes was relatively higher at m2 stage compared to any other stage. this might explain why most clinical signs are seen at this stage and also suggests that the m2 stage is the most infectious to other animals.  digital dermatitis can be treated individually or at herd level. a herd level treatment may consist of a walkthrough footbath with zinc sulphate, copper sulphate, antibiotics or, in the netherlands, a 4% formalin solution (holzhauer et al., 2012; wvab, 2016). a common individual treatment is the topical administration of chlortetracycline (ctc) spray, with the antibiotic chlortetracycline as its active compound (wvab, 2016; cbg-meb, 2013; holzhauer et al., 2011). in several countries, the use of antibiotics in footbaths is not licensed and abundant use of antibiotics in farm animals is increasingly criticised for the potential selection of antibiotic resistance. thus, obtaining effective preventive measures and treatments of dd without antibiotics is desirable. an individual topical treatment with a gel containing copper and zinc chelate was already shown to be effective (holzhauer et al., 2011), but it was suggested that a spray would be more convenient to use than a gel. the aim of this study was to investigate the therapeutic effect of intra epidine spray containing copper and zinc chelate (ie; intracare, veghel, the netherlands) on m2 dd lesions compared to a treatment with ctc spray (ctc; eurovet animal health, bladel, the netherlands) in the context of non-inferiority testing for market authorisation. methods selection of herds intracare (veghel, the netherlands) selected participating herds for the trial using several selection criteria. for practical and logistic reasons, we aimed to include herds of at least 100 cows with a dd prevalence of 20-25 percent in order to obtain a reasonable number of observations per farm. furthermore, it was preferred to include herds that reflected the average situation in the netherlands, with holstein friesian cows and freestalls. during the trial, it appeared that the strict use of these criteria did not result in the recruitment of sufficient affected legs. therefore, it was accepted that not all herds fulfilled the requirements. they for example did not reach the minimum of 100 dairy cows or appeared to have a prevalence of dd of less than 20 percent. one herd had access to pasture during the study, whereas all other herds were housed indoors. farmers were not allowed to use walk-through footbaths or other treatments in the last three weeks before and during the trial. all participating herds were located in the northern part of the netherlands. the trial took place from october until december 2013, at the start of the indoor housed winter period.   selection and treatment of cows and legs professional hoof trimmers trimmed the hind legs of the cows on day 0. four observers were trained with photos and clinical cases. they collectively selected all hind legs with dd in the trimming chute and scored the lesions, using the scoring system described by döpfer et al. (1997). they included only hind legs that were scored with ulcerative m2 lesions by all of them for this study as this lesion was regarded most relevant from a clinical point of view (döpfer et al., 1997; mumba et al., 1999). one leg was regarded as experimental unit. the first hind leg with an m2 lesion in a herd was allocated in one of the treatment groups a or b by flipping a coin. the following hind legs with m2 lesions were alternately allocated to the two treatments. when both hind legs of a cow were affected, each was treated with a different product.  all included legs were photographed, followed by the labelled used of two different products (treatment a and b). treatment a consisted of an administration of ie spray, once for 3 seconds from 15 centimetres distance, on day 0. the observers covered the lesions, after drying for 30 seconds, with cotton wool, held in place by an elastic bandage (corip flexible cohesive bandage gb11). the bandage was removed on day 3 and the legs were sprayed again with ie spray for 3 seconds on day 3 and day 7, but left uncovered. treatment b consisted of a therapy with ctc spray according to the instructions of the manufacturers. thus, the observers spraying the lesions two times for 3 seconds from 15 to 20 centimetres distance with a drying interval of 30 seconds on day 0. this treatment was repeated on day 1 and day 2. all repeated treatments were applied by the four observers as well, in groups of two. after consulting the ethical committee of utrecht university, it appeared not necessary to obtain formal ethical approval as the trial was performed with registered active compounds approved to use on animals.   scoring and blinding the same four observers as day 0 scored and photographed all lesions during the treatment evaluation on day 10. clinical improvement was defined as the transition of an ulcerative m2 lesion to any other lesion at day 10, either m0, m1, m3 or m4. all observers collectively checked all included legs for side effects at each treatment moment (day 1, 2, 3, 7, 10). two independent trained and experienced observers, not actively involved in the data collection, checked inclusion and clinical improvement of legs afterwards, using the photographs. blinding was not always achieved as the photographs occasionally showed a touch of green or blue from respectively ie spray and ctc spray. the colours of the products are well known to everybody working in this field and it was not possible to change the colours for the sake of this trial.   sample size sample size was calculated for non-inferiority testing of 10 percent relative to the antibiotic product using nquery (cork, ireland). the expected improvement rate of ctc spray, based on research of holzhauer et al. (2011), was 60 percent. thus, improvement rate of ie spray should be higher than 50 percent to be considered not inferior to ctc spray. the researchers assumed that healing of lesions within 10 days was not greatly affected by the fact that animals of both treatment groups were housed in the same herd. therefore, clustering of cows within herds was neglected for the power calculation. considering 95 percent confidence and 80 percent power this resulted in a sample size of 300 hind legs with m2 lesions for each group. after the first batch of seven farms at approximately half of the sample size, a planned interim analysis showed that non-inferiority was clearly present and therefore the trial was stopped.    statistical methods the data was analysed before unblinding of the treatments. one leg was randomly selected from cows with two affected legs. risk differences were calculated for comparisons within individual herds. a logistic regression model with herd and treatment as fixed factors was used to estimate an adjusted odds ratio over all herds. with the herd adjusted results of the logistic regression, an estimated relative risk was calculated using the method described by beaudeau and fourichon (1998). basically, the relative risk is recalculated based on the point estimate of the odds ratio from the multivariable logistic regression, in combination with the observed incidence rates in both treatment groups (not case-control design). for illustration purposes, calculations of the confidence intervals of the treatment difference were calculated using the square root of the sum of the variances of the two treatments (schukken et al., 2013). results descriptive statistics during this study 285 legs in seven different herds were treated, of which 143 with ie spray and 142 with ctc spray. no adverse effect of either treatment was observed. one ie treated cow was found to have a swollen claw and was diagnosed with foot rot at day 1. the animal was treated by a veterinarian and excluded from the analysis. another cow was excluded from the ctc group due to missing data. the resulting 283 treated legs were found in 231 cows, indicating that 52 animals had two affected legs. for the analysis, one leg of each of these pairs was randomly removed from the dataset, leaving 231 non-paired legs eligible for analysis. a flow diagram of leg inclusion is depicted in figure 1. figure 1: flow chart of leg inclusion, according to reflect (2010) treatment outcome the distribution of the scores on day 10 is depicted in figure 2a and 2b. after treatment with ie spray, most m2 lesions (71%) transitioned into m3. the percentage of m1 and m2 lesions was almost equal (respectively 14% and 13%). after treatment with ctc spray most lesions remained m2 (52%). the percentage of m1 lesions after treatment with ctc spray is a little higher compared to treatment with ie spray (19%). only 1% and 3% for respectively ie spray and ctc spray transitioned to m0. figure 2a: percentages of dd stages of 114 included legs in seven dairy herds, 10 days after first treatment of m2 lesions with ie spray. figure 2b: percentages of dd stages of 117 included legs in seven dairy herds, 10 days after first treatment of m2 lesions with ctc spray. clinical improvement rate table 1 shows the number of included legs and the number of clinically improved m2 lesions on day 10. the overall clinical improvement rate was 86.8% (herd range 61.5% 100.0%) for ie treatment and 47.9% (herd range 17.7% 85.2%) for the ctc spray. there was no interaction between herd and treatment. table 1: number of included legs with an m2 lesion (one per cow) in each herd and their clinical improvement rate after 10 days for ie spray and ctc spray. risk differences figure 3 illustrates the clinical improvement, which was numerically higher for ie spray compared to ctc spray and significantly higher in three herds (herd 2, 4, 5). the graph shows that ie spray is non-inferior and might be superior. this was confirmed in the logistic regression, in which clinical improvement was statistically different between treatments (p<0.001) and between herds (p<0.001). the odds ratio, adjusted for herd effects, for ie spray versus ctc spray was 8.2 (95% ci: 4.2 – 15.7). the estimated relative risk for clinical improvement derived from this adjusted odds ratio was 1.9 for ie spray versus ctc spray. figure 3: overall and per herd estimated risk difference for clinical improvement of digital dermatitis m2 lesions. black boxes and bars indicate the risk differences with their 95% confidence intervals. the shaded area right from the vertical interrupted line indicates the zone of non-inferiority for treatment with ie spray compared to ctc spray. discussion the overall clinical improvement rate of ie spray in the selected herds was 86.8% (range 61.5% 100.0%). this is similar to the clinical improvement rate of an ie gel with similar active components 92% (range 86% 94%) as found by holzhauer et al. (2011). the overall clinical improvement rate of ctc spray varied greatly from 17.7% to 85.2% between farms. improvement rates of 58% (holzhauer et al., 2011), 68% (berry et al., 2010) and 87% (manske et al., 2002) were reported for either ctc or comparable oxytetracycline spray. this may be explained by differences in follow-up period between studies. potential antibiotic resistance due to regular use of ctc spray on selected farms could play a role as well, as observed by shearer et al. (2002). apart from differences in active components between treatments with ie and ctc spray, the application protocol differed as well, as legs were treated in compliance with manufacturer’s instructions. application of a bandage, as is done after treatment with ie spray, protects the lesion from dirt, prevents the medication from draining away and may have been a factor in the observed clinical improvement. conversely, a bandage is likely to create a moist, anaerobic environment. as the spirochetes associated with dd are usually regarded as anaerobic, it could be speculated that using the bandage may also hamper clinical improvement (holzhauer et al., 2006; schroeder et al., 2003; somers et al., 2005a). the interval between last application and evaluation also differed for both treatments. the observed differences in clinical improvement may result from differences in active components, different application protocols, difference in time after last application, or a combination of these factors. these issues cannot be differentiated within the current study design and would need further investigation. clinical improvement of m2 lesions was defined as the primary outcome, as these severe ulcerative and highly painful lesions are related to clinical lameness. all transitions to other lesion categories indicate clinical improvement, which is certainly not the same as bacteriological cure. thus, transition of a m2 lesion to m0, m1, m3 and m4 were weighed similar, although long term effects on herd level might be different. it was decided to use a short term study, in order to minimize effects of reinfections from the environment (berry et al., 2010; berry et al., 2012). this study period showed a difference in short term clinical improvement between the two topical treatments. significant farm effects were observed, in particular a larger variation in short term clinical improvement for ctc spray and a better clinical improvement for the treatment protocol with ie spray. it seems unlikely that topical treatment with either of the investigated drugs would result in elimination of dd within herds, because of persistent reservoirs of infection in the environment and untreated cows. measures at herd level such as periodically hoof trimming, improvement of hygienic conditions and the use of footbaths may be more effective (holzhauer et al., 2006; holzhauer et al., 2012; somers et al., 2005a). on the other hand, a reduction of the painful ulcerative m2 lesions in both treatment groups was observed, resulting in pain reduction and higher well-being for the affected animals. conflict of interest acknowledgments: the authors gratefully acknowledge the participating farmers and others involved in this trial. eline willems assisted in data analysis and support during the trial, sophie versteegen, emma van vliet and paulien de weerd assisted with collecting data, martien van bostelen, pieter achtien, wiebren altena, theo flapper, onno jansma and ype van der woude were involved in the claw trimming. funding: this study was funded by intracare. intracare did not have any participation in the study design, in the collection, analysis and interpretation of data, in the writing of this manuscript and in the decision to submit the manuscript for publication. contributor acknowledgement: gerwen lammers is an employee of intracare and contacted potential farmers and arranged that all cows were trimmed by professional hoof trimmers, and that included cows treated. they also checked the manuscript for mistakes. references beaudeau, f., fourichon, c., (1998). estimating relative risk of disease from outputs of logistic regression when the disease is not rare. preventive veterinary medicine, 36, 243-56. doi: http://dx.doi.org/10.1016/s0167-5877(98)00095-6 berry, s., read, d., walker, r., et al., (2010). clinical, histologic, and bacteriologic findings in dairy cows with digital dermatitis (footwarts) one month after topical treatment with lincomycin 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papillomatous digital dermatitis (footwarts) in california dairy cattle: clinical and gross pathologic findings. journal of veterinary diagnostic investigation, 10, 67-76. doi: http://dx.doi.org/10.1177/104063879801000112 refaai, w., aert, m., el aal, a., et al., (2013). infectious diseases causing lameness in cattle with a main emphasis on digital dermatitis (mortellaro disease). livestock science, 156, 53-63. doi: http://dx.doi.org/10.1016/j.livsci.2013.06.004 reflect, 2010. the reflect statement: reporting guidelines for randomized controlled trials in livestock and food safety: explanation and elaboration. http://www.reflect-statement.org/statement/ (accessed 20 june 2014). schroeder, c., parlor, k., marsh, t., et al., (2003). characterization of the predominant anaerobic bacterium recovered from digital dermatitis lesions in three michigan dairy cows. anaerobe, 9, 151-5. doi: http://dx.doi.org/10.1016/s1075-9964(03)00084-2 schukken, y., zurakowski, m., rauch, b., et al., (2013). noninferiority trial comparing a first-generation cephalosporin with a third-generation cephalosporin in the treatment of nonsevere clinical mastitis in dairy cows. journal of dairy science, 96, 6763-74. doi: http://dx.doi.org/10.3168/jds.2013-6713 shearer, j.k., hernandez, j., (2000). efficacy of two modified nonantibiotic formulations (victory) for treatment of papillomatous digital dermatitis in dairy cows. journal of dairy science, 83, 741-75. doi: http://dx.doi.org/10.3168/jds.s0022-0302(00)74936-8 somers, j., frankena, k., noordhuizen-stassen, e., et al., (2005a). risk factors for digital dermatitis in dairy cows kept in cubicle houses in the netherlands. preventive veterinary medicine, 71, 11-21. doi: http://dx.doi.org/10.1016/j.prevetmed.2005.05.002 somers, j., schouten, w., frankena, k., et al., (2005b). development of claw traits and claw lesions in dairy cows kept on different floor systems. journal of dairy science, 88, 110-20. doi: http://dx.doi.org/10.3168/jds.s0022-0302(05)72668-0 stamm, l., bergen, h., walker, r., (2002). molecular typing of papillomatous digital dermatitis-associated treponema isolates based on analysis of 16s-23s ribosomal dna intergenic spacer regions. journal of clinical microbiology, 40, 3463-9. doi: http://dx.doi.org/10.1128/jcm.40.9.3463-3469.2002 wvab, (2016). werkgroep veterinair antibioticum beleid knmvd, 2016. formularium melkvee versie 1.1, 2.5.5 mortellaro (dermatitis digitalis). in dutch. http://wvab.knmvd.nl/formularia (accessed 20 august 2017). supplementary files, images & tables all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. is tta better than lateral suture in small dogs with cruciate disease? a knowledge summary by tafara mapuvire bvsc, pgcertacp, savc1* 1surgivet veterinary consultancy, 17 spartacus, 20 paul smit road, boksburg, johannesburg, south africa 1459 *corresponding author (tmapuvire@surgivet.co.za) vol 5, issue 2 (2020) published: 13 may 2020 reviewed by: nina r kieves (dvm, dacvs-sa, dacvsmr) and catrina pennington (bvm&s, mrcvs) next review date: 04 jun 2021 doi: 10.18849/ve.v5i2.297 pico question in dogs weighing under 15 kg with unilateral cranial cruciate ligament disease, does tibial tuberosity advancement lead to better long-term functional outcomes than lateral fabellar suture?   clinical bottom line category of research question treatment the number and type of study designs reviewed there were no papers that answered the pico question strength of evidence zero outcomes reported between tta and lfs none of the techniques was shown to provide better long-term functional outcomes than the other in dogs weighing less than 15 kg conclusion given the absence of evidence answering the pico question, choice and recommendation of procedure between tta and lfs in dogs weighing under 15 kg should be guided by what the surgeon deems to be in the best interest of the patient   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are presented with a 10 kg fox terrier with a complete rupture of the cranial cruciate ligament of the left stifle. the right stifle is unaffected. the veterinarians in your practice are experienced in performing the lateral fabellar suture (lfs) technique to manage cranial cruciate ligament disease in small dogs, typically with good outcomes. you have recently attended a tibial tuberosity advancement (tta) wetlab and were advised this technique is suitable for all sizes of dogs. in an endeavour to advise the client appropriately, you search for evidence comparing the long-term outcomes of these two procedures in dogs weighing under 15 kg. the evidence there is no evidence comparing functional outcomes of tta and lfs for unilateral cranial cruciate ligament disease in dogs weighing less than 15 kg.in view of this absence of evidence, it is recommended that practitioners use their personal experiences and preferences to advise clients and decide on which of the procedures to perform in small dogs. summary of the evidence there was no evidence that addressed the pico question from the literature search. appraisal, application and reflection there was no evidence that addressed the pico question. in combination, two prospective clinical trial studies by krotscheck et al. (2013) and krotschek et al. (2016) objectively compared the long-term functional outcomes of tibial plateau levelling osteotomy (tplo), tta and extracapsular reconstruction (ecr) by lfs. in the 2013 study, data for normal dogs, ecr and tplo groups were reported. data for the control group and tta group in the 2016 study were reported and compared to data for the control group, tplo group and ecr (lfs) group reported in the 2013 study. both studies were identical in design. in the 2016 study, owners with dogs suffering from naturally occurring cranial cruciate ligament disease were offered three surgical interventions, that is, tplo, ecr (lfs), and tta. owners that opted for tta were given the option to participate in the study. inclusion criteria were a body mass greater than 15 kg, diagnosis of unilateral cranial cruciate ligament disease and absence of any other orthopaedic abnormalities. standard tta was performed on all dogs in the study (n=14) with standardised perioperative care. force plate gait analysis was performed on normal control dogs and study dogs preoperatively and at 2 weeks, 8 weeks, 6 months and 12 months postoperatively. at 12 months postoperatively, the tta group had a better functional outcome at the walk than the ecr (lfs) group and was indistinguishable from the control group. at 12 months postoperatively, the functional outcomes of the tta and the ecr (lfs) groups were indistinguishable at the trot but inferior to the control group. the tta group had more postoperative complications than the ecr (lfs) group. at 12 months postoperatively, the tplo group had functional outcomes indistinguishable from the control group at both the walk and the trot, suggesting superior long-term functional outcomes of the tplo group to both the tta and ecr (lfs) groups. however, long-term functional outcomes of the tplo group are irrelevant to the pico. although the results of the two studies suggest better long-term functional outcomes in the tta group compared to the ecr (lfs) group, both studies excluded dogs weighing less than 15 kg, and thus the results may not be applicable to this pico. a study by di donna et al. (2015) compared objective, validated long-term functional outcomes of tta and lfs using force plate analysis. dogs in both groups had good to excellent outcomes but kinematic results indicated superior surgical outcome with the tta group at 6 month follow-up. however, the conference abstract available lacked important detail on inclusion criteria and statistical inference in its methodology and did not specify whether the study population included dogs weighing below 15 kg, making it difficult to determine its evidentiary value to this pico. it has been previously recommended that dogs weighing less than 15 kg do not require surgery. this was based on a 1984 study by vasseur where 85.7% of dogs weighing under 15 kg were considered clinically normal after an average follow-up period of 36.6 months following conservative non-surgical management, compared to 19.3% of dogs weighing over 15 kg after an average follow-up period of 49.1 months. however, it has since been demonstrated that conservatively managed dogs develop more severe osteoarthritis in the long-term than surgically managed dogs. in view of this, surgery in one form or another is recommended (innes, 2012; hamilton, 2016; and mölsä et al. 2014). the literature does not specify whether this has been demonstrated in dogs weighing under 15 kg so the relevance of this observation regarding small dogs cannot be determined.  in order to address the pico question, the ideal study would be a blinded, randomised, controlled clinical trial (bergh et al., 2014) addressing the specific weight class, with objective assessment of long-term functional outcomes of tta and lfs. mölsa et al. compared long-term surgical outcomes in dogs following surgery for cruciate ligament disease in a 2014 retrospective study. they used force plate analysis, orthopaedic and radiographic examination, and physiotherapeutic examination as objective, validated methods to measure and compare long-term functional outcomes in dogs that had undergone intracapsular, extracapsular and osteotomy techniques. the dogs that had undergone osteotomy techniques had less radiographic osteoarthritis than the dogs that had undergone intracapsular and extracapsular techniques. the low number of dogs treated with the extracapsular technique did not allow for comparison of ground reaction forces with the osteotomy and intracapsular techniques. there were no other significant differences. the limitations of the study are that it excluded dogs weighing less than 17 kg, largely focused on comparing surgically treated limbs to contralateral, healthy limbs, and compared broad surgical technique classifications namely intracapsular, extracapsular and osteotomy techniques rather than specific surgical techniques such as tta and lfs. the study is, therefore, irrelevant to the pico question as it excluded dogs weighing under 17 kg and the singular contributions of tta and lfs to the findings cannot be determined.  a 2013 study by mölsa et al. compared long-term surgical outcome and chronic pain in dogs that underwent intracapsular, extracapsular and osteotomy techniques for cranial cruciate ligament disease. the helsinki chronic pain index (hcpi) was used to evaluate chronic pain following surgery for cranial cruciate ligament disease. there were no significant differences in chronic pain indices between the different techniques. the study was carried out on a heterogenous population of dogs and does not indicate whether dogs weighing under 15 kg were included. the hcpi questionnaire used, although validated, remains subjective. this study also compared broad surgical technique classification rather than specific surgical techniques such as tta and lfs. progressive osteoarthritis which always develops secondary to cranial cruciate ligament disease regardless of surgical technique used to manage the condition may be responsible for chronic pain (muir, 2018). the use of chronic pain to evaluate long-term surgical outcome is therefore limited as chronic pain may have other sources unrelated to surgery. the relevance of this study to the pico given these limitations is therefore not possible to determine. based on the absence of evidence, the choice of procedure between lfs and tta should be guided by what the surgeon deems to be in the patient’s best interests. there is currently zero evidence to base choice between performing tta or lfs in dogs weighing under 15 kg. however, surgeons should be guided by the patient’s best interests in choosing between which of the two to perform in dogs weighing under 15 kg. methodology section search strategy databases searched and dates covered: cab abstracts on the ovid interface 1973 to week 21 2019 pubmed accessed via the ncbi website 1910 to may 2019 search strategy: cab abstracts: dog or dogs or canine or canines or bitch or bitches or exp dogs/ or exp canis/ oe exp bitches/ cranial and cruciate tibial tuberosity advancement or tta lateral or fabellar or fabellotibial or tibiofabellar or extracapsular or extra-capsular or lfs or de angelis or ‘modified retinacular imbrication’ or mrit 1 and 2 and 3 and 4   pubmed: dog or dogs or canine or canines or bitch or bitches cranial and cruciate tibial tuberosity advancement or tta lateral or fabellar or fabellotibial or tibiofabellar or extracapsular or extra-capsular or lfs or de angelis or ‘modified retinacular imbrication’ or mrit 1 and 2 and 3 and 4 dates searches performed: 04/06/2019 exclusion / inclusion criteria exclusion: only one technique included wrong techniques book chapters expert opinions reviews articles not available in english irrelevant to the pico question inclusion: prospective and retrospective studies compare outcomes for both tta and lfs techniques in dogs weighing less than 15 kg objective assessment of long term outcomes at least 6 months postoperative follow-up period search outcome database number of results excluded – article not in english excluded – reviews excluded – expert opinions excluded – not relevant to pico question total relevant papers cab abstracts 30 3 2 2 23 0 pubmed 20 0 1 1 18 0 total relevant papers when duplicates removed 0 conflict of interest the author declares no conflicts of interest.  the literature search was developed by clare boulton. this knowledge summary, albeit with some changes, was originally submitted as an assignment in the ebvm course of the mvetsci programme offered by the university of edinburgh.   acknowledgement the author would like to acknowledge louise buckley of the university of edinburgh college of medicine & veterinary medicine for her extensive contribution towards the structure of this knowledge summary. references bergh, m.s., sullivan, c., ferrell, c. l., troy, j. & budsberg, s.c. 2014. ‘systematic review of surgical treatments for cranial cruciate ligament disease in dogs.’ journal of the american animal hospital association. 50(5): 315–321. doi: http://dx.doi.org/10.5326/jaaha-ms-6356 di dona, f., della valle, g., lamagna, f., balestriere, c., del prete, c. & fatone, g. 2015. ‘force plate analysis for comparison of lateral fabellar suture and maquet modified procedure tibial tuberosity advancement techniques for treatment of dogs with cranial cruciate ligament disease.’ joint meeting, lxix convegno sisvet, xv convegno sicv, xiii convegno sira, xii convegno aipvet, xi convegno sofivet, ii convegno rniv, perugia, italia 15–17 giugno 2015. atti 2015. 229. hamilton, m. 2016. ‘tplo, tta or lateral suture? what's the difference?’ bsava congress 2016 proceedings, 7–10 april 2016, birmingham, uk. 324. doi: https://doi.org/22233/9781910443446.35.2 innes, j.f. 2012. ‘management of cruciate ligament rupture: what is 'best practice'?’ veterinary ireland journal. 2(1): 36–41. krotscheck, u., nelson, s.a., todhunter, r.j., stone, m. & zhang, z. 2016. ‘long term functional outcome of tibial tuberosity advancement vs. tibial plateau leveling osteotomy and extracapsular repair in a heterogeneous population of dogs.’ veterinary surgery. 45(2): 261–268. doi: https://doi.org/10.1111/vsu.12445 krotschek, u., nelson, s.a., rawlinson, j., todhunter, r.j., stone, m., zhang, z. & mohammed, h. ‘long-term functional outcome of tibial plateau leveling osteotomy versus extracapsular repair in a heterogenous population of dogs’, veterinary surgery. 42(1): 38–50. doi: https://doi.org/10.1111/j.1532-950x.2012.01052.x mölsä, s.h., hyytiäinen, h.k., hielm-björkman, a.k. & laitinen-vapaavuori, o.m. 2014. ‘long-term functional outcome after surgical repair of cranial cruciate ligament disease in dogs.’ bmc veterinary research, 10: 266. doi: http://dx.doi.org/10.1186/s12917-014-0266-8 mölsä, s.h., hyytiäinen, h.k., hielm-björkman, a.k. & laitinen-vapaavuori, o.m. 201 ‘use of an owner questionnaire to evaluate long-term surgical outcome and chronic pain after cranial cruciate ligament repair in dogs: 253 cases (2004–2006).’ journal of the american veterinary medical association. 243(5): 689–695. doi: http://dx.doi.org/10.2460/javma.243.5.689 muir, p. 2018. advances in the cranial cruciate ligament, 2nd hoboken:nj: wiley: american college of veterinary surgeons, p.202. vasseur, p.b. 1984. ‘clinical results following nonoperative management for rupture of the cranial cruciate ligament in dogs’ veterinary surgery. 13(4): 243–246. doi: http://dx.doi.org/10.1111/j.1532-950x.1984.tb00801.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. can cytosine arabinoside with prednisolone treatment for canine meningoencephalitis of unknown origin increase survival time compared to prednisolone treatment alone? a knowledge summary by christopher stephen francis kozlowski hoey bvetmed bsc (hons) pgdipvcp mrcvs1* christina maunder bvm&s(edin), certsam(rcvs), dipecvim-ca, mrcvs1 1university of bristol, bristol veterinary school, langford house, langford, bristol bs40 5du *corresponding author (choey@rvc.ac.uk) vol 3, issue 3 (2018) published: 10 jul 2018 reviewed by: mary fraser (bvms, phd, certvd, pgche, fhea, frsph, cbiol, frsb, mrcvs) and virginia fajt (dvm, phd, dacvcp) next review date: 10 jul 2020 doi: 10.18849/ve.v3i3.142 pico question in treatment of canine patients with meningoencephalitis of unknown origin (muo), is combination therapy of cytosine arabinoside (ca) with prednisolone more effective than prednisolone as a sole therapy at increasing survival time? clinical bottom line based on current available evidence, cytosine arabinoside with prednisolone has greater median survival time than prednisolone as a sole therapy in dogs with meningoencephalitis of unknown origin. the evidence to support this is very weak, as there are currently a low number of published papers with a relatively small number of cases reported in these studies evaluating cytosine arabinoside with prednisolone or prednisolone as a sole therapy for treatment of meningoencephalitis of unknown origin. clinical scenario you are presented with a 4-year-old male neutered boston terrier with a five day history of seizures, progressive mentation changes and compulsive circling. the patient has had no previous ailments or been on any previous treatments. multifocal intensities were noted within the forebrain on mri (t2-weighted). mixed mononuclear pleocytosis with increased protein concentration was noted on cerebrospinal fluid (csf) examination. negative serology and csf titres for neospora caninum and toxoplasma gondii were performed. a provisional diagnosis of muo is made for which you want to start treatment soonest, but you are unsure of the effectiveness of using a combination of cytosine arabinoside with prednisolone compared with prednisolone alone. the evidence there is limited available evidence for treating muo involving ca in combination therapy with prednisolone or prednisolone alone. five studies were located examining the effect of ca in combination with prednisolone, with a relatively small number of cases reported in each of these. only one paper was identified studying the use of prednisolone alone for treatment of muo. the available evidence is weak as five studies were case series, with high likelihood of bias, the inability to detect much of the bias, and the inability to estimate a treatment effect. a repeat literature search involving different chemotherapeutic treatment options for muo could be beneficial. whilst there is no direct comparison between these two treatment options, ca with prednisolone had greater actual and estimated median survival time than prednisolone as a sole therapy in dogs with muo. summary of the evidence lowrie (2016) population: dogs with presumptive muo presenting to the small animal neurology service at davies veterinary specialists between may 2006 and august 2015. sample size: 80; 39 historical control from lowrie et al (2013) treated with subcutaneous (sc) ca, 41 prospectively recruited to receive continuous rate infusion (cri) ca. intervention details: the cri ca dogs received a neurologic examination, complete blood count (cbc), serum biochemistry profile, serum antibody titres to neospora caninum and toxoplasma gondii, brain mri, csf analysis. the sc ca control group received the same with the exception to testing for toxoplasma gondi. both groups were treated with a standard protocol for immunosuppressive doses of oral prednisolone (1mg/kg twice daily (bid) with tapering doses after 4 weeks). this was reduced to 0.5mg/kg bid for 6 weeks, then 0.25mg/kg bid for 6 weeks, then 0.25mg/kg once daily for 6 weeks, then 0.25mg/kg every 48hours for 6 weeks followed by 0.25mg/kg every 72 hours for 6 weeks. dogs in the historical control group (lowrie et al 2013) received subcutaneous ca at 50mg/m2 every 12 hours for 2 days repeated every 3 weeks before increasing the treatment intervals by a week every 4 treatment cycles. dogs prospectively recruited received ca cri at 100mg/m2 over 24 hours. they then received 50mg/m2 sc ca every 12 hours for 2 days every 3 weeks for 3 cycles before increasing the treatment by a week every 4 treatment cycles. repeat mri and csf analysis at 3 months following the start of treatment for the prospectively recruited cri group and historical sc group. study design: prospective cohort study with historical control group outcome studied: the effect of a ca cri on mortality in dogs with muo and compare ca cri to ca sc. objective: mortality at 3 months (dogs that died or were euthanised were recorded and survival was compared as a binary value with a group of historical control dogs). occurrence of mri and csf abnormalities at follow-up. main findings (relevant to pico question): mortality of 4/41 (10%) in ca cri group (compared with 22/39 (56%) with in ca sc group) at 3 months. log rank analysis of the kaplan-meier survival curves represented a significantly better survival with ca cri. all dogs alive at 3 months in both groups were alive at 12 months. 34/37 surviving dogs in the cri group had a normal mri scan at 3 months compared with 7/17 surviving dogs in the sc group (statistically significant difference between the groups). csf was normal in a significantly higher proportion of dogs in the ca cri group (36/37) compared to the sc group (10/17). limitations: historical control data gathered at a different time period from a different study. patients not followed up until death or euthanasia for survival. dogs with a more aggressive form of inflammatory cns disease were excluded from the study (focal cortical hyperintense lesions on mri t1-w1) as they were likely to represent necrotizing encephalitis, which may affect survival and mortality analysis. comparative dosage of the treatments was not equal. diagnosis of muo was presumptive. lowrie (2013) population: dogs with clinically confirmed muo presenting to the small animal neurology service at davies veterinary specialists between may 2006 and august 2011. sample size: 39 intervention details: all dogs received a neurologic examination, complete blood count, serum biochemistry profile, serum antibody titres to neospora caninum, brain mri, csf analysis. all dogs were treated with a standard protocol initiated with immunosuppressive doses of oral prednisolone; 1mg/kg twice daily (bid) with tapering doses after 4 weeks to 0.5mg/kg bid po for 6 weeks, followed by 0.25mg/kg bid for 6 weeks, followed by 0.25mg/kg once daily (sid) for 6 weeks, followed by 0.25mg/kg every 48 hours for 6 weeks, followed by 0.25mg/kg every 72 hours for 6 weeks. dogs received subcutaneous ca at 50mg/m2 every 12 hours for 2 days repeated every 3 weeks for 4 cycles, before decreasing the frequency at the same dose to every 4 weeks for 4 cycles, then every 5 weeks for 4 cycles followed by every 6 weeks for 4 cycles. repeat mri and csf analysis at 3 months following the start of treatment. if abnormal the treatment regime was altered accordingly to prolong treatment. if a relapse occurred the protocol was restarted. study design: prospective case series outcome studied: prognostic factors and outcome of dogs with muo using a standard treatment protocol subjective: long-term follow-up of more than 18 months after diagnosis when treatment was anticipated to have been discontinued. defined by owner/referring vet as either excellent if all treatment discontinued and normal, good if the dog remained on treatment and was normal and poor if the dog was on treatment but abnormal (assessed at re-exam or phone consultation with referring vet or owner). objective: relapse with recurrence of neurologic signs suspected or confirmed with mri with an increase in seizure frequency of over 50% (however if controlled to under 50% of seizure frequency at time of initial presentation with or without anti-epileptic treatment then a relapse was not suspected). occurrence of mri and csf abnormalities at 3 month follow-up. mortality rate. main findings (relevant to pico question): 22 dogs died or were euthanised following diagnosis of muo (13 within 0-3 days, 3 in 4-14 days and 6 between 15 and 52 days). median survival time following diagnosis in all deceased dogs was 2 days (range 0-52 days). dogs that died did so within the first 3 months following diagnosis. overall mean survival time was 26 days (range 0-2250 days). survival was not affected by age at presentation, occurrence of seizures, csf cell count or csf protein concentration at initial diagnosis. of the mri features examined, evidence of foramen magnum herniation, loss of cerebral sulci and mass effect were all significantly associated with mortality. 17 dogs survived to 3 month re-examination. repeat mri and csf collection was performed. all dogs alive at 3 months were still alive at 18 month follow-up. long term follow up of surviving dogs ranged from 562 to 2250 days (median 1616 days). a good or excellent outcome was seen in 12/17 dogs with long-term follow-up; excellent in 7 dogs, good in 5 dogs and poor in 5 dogs. relapse was recorded in 11/17 surviving dogs (median of 210 days following diagnosis, range 106-826 days) and was not significantly associated with outcome. limitations: no histopathological data to confirm type of meningioencephalitis. dogs with optic form of gme were excluded from the study. flegel (2011) population: dogs presenting to department of small animal medicine, university of leipzig or department of clinical neurology, university of bern, between june 2000 and september 2008 with presumptive or diagnosed granulomatous meningoencephalitis (gme) or necrotizing (nme)/necrotizing leukocephalitis (nle). sample size: 43 dogs; 25 with gme and 18 with nme/nle split into 1 of 2 treatment groups based on treatment received. dogs with gme in group 1 (n = 14) treated with a combination of lomustine and prednisolone and group 2 (n = 11) treated with prednisolone alone. dogs with nme/nle in group 3 treated with a combination of lomustine (n = 10) and prednisolone and group 4 treated with prednisolone alone (n = 8).   intervention details: all dogs received a neurologic examination, complete blood count, serum biochemistry profile, serum antibody titres to neospora caninum, toxoplasma gondii and erlichia canis, brain mri, csf analysis and antibodies against canine distemper in 19/25 dogs with gme. some dogs received a needle brain biopsy for diagnosis of gme/nle/nme otherwise it was considered a presumptive diagnosis of meningoencephalitis. all dogs were initially treated with 0.17-2.5mg/kg oral prednisolone twice daily immediately after diagnostic tests had been completed. 14 dogs with presumed or diagnosed gme and ten dogs with presumed or diagnosed nme/nle were given oral lomustine (44 to 88mg/m2 every 6 weeks) and prednisolone. lomustine dose was reduced by 25% if leukopenia developed. prednisolone dose was assessed every 6 weeks and reductions made in decrements of 20% (frequency of administration remained constant at twice daily) in the absence of neurological deficits, less than one seizure per month and clinicopathologic results analysis (cbc). 11 dogs with presumed or diagnosed gme and eight dogs with presumed or diagnosed nme/nle were treated with prednisolone as a sole therapy. dose reductions were attempted every 6 to 8 weeks (in decrements of 20% while maintaining dose frequency) in accordance with the absence of neurological deficits, under one seizure a month, assessed through a neurological examination or communication with the owner. in some instances owners made their own decision in reducing dosages. study design: retrospective cohort study outcome studied: comparing oral lomustine and prednisolone to prednisolone alone as for treatment of muo. objective measured: survival main findings (relevant to pico question): diagnosis was confirmed in 8/25 gme dogs and 5/18 nme/nle dogs. 2 dogs with gme and 2 dogs with nme/nle via histologic examination of brain biopsy specimens and 6 gme dogs and 3 nme/nle dogs at necropsy. 9/13 dogs that died in group 1 had documented cause of death; 3 due to recurrence of neurological signs and 6 due to non-neurologic conditions (renal failure, cardiac failure, hemorrhagic gastroenteritis, septic shock and suspected liver failure). 5/8 dogs that died in group 2 had documented causes of death; 4 due to lack of improvement or relapse of neurologic signs and 1 due to chronic renal failure. all dogs in group 3 (8/8) had documented cause of death; 3 due to recurrence of neurologic signs and 5 due to other medical conditions (such as pleural effusion, cardiac failure, septic shock, gastrointestinal hemorrhage). 5/8 dogs reason for euthanasia was documented in group 4, all due to lack of improvement or relapse of neurologic signs. median survival was 323 days (39-542 days) in dogs treated with prednisolone as a sole therapy with gme, and 457 days (107-709 days) in dogs treated with lomustine and prednisolone. no significant difference was found between these groups (1 and 2).  median survival was 91 days (7-494 days) in dogs treated with prednisolone as a sole therapy with nme/nle, and 329 days (98-628 days) in dogs treated with prednisolone and lomustine. no significant difference was found between these groups (3 and 4). reduction in median prednisolone dose per day within the first 12 months of treatment was seen in in dogs with gme treated with lomustine and prednisolone from 2.1 to 0.2mg/kg/day compared to 1.4 to 0.6mg/kg/day for dogs treated with prednisolone alone. reduction in median prednisolone dose per day within the first 12 months of treatment was seen in in dogs with nme/nle treated with lomustine and prednisolone from 1.9 to 0mg/kg/day compared to 2.1 to 1.0mg/kg/day for dogs treated with prednisolone alone. in 4 dogs with gme and 4 dogs with nme/nle prednsisolone administration was able to be discontinued. in 3 of these gme affected dogs lomustine was also discontinued.  limitations: no standard treatment protocol, differing dose ranges (including owners making decisions on tapering doses). small number of cases, no power calculation performed. diagnosis in (number) of dogs was carried out at post mortem. smith (2009) population: dogs presenting to queen’s veterinary school hospital, university of cambridge between march 2004 and november 2006 with presumptive muo. sample size: 19 dogs split into 2 groups; group 1 treated with prednisolone in combination with vincristine and cyclophosphamide (n=10) and group 2 treated with prednisolone with cytosine arabinoside (n=9). group 2 had 10 cases but one was retrospectively excluded for failing to meet the inclusion criteria.     intervention details: all dogs received a neurologic examination, serum antibody titres to neospora and toxoplasma, brain mri or myelogram, csf analysis, canine distemper virus testing (other individual specific tests if clinical suspicion including anaplasma phagocytophilum and borrelia). dogs were randomly allocated to receive a low dose lymphoma ‘cop’ (copcyclophosphamide (oral 50mg/m2 every 48 hours for 8 weeks, then the same regimen given over alternate weeks), vincristine (0.5mg/m2 every 7 days for 8 weeks, then every 14 days) and prednisolone) protocol or the same dose of prednisolone (40mg/m2 orally once daily) with the addition of ca. intravenous (iv) ca was given once at the start of therapy over 24 hours at a total dose of 100mg/m2. no further treatment of ca was given. in groups 1 and 2, oral prednisolone was reduced from 40mg/m2 every 24 hours doe 7 days to 20mg/m2 every 48 hours for 7 weeks, then the same regimen given in alternate weeks. the dose of prednisolone was tapered to suit individual requirements after 6 months and stopped if possible. patients were followed for survival analysis and those alive at the time of writing were censored from survival estimate using an intention-to-treat analysis. the proportion of animal surviving 1 and 12 months was calculated excluding the censored cases in kaplan-meier analysis. study design: randomised control trial (double blinded) outcome studied: comparing cop lymphoma protocol to prednisolone with ca treatment for muo   objective: survival analysis; kaplin-meier analysis. treatment failure analysis. drug-related complications. main findings (relevant to pico question): for survival analysis three dogs were censored from group 2 including two that were euthanised for non-neurological disease (lymphoma and pneumonia) and one whose treatment was altered after a relapse (surviving for over a year receiving only prednisolone). two were censored from group 1, both of whose treatment were stopped. 3 dogs were alive at time of writing in group 2 and 4 dogs in group 1, which were censored. median survival was estimated at 1,063 days in dogs treated with prednisolone and ca (group 2). it was unable to be performed for group 1 because of the large number of censored cases. intention-to-treat analysis showed a median survival time of 735 days (195-1274) in group 2 and 198 days (247-914) in group 1. proportion of animals surviving 1 and 12 months was calculated (excluding the censored cases) in kaplan-meier analysis leaving 7 animals in group 2 and 8 animals in group 1. 5/7 animals were alive at both 1 and 12 months in group 2, 5/8 animals were alive at 1 month and 4/8 were alive at 12 months for group 1. one animal in group 2 which worsened at day 40 but ultimately survived for 376 days (kaplin-meier plot of time-to-treatment failure with a median value of 1063 days in group 2 (102-2023)). limitations: small population size. one case excluded from ca and prednisolone group due to csf sample containing 90% neutrophils. lack of follow-up and survival times. two cases of possible infectious disease not ruled out due to severity of cases and need to start treatment. confusing results difficult to interpret survival analysis. in group 2, the removal of censored cases is unclear for the specific test and analysis (3 cases censored due to being alive and 3 due to euthanasia or treatment change).   menaut (2008) population: dogs presenting to the national veterinary school of toulouse between september 2003 and january 2005 with presumptive or diagnosed muo. sample size: 11 intervention details: dogs were selected based on treatment with a combination of steroids and ca. covered some of the six criteria for muo presumptive diagnosis including focal or multifocal central nervous system (cns) signs, negative pcr and csf analysis for infectious disease (distemper, neospora, toxoplasma, erlichiosis), csf protein and white blood cell (wbc) analysis, ct signs consistent with muo, ophthalmoscopy signs of optic neuritis, histopathological diagnosis. all dogs were treated with oral immunosuppressive prednisolone (1-2 mg/kg twice daily tapered over 3 months) and subcutaneous ca (50mg/m2 every 12 hours for 48 hours repeated every 3 weeks). at week 28 the ca treatment interval was tried to be lengthened by one week every 4 weeks. prednisolone dose was tapered from 2mg/kg twice daily (bid) for 1 week, to 1.5mg/kg bid for 1 week, then 1mg/kg bid for 1 week, then 0.75mg/kg bid for 1 week, then 0.5mg/kg bid for 2 weeks, then 1mg/kg every other day for 3 weeks, then 1mg/kg every third day for 2 weeks then to be stopped if possible. intravenous steroid therapy was initiated for 2-3 days in nine of the dogs without reason given for this. where possible a cbc was performed at 7 days after each ca treatment. study design: retrospective case series outcome studied: response to prednisolone and subcutaneous ca treatment in dogs with muo. subjective quality of life was judged by the owner and referring veterinarian. objective: survival time and cumulative probability of survival at 2 years. main findings (relevant to pico question): at the end of the study seven dogs were alive and four had died (one due to drowning, one due to neurologically associated pancreatitis and hypoglycaemia, one dog euthanised at the first relapse and the other dog euthanised at the fourth relapse). median survival 384 days, range 78-603. median survival time could not be calculated using kaplan-meier analysis as fewer than half the animals had died. the cumulative probability of survival at 2 years was 58.4%. initial response to treatment was judged as excellent with total remission of clinical signs and excellent quality of life in five dogs, good with partial remission and good quality of life in five dogs, and poor with poor control of disease in one dog. seven dogs experienced relapses. in three of these relapse occurred due to steroid dose reduction. in one of these dogs another relapse occurred due to a delay in ca treatment due to pyometra. one dog had a relapse with discontinuation of its ca treatment by the owners. in three cases the cause of relapse was unknown. one of the dogs who relapsed after 3 months of treatment was euthanised as the owner would not accept further treatment. limitations: no standard treatment protocol, tapering dose altered by clinicians depending on each dog’s response to treatment, side effects, number of relapses and owner compliance. varied ca treatment cycles ranging from 4 to 37 treatments. only one dog had clinical confirmation of gme. only included cases that survived long enough for ca therapy. small number of cases collected for the study. no mention of survival in text only in table form. no account for 3/7 cases of relapse. subjective quality of life assessment. zarfoss (2006) population: dogs presenting to the cornell university hospital for animals with muo sample size: 10 intervention details: dogs were selected based on treatment with a combination of steroids and ca. covered some of the six criteria for muo presumptive diagnosis including focal or multifocal cns signs, negative pcr and csf analysis for infectious disease (five dogs), csf protein and wbc analysis (csf mononuclear pleocytosis), ct signs consistent with muo (nine dogs), ophthalmoscopy signs of optic neuritis, histopathological diagnosis. a minimum database of cbc, serum biochemistry profie, blood serology for infectious encephalopathies (anaplasma phagocytophilum, ehrlichia canis, toxoplasma gondii, neospora canis, cryptococcus (in nine dogs). antinuclear antibody titres were performed in two dogs with immune-mediated disease. each dog was treated with immunosuppressive doses of corticosteroids. six dogs received 0.1-1.0mg/kg oral dexamethasone sodium phosphate or 10-30mg/kg methylp sodium succinate. all dogs received 1-2mg/kg prednisolone twice daily at the time of diagnosis. approximately 15mg/kg clindamycin was given twice daily and 5mg/kg doxycycline twice daily were given initially but discontinued after negative infectious disease titres (5-7 days after diagnosis). ca treatment was initiated at variable intervals (from 0 to 60 days later) at 50mg/m2 subcutaneously twice a day for two consecutive days. the ca protocol was repeated every 3 weeks for 4 months (where the treatment interval was then lengthened by a week every 4 months with a maximum final interval of every 8 weeks). one dog had repeat ct at 7 months and two dogs (including the dog with repeat ct) had repeat csf analysis. study design: retrospective case series outcome studied: whether prednisolone with subcutaneous ca is safe for use in canine muo. subjective: clinical response to therapy through follow-up appointments, telephone follow-ups with owners or referring vets. objective: survival time main findings (relevant to pico question): partial (over 50% reduction of clinical signs) or complete remission was achieved in all dogs receiving corticosteroid and ca treatment. median survival for all dogs was 531 days (kaplin-meier product limit method). survival ranged from 564 to 1025 days at the time of writing. the dog with survival time of 46 days was the only dog in which post-mortem histopathology was available disclosing nle and excluded from survival range data. two dogs required tertiary immunosuppressive chemotherapy of procarbazine or leflunomide. one dog received azathioprine for a history of immune-mediated haemolytic anemia (imha) until ca treatment was established. two dogs received phenobarbitol and/or potassium bromide for persistent episodic seizures. in one dog, at attempts to increase ca treatment interval the dog relapsed neurologically. dogs starting ca treatment earlier did not have longer survival times compared to those started at 60 days after prednisolone therapy. limitations: no standard treatment protocol, differing dose ranges and ca administered at different time periods after diagnosis. diagnosis and exclusion of a case of nle post-mortem but no other definitive diagnostic information for other cases. small number of cases collected for the study. only included cases that survived long enough for ca therapy. one dog had a positive csf culture with no information of repeat to rule out positive infection, even if contamination suspected. three dogs had a history of immune-mediated disease; keratoconjunctivitis sicca and generalised vaccine reaction, imha and juvenile addison’s disease. appraisal, application and reflection all cases of muo were assumed through neurological examination and included some or all of advanced imaging techniques, csf analysis or diagnosed with antemortem brain biopsy or postmortem histopathology. it should be taken into account that each of these studies is focused on populations of animals attending referral centers rather than general practice. none of the studies directly compared the treatment of muo with either a combination therapy of ca with prednisolone to prednisolone as a sole therapy. only one study evaluated the use of prednisolone as a sole therapy for treatment of muo, but was used as a comparison for a different chemotherapeutic agent and involved a range of different treatment doses, including at the initiation of therapy. three out of six studies were performed by a retrospective search of cases. this may lead to selection bias and may not give accurate representation evaluating treatment of muo as some cases may die shortly after admission or prior to commencing treatment (e.g. lowrie et al., 2016). retrospective case series sit low on the hierarchy of evidence and despite some of the studies having greater strength (randomised controlled trial > cohort study > case series), it is difficult to draw definitive conclusions from the available literature. a treatment protocol was implemented in three of the studies, however the prednisolone dose or frequency in these, as well as the studies without a treatment protocol, would be altered to the individual patients based upon relapses and clinical signs. of the five studies receiving ca, three received sc ca (not including lowrie et al., (2016) historical control group), one a single iv dose of ca, and one iv ca followed by sc ca. lowrie et al (2016) found significantly better survival with dogs receiving their first dose of ca by cri followed by sc compared with dogs receiving only sc ca. smith et al (2009) also noted an increase in estimated mean survival when compared with other studies (median survival estimate 1063 days). almost all dogs treated with ca and prednisolone surviving to 3 months went on to survive to 12 months (lowrie et al., 2016; lowrie et al., 2013; smith et al., 2009). it is not possible to directly compare ca with prednisolone to prednisolone as a sole therapy for treatment of muo from the available literature. when comparing actual or estimated survival between the studies, ca with prednisolone has greater median survival time in all studies compared to prednisolone as a sole therapy. it should be noted that in lowrie et al (2013), 13/39 dogs died within 3 days of diagnosis regardless of treatment regime. in order to better evaluate the effect of ca with prednisolone as a treatment option a prospective randomised clinical trial using a standardised treatment protocol is required.  this review highlights the matter that limited studies have been performed investigating the use of combination therapy of ca and prednisolone in muo. methodology section search strategy databases searched and dates covered: the search was applied to cab abstracts and medline databases from 1946 to january 2017. search terms: canine or dog or dogs or dog diseases and meningoencephalitis or granulomatous meningioencephalitis or meningioencephalomyelitis or muo or gme or mue or nle or nme or reticulosis and cytarabine or cystosine arabinoside or cytosine arabinoside or prednisolone or prednisone. dates searches performed: monday 2nd january 2017 exclusion / inclusion criteria exclusion: single-case reports, duplicate papers, articles in which cytarabine with prednsiolone or prednisolone as a sole therapy for treatment of muo was not evaluated, or articles where the full text was not available in english or able to be located. inclusion: articles published between 1946 and present investigating the effect of cytarabine in combination with prednisolone or prednisolone as a sole therapy for treatment of mengioencephalitis of unknown origin. search outcome database number of results excluded – single case report excluded – not relevant to the pico excluded – not available in the english language total relevant papers cab abstracts 40 16 17 1 6 medline 29 11 11 1 6 total relevant papers when duplicates removed 6 conflict of interest the authors declare no conflicts of interest. references flegel, t., boettcher, i., matiasek, k., et al, 2011. comparison of oral administration of lomustine and prednisolone or prednisolone alone as treatment for granulomatous meningoencephalomyelitis or necrotizing encephalitis in dogs. journal of the american veterinary medical association, 238(3), pp.337-345. http://dx.doi.org/10.2460/javma.238.3.337 lowrie, m., thomson, s., smith, p., et al, 2016. effect of a constant rate infusion of cytosine arabinoside on mortality in dogs with meningoencephalitis of unknown origin. the veterinary journal, 213, pp.1-5. http://dx.doi.org/10.1016/j.tvjl.2016.03.026 lowrie, m., smith, p. and garosi, l., 2013. meningoencephalitis of unknown origin: investigation of prognostic factors and outcome using a standard treatment protocol. vet rec, 172(20), p.527. http://dx.doi.org/10.1136/vr.101431 menaut, p., landart, j., behr, s., et al, 2008. treatment of 11 dogs with meningoencephalomyelitis of unknown origin with a combination of prednisolone and cytosine arabinoside. veterinary record: journal of the british veterinary association, 162(8). http://dx.doi.org/10.1136/vr.162.8.241 smith, p., stalin, c., shaw, d., et al, 2009. comparison of two regimens for the treatment of meningoencephalomyelitis of unknown etiology. journal of veterinary internal medicine, 23(3), pp.520-526. zarfoss, m., schatzberg, s., venator, k., et al, 2006. combined cytosine arabinoside and prednisone therapy for meningoencephalitis of unknown aetiology in 10 dogs. journal of small animal practice, 47(10), pp.588-595. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. reluxation rates following different techniques for open stabilisation of feline coxofemoral dislocations a knowledge summary by elly russell ma, vetmb, cert avp, mrcvs 1* 1the minster veterinary ptactice, salisbury road, york, yo26 4yn *corresponding author (ellythevet@hotmail.com) vol 4, issue 1 (2019) published: 24 jan 2019 reviewed by: andy morris (bsc(hons) bvsc certavp(gsas) mrcvs) and stephen jones (mvb, ms, dacvs) next review date: 24 jan 2021 doi: 10.18849/ve.v4i1.185 pico question in cats with craniodorsal coxofemoral luxation does surgical stabilisation using a toggle rod technique result in a lower rate of reluxation than using a transarticular pin? clinical bottom line there is currently insufficient evidence to identify if transarticular pinning or a toggle rod technique result in lower rates of reluxation following surgical management of craniodorsal coxofemoral luxations in cats. both transarticular pinning and toggling using the arthrex mini tightrope system with arthrex fiberwire suture resulted in 0% reluxation rates at short-term radiographic follow up with 0/20 joints reluxated at 2–6 weeks post-transarticular pinning and 0/4 joints reluxated at 6 weeks post-toggling. toggling using an imex toggle (imex veterinary inc.) and polydioxanone (pds ii, ethicon) suture had a higher reluxation rate of 14% (2/14 joints) at 3.5 to 6 weeks postsurgery. longer term follow up of joints stabilised using transarticular pinning found 16.6% reluxation (2/13 joints) when radiographed at least 6 months after surgery. small sample sizes, and variations in the length of follow up, inclusion and exclusion criteria and surgical technique significantly challenges any conclusions that may be drawn. it does appear that reluxation rates for all three techniques investigated here compare favourably to generally quoted reluxation rates following open reduction (28% quoted by rochereau et al., 2012) and that the use of all reported techniques can be justified for the management of craniodorsal coxofemoral luxations in cats. clinical scenario a 4 kg 3-year-old male neutered domestic short-haired cat has been presented to you following a road traffic accident. after initial stabilisation, radiographs have identified a craniodorsal luxation of the right coxofemoral joint. closed reduction was performed but the joint could not be maintained in reduction. no concurrent orthopaedic or other body system injuries have been identified. you advise the owners that surgical stabilisation would be the best course of action, particularly for a young active cat, and whilst the patient is not insured the owners are happy to make funds available for surgery at your practice. you have previously performed stabilisation of coxofemoral luxations in three feline patients using the transarticular pinning technique and whilst two patients recovered uneventfully, the third experienced reluxation. a colleague has recently attended a cpd course on treatment of common feline orthopaedic conditions and advises you that stabilisation using a toggle rod technique results in lower reluxation rates. you wonder which procedure should be performed in this case. the evidence three studies were identified which addressed the pico question and fitted the inclusion and exclusion criteria applied. all the studies identified were noncomparative case series. the number of cases included in the studies was low: 4, 14 and 20 (median 14). some other case series reporting outcomes for both feline and canine patients were excluded due to the low number of feline patients (three or less), along with a number of case reports. all three studies described a surgical technique used for the open reduction and stabilisation of craniodorsal coxofemoral luxations in feline patients from a referral population. two of the studies (sissener et al., (2009) and pratesi et al., (2012)) presented only feline patients, whilst ash et al., (2012) presented findings for four feline patients and five small dogs. only the results as they applied to the feline patients were considered. sissener et al., (2009) described the use of transarticular pins (1.6 mm diameter in the majority of cases with 1.2 mm and 2.0 mm pins also used) left in-situ for between 2 to 6 weeks in 20 cases. radiographic follow up was performed at pin removal and, for 12 of the cases, at a time point > 6 months postsurgery. no reluxations were identified at short-term follow up, but two patients radiographed > 6 months later demonstrated reluxation. in addition to reluxation, complications included a bent 1.2 mm pin identified 6 weeks postoperatively in one patient and spontaneous resorption of the femoral head and neck identified 6 months postoperatively in another. pratesi et al., (2012) described a toggle rod technique used in 14 cases. a 3.2 mm imex toggle rod with two strands of 4 metric polydioxanone was used for the majority of cases. in two cases three strands of 4 metric polydioxanone were used and in one case the polydioxanone size was increased to 5 metric. a single case also had a smaller 2.7 mm toggle used. short-term radiographic follow up was performed at 3.5–8 weeks postoperatively, revealing two patients had suffered reluxations. no other complications were reported. ash et al., (2012) applied an identical technique to all four feline cases, using an arthrex mini tightrope toggle and arthrex fiberwire suture. no reluxation was noted at 6 week postoperative radiographs and none of the feline patients experienced any other complications. reluxation rates including time of assessment for all three studies are summarised in the following table (table 1): table 1: reluxation rates and assessment times for the 3 studies all three studies also presented other, subjective, outcome measures that were not directly applicable to the pico question. these included lameness assessments performed by a veterinarian and owner outcome questionnaires conducted by telephone. along with the subjective nature of these assessments, all studies failed to describe observer standardisation, introducing observer bias, and time to follow up with owners varied widely introducing recall bias. summary of the evidence sissener et al., (2009) population: feline patients presenting to two referral centres with craniodorsal coxofemoral luxation and selected for surgical management using transarticular pinning between 1998 and 2003. selection criteria for use of this technique were: acute traumatic hip luxation that could not be reduced or maintained in reduction hip luxation > 3 days or recurrent reluxation following closed reduction hip luxation presenting concurrently with other orthopaedic injuries revision of failed previous surgical reduction. this resulted in 17/20 patients with concurrent orthopaedic injuries, two patients where closed reduction and ehmer sling application had failed and a final patient with no previous reduction attempts or concurrent injuries. patients ranged from 6 months to 12 years. sample size: 20 cats (21 coxofemoral joints) n = 20 intervention details: 21 coxofemoral joint luxations (19 unilateral, 1 bilateral) were managed with open reduction and stabilisation using transarticular pinning. a variety of methods were utilised for pin placement including direct normograde pin placement, retrograde pre-drilling prior to pin placement or normograde pre-drilling using a c guide. hand-chuck or power drill were used for pin placement. 1 x 1.2 mm, 17 x 1.6 mm and 3 x 2.0 mm pins were placed with estimation of pin size based on recommendations made in previous reports of this technique in dogs. a greater trochanteric osteotomy was performed in one case. primary closure of the joint capsule is reported to have been performed where possible. study design: retrospective dual-centre case series outcome studied: telephone questionnaire with owners 21 months (mean: range 6– 66 months) post-treatment. outcome measures for owners’s questionnaires were description of cats gait, ability to jump, stiffness after rest or exercise, was cat receiving any medication with owners and grading overall outcome. 13/20 cats were presented for physical examination by authors at least 6 months post-treatment and outcome was graded: poor, fair, good, very good or excellent based on criteria described by nunamaker (1973). 19/20 cats were radiographed prior to pin removal 2– 6 weeks postsurgery: maintenance of coxofemoral reduction was noted. 12/20 cats were radiographed at least 6 months following treatment. maintenance of coxofemoral reduction and presence of degenerative joint disease were assessed. overall outcome is reported as functional joint with intact coxofemoral joint confirmed on radiography at least 6 months after treatment. main findings (relevant to pico question): overall success rate defined as a functional, intact coxofemoral joint confirmed to have remained reduced at > 6 months post-treatment was 77% consisting of 10/13 joints radiographed > 6 months postsurgery that met this definition. reluxation occurred in 2/13 joints presented for radiography > 6 months post-treatment giving a long term reluxation rate of 15%. 1/13 joints presented for radiography > 6 months post-treatment had experienced femoral head and neck resorption. of the cats that presented for radiography and pin removal (19/20) 2–6 weeks post-treatment, all had maintained coxofemoral reduction at this stage, resulting in a short-term relaxation rate of 0% (0/20 joints). the 1.2 mm pin was bent at time of pin removal. owner outcome for patients with reluxations were both still graded as very good. one patient was lost to any follow up with a total of eight patients lost to long term follow up. limitations: retrospective case series are a low level evidence on hierarchy of evidence available. noncomparative study. referral population studied, so does not directly relate to clinical scenario. 17/20 concurrent injuries. some signalment details (weight and breed) which may be relevant to outcome were not given in the study. no details of standardisation of veterinary surgeons, as a two centre study. also variation in size of pin selected and technique for placement. both short and long-term radiographic follow up occurs at variable time points. mean follow up times are quoted, but given the wide ranges, medians would be more appropriate. radiograph observer is standardised for long-term follow up but not short-term follow up. 8/20 cats lost to long term follow up. given reluxation was identified at long-term follow up but not short-term follow up, this is significant. ash et al., (2012) population: feline and small canine patients presenting to a single referral centre for management of traumatic craniodorsal coxofemoral luxation and undergoing surgical stabilisation using a toggle technique (arthrex tightrope and mini tightrope systems). for feline patients, trauma to surgery ranged from 2–4 days, and patients’s weights ranged from 3.7–4.7 kg. all were domestic short-haired cats. presence of any concurrent injuries is not given. patients were excluded if there was radiographic evidence of periarticular fractures, hip dysplasia or osteoarthritis. sample size: 4 felines and 5 canines n = 4 relevant to pico intervention details: all four feline patients had craniodorsal coxofemoral luxation managed using surgical stabilisation with arthrex mini tightrope toggle and arthrex fiberwire suture. postoperative management was standardised with enforced cage rest for 2 weeks and unrestricted exercise after 10 weeks. no greater trochanter osteotomies are described and there is no reference to primary closure of any remnants of joint capsule. study design: retrospective single centre case series outcome studied: number of days to postoperative weight bearing. lameness evaluation performed 2 and 6 weeks postoperatively. scored 0 = normal gait, 1 = mild weight bearing lameness, 2 = moderate weight bearing lameness, 3 = severe weight bearing lameness, 4 = severe intermittent weight bearing lameness, 5 = severe continuous non-weight bearing lameness. radiographic (orthogonal views) follow up 6 weeks postoperatively. telephone follow up with owners using standardised questionnaire conducted 16–44 weeks postoperatively. descriptive recording of complications. no loss to follow up. main findings (relevant to pico question): radiographic follow up at 6 weeks postoperatively showed unchanged quality of hip reduction and toggle position and absence of periarticular osteophytosis or coxofemoral remodelling. reluxation rate at 6 weeks postoperatively was therefore 0%. limitations: retrospective case series are a low level of evidence on hierarchy of evidence available. noncomparative study. inclusion criteria not clear with no detail of any concurrent injuries given. some signalment details including weight and age, which may be relevant to outcome were not given in the study. surgical procedure and postoperative care standardised but no detail of the number of surgeons. subjective outcome measures without observer standardisation. wide range of follow up time, although quoting median time rather than mean is helpful. small sample size in target species. pratesi et al., (2012) population: feline patients presenting to single referral centre for management of unilateral craniodorsal coxofemoral luxation. cases represent consecutive cases managed by toggle rod stabilisation. mean days from trauma to surgery was 3.2 days (range from 1–6 days). 9/14 patients are reported to have concurrent orthopaedic injuries and 3/5 patients presenting with coxofemoral luxation only had small articular bone fragments from either femoral head or dorsal acetabular rim. in six cases a referring vet had attempted closed reduction. patients’s weight ranged from 2.8–6.8 kg, ages from 7 months to 10 years and breeds were 11 domestic short-haired, 1 domestic long-haired and 2 british short-haired cats. sample size: 14 cats n = 14 intervention details: all cases were managed with open reduction and stabilisation using a toggle rod technique. a 3.2 mm imex toggle rod with two strands of 4 metric polydioxanone were used in ten cases. variations in this were used of 2.7 mm toggle (1 cases), use of three strands of 4 metric polydioxanone (2 cases) and use of two strands of 5 metric polydioxanone (1 case). a 2.0 mm femoral bone tunnel was used in 9 cases with 1.5 mm (1 case), 1.6 mm (1 case) and 2.5 mm (3 cases) also used. surgical technique altered slightly to allow management of concurrent injures (as above). use of greater trochanter osteotomy is not described, but partial deep gluteal tenotomy was variably used in the approach. joint capsule repair was possible in one cat. immediate postoperative care was standardised and cage rest implemented for 4–8 weeks dependent on presence of other orthopaedic injuries. study design: retrospective single centre case series outcome studied: veterinary assessment and follow up radiographs performed 3.5–8 weeks postoperatively. clinical examination findings recorded were use of affected limb and range of movement and hip stability assessed under sedation. radiographs assessed maintenance of coxofemoral reduction and percentage of pelvic canal narrowing due to presence of toggle rod. telephone follow up was performed with 11/13 owners 4–42 months postoperatively (mean follow up 15.5 months). two patients with coxofemoral reluxation at previous radiographic assessment were excluded from this follow up. details recorded were: time to achieve good use on operated leg, use of any medication, use of litter tray and any concerns about urination and defecation and an overall quality of life assessment (poor, fair, good, very good or excellent). owners also completed questionnaire designed to assess degenerative joint disease associated pain with nine specific functions and four behaviours assessed on five point scale. main findings (relevant to pico question): all cats were weight bearing on the affected limb the day after surgery. radiography at 3.5–8 weeks postoperatively revealed reluxation in 2/14 cases, a 14% reluxation rate. for cats without reluxation, limb use was considered normal on clinical exam, and hip stability and range of movement normal under sedation. good limb use despite reluxation was noted in these two cases. the 11 cats without reluxation had longer term follow up at 15.5 months (mean time to follow up) by owner questionnaire. 10/11 owners reported excellent quality of life for their cats and 7/11 considered their cats to have normal limb function. limitations: retrospective case series are a low level of evidence on hierarchy of evidence available. noncomparative study. inclusion and exclusion criteria are not defined. variability in surgical technique, although all surgeries were performed by one of two boarded surgeons. subjective outcome assessments including veterinary assessment, radiographic assessment and owner survey. details of observers of radiographic and veterinary assessment not given. time from surgery to owner survey is very variable (range 1.5–39 months) and would be better expressed as median time to surgery rather than mean. two patients experiencing reluxation are excluded from long-term follow up, and one further case is lost to longer-term follow up. appraisal, application and reflection there is a lack of high quality evidence available to address the clinical question as all of the relevant studies identified and appraised here are retrospective case series. these sit low on the hierarchy of evidence and, particularly as they are not comparative studies, are not appropriate for assessing the impact of a specific surgical technique on outcome. randomised, controlled, blinded studies that compare the two surgical techniques are needed to generate high quality evidence on which to base clinical decisions. a large number of surgical stabilisation procedures are described for the management of coxofemoral luxation, but there is little evidence to guide technique choice (moore, 2006). reluxation is reported to be the most common complication following open reduction and surgical stabilisation of coxofemoral luxations. rochereau et al., (2012) reports rates of around 28% for a variety of open reduction techniques including extra-articular stabilisation and ventral approach for the placement of stainless steel rope cases. it should be noted that many of the studies quoted examine reluxation rates for studies in dogs only. the reluxation rates quoted in all the studies (table 1) appear to compare favourably with this, providing some evidence to support the use of these techniques. however, alongside the low case numbers, the variability in follow up time reduces the quality of information generated. in addition to this, none of the three studies described standardise the observer for short-term follow up radiographic assessments and whilst presence of coxofemoral luxation on a radiograph is relatively objective, observer bias is possible. longer-term radiographic follow up is only performed in the transarticular pinning study (sissener et al., 2009). it is interesting that reluxation was first identified at least 6 months after surgery, at least 5 months after pin removal, in two cases. ash et al., (2012) argues that 6 week follow up is adequate for assessing reluxation rates since long term periarticular fibrosis is responsible for stability after this stage and reluxation rates beyond this time frame are very low. however, the findings of the sissener et al., (2009) study suggest that longer-term follow up is important in establishing reluxation rates. the evidence generated by these studies would be more valuable if follow up was standardised and long term, greater than 12 months, follow up was available for all the surgical techniques. all of the studies identified describe management of cases at referral centres. this means the cases reported are unlikely to directly reflect those managed in the primary care setting. specifically, cases are likely to have a higher incidence of concurrent injuries and for more time to have elapsed between luxation and treatment. both of these factors might be expected to increase reluxation rates. pre-surgical management is also variable and variably reported. duration of luxation is not reported by sissener et al., (2009) whilst pre-referral management is not described by ash et al., (2012). postoperative care is also affected by management of concurrent injuries and therefore the patients in these studies are not always subject to the same postoperative management, which would be expected to impact on reluxation rates. differences in inclusion and exclusion critera, or the lack of these criteria, across the studies compromises the ability to compare reluxation rates for the different surgical procedures. ash et al., (2012) excludes patients with radiographic evidence of periarticular fracture, hip dysplasia or osteoarthritis whilst pratesi et al., (2012) includes two patients with suspected pre-existing hip dysplasia (hd) and three with periarticular bone fragments. sissener et al., (2009) details inclusion criteria including concurrent injuries and failure of previous surgical stabilisation but does not mention hd or periarticular fractures. it is interesting to note that one of the 2/14 cases experiencing reluxation in the pratesi et al., (2012) study had hip dysplasia since pre-existing pathology such as this might be expected to impact upon the success of open reduction and stabilisation of traumatic luxations. for this reason, inclusion of these cases in the pratesi et al., (2012) and possibly in the sissener et al., (2009) study limits the conclusions we can draw on reluxation rates from these studies. for the transarticular pinning technique, accurate placement of the transarticular pin is crucial for correct seating of the femoral head in the acetabulum, which is very likely to correlate with reluxation rates. sissener et al., (2009) reports three separate methods for pin placement were used, it would be useful to assess if any of these methods resulted in a better outcome. similarly, pin size selection is poorly described and weight, which we would expect to guide size selection, is omitted from signalment. evidence to guide pin size selection and placement technique would be useful but is lacking. for the toggle techniques, pratesi et al., (2012) uses different toggle sizes, suture sizes and thread numbers. reasons for these variations are not always stated (although one patient received three strands of suture due to suspected pre-existing hd) and there is no obvious trend, for example increasing suture size or number with increasing patient weight. again, the variation in surgical technique limits the conclusions we are able to draw about reluxation rates, and the study fails to generate guidelines for selection of toggle size or suture. the surgical technique described by ash et al., (2012) is consistently applied across all cases, which allows better assessment of the procedure’s impact on reluxation rates. the toggle system reported by pratesi et al., (2012) used both different toggle (arthrex minitightrope) and suture (arthrex fiberwire) than the ash et al., (2012) study. suture type/strength and toggle construct are likely to impact upon reluxation rates. this limits the potential to combine data about ‘toggle procedures’ from these two studies (ash et al., 2012 and pratesi et al., 2012). further, this difference in suture material highlights again the need for longer-term follow up, since polydioxanone utilised in the pratesi et al., (2012) study will lose tensile strength at around 3–4 weeks, whilst the arthrex fiberwire is more durable. the discovery of reluxation > 6 months postoperatively (sissener et al., 2009) might suggest that maintaining reduction requires more persistent implants and that periarticular fibrosis alone may be insufficient. it should be noted that sissener et al., (2009) reports owner outcomes for the patients with reluxations > 6 months postoperatively to be very good and pratesi et al., (2012) describes limb use as good despite reluxation within 6 weeks of surgery in two cases, one of which received no further treatment. it is important to consider if reluxation is the most clinically useful outcome measure. all the studies include other outcome measures, all subjective, including veterinary lameness assessments without observer standardisation and owner questionnaires completed at very wide ranging time points. long-term degenerative joint disease may be a more important clinical comparator between surgical techniques and more objective outcome measures such as measuring ground reaction force on pressure sensitive walkways (schnabl et al., 2015) could be considered. in general, the studies fail to generate any descriptive rationale for the selection of one surgical procedure over another. all the cases in the ash et al., (2012) study seem to have been managed using the toggle technique, and similarly in the sissener et al., (2009) study for the pinning technique, whilst pratesi et al., (2012) implies not all presenting cases were managed with the toggle technique but does not explain the choice of this technique for these cases. further studies using randomised, controlled, blinded trials comparing two standardised surgical techniques, ideally in a primary care setting, with objective outcome measures are needed. methodology section search strategy databases searched and dates covered: cab abstracts on cabi direct platform 1973 to week 8 2018 medline on ovid platform 1946 to week 8 2018 scopus 1973 to week 8 2018 web of science 1973 to week 8 2018 search terms: (cat or cats or feline or felines) and (hip dislocation or hip luxation or coxofemoral dislocation or coxofemoral luxation) and (transartic* or transtroch* or pin* or togg* or rod) dates searches performed: feb 25th 2018 exclusion / inclusion criteria exclusion: wrong species luxation not craniodorsal surgical technique not recognisable as transarticular pinning or toggle rod reluxation not given as outcome measure not english language conference proceedings review articles case reports or case series with < 3 feline cases inclusion: correct species, craniodorsal luxation managed surgically with technique recognisable as transarticular pinning or toggle rod with outcome measures including reluxation. search outcome database number of results excluded – non-english language publication excluded – case reports, reviews, conference proceedings excluded – does not address pico question excluded – full text not available total relevant papers cab abstracts 21 6 5 7 1 2 medline 14 1 1 9 1 2 scopus 8 2 1 3 0 2 web of science 38 7 3 25 0 3 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflict of interest. references ash, k., rosselli, d., danielski, a., farrel, m., hamilton, m. & fitzpatrick, n. (2012) correction of craniodorsal coxofemoral luxation in cats and small breed dogs using a modified knowles technique with the braided polyblend tightrope systems. vet comp ortho traumatol, 25 (1), pp. 54-60. http://dx.doi.org/10.3415/vcot-11-02-0019  nunamaker, d. m. (1973) repair of femoral head and neck fractures by interfragmentary compression. javma,162, 569-572 moore, a. (2006) decision making in the management of hip luxations in dogs and cats. in practice, 28 (10), pp. 570-576. http://dx.doi.org/10.1136/inpract.28.10.570 pratesi, a., grierson, j. & moores, a. (2012) toggle rod stabilisation of coxofemoral luxation in 14 cats. jsap, 53 (5), pp. 260-266. https://doi.org/10.1111/j.1748-5827.2012.01199.x rochereau, p. & bernardé, a. (2012) stabilization of coxofemoral luxation using tenodesis of the deep gluteal muscle. technique description and reluxation rate in 65 dogs and cats (1995-2008). vet comp ortho traumatol, 25 (1), pp. 49-53. schnabl, e. & bockstahler, b. (2015) systematic review of ground reaction force measurements in cats. the veterinary journal, 206 (1), pp. 83-90. http://dx.doi.org/10.1016/j.tvjl.2015.05.017 sissener, t.r., whitelock, r.g. & langley-hobbs, s, (2009) long-term results of transarticular pinning for surgical stabilisation of coxofemoral luxation in 20 cats. jsap, 50 (3), pp. 112-7. http://dx.doi.org/10.1111/j.1748-5827.2008.00625.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. introduction to systematic reviews mike clarke 1* 1centre for public health, queen’s university belfast *corresponding author (m.clarke@qub.ac.uk) vol 2, issue 2 (2017) published: 30 jun 2017 doi: 10.18849/ve.v2i2.131 in this talk, from the veterinary evidence today conference 2016, mike clarke gives an introduction to systematic reviews. find out more about mike. view presentation slides comments: is an anchoring or pocket technique best for surgical repair of cherry eye in dogs? a knowledge summary by jim connah bvsc manzcvs 1* 1tasmanian animal hospitals, 29-31 clarence st, bellerive tas 7018 australia *corresponding author (jimconnah@bigpond.com) vol 4, issue 1 (2019) published: 12 feb 2019 reviewed by: victoria arbona (dvm, ms) and kazuya oikawa (dvm) next review date: 12 feb 2021 doi: 10.18849/ve.v4i1.182 pico question in dogs undergoing surgery for repair of a prolapsed gland of the third eyelid (cherry eye), is a pocket technique superior to an anchoring technique in preventing recurrence? clinical bottom line for surgical treatment of a prolapsed gland of the third eyelid (cherry eye), there is currently no evidence to suggest that either an anchoring technique or a pocket technique is significantly better than the other when comparing recurrence rates. in practice, and until randomised controlled trials are carried out, veterinary surgeon preference and previous experience would be the relevant factors in choosing which operation to perform. clinical scenario you are presented with a 1-year-old beagle with a unilateral cherry eye. it has been present for two months and is not bothering the dog. the owner wants to know what to do. you ring the two veterinary ophthalmologists in the local area for advice. one routinely performs an anchoring technique, whilst the other has had good results with a mucosal pocket technique. having only two expert opinions to go by, you decide to look for any available higher level evidence. the evidence there is no evidence to suggest that one technique is superior to another. whilst all the cited studies compared techniques, and reported excellent outcomes for both, only one (multari et al., 2016) conducted any statistical analysis. this latter article did not show any significant difference in rates of recurrence. it was limited, however, by comparing a pocket technique with a pocket plus anchor technique. summary of the evidence morgan, duddy & mcclurg (1993) population: case records of dogs presented with either unilateral or bilateral cherry eye. sample size: 125 eyes in 89 dogs. intervention details: the medical records of dogs with a prolapsed gland of the third eyelid between june 1980 to june 1990 were examined. four groups of dogs: excision of the gland (43 eyes), gross & blogg tacking (anchoring) technique (gross, 1983) (59 eyes), morgan pocket technique (18 eyes) and no treatment (5 eyes). follow up period: 2–10 years. study design: retrospective cohort study. outcome studied: development of keratoconjunctivitis sicca (kcs). recurrence of prolapse (anchoring and pocket groups). main findings (relevant to pico question): high recurrence rate in anchoring group (30/51), usually within 1–8 weeks after the initial surgery (eight dogs were lost to follow up). only 1/17 prolapses recurred with the pocket technique (one dog was lost to follow up). limitations: no statistical analysis provided, so no direct comparisons of treatment efficacy could be made. no indication of how long the follow up period was for determining recurrence in all dogs. nine animals lost to follow up. retrospective study, which is lower in evidence hierarchy. the anchoring technique used in this paper is outdated, no longer recommended and therefore less relevant to the pico question. the morgan technique was developed by the authors due to the high failure rate of the gross technique – the discussion notes that the kaswan anchoring technique (kaswan & martin, 1985) was tried but the cosmetic results were unacceptable (there was no recurrence). there is no record of this in either the methods or results sections and indeed if these dogs were reoperated on. lin & lin (2003) population: dogs presented with either unilateral or bilateral cherry eye. sample size: seven eyes in five dogs. intervention details: two groups of dogs: morgan pocket technique (morgan et al., 1993) (6 eyes) and kaswan anchoring technique (kaswan & martin, 1985) (1 eye). follow up period: 6–12 months. study design: prospective non-randomised cohort study. outcome studied: detection of kcs. re-prolapse of the gland. main findings (relevant to pico question): during the follow up period, there were no cases of kcs or recurrence of prolapse. noted in discussion that the pocket technique was easier to perform. limitations: small sample size. no indication why different techniques were employed, and under what criteria dogs were allocated to groups. gupta et al., (2016) population: dogs presented with either unilateral or bilateral cherry eye. sample size: 16 eyes in 10 dogs. intervention details: three groups of dogs: removal of gland (8 eyes of five dogs), kaswan anchoring technique (kaswan & martin, 1985) (4 eyes of three dogs) or modified morgan pocket technique (morgan et al., 1993) (4 eyes of three dogs). study design: prospective non-randomised cohort study. outcome studied: recurrence of prolapse. detection of kcs in all techniques. main findings (relevant to pico question): no cases of recurrence with the anchoring technique, although there was one case of persistent protrusion of the third eyelid. no cases of recurrence with the pocket technique. limitations: no indication of how long the follow up period was. no indication why different techniques were employed, and how dogs were allocated to groups. multari et al., (2016) population: case records of dogs presented with either unilateral or bilateral cherry eye. sample size: 420 eyes in 353 dogs. intervention details: the medical records of dogs undergoing surgical repair of a prolapsed gland of the third eyelid between january 2002 and june 2013 were examined. two groups of dogs: morgan pocket technique (morgan et al., 1993) (234 eyes) and morgan pocket technique combined with a modified stanley and kaswan anchoring technique (stanley & kaswan, 1994) (186 eyes). study design: retrospective cohort study. outcome studied: recurrence of prolapse. main findings (relevant to pico question): there were recurrences in 12/234 eyes with the morgan pocket technique and in 9/186 eyes with the combined technique (no significant difference, p = 0.892). recurrences were generally 1–2 months postoperatively. the techniques were compared within some breeds, but only statistical analysis was provided for the cane corso (no significant difference, p = 0.66). limitations: no comparison between a pocket technique group and an anchoring alone technique group. no indication of times of follow up for any of the dogs. retrospective study, which is lower in evidence hierarchy. the study was non-randomised: dogs had been selected for the combined technique if the surgeon had thought the pocket technique alone would fail (chronic cases, large glands, and dogs with poor temperament). appraisal, application and reflection there are many published studies which purport the efficacy of various individual surgical treatments for repair of prolapsed glands of the third eyelid (cherry eye). these were excluded from the search as they did not compare the efficacy of any new surgical approaches to older ones. white & brennan (2018) have recently reviewed the surgical techniques for the correction of prolapsed glands of the third eyelid. there was insufficient evidence to recommend one technique over another with regards to recurrence rates or development of kcs.  a meta-analysis performed for studies reporting outcomes of the morgan pocket and anchoring techniques, however, showed that there was a similar surgical failure rate (2–3%) between the two techniques (white & brennan, 2018). the morgan pocket technique was developed by morgan, duddy & mcclurg (1993) because an outdated tacking technique resulted in too many treatment failures. there was no statistical analysis performed, but the former technique appeared to be more efficacious. whilst cohort studies generally appear higher in the hierarchy of evidence based veterinary medicine, the two included in this knowledge summary (lin & lin, (2003); gupta et al., (2016)) suffered from having no control groups. another cohort study (gökçe, 2001) which compared removal of the gland (8 eyes of five dogs), the kaswan anchoring technique (4 eyes of three dogs) and the modified morgan pocket technique (4 eyes of three dogs) was only available in english as an abstract. it noted, however, that there was a higher recurrence rate with the anchoring technique (no statistical analysis was available). only one study (multari et al., (2016)) compared recurrences after two techniques with statistical analysis, but no significance was found (p = 0.892). unfortunately, this study compared the morgan pocket technique with a combined morgan pocket and stanley and kaswan anchoring technique. this made the study less relevant to the pico question. there is clearly a need for randomised controlled studies to determine the answer to the pico question. large numbers of eyes need to be treated across multiple institutions with multiple veterinary surgeons. an especially useful group of dogs may be those which present with bilateral cherry eye: an anchoring procedure could be performed in one eye and a pocket in the other. outcomes could then be compared in the same animal. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform 1973 to 2018 week 15 medline on ovid platform 1946 to april week 2, 2018 web of science core collection 1900–present search terms: cab abstracts and medline:   (dog or dog* or canine or canis or exp dogs/) and (surg* or repair or replacement) and (cherry eye or eyelid adj3 prolaps* or third adj3 prolaps* or nictita* adj3 prolaps* or gland adj4 prolaps* or gland adj4 third or gland adj4 eyelid or gland adj4 nictita*) and (pocket techni* or tacking or anchor* techni* or mucosa* adj3 pocket or anchor* adj4 orbital or anchor* adj4 rim or imbricat*)   web of science:   (dog or dog* or canine or canis) and (surg* or repair or replacement) and (cherry eye or eyelid near/3 prolaps* or third near/3 prolaps* or nictita* near/3 prolaps* or gland near/4 prolaps* or gland near/4 third or gland near/4 eyelid or gland near/4 nictita*) and (pocket techni* or tacking or anchor* techni* or mucosa* near/3 pocket or anchor* near/4 orbital or anchor* near/4 rim or imbricat*) dates searches performed: 24 april 2018 exclusion / inclusion criteria exclusion: only one technique performed (i.e. only anchoring or mucosal pocket) within the study group full article not available in english wrong species wrong disease book chapters inclusion: both anchoring and mucosal pocket techniques used amongst the study group full text articles available in english dogs only search outcome database number of results excluded – only one technique performed excluded – not in english excluded – wrong species excluded – not relevant to pico question excluded – book chapters total relevant papers cab abstracts 26 17 2 0 2 1 4 medline 6 3 0 1 1 0 1 web of science 15 6 1 4 2 0 2 total relevant papers when duplicates removed 4 conflict of interest the author declares no conflicts of interest. references gökçe, a.p. (2001) comparison of the surgical treatment methods of prolapsed gland of the third eyelid in dogs: a retrospectif [sic] study of 66 cases (1995–2000). veteriner cerrahi dergisi, 7 (1–2), 44–47 [turkish, abstract in english]. gross, s.l. (1983) effectiveness of a modification of the blogg technique for replacing the prolapsed gland of the canine third eyelid. proceedings of the american college of veterinary ophthalmologists, 13, 38-42. gupta, a.k., kushwaha, r.b., bhadwal, m.s., sharma, a., dwivedi, d.k. & arafath, i. (2016) management of cherry eye using different surgical techniques – a study of 10 dogs. intas polivet, 17 (11), 411–413. kaswan, r.l. & martin, c.l. (1985) surgical correction of third eyelid prolapse in dogs. journal of the american veterinary medical association, 186 (1), 83. lin, c.-t. & lin, n.-y. (2003) surgical reposition of third eyelid gland prolapse (cherry eye) in the dog. taiwan veterinary journal, 29 (2), 85–89. morgan, r.v., duddy, j.m. & mcclurg, k. (1993) prolapse of the gland of the third eyelid in dogs: a retrospective study of 89 cases (1980 to 1990). journal of the american animal hospital association, 29 (1–2), 56–60. multari, d., perazzi, a., contiero, b., de mattia, g. & iacopetti, i. (2016) pocket technique or pocket technique with modified orbital rim anchorage for the replacement of a prolapsed gland of the third eyelid in dogs: 353 dogs. veterinary ophthalmology, 19 (3), 214–219. doi: 1111/vop.12286 stanley, r.g. & kaswan, r.l. (1994) modification of the orbital rim anchorage method for surgical replacement of the gland of the third eyelid in dogs. journal of the american veterinary medical association, 205 (10), 1412-1414. white, c. & brennan, m.l. (2018) an evidence-based rapid review of surgical techniques for correction of prolapsed nictitans glands in dogs. veterinary sciences, 5 (75), 1–16. doi: 3390/vetsci5030075 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. current thoughts on the treatment of malassezia in canine otitis externa mary fraser bvms, phd, certvd, pgche, fhea, frsph, cbiol, frsb, mrcvs1* 1girling and fraser ltd training and consultancy, muirfield, arngask glenfarg ph2 9qd perth *corresponding author (mary.fraser@vets-now.com) vol 2, issue 3 (2017) published: 12 jul 2017 doi: 10.18849/ve.v2i3.136 otitis externa is a commonly diagnosed disorder of canine patients (rosser, 2004) and can be caused by a number of different factors including infection, allergy, foreign bodies and breed/ear conformation. malassezia pachydermatis is a yeast which is found as a commensal on canine skin, but may also contribute to the development and perpetuation of the condition. the aim of this paper was to assess current knowledge and approaches to the treatment of m. pachydermatis when found to be present in cases of canine otitis externa. a literature search was carried out using pubmed database. search terms malassezia, dogs / canine, otitis and therapy/treatment/therapeutics were utilised. this identified 26 results from 2005 2015. examination of these papers focussed the review to 11 papers that were clinically relevant. the excluded papers were either concerned with laboratory storage/growth of m. pachydermatis, did not include therapy of the condition, or focussed on other skin conditions. of the 11 papers deemed relevant to this study, only three were double blind, randomised controlled trials (rougier et al, 2005, bensignor & grandemange, 2006, hensel et al, 2009); one paper was a review of current literature relating to dermatology, including otitis externa (bond, 2010) and the remainder were focussed on in vitro work with m. pachydermatis. many different therapeutics were used, namely thiabendazole, amphotericin b, itraconazole, ketoconazole, clotrimazole, miconazole, nystatin, chelating agents and various ear cleaners. within the controlled trials, a chelating agent was shown to improve therapeutic effectiveness of topical medication, combination therapy (antifungal, antibacterial and anti-inflammatory agents) was more effective than antifungal agent alone and no significant difference was noted when comparing combination therapies. a clear difference was found between different ear cleaners. this review highlights the variety of different medications that can be used in the treatment of malassezia otitis externa and the need for a greater number of robust clinical trials. find out more about mary. comments: an analysis of recovery probability from high somatic cell counts in uk dairy cows madeleine archer bsc (hons), msc1 nicholas taylor bsc, bvsc, msc, mrcvs1* james hanks bsc, msc, phd1 yiorgos gadanakis bsc, msc, phd1 1school of agriculture, policy and development, university of reading, whiteknights, po box 237, reading, rg6 6ar, uk *corresponding author (n.m.taylor@reading.ac.uk) vol 4, issue 4 (2019) published: 11 dec 2019 reviewed by: chris watson (ma, vetmb, mrcvs) and john fishwick (ma, vetmb, dchp, dipecbhm, mrcvs) doi: 10.18849/ve.v4i4.205 section index:    abstract | introduction | methods | results | discussion | footnotes | conflict of interest | references abstract objective: the particular interest of this study was to identify the relative impacts of magnitude and category of high scc on ‘recovery’, once other factors were taken into account. background: a high scc (≥200 thousand cells/ml) is commonly associated with intra-mammary infection (imi), one of the most economically important diseases faced by the dairy industry. high scc is important in its own right because the bulk milk tank scc is a determinant of the price farmers receive for their milk. evidentiary value: a high scc may be transient, returning (‘recovering’) to low scc at the next monthly milk recording. better understanding of factors influencing the probability of ‘recovery’ from high scc, could improve decision making on how to manage cows with high sccs in the most effective manner to minimise both production loss and unnecessary interventions that may include antimicrobial use. methods: this research used monthly milk recording data to explore how the probability of ‘recovery’ from high somatic cell count (scc) is associated with different factors such as parity, stage of lactation, the magnitude of scc and category of high scc (e.g. new or chronic). different factors (scc magnitude; category of high scc, e.g. new or chronic; parity; and lactation stage) were analysed using a multilevel, mixed effect logistic regression model to assess the association with recovery probability. data of 12,250 full lactation records from 499 milk-recorded uk dairy herds were used, from which 30,080 high scc ‘cases’ were analysed. results: in line with established evidence, increasing parity, increasing days in lactation and increasing magnitude of scc are associated with decreased probability of recovery. the important result is that the category of high scc is the most influential factor, with probability of recovery after two consecutive high scc being around half or less the probability of recovery after just one high scc. conclusion: the results provide evidential support for category of high scc to be used ahead of magnitude of scc when advising farmers about prioritising high scc cases for investigation and possible treatment, drying-off or culling. application: dairy herd management software companies should work with farmers and their advisors to ensure scc data are presented in the most useful way, allowing easy interpretation and translation into the most effective interventions that can increase the efficiency of the dairy industry as well as avoiding needless or ineffectual interventions, that may include use of antimicrobials.   introduction mastitis, which is usually caused by bacterial intramammary infection (imi), is one of the most economically damaging issues affecting the global dairy industry (halasa et al., 2007 and van soest et al., 2016). high (≥200 thousand cells/ml) somatic cell count (scc) has long been associated with imi (dohoo and leslie, 1991; bradley and green, 2005) and scc provided for monthly individual cow milk samples have commonly been used as an indicator of a herd’s mastitis situation, particularly subclinical mastitis. a high scc in the absence of clinically apparent inflammation of the udder may indicate the presence of subclinical mastitis which is caused by contagious mastitis organisms, especially staphylococcus aureus, streptococcus dysgalactiae and streptococcus agalactiae (edmondson and blowey, 1998), although 20–35% of milk samples taken from animals with a high scc give a negative result to bacterial culture analysis (herlekar et al., 2013). however, bacteria involved in environmental mastitis, mainly escherichia coli and streptococcus uberis are rapidly eliminated from the udder and clinical mastitis caused by these organisms is not closely linked with scc (edmondson and blowey, 1998). in recent decades the relative importance of environmental mastitis in uk dairy herds has increased while contagious mastitis has decreased (biggs, 2017a; biggs, 2017b) limiting the utility of scc as a direct indicator of clinical mastitis occurrence. as well as a detrimental impact on milk yield, culling of cows and other costs associated with imi (halasa et al., 2007; van soest et al., 2016), the scc of individual cows’ milk is also important in its own right because it contributes to the scc in the bulk milk tank. this is important because bulk milk tank scc is one of the determinants of the price farmers receive for their milk, with premiums and penalties applied according to the milk supply contract. it is therefore important for dairy farmers to carefully manage the scc of cows in their milking herd. this might include prevention and control of sub-clinical and clinical mastitis, treatment of clinical cases and management of sub-clinical cases, and also withholding high scc milk from the bulk tank, and the culling of persistent high scc cows. a high scc may be apparently transient, with milk returning to a low scc at the subsequent milk recording (mr). past research has focused on the factors which affect the occurrence of high scc and the associations between high sccs and herd productivity, reproduction and health (archer et al., 2013; morris et al., 2013). in contrast, this research explored how the probability of ‘recovery’ from high scc is associated with different factors such as parity, stage of lactation, the magnitude of scc and category of high scc (e.g. new or chronic). the particular interest of this study was to identify the relative impacts of magnitude and category of high scc on ‘recovery’, once the other factors were taken into account. a better understanding of the factors influencing the probability of such ‘recovery’ could improve farmers’ and veterinarians’ decision making on how to manage cows with high sccs in the most effective manner to minimise both unnecessary or ineffectual interventions that may include use of antimicrobials and loss in productivity.   methods this study examined sequential data from cows milk-recorded at monthly intervals to evaluate the probability that a high scc case will return to a low scc (‘recovery’) at the next mr. a multilevel, mixed effect longitudinal logistic regression analysis was carried out to assess the association of different factors (magnitude of scc; the category of high scc, e.g. new or chronic; parity of the cow; and stage in lactation) with lower or higher probability of ‘recovery’. the data source for this study was a group of 500 uk dairy herds used in the university of reading annual benchmarking survey for the year ending 31 august 2014 (hanks and kossaibati, 2014). these herds are randomly selected from a population of predominantly black and white (holstein/friesian) uk dairy herds that must be routinely milk-recorded and also meet minimum standards of event recording (including calving, service, pregnancy diagnosis, sales, culls). to ensure that complete lactation records were available, data for the lactations of all cows calving between 1 september 2012 and 31 august 2013 were extracted. data were available from each mr during the lactations, carried out approximately monthly by national milk records (nmr). the data items extracted for each lactation included: herd identity (id); animal id; calving date; parity; dry date; scc at the last mr of the previous lactation; total mrs recorded in the current lactation; dates of mrs and scc results for up to the first 12 mrs in the current lactation. using the herd id, the average number of cows in each herd during the year between 1 september 2012 and 31 august 2013 was also derived. a ‘study population’ of lactations was extracted by excluding lactation records that did not include at least one mr with a high scc (defined as ≥200 thousand cells/ml). next, a random sample of 15,000 lactations was drawn from the study population using a randomised sorting process. a number of records were removed from the initial selection of 15,000 lactations as these were found to be incomplete. the following cases were considered as incomplete: a) the sequence of milk records was incomplete with a gap of over 50 days between any of the mrs; b) there was just one mr for the entire lactation, and; c) there were obvious anomalies in the data such as having a mr date before calving date or after the dry date. for the purpose of analysis a ‘case’ was a mr with scc ≥200 thousand cells/ml and the outcome of a case was defined as ‘recovery’ when the scc at the next month’s mr was <200 thousand cells/ml. the recovery probability for cases of high scc mrs in the sample was estimated using a longitudinal multilevel logistic regression model in which the outcome (dependent variable) had the form of a binary variable where 1 was for a case that ‘recovered’ and 0 for those ‘not recovered’. the data structure takes the form of repeated measurements (level 1) of sccs nested (level 2) within the individual cow which in turn is nested within a higher-level cluster (i.e. herd) at level 3. thus, we consider a 3 level model in the analysis. the use of a multilevel model allows us to use a non-balanced data set since the frequency and number of measurements can vary amongst individuals (i.e. cows). the model is fitted using a generalised linear mixed model, which incorporates both fixed-effects parameters and random effects in a linear predictor, by maximum likelihood (laplace approximation). the objective is to predict the log-odds (recovery) for an individual cow in a herd. the technical details of this approach are beyond the scope of this article and the interested reader can investigate this further in the works of quené and van den bergh (2004), baayen et al. (2008) and goldstein (2003). the potential explanatory variables in the analysis were: stage of lactation (days in milk[1]); magnitude of scc (cells/ml); the category of high scc; parity of the cow and the average size of the herd. each of these variables was defined in the multilevel model by assigning categories. the numbers of categories and the thresholds between categories were decided based on the initial exploration of the data using univariate techniques. stage in lactation was categorised according to days in milk (dim): dim.c1, up to 100 days; dim.c2, 101 to 200 days; dim.c3, > 200 days. note that there were no mrs at less than 4 dim. the magnitude of scc was initially split into 17 categories though statistical analysis showed no significant difference between certain categories so they were simplified into 5 categories: scc.c1, 200–249 thousand cells/ml; scc.c2, 250–299 thousand cells/ml; scc.c3, 300–349 thousand cells/ml; scc.c4, 350–699 thousand cells/ml and; scc.c5, ≥700 thousand cells/ml. the high scc category describes the position of the high scc in the sequence of a cow’s lactation mrs. the different categories of high scc are explained in table 1. parities were categorised as: first; second; third; fourth to sixth; and, seventh and above. herd size was assigned as: small (≤ 100 cows); medium (101–200 cows) and; large (>200 cows). each variable in the model was then assessed using series of ‘dummy’ variables which were compared to a reference case.   [1] days in milk (dim) in this analysis was derived as the difference between mr date and calving date, therefore the same as ‘days after calving’.   …if it is the first mr in the lactation… first heifer heifer calving with a high scc in first mr first new cow calving with a high scc in first mr – the last mr of previous lactation was low first chronic cow calving with a high scc in first mr – the last mr of previous lactation was high …if it is not the first mr in the lactation… new the first high scc in a lactation (that is not the first mr) chronic i a high scc consecutively following ‘i’ previous consecutive high sccs (i = 1 … 10) repeat a high scc that follows a low scc, but is not the first high scc in the lactation table 1: categories of high scc and definition   results descriptive results the data cleaning reduced the sample dataset from 15,000 to 12,250 lactation records, each from a different animal from 499 different herds. these 12,250 lactation records contained data from 126,510 individual mrs, of which 36,731 (29%) had a high scc. the outcome of high sccs occurring at the twelfth and final mr extracted, or at the end of a lactation, could not be determined. therefore, these mrs (6,651) were omitted from the analysis, leaving a total of 30,080 of high scc cases in the analysis. the distribution of cases by different categories of each of the variables used in the mixed effect logistic regression model, and the ‘raw’ recovery probabilities, are presented in table 2. consistent with other researchers’ findings (e.g. schepers et al., 1997) and possibly related to decreasing yield resulting in higher concentration of cells present, a higher proportion of the high scc mrs occurred in later lactation (>200 dim) in particular 42% in the later stage compared with 29% in 1–100 days and 29% in 101–200 days. the magnitude of the high scc was evenly distributed, with 35% less than 300 thousand cells/ml, 34% between 300 thousand and 699 thousand cells/ml and 32% ≥700 thousand cells/ml. 22% of the high scc mrs were of the ‘new’ category, with a further 11% occurring at the first mr of the lactation and 16% being ‘repeat’ highs. therefore, just over 50% of the high scc mrs were ‘chronic’ (i.e. one of a sequence of consecutive high mrs within the lactation). the distribution of high scc mrs by parity and by herd size reflected the distribution of the lactation records by parity and herd size indicating that there was no great tendency for high scc to occur in any particular parity or herd size more than another.   variable category (level) all cases recovery cases n % in each category n proportion total cases used in analysis (mr with high scc) 30,080   11,110 (0.37) days in milk (days)   dim.c1 (≤100)‡ 8,653 (29%) 4,225 (0.49)   dim.c2 (101 to 200) 8,864 (29%) 3,205 (0.36)   dim.c3 (>200) 12,563 (42%) 3,680 (0.29) somatic cell count (thousand cells per ml)   scc.c1 (200 to 249)‡ 6,171 (21%) 3,275 (0.53)   scc.c2 (250 to 299) 4,228 (14%) 1,810 (0.43)   scc.c3 (300 to 349) 2,900 (10%) 1,088 (0.38)   scc.c4 (350 to 699) 7,190 (24%) 2,293 (0.32)   scc.c5 (scc ≥700) 9,591 (32%) 2,644 (0.28) high scc category (descriptive)   new‡ 6,735 (22%) 4,047 (0.60)   first heifer 1,017 (3%) 736 (0.72)   first new 1,160 (4%) 692 (0.60)   first chronic 1,234 (4%) 589 (0.48)   repeat 4,752 (16%) 2,180 (0.46)   chronic 1 5,449 (18%) 1,528 (0.28)   chronic 2 3,192 (11%) 595 (0.19)   chronic 3 2,088 (7%) 278 (0.13)   chronic 4 1,485 (5%) 203 (0.14)   chronic 5 1,013 (3%) 98 (0.10)   chronic 6 733 (2%) 63 (0.09)   chronic 7, 8, 9, 10 1,211 (4%) 96 (0.08) parity (number of calvings)   first calving (heifer)‡ 5,885 (20%) 3,163 (0.54)   second calving 5,349 (18%) 2,193 (0.41)   third calving 5,873 (20%) 2,108 (0.36)   fourth to sixth calving 10,242 (34%) 2,958 (0.29)   seventh and above calvings 2,731 (9%) 688 (0.25) size of the herd (number of cows)   small (≤100 cows)‡ 4,858 (16%) 1,711 (0.35)   medium (101 to 200 cows) 13,653 (45%) 5,002 (0.37)   large (>200 cows) 11,569 (38%) 4,397 (0.38) ‡ used as the reference case in the multilevel, mixed effect logistic regression model table 2: distribution of cases by different categories of each of the variables used in the multilevel, mixed effect logistic regression model and the ‘raw’ recovery probabilities   overall, 37% of the high scc mrs were followed by a scc lower than 200 thousand cells/ml (representing the overall probability of ‘recovery’ across all cases). the proportion of cases ‘recovering’ was similar for the three herd size categories. table 2 shows that the proportion of cases ‘recovering’ after a high scc declined with increasing dim, increasing magnitude of scc and increasing parity. when all chronic cases are aggregated, the recovery probability is 19% (2,861/15,171) compared with the aggregate recovery probability of the rest of the cases of 55% (8,244/14,898). for the ‘chronic 1’, ‘chronic 2’, ‘chronic 3’ etc. categories of high scc in particular, the proportion of recoveries declines as the chronic sequence progresses. figure 1 shows the distribution of high scc mrs between scc magnitude categories for the different categories of high scc. figure 1: distribution of high scc mrs between scc magnitude categories for the different categories of high scc although the ‘new’ high scc mrs and the ‘repeat’ high scc have a similar profile (over 30% have a value of <250 thousand cells/ml and almost 50% are <300 thousand cells/ml) (fig. 1) the proportion of cows recovering from ‘repeat’ high scc mrs is lower compared to recovery from “new” high scc mrs (table 2). in addition, although the three categories of ‘first’ high scc mrs include similarly high proportions with sccs ≥700 thousand cells/ml and fewer sccs of <300 thousand cells/ml, the proportion of cows recovering for the ‘first heifer’ and ‘first new’ categories are at least as high as for a ‘new’ high scc (table 2). however, the proportion that recover from the ‘first chronic’ category is much lower (table 2). these findings suggest that for these categories of high scc at least, recovery probability is influenced by factors other than simply the magnitude of high scc. high scc mrs that are in a chronic sequence show a progressive trend to higher magnitude scc categories up to the sixth consecutive high scc (fig.1). this is in parallel with progressively lower recovery probability (table 2). high scc in the sequence beyond ‘chronic 6’ have a similar scc profile and similar proportion of recovery. figure 2 shows the distribution of high scc mrs between scc magnitude categories for different parities. figure 2: distribution of high scc mrs between scc magnitude categories for different parities on aggregate, 29% of high scc in parity 3 and above had a magnitude of ≥700 thousand cells/ml, compared with 23% in second parity and 24% in first parity. the proportions of lower magnitude scc categories tend to decrease and higher magnitude scc categories tend to increase with increasing parity. this is in parallel with progressively lower recovery probability with increasing parity (table 2). a separate breakdown of high scc type between different parities also showed that the proportion of high scc that were chronic was greater in higher parities (55% chronic in parity 3 and above, compared with 47% in second parity and 39% in first parity). figure 3 shows the distribution of high scc mrs between scc magnitude categories for different stages of lactation. figure 3: distribution of high scc mrs between scc magnitude categories for different stages of lactation the proportion of very high magnitude high scc decreases from early to late lactation, whilst the probability of recovery also decreases (table 2). a separate breakdown of high scc type between different stages of lactation also showed that the proportion of high scc that were chronic was greater in mid and late lactation compared with early lactation (58% and 57% chronic in late and mid lactation, compared with 33% in early lactation).   odds and probability of recovery estimated by mixed effect logistic regression modelling the above descriptive analysis indicated that the magnitude and category of high scc, the parity of the lactation and the stage of lactation could all influence the recovery probability (table 2). however, figures 1, 2 and 3 show that these factors are potentially confounded, so the descriptive analysis alone cannot determine the relative importance of these three factors. therefore, a multilevel longitudinal logistic regression model was used to clarify the associations between the various explanatory factors and recovery probability. the results of the mixed effect logistic regression model are summarised in table 3.   random effects         groups name variance   standard deviation   individual animal (intercept) 0.03862   0.1965   herd (intercept) 0.04488   0.2118   fixed effects           variable level estimate standard error odds/odds ratio 95% confidence interval fixed effects           intercept   1.58** 0.07 4.85 4.23–5.57 days in milk (days) dim.c1 (≤ 100)‡ 0.00       dim.c2 (101 to 200) -0.08* 0.04 0.92 0.85–1.00 dim.c3 (> 200) -0.41** 0.04 0.67 0.61–0.72 scc (thousand cells per ml) scc.c1 (200 to 249)‡ 0.00       scc.c2 (250 to 299) -0.30** 0.04 0.74 0.68–0.81 scc.c3 (300 to 349) -0.47** 0.05 0.62 0.56–0.69 scc.c4 (350 to 699) -0.66** 0.04 0.52 0.48–0.56 scc.c5 (scc ≥ 700) -0.82** 0.04 0.44 0.41–0.48 high scc category (descriptive) new‡ 0.00       first heifer -0.07 0.09 0.94 0.79–1.11 first new 0.06 0.07 1.06 0.92–1.22 first chronic -0.27** 0.07 0.76 0.66–0.87 repeat -0.54** 0.04 0.58 0.53–0.63 chronic 1 -1.25** 0.04 0.29 0.26–0.31 chronic 2 -1.68** 0.06 0.19 0.17–0.21 chronic 3 -2.01** 0.08 0.13 0.12–0.15 chronic 4 -1.93** 0.09 0.15 0.12–0.17 chronic 5 -2.28** 0.12 0.10 0.08–0.13 chronic 6 -2.28** 0.14 0.10 0.06–0.13 chronic 7, 8, 9, 10 -2.41** 0.11 0.09 0.07–0.12 parity (number of calvings) first calving (heifer)‡ 0.00       second calving -0.49** 0.05 0.61 0.56–0.67 third calving -0.65** 0.05 0.52 0.47–0.57 fourth to sixth calving -0.92** 0.05 0.40 0.37–0.44 seventh and above calvings -1.04** 0.07 0.35 0.31–0.40 size of the herd (number of cows) small (≤100 cows)‡ 0.00       medium (101 to 200 cows) 0.01 0.05 1.01 0.92–1.11 large (>200 cows) 0.06 0.0 1.06 0.96–1.17 ‡ used as the reference case in the multilevel, mixed effect logistic regression model statistical significance indicated by asterisks: ** p<=0.001; * p<=0.05 null deviance = 32998.4 (on 30040 df), pseudo-r2: marginal = 0.27 (represents the variance explained by the fixed effects), conditional = 0.28 (is interpreted as a variance explained by the entire model, including both fixed and random effects) . aic = 33056.4 < aic null model (just the random effects) =  36730.6; bic = 33297.5 < bic null model (just the random effects) = 36755.5 table 3: summary of the multilevel, mixed effect logistic regression   the results of the model provide information on both the random as well as the fixed effects within the sample. the different measurements and hence recovery probabilities are considered for each individual animal which is also clustered within different herds. according to the outcome of the model, small variability is observed amongst the individual animals (0.0386) and the same can be concluded for the variability amongst the different herds (0.04488). in table 3 the intercept is the log of the estimated odds of recovery for the reference case of high scc (i.e. a first parity animal in a small herd that is in early lactation with a ‘new’ high scc of 200–249 thousand cells/ml). this is referred to as the overall intercept in the linear relationship between the log of odds and the independent variables of the model. the antilog of this gives the odds of recovery (4.85). the estimate for each level of each variable is the log of the odds ratio (or) comparing the odds of an animal recovering with the odds for the reference case. the antilog of this estimate gives the or itself, which is shown in table 3 with the 95% confidence interval. if the 95% confidence interval of the or does not include unity then there is a significant difference (p<=0.05) in recovery odds, and also probability, between the reference case and a case in which only that factor is different (at the relevant level). a statistically significant association was not observed between herd size and recovery probability, but we chose to keep the herd size factor in the model for completeness having checked that removing the factor did not affect the other estimates. recovery odds can be converted to recovery probability (expressed as a decimal number between 0 and 1), which is easier to interpret, using the equation: probability = odds / (1+odds). for the reference case this gives a recovery probability of [4.85 / (1 + 4.85)] = 0.83 (i.e. the model suggests that 83% of cases like the reference case are expected to recover). table 4 shows the estimated recovery probabilities for cases that differ from the reference case in only one aspect at each level of the different variables in the model. for example, the recovery probability for a case with scc category 2 (with other variables the same as the reference case) is estimated as 0.78. the results of the mixed effect logistic regression model, as shown in tables 3 and 4, indicate that the ‘first heifer’ and ‘first new’ category of high scc did not have significantly different recovery probability for when compared to the reference case (‘new’). most importantly, table 4 clearly indicates that the chronic categories of high scc are associated with the most dramatic reductions in recovery probability. the model indicates that the recovery probability is dramatically reduced even after just two consecutive high scc, from 0.83 (reference case) to 0.58 (‘chronic 1’). the estimated recovery probabilities for ‘chronic 2’ and above are increasingly reduced. increasing magnitude of scc also significantly reduces recovery probability, but by a smaller margin than even ‘chronic 1’ compared to ‘new’.   variable level probability intercept (reference case) dim ≤100; scc 200 to 249; ‘new’; first calving; small herd (≤100 cows) 0.83** days in milk (days) dim.c2 (101 to 200) 0.82* dim.c3 (>200) 0.76** scc (thousand cells per ml) scc.c2 (250 to 299) 0.78** scc.c3 (300 to 349) 0.75** scc.c4 (350 to 699) 0.72** scc.c5 (scc ≥ 700) 0.68** high scc category (descriptive) first heifer 0.82 first new 0.84 first chronic 0.79** repeat 0.74** chronic 1 0.58** chronic 2 0.47** chronic 3 0.39** chronic 4 0.41** chronic 5 0.33** chronic 6 0.33** chronic 7, 8, 9, 10 0.30** parity (number of calvings) second calving 0.75** third calving 0.72** fourth to sixth calving 0.66** seventh and above calvings 0.63** size of the herd (number of cows) medium (101 to 200 cows) 0.83 large (>200 cows) 0.84 statistical significance indicated by asterisks: ** p<=0.001; * p<=0.05 table 4: estimates of recovery probability for each level of the different variables   examples of estimating the expected recovery probabilities for specific high scc cases using the output of the regression model the expected recovery odds for cases with any combination of variable levels can be estimated by summing all the relevant log ors (for different variable levels) and adding to the log odds (intercept/reference case), then antilogging. the odds can then be converted to probability of recovery using the equation: probability = odds/(1+odds). for example, figures 4a and 4b show the estimated recovery probabilities for a third parity cow in a medium sized herd. figure 4a illustrates expected recovery probabilities for different categories of high scc occurring in mid-lactation, by magnitude of scc. figure 4b illustrates expected recovery probabilities for different categories of high scc, with a scc between 300 and 349 thousand cells/ml, by stage of lactation. note that these recovery probabilities represent the expectation for the ‘average’ high scc case in the dataset used for this analysis. these charts show that more than 50% of ‘new’ high scc cases may be expected to recover regardless of the magnitude of the scc or stage of lactation, within the range of the scenarios illustrated. in contrast less than 40% of ‘chronic’ high scc cases may be expected to recover in all comparable scenarios. the recovery probability for a ‘repeat’ high scc may be above or below 50% depending on the magnitude of the scc. figure 4 demonstrates the large difference in recovery probabilities between ‘new’ and ‘chronic’ cases. in particular there is a large decrease in recovery probability between ‘new’ and ‘chronic 1’. recovery probability declines further as a consecutive high scc sequence progresses. note that the model does not estimate significantly different recovery probabilities for ‘chronic 3’ and ‘chronic 4’ or for any cases including and beyond ‘chronic 5’. the slopes of the lines in figure 4a flatten out as the categories of high scc move from ‘new’ to ‘chronic 1’ through to ‘chronic 7, 8, 9, 10’. this indicates that the magnitude of scc becomes less influential for recovery probability in these chronic cases. figure 4: estimated recovery probabilities for different categories of high scc, for a third parity cow in a medium sized herd, by magnitude of scc (fig. 4a) and by stage of lactation (fig. 4b) figure 4b shows that expected recovery rates are slightly lower in late lactation than in early and mid-lactation. however, the impact of type of high scc is far greater: for all magnitudes of high scc, except the very lowest, and in all stages of lactation expected recovery probability for a chronic 1 high scc (i.e. after just two consecutive high scc) is around half or less of the probability for a ‘new’ high scc.   discussion late stage of lactation, increasing magnitude of scc and increasing parity of the cow all have significant influence on decreasing recovery probability, but the most dramatic reductions in recovery probability are associated with chronic high scc. the expected recovery probability after just two consecutive high sccs is around half or less the probability expected for a ‘new’ high scc. none of the factors other than chronicity reduce the recovery probability by more than 0.2 on average, but having even just two consecutive high scc (i.e. ‘chronic 1’) reduces the recovery probability by over 0.2 on average. once there have been three or more consecutive high scc (‘chronic 2’ and above) the recovery probability is reduced by between 0.3 and 0.5. as an example, figure 4a shows that ‘on average in this dataset’ a mid-lactation third parity cow with a ‘new’ high scc has a greater than 50% recovery probability even if the scc is ≥700 thousand cells/ml whereas a similar cow with any chronic high scc has a less than 50% recovery probability regardless of the magnitude of the scc. limitations and strengths of the study a limitation in the data is that there is no information about management interventions or treatments applied to the high scc cases, which would doubtless be an important determinant of recovery. however, compared to the number of high scc cases included in the dataset, the number of interventions is likely to be small enough as to have little effect on the main conclusions of the study. the monthly frequency of mrs also means that shorter term variations in scc, particular above and below 200 thousand cells/ml, are not captured. however, this analysis is based on exactly the same quality of data as is routinely available to farmers and veterinarians and therefore the results should be directly applicable to the ‘real world’ situation they face. this large dataset provides an overview of ‘average’ probabilities that high scc cases will recover to low scc at the next month’s mr, under prevailing ‘real-life’ conditions (which no doubt included a variety of interventions in some cases) and as such, provides valid evidence to support decisions about management of scc in farmers’ herds. the analysis is based on a sample of high scc cases from 499 uk dairy herds. while there may be different herd-specific factors influencing recovery in individual herds, the trends in recovery probabilities observed in this dataset could reasonably be expected to apply to other similar dairy herds in uk. the descriptive analysis of the data showed that factors that potentially influence the probability of recovery from a high scc to low are inter-linked. for example: high magnitude scc (≥700 thousand cells/ml) have a lower recovery probability; chronic high scc have a lower recovery probability (decreasing as the chronic sequence progresses); also the percentage of high scc with ≥700 thousand cells/ml is increased in chronic high scc (and increasing as the chronic sequence progresses) and also a higher percentage of high magnitude scc are chronic compared to lower magnitude scc. so, the question arises as to whether the reduced recovery probabilities seen in high magnitude scc and chronic scc are related to the magnitude of scc or the chronicity of the high scc, or a combination of both factors. the multilevel, mixed effect logistic regression model analysis, including several factors in the one model is a tool to answer this question. fitting the data in a regression model is a way to estimate the significance and relative strengths of the influences of several different factors on recovery probability when all factors are taken into account together. implications of the results dealing with cows with persistently high scc is important because there is a strong correlation between the percentage of chronic high scc recorded by a herd and the herd average scc, reflected in the bulk milk scc (bmscc) that may determine price penalties. hanks and james (2011) discussed the need for monitoring cows with chronic high scc and preventing cows persisting with chronic high scc. analysis of annual key performance indicators in 500 herds showed that of herds where under 10% of milk samples were classed as chronic high scc, just 9% had an annual average herd cell count above the penalty level of 200 thousand cells/ml. on the other hand, of herds where over 15% of milk samples were classed as chronic high scc, 92% had an annual average herd cell count above the penalty level. while the numbers of herds with under 10% of milk samples classed as chronic high scc has increased over the years, and the numbers of herds with over 15% of milk samples classed as chronic high scc has decreased, the relationship between the percentage of chronic high scc recorded and the average herd scc has remained both qualitatively and quantitatively consistent (hanks and kossaibati, 2018). a high scc may be apparently transient, returning (‘recovering’) to low scc at the next monthly milk recording. with better understanding of factors influencing the probability of ‘recovery’, decision making on how to manage cows with high sccs in the most effective manner to minimise both production loss and unnecessary interventions that might include antimicrobial use could be improved. recognising factors associated with an increased probability that a cow will ‘recover’ from a high scc, e.g. a ‘new’ high scc in a young cow, not in late lactation, would support a decision not to intervene. on the other hand, these results show a dramatic and progressive reduction in recovery probability for chronic high scc cases after just two consecutive high scc. this supports prioritising management intervention for cows that record two consecutive high scc, rather than continue to ‘wait and see next month’ (e.g. bacteriological sampling, only to be followed by use of appropriate antimicrobials if clinically justifiable). sol et al. (1997) presented an analysis of factors associated with success rates of in-lactation treatment of subclinical mastitis. among their findings was that lower scc resulted in a better cure rate, which suggests the treatment option should only be considered favourably for cows with a chronic sequence of high scc if the magnitude of high scc is not too great. if a cow has had more than two consecutive high scc, alternative interventions such as drying-off the affected quarter only, early dry-off with antimicrobial dry cow therapy or cull may be considered. deluyker et al. (2005) also present analysis of factors affecting cure and also reduction in scc after different interventions on sub-clinical mastitis. significant factors included bacteriological factors, highlighting the importance of bacteriological investigation before making intervention decisions. these results could be utilised in a decision-support application to be applied at cow level to assess recovery probability and compare the estimated cost of not intervening with the costs and benefits of intervention options such as early drying-off, cull or other ‘in-lactation’ treatments. an application could take into account the factors included in the analysis presented here and several other factors such as the recorded scc and mastitis history of the cow in previous lactations, the likelihood of a treatment to succeed, and the potential loss of milk output versus the potential reduction in bulk milk tank scc if a high scc is dried-off early. evidence from other studies could be included in such an application: for example sol et al. (1997) and deluyker et al. (2005). dairy herd management software frequently presents scc reports that sort in descending order of scc magnitude, leading the farmer to focus attention on the cows with the highest scc. this analysis clearly shows that the category of high scc (scc history, chronicity) is a more important consideration in terms of the prognosis for the cow and the most important factor to consider when deciding on the course of action. furthermore, this analysis has brought out the importance of including the number of consecutive high scc associated with a chronic high scc in reports. cows having had two consecutive high scc (‘chronic 1’ in this study) should be highlighted separately from cows with more consecutive high scc mrs. currently dairy herd management software often presents the percentage of chronic high scc, but if farmers are targeting scc management interventions particularly on the ‘chronic 1’ cases, the success of scc management could be assessed by monitoring the percentage of ‘chronic 2’ and above. dairy herd management software is capable of presenting this level of detail. dairy herd management software companies should work with farmers and their advisors to ensure scc data are presented in the most useful way, allowing easy interpretation and translation into the most effective interventions that can increase the efficiency of the dairy industry as well as avoiding needless or ineffectual interventions, that may include use of antimicrobials.   conflict of interest acknowledgments: the authors would like to thank the farmers who gave permission for their data to be used in this analysis and national milk records (nmr) for making the data accessible. funding: the authors would like to thank the university of reading for providing funding for the first author under the undergraduate research opportunity programme (urop). competing interests: the authors declare no conflict of interest.   references archer, s.c., mc coy, f., wapenaar, w. & green, m.j. 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(2016). failure and preventive costs of mastitis on dutch dairy farms. j. dairy sci. 99, 8365–8374. doi: http://dx.doi.org/10.3168/jds.2015-10561   intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. survival and presenting complaint of canine and feline paediatric emergencies presenting to uk emergency clinics emma donnelly bsc. (hons), bvms, mrcvs1* amanda boag ma vetmb dacvim dacvecc fhea decvecc mrcvs1 daniel h lewis ma vetmb cva dacvecc decvecc mrcvs1 ide hearun bvms (hons)2 laura playforth bvm&s, mrcvs1 1vets now, 123 north street, glasgow, g3 7da 2university of melbourne veterinary hospital, 250 princes highway werribee, victoria 3030, australia *corresponding author (emma.donnelly@vets-now.com) vol 3, issue 3 (2018) published: 04 jul 2018 reviewed by: bruce smith (bvsc ms fanzcvs dacvs) and shailen jasani (ma vetmb mrcvs dacvecc) doi: 10.18849/ve.v3i3.174 section index:    abstract | introduction | methods | results | discussion | footnotes | conflict of interest | references | supplementary files abstract objective: to describe the presenting problems for paediatric dogs and cats presented to emergency clinics, and to determine what factors influence mortality. background: there is a lack of published literature available on canine and feline paediatric emergencies, their survival rates and factors that contribute to mortality. experience and opinion largely replace evidence-based medicine when treating this subset of the emergency population. evidentiary value: evidentiary value for primary and emergency care practitioners is strong as the data is based on a large primary emergency care database. the paediatric population analysed consisted of 3142 paediatric canine and feline patients. methods: a retrospective review of canine and feline emergency admissions to emergency out-of-hours clinics (may 2012-january 2014) was conducted. data recorded included age, nature of complaint, euthanasia/death during treatment, and survival to discharge. survival to discharge included all patients who presented to the clinic for examination, received treatment and were subsequently discharged; this includes those patients who were discharged  home or to their primary vets care. patients were divided into four groups: canine patients ≤ 3 months of age and 3-6 months and feline patients ≤ 3 months of age and 3-6 months. results: paediatric patients represented around 3% of the emergency cases identified in the database. survival to discharge in patients ≤3 months of age was significantly reduced in comparison to patients between 3-6 months of age, in both species. feline paediatric patients had reduced survival to discharge compared to their canine counterparts. conclusion: paediatric patients have a low survival rate, indiscriminate of species and reason for presentation, with lower survival in younger animals; with a significant difference in survival between canine and feline patients. application: the results of this study are important to small animal veterinarians in both emergency and non-emergency practice. introduction paediatric and neonatal patients are intrinsically less able to adapt and respond to changes and insults. in the author’s opinion, this group frequently presents to out-of-hours clinics as emergency patients. however, there is no epidemiological data available to confirm this. although there is no universally agreed nomenclature, generally speaking, patients between two and six weeks are referred to as infants, between six and 12 weeks as weanlings and those between 12 weeks of age and six months are referred to as juvenile patients (mathews 2005). in more general nomenclature, the term ‘neonate’ describes those from birth to two weeks of age while ‘paediatric’ describes those from two weeks to six months (mcmichael 2015).  given this lack of consensus in the nomenclature, but the commonly accepted observation that dogs and cats <6 months of age represent an easily identified, immature population, for the purposes of this article we will describe all dogs and cats <6 months of age as ‘paediatric’. paediatric and neonatal canine and feline patients have low body energy reserves, an immature physiology, an altricial (or highly dam-dependent) nature and a high metabolic rate, which can lead to rapid changes in their clinical status and subsequent presentation in a critical condition (gunn-moore 2006; centre et al. 1995). they also have a developing immune system and so are inherently more susceptible to infectious disease (munnich et al. 2014). in comparison to adult canine and feline patients, their altered physiology and the differing underlying aetiologies of conditions can also complicate clinical examination and treatment decisions (mcmichael 2015). feline and canine neonatal and paediatric patients are tachycardic in comparison to their adult counterparts, with a normal paediatric heart rate being around 200 bpm for puppies and 250 bpm for kittens. they also have lower blood pressure than adult patients (magrini 1978); however, their blood pressure increases as their sympathetic nervous system matures over the first few months of life. in the canine patient, mean arterial blood pressure does not reach a ‘normal’ adult value until around nine months of age. at one month of age, a systolic pressure of 48mmhg is thought to be normal (magrini 1978); this is not only lower than that of adults but below even the mean arterial pressure at which impaired tissue perfusion is often considered to be occurring in most adult patients (cooper 2015). auscultation of the lungs of paediatric patients can be complicated by their increased respiratory rate and inherently higher interstitial fluid content (tonneson et al. 2012), leading to normal breath sounds being interpreted as adventitious. such differences in the respiratory and cardiovascular systems can complicate assessment of perfusion in these patients. a prospective study in 68 puppies and 30 adult dogs revealed that lactate has the potential to be a suitable marker of hypoperfusion (mcmichael 2005). however, as with other haematological and biochemical values, adult reference ranges cannot be applied to neonatal dogs and cats. a definitive reference range for lactate has not yet been established. physiological and behavioural responses to critical illness differ from adult patients, sometimes masking the severity of the situation; this disparity is described well in human paediatric medicine (woollard et al. 2004), although it is often under-emphasised in the veterinary literature. a thorough understanding of small animal paediatric patients’ clinical, haematological, biochemical and pharmacological differences from their adult counterparts is vital in triaging, stabilising and treating such patients. in human medicine there is recognition of the limitations of treating paediatric patients in an adult-focused environment and as such paediatric emergency and critical care has become a separate sub-speciality (rcph, 2008).  there is little published literature available for paediatric and neonatal veterinary patients, particularly dogs and cats. in canine neonatal patients, infectious diseases are the second leading cause of mortality (nielen 1988). a limited number of case reports for small animal neonatal patients can be found in the literature, however, to the authors’ knowledge, there are no large-scale epidemiological studies available (chellani et al. 1985; gupta, et al. 1996). a greater body of literature exists for neonatal disease in other species, such as horses, perhaps due to their perceived greater individual value. the mortality rate of adult canine and feline patients presenting to out-of-hours emergency practice has been reported as 11.9% and 20.2% respectively (firth et al. 2014), however no such data has as yet been explored for paediatric patients. given these differences between paediatric and adult patients and due to the lack of literature available, this study aimed to identify the most common causes for presentation of canine and feline paediatric patients to a group of emergency out-of-hour clinics, to ascertain the survival to discharge for such patients and to determine whether factors such as the presenting complaint or age influence survival. methods data collection: the electronic medical record (emr) database of 50 dedicated emergency clinics between may 2012 and january 2014 was used as the data source. all emergency clinics use the same centralised clinical records system1 on which the data of all patients who contact the clinics is recorded; first contact with the clinic is primarily by telephone . all canine and feline paediatric patients (defined as less than six months of age at the time of presentation) were identified and the following information was recorded for the patients who contacted the clinics: species, age, presenting complaint and outcome. presenting complaint was coded using standardised nomenclature (venom) accessed via a drop-down menu in the electronic medical record. the responsible clinician for each patient selected the most appropriate presenting complaint; the computer software allows one complaint to be recorded for each patient. the paediatric patients who did not present to a clinic following initial contact  and those who presented but were subsequently discharged against veterinary advice with no further treatment were excluded from the study. outcome was recorded as survival to discharge or non-survival (including death during hospitalisation, dead-on-arrival and euthanasia). for analysis, the patients were further subdivided into species and then into age groups: those ≤3 months of age at presentation (canine group a, feline group c) and those between three and six months of age at presentation (canine group b, feline group d). statistical analysis: descriptive statistics and chi-square analysis was performed using a standard software package2 to compare survival to discharge versus non-survival between canine (groups a and b) and feline patients (groups c and d), between inter-species cohorts (groups a and b vs groups c and d) and the presenting complaint of all patients (group a, b, c and d). results a total of 119261 emergency canine and feline cases contacted the clinics during the studied period; of these, 81241 patients were canine, and 38020 were feline. a total of 3236 of these patients were paediatric as previously defined: 2311 were puppies, and 925 were kittens. ninety-seven percent of canine paediatric patients (2250/2311) and 98% of feline patients (910/925) presented for examination. patients who did not present to the clinic or presented to the clinic but were discharged against veterinary advice were excluded from further study (table 1). patients that underwent further veterinary evaluation were grouped according to species and their age at presentation.  group a (dogs ≤ 3months of age at presentation) and group b (dogs 3-6 months) consisted of 545 and 1688 puppies respectively.  group c (cats ≤ 3months) and group d (cats 3-6 months of age) contained a total of 243 and 666 kittens. there was no statistically significant difference between contact and subsequent presentation to the clinic between species (p=0.8). table 1: outcome recorded for all canine/feline patients whose owners contacted the out-of-hours clinics for advice group a group a’s overall survival was 62.5% (table 1). the three most common presenting complaints were vomiting (17%), diarrhoea (8%) and collapse (7%). patients who presented for vomiting had a survival rate of 71% while those presenting for diarrhoea had a survival rate of 78.6%. group a patients presenting with vomiting and diarrhoea were not significantly less likely to survive than the other paediatric patients however, those who presented collapsed had a significantly lower survival rate (22.5%) than other paediatric patients irrespective of age, species or presenting complaint (table 2) (p<0.001). of the patients who did not survive to discharge in group a, 81% were euthanised (figure 2). table 2: outcome recorded for the three most common presentations for the canine patients < 3months old who attended the clinic and followed veterinary advice. categories indicated by matching symbols (* ǂ § ʃ ¢) indicate pairs where survival was significantly different group b group b’s overall survival was 82.3%. the three most common presenting complaints were vomiting (18%), diarrhoea (9%) and trauma (7%).  patients who presented for vomiting had a survival rate of 91%; this was significantly higher than puppies within the same age category    presenting with other complaints (p <.001). patients in group b presenting for diarrhoea had a survival rate of 89.9%; this was significantly higher  than paediatric patients in groups a, c and d (p <.001). however, these patients  (group b patients presenting for diarrhoea) were not significantly more likely to survive than other group b puppies.   patients who presented following trauma had a survival rate of 74.1%; this was not significantly different to other paediatric patients. (table 3). of the patients who did not survive within group b, 82.4% were euthanised (figure 2). table 3: outcome recorded for the three most common presentations for canine patients 3-6 months old who attended the clinic and followed veterinary advice.  categories indicated by matching symbols ( * ǂ § ʃ ¢) indicate pairs where survival was significantly different group c group c’s overall survival was 26.3%. the most common causes of presentation were collapse (23%), trauma (17%) and lethargy (11%).  feline patients less than 3 months of age had a significantly lower survival rate when compared to other paediatric patients, regardless of species. within this group, those who presented collapsed and following trauma were significantly less likely to survive than other paediatric patients (group a, b and d), with survival of 10.7% and 19% respectively (p <.001). however, they were not significantly less likely to survive than other patients within the same age group presenting with different complaints. the survival rate (44.4%) of group c kittens presenting with lethargy was not significantly lower than other feline paediatric patients (table 4). of the patients who did not survive to discharge within group c, 90.5% were euthanised (figure 2). table 4: outcome recorded for the three most common presentations for the feline patients < 3months old who attended the clinic and followed veterinary advice. categories indicated by matching symbols ( * ǂ § ʃ ¢) indicate pairs where survival was significantly different group d group d’s overall survival was 55.6%. the most common presenting complaints for group d patients included trauma (15%), collapse (12%) and lethargy (11%). patients who presented following trauma were significantly less likely to survive than kittens of the same age who presented for other complaints, with a survival rate of 40% (p <.01). collapsed patients (survival rate of 23%) were less likely to survive than other paediatric patients regardless of species, complaint or age (p <.001). patients who presented for lethargy had a survival rate of 65.2%; these patients were more likely to survive than other paediatric kittens (table 5) (p <.005). of the patients who did not survive to discharge within group d, 92% were euthanised. table 5: outcome recorded for the three most common presentations for the feline patients 3-6 months old who attended the clinic and followed veterinary advice. categories indicated by matching symbols ( * ǂ § ʃ ¢) indicate pairs where survival was significantly different summary younger puppies, as a group, had a lower survival to discharge than the older group of puppies (table 1) (p <.001). kittens ≤ 3 months of age at presentation (group c) were less likely to survive to discharge than puppies within the same age range (group c) (p <.001),    with kittens having a relative risk of death of 1.96. younger paediatric patients (groups a and c) had a lower survival to discharge than older pediatric patients (groups b and d) (p <.001), with a relative risk of death of 1.94. puppies between three and six months of age (group c) were more likely to survive to discharge than kittens in the equivalent age group (group d) (p <.001), with a relative risk of death of 2.54. paediatric kittens (groups c and d) were less likely to survive than puppies (groups a and b) (figure 1) (p <. 001), with a relative risk of death of 2.33. figure 1: % survival for paediatric patients who received veterinary treatment. group a canine patients ≤3 months of age; group b canine patients 3-6 months of age; group c feline patients ≤3 months of age; group d feline patients 3-6 months of age figure 2: displays the number of patients who did not survive to discharge; detailing those who died during treatment and those who were euthanised. (group a canine patients ≤3 months of age; group b canine patients 3-6 months of age; group c feline patients ≤3 months of age; group d feline patients 3-6 months of age.) discussion our study revealed that older paediatric patients were significantly more likely to survive than younger paediatric patients.  as described earlier, paediatric animals have inherently smaller reserve capacities, both in terms of energy stores and in homeostatic function (gunn-moore 2006). as these patients age, these capacities increase as their physiology approaches that of their adult counterparts. the impoverished veterinary literature regarding small animal paediatric medicine may translate into reduced clinician knowledge and familiarity with this population; hence, the low survival rate may therefore also highlight a gap in our understanding of such patients, making their treatment less effective. a future study of a similar population could be designed to determine the impact of clinician experience/qualification upon the survival of these patients. there are notable species differences, with canine paediatric patients having a much greater chance of survival compared to feline paediatric patients. this finding appears to be universally true, irrespective of the age groups considered. the most common presenting complaints differed between the two species and  also differed within species when the two age groups were compared; canine patients were more likely to be presented for vomiting and diarrhoea. however, the third most common complaint differed between the age groups with younger puppies presenting for collapse whilst older puppies presented following trauma.. feline paediatric patients presented most commonly for lethargy, collapse and trauma; the incidences for each differed  between the age groups with trauma being more common within the older feline patients. one difficulty with the retrospective nature of this study is that patients are placed into distinct categories for their presenting complaint, which is chosen subjectively: for example, patients with gastrointestinal signs could be placed into the collapsed or lethargic categories according to clinician opinion. the ability to record only one presenting complaint is a limitation of the database recording system used in this study and future studies should be designed to overcome this issue. specific abnormalities such as hypoglycaemia, hypovolaemia, dehydration and hypothermic episodes may accompany many of the recorded presenting complaints and may contribute to hospital presentation as they are a frequent complication in puppies and kittens. however, this study did not allow analysis of the medical records in this level of detail. of the most common emergency presentations amongst canine paediatric patients, the collapsed patients had the highest mortality rate as previously described; the survival rate in puppies ≤3 months of age was 22.5%, in feline patients ≤3 months of age was 10.7% and in feline patients 3-6 months of age was 23.2%. this is less than the reported survival of 43% for collapsed adult patients (firth et al. 2014). a lower survival rate could be explained by the different causes of collapse and the physiologic limitations of paediatric patients. hypoglycaemia is a commonly reported problem in young small breed puppies and can lead to weakness and collapse (koenig 2015), with blood glucose levels <2.2mmol/l associated with the development of clinical signs (bergman 2005). neonatal and paediatric patients have a higher demand for glucose but are less able to respond to increasing needs for glucose as they have impaired hepatic gluconeogenesis. in addition to this they also have a reduced ability to respond appropriately to hypoglycaemic episodes when calorie intake is reduced for any reason, such as gastrointestinal disease and pain secondary to trauma.  diagnosing hypoglycaemia can be more difficult in this population as their response to a hypoglycaemic episode differs from adults. as this study is retrospective we do not know the percentage of paediatric patients who were hypoglycaemic at the time of presentation. given the marked effects of hypoglycemia in paediatric patients, assessment of blood glucose level should form part of the minimum database collected for emergency paediatric patients.  gastrointestinal disease was the most common emergency presentation in canine paediatric patients; survival to discharge increased with increasing age but remained lower than that reported for adult patients (95%) (firth et al. 2014). vomiting and diarrhoea are common emergencies in paediatric patients and often occur due to gastrointestinal disease; their limited capacity to cope with illness means that these patients can become rapidly dehydrated and hypovolaemic, which can contribute to collapse. adult patients will respond to dehydration by reabsorbing water via their kidneys, however younger patients cannot concentrate their urine (booth 1992; holster 1971; fetuin 1991).  this can lead rapidly to hypovolaemia secondary to severe dehydration.  adults respond to hypovolaemia by increasing their heart rate and vasoconstriction to maintain blood pressure. in our group of patients, the sympathetic nervous system is immature, and so this response is limited particularly before eight weeks of age; their physiological immaturity may predispose them to increased morbidity and mortality when gastrointestinal disease is present.  determining the level of dehydration is difficult as paediatric patients will continue to have moist mucous membranes whilst being severely dehydrated; they have a higher water content present within their skin than adults, and therefore skin tenting is not a useful part of the clinical examination (mcmichael 2015). difficulties in assessing the level of hydration may contribute to the reduction in survival rate; inadequate fluid resuscitation may exacerbate hypovolaemia in these more vulnerable patients. infectious disease, parasitic infection, intussusception and foreign bodies are common causes of gastrointestinal disease in puppies and kittens. paediatric patients are not immunologically or physiologically mature; and as patients mature, survival increases. another factor associated with this, which may in part also contribute to the differing survival in canine patients ≤3 months and ≤6 months, would be vaccination. canine parvovirus is a devastating disease with a reported mortality rate up to 91% in untreated patients (prittie 2004). we would expect that patients between three and six months of age may be vaccinated whilst those <3months of age may be less likely to have completed their vaccination course.  there is an expectation that maternally derived antibodies protect younger puppies against disease prior to vaccination. however, it cannot be said that this level of protection is uniform and the timing of susceptibility when these antibodies wane is variable (day 2014). one study evaluating the risk factors associated with parvoviral enteritis in dogs found that those who were unvaccinated were 1.7 times more likely to require hospital admission than those who had been vaccinated (hooston 1996). due to the retrospective nature of this study the vaccination status of our patients is unknown; future prospective studies investigating the underlying cause of diarrhoea and documenting the patient’s vaccination status would be beneficial. feline patients were seen more commonly for collapse and trauma. increasing age was associated with an increase in survival to discharge following trauma. patients less than six months old had a lower survival rate following trauma than their adult counterparts, reported as 77% (firth et al. 2014). feline patients’ small size may make them more susceptible to falling from a height such as from owners arms and they may be more likely to be stepped on in the home. another consideration that could account for the low survival is that the small size of these patients makes gaining intravenous access, placement of feeding tubes and general management more challenging.  veins are often small and peripheral blood pressure is lower in healthy paediatric patients compared to the adult dog and cat; in reality intravenous access is perhaps not any more challenging to attain, however, the perception of difficulty may deter repeated attempts to gain vascular access.  determining the success of resuscitation is also more challenging in younger patients as the end-points of resuscitation are not as easily identified.  blood pressure is an important indicator of macro-perfusion, therefore differences between neonatal and adult patients may lead to errors in ascertaining response to resuscitation effort. micro-perfusion can also be difficult to determine as both puppies and kittens are reported to have higher lactate values than their adult counterparts (mcmichael 2005), however a definitive normal reference range has not been established.  this may in part explain the low survival rate in paediatric patients presenting collapsed; their response to treatment is inherently more difficult to assess, limiting the practice of goal-directed therapy. in our study, irrespective of the group, euthanasia was the greatest reason that the patients were ‘non-survivors’; the reasons for this are unfortunately beyond the scope of this study. as previously described financial implications must be considered to be a leading cause, although in the authors’ opinion the decision to euthanise these patients is most likely to be multi-factorial.   it is possible that, unfortunately, the human-animal bond may not be as strong with paediatric patients, and so clients may be more inclined to euthanise on financial grounds rather than proceed with veterinary treatment.  euthanasia itself prohibits the development of paediatric veterinary medicine; it limits clinician experience with this age group but also precludes clinical research. as a consequence, anecdotal experience often replaces evidence-based medicine. this is vastly different from our human medicine colleagues who are afforded the opportunity to invest time and finances in treating their patients. the mortality rate following paediatric admission to emergency departments is very low in human medicine reported as less than 1% in english and welsh hospitals in 2015/2016 (keeble 2017). this study provides important information regarding mortality rates in a large population of paediatric animals presenting as emergencies to multiple out-of-hours clinics. the study is limited by its retrospective nature no diagnosis was recorded for patients and the single, broad categories for presentation recorded are likely to lead to overlap between groups in terms of the reported complaint. as discussed there is no recording of the reasons for euthanasia such as financial limitations or medical/welfare grounds. also, as a diagnosis is not recorded we cannot say if the decision to euthanise was based on the patient’s perceived prognosis. as the data was sourced from a large central body obtained from multiple sites it was not possible to ascertain if there were geographical differences in relation to survival. as it was a multi-centre study the clinical outcome may have been affected by differences in clinician approach. however, despite the limitations, the conclusions of this study are clear: survival of paediatric patients presented to emergency clinics within the uk is low but increases with patient age. moreover, paediatric feline patients have significantly lower survival rates than canine patients. further prospective studies are required to fully elucidate the causes of mortality in neonatal and paediatric patients, as well as to investigate whether clinician experience or the application of an algorithmic approach to these patients might alter survival. such bundles of care have been introduced in both human medicine, the surviving sepsis campaign3, and in veterinary medicine, the recover 4 guidelines. the increased evidence base that such research would create, together with its promulgation to practising veterinarians, should drive improvements in clinical care in order to decrease the gap in survival between small animal paediatric patients and their adult counterparts in the future. footnotes helix socscistatistics http://survivingsepsis.org/pages/default.aspx http://www.acvecc-recover.org conflict of interest the authors declare no conflicts of interest. acknowledgement is given to the many and various members of staff at the emergency clinics sampled in this study, for the recording of the clinical data used. references role of consultant paediatrician with subspecialty in paediatric emergency medicine, rcpch, 2008. http://www.rcpch.ac.uk/child-health/standards-care/service-configuration/emergency-and-urgent-care/ emergency-and-urgent-care. bergman, r.l., coates, j.r. 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(2012) canine perinatal mortality: a cohort study of 224 breeds.theriogenology 77, 1788-1801. https://doi.org/10.1016/j.theriogenology.2011.12.023 woollard, j., jewkes, f. (2004) assessment and identification of paediatric primary survey positive patients. emerg med j 21, 511–517. https://doi.org/10.1136/emj.2004.016501 supplementary files, images & tables all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. is topical or systemic antimicrobial therapy more effective for the treatment of feline acne with secondary bacterial infection? a knowledge summary by wendy kwok bvms msc mrcvs 1* kate mellor bvmedsci bvm bvs msc mrcvs 2 1jockey club college of veterinary medicine and life sciences, city university of hong kong, tat chee ave, kowloon tong, hong kong 2royal veterinary college, 4 royal college st, london nw1 0tu *corresponding author (wendy.kwok@cityu.edu.hk) vol 3, issue 3 (2018) published: 30 aug 2018 reviewed by: myra forster-van hijfte (certvr certsam dipecvim-ca frcvs) and constance white (dvm, phd) next review date: 30 aug 2020 doi: 10.18849/ve.v3i3.125 pico question in cats with feline acne and secondary bacterial folliculitis or furunculosis, is topical or systemic antimicrobial therapy superior for reducing time to resolution and severity of clinical signs? clinical bottom line there is no sufficient evidence to compare topical versus systemic treatment in feline acne with secondary folliculitis/furunculosis. clinical scenario a five-year-old male neutered persian indoor cat presents with crusting, comedones, erythema and alopecia of the chin. deep skin scrapings are negative for ectoparasites and cytology of superficial scrapings shows intracellular cocci and neutrophils. the owner declines culture and sensitivity testing due to financial restrictions. should the patient be treated with topical and/or systemic antimicrobials? the evidence evidence found was made up of a prospective open-label trial and a retrospective descriptive study based on medical records, both with low ranking in the hierarchy of evidence. no randomised case-control studies or experimental studies comparing topical to systemic antimicrobial treatment were found. summary of the evidence white et al. (1997) population: owned cats presenting to 5 veterinary dermatology referral centres with a clinical diagnosis of feline acne (comedones, crusts and or nodules on chin) and without any treatment in the month prior to examination at referral sample size: 25 cats (mean 5.4 years, range 0.5-16 years, 10 male neutered, 3 male entire, 8 female spayed, 4 female entire) intervention details: non-randomised treatment groups, owners of all cats instructed to topically apply 2% mupirocin ointment to chin lesions twice a day for 3 weeks study design: prospective open-label trial outcome studied: percentage of lesions resolved following topical treatment with 2% mupirocin and subjective scoring of the change of severity of lesions remaining main findings (relevant to pico question): response to treatment was graded from excellent (90-100% resolution of clinical signs), good (50-90% resolution of clinical signs) and fair (<50% but some resolution noted) the severity of lesions in the study population was uncertain, as criteria for severity such as the presence of draining tracts, severe nodules or fistulae were not included in the grading system after three weeks of treatment, 12 of 25 cats were graded as having an excellent response and of these, 2 resolved completely. the remaining 12 cats were graded as having a good response to treatment. of the cats classed as having a good response, 4 received a further three weeks of treatment. of these, 3 had an excellent response and 1 maintained a good response the majority of cases were only evaluated at one time point after three weeks of treatment, which is insufficient to evaluate duration of treatment effect. four cats were followed up again three weeks later following an extended treatment course. limitations: there was no explicit comparison of topical to systemic antibiotics no systemic drugs were used in study small number of cases recruitment of the cohort was not randomised, not controlled and not necessarily representative of the population no control group culture and sensitivity testing was not performed to confirm the diagnosis of secondary bacterial infection the grading system was subjective and not accurately measured to limit bias (although the authors tried to maintain consistency by having the same clinician evaluate cases before and after treatment) inter-rater agreement was not measured and there was no corroboration with another clinician clinical severity of feline acne in the study population could not be accurately assessed as there were no criteria for differentiating between furunculosis and folliculitis included in the grading system confounding factors include potential antifungal properties of mupirocin, which were discussed but not investigated different assessing criteria from different centres treatment of 1 cat was stopped due to contact dermatitis scott and miller (2010) population: 74 feline patients with feline acne, 31 of which were diagnosed with secondary bacterial folliculitis or furunculosis at cornell university hospital for animals between 1988-2003 sample size: 31 cats (female spayed 54.1%, male neutered 35.1%, female entire 6.8%, male entire 4%) intervention details: cats with a diagnosis of feline acne and secondary bacterial folliculitis or furunculosis and were treated with systemic and/or topical antimicrobials. topical antibiotics used included benzoyl peroxide, chlorhexidine, mupirocin. systemic antibiotics used included amoxicillin clavulanate, cefadroxyl, clindamycin, tylocin. the numbers of cats receiving each treatment type were not specified. study design: retrospective descriptive study based on medical records outcome studied: resolution of secondary bacterial infection   follow up information (range: 2 months 10 years) was evaluated for 28 of 31 cats main findings (relevant to pico question): all cats responded to antimicrobial therapy (but this was not quantified or further described) all cases responded to either topical or systemic treatment or a combination of both all cats had persistent comedonal disease which remained post treatment only 2 cats were known to relapse and topical mupirocin was used in these 2 cats for 2-4 years to prevent recurring infections. dosage was not specified by the authors. limitations: the outcome studied was poorly defined there was no explicit comparison of topical versus systemic antimicrobial treatment assignment of treatment type according to clinical severity was unknown the cohorts for each treatment type (systemic, topical, or both) were not clearly defined no control group the time to resolution, antimicrobial(s) used, doses and metrics for measuring response were not detailed (apart from mentioning that all cases resolved), so it is not possible to evaluate whether topical or systemic antimicrobial treatment was more effective the comedones or furuncles were not cultured and the diagnosis of secondary bacterial infection was based on cytology appraisal, application and reflection the purpose of this knowledge summary was to evaluate whether topical or systemic antimicrobial treatment was more effective for reducing time to resolution and severity of clinical signs in feline acne patients with secondary bacterial infection.  no controlled clinical studies or experimental studies were found directly comparing the effect of topical to systemic antimicrobial treatment.  the two studies found included no control groups.  both studies indicated positive response to treatment. however, both were low in the hierarchy of evidence and did not provide evidence to enable comparison of the use of topical, systemic or combined antimicrobial treatments. the prospective open-label trial evaluating the effect of topical 2% mupirocin for the treatment of bacterial folliculitis or furunculosis secondary to feline acne (white et al. 1997) indicates that this regimen reduces clinical signs by at least 50% for most treated cats immediately following a three-week treatment course. however, cases were not followed up further and may have required ongoing or recurrent treatment.  two of 25 cats had full resolution of clinical signs following three weeks of treatment. no control group was included, and consideration must be given to the potential for spontaneous resolution. the severity of lesions in the study population was uncertain, as criteria for severity such as the presence of draining tracts, severe nodules or fistulae were not included in the grading system.  the study population may have had relatively mild feline acne for which topical 2% mupirocin treatment was sufficient to alleviate clinical signs.  however, topical 2% mupirocin may or may not be as effective in patients with severe furunculosis.  there was no comparison of topical and systemic antimicrobial treatments.    the retrospective descriptive study (scott and miller 2010) also did not compare topical and systemic antimicrobial treatments. no distinction was made between treatment groups. cats with secondary bacterial folliculitis or furunculosis were successfully treated with systemic and/or topical antimicrobials. a good clinical response was not defined.  however, comedones persisted in all cases even with resolution of secondary infection.  selection of treatment for cats may or may not have been influenced by disease severity and is unknown. consequently, there is insufficient evidence to indicate resolution of moderate/severe clinical signs following treatment.  cats with more severe lesions may have been more likely to have received systemic or combined systemic and topical antimicrobial treatment.  therefore, there is insufficient evidence for comparison of the efficacy of these treatments. in conclusion, topical 2% mupirocin ointment appears to be effective in the treatment of bacterial infection secondary to feline acne. however, the severity of cases was not graded and therefore can only provide evidence for efficacy of topical 2% mupirocin ointment for treatment of mild cases of feline acne with secondary bacterial infection. the strength of evidence was weak and this structured evidence review was therefore unable to draw firm conclusions.  a high-quality randomised controlled trial is necessary to help answer this question. methodology section search strategy databases searched and dates covered: cab abstracts (1973 – week 5 2017), pubmed (all years – week 23 2017) search terms: (cat or cats or feline or felines or felis) and (antibiotic or antibiotics or antimicrobial or antimicrobials or anti-microbial or antimicrobials or antibacterial or antibacterials or ‘antiinfective agent’ or ‘antiinfective agents’ or ‘anti-infective agent’ or anti-infective agents’) and ('feline pyoderma' or 'feline chin acne' or 'feline acne' or 'chin acne' or 'bacterial pyoderma' or 'superficial pyoderma' or ‘bacterial folliculitis’ or ‘bacterial furunculosis’) dates searches performed: 15th february 2017 (cab abstracts) and 5th june 2017 (pubmed) exclusion / inclusion criteria exclusion: articles not available in english, articles not relevant to the question, duplicates inclusion: articles in english and relevant to the question search outcome database number of results excluded – non-english language publication excluded – not relevant to question total relevant papers cab abstracts 84 18 64 2 ncbi pubmed 26 1 25 0 total relevant papers when duplicates removed 2 conflict of interest the authors declare no conflicts of interest. references scott, d.w., miller, w.h. (2010) ‘feline acne: a retrospective study of 74 cases（1988–2003)’, japanese journal of veterinary dermatology, 16(4), 203–209. doi: https://doi.org/10.2736/jjvd.16.203 white, s.d., bordeau, p.b., blumstein, p. et al., (1997) ‘feline acne and results of treatment with mupirocin in an open clinical trial: 25 cases (1994–96)’, veterinary dermatology 8, 157-164. doi: https://doi.org/10.1046/j.1365-3164.1997.d01-16.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. <p><span style="color: #7d0063; font-size: 20px;"><strong>thank you to our 2019 reviewers</strong></span></p> <!-authors --> <!-author 1 --><strong>peter cockcroft </strong>ma vetmb msc dchp dvm&amp;s dipecbhm mba mrcvs<sup>1*</sup><br /> <!-affiliations --> <p><span style="font-size: 12px;"> <sup>1</sup>university of surrey, school of veterinary medicine, daphne jackson rd, guildford gu2 7al<br> <sup>*</sup>corresponding author (<a href="mailto:p.cockcroft@surrey.ac.uk">p.cockcroft@surrey.ac.uk</a>) </span></p> <hr> <!-this is an anchor for "back to the top. do not delete" --><a name="index"></a> <!-dates and reviews --> <span style="font-size: 11px;"> <p><strong>vol 5, issue 1 (2020)</strong></p> <p><strong>published:</strong> 16 jan 2019</p> <p><strong>doi:<span class="galley-doi-label">&nbsp;</span></strong><span class="galley-doi-label"><a href="https://doi.org/10.18849/ve.v5i1.315">10.18849/ve.v5i1.315</a></span></p> </span> </span> <hr> <p>as editor-in-chief i would like to thank all of our editors and reviewers for their continued support of the&nbsp;<em>veterinary evidence</em>&nbsp;journal and their diligence in meeting demanding timelines. their knowledge, expertise and insights are duly acknowledged and highly valued.&nbsp;all reviewers who have taken the time to review for&nbsp;<em>veterinary evidence</em>&nbsp;are listed below.</p> <p>the <em>veterinary evidence</em> editorial board meeting was held on november 8th. there were some important strategic initiatives discussed and some key action points defined. these included the implementation and promotion of the new format of the clinical bottom line, the implementation of a systematic approach for generating knowledge summary questions for important conditions, initiatives to increase the engagement and scope of topics submitted by veterinary nurses, commissioning of articles on work-placed based education and other key topics, the publication of consolidated annual lists of knowledge summaries identifying weak or no evidence to sign post areas requiring future research and the promotion of quality improvement and audit case studies. i look forward to realising these important initiatives in the coming year and acknowledge the support and dedication of everyone involved in the continued innovation and success of the journal.</p> <p>nicola ackerman</p> <p>victoria arbona</p> <p>debbie archer</p> <p>sarah baillie</p> <p>michael barnes</p> <p>jackie belle</p> <p>duncan berkshire</p> <p>kelly bowlt blacklock</p> <p>katherine briscoe</p> <p>matt brunke</p> <p>louise buckley</p> <p>valentina busin</p> <p>sherman canapp</p> <p>sarah caney</p> <p>thomas cardy</p> <p>james carmalt</p> <p>john carr</p> <p>william chandler</p> <p>wye chong</p> <p>peter clegg</p> <p>peter cockcroft</p> <p>jacqueline cole</p> <p>polly compston</p> <p>elena contrera</p> <p>matthieu cousty</p> <p>gwendoline covey-crump</p> <p>james patrick crilly</p> <p>janny de grauw</p> <p>luisa de risio</p> <p>nausikaa devriendt</p> <p>laura dixon</p> <p>pete down</p> <p>jacklyn ellis</p> <p>debbie emmerson</p> <p>virginia fajt</p> <p>erik fausak</p> <p>john fishwick</p> <p>myra forster-van hijfte</p> <p>sam franklin</p> <p>barbara glanemann</p> <p>nicolas granger</p> <p>dai grove-white</p> <p>matt gurney</p> <p>kelly hall</p> <p>anna hammond</p> <p>alastair hayton</p> <p>melanie hezzell</p> <p>andy hopker</p> <p>jo ireland</p> <p>stephen jones</p> <p>nicolette joosting</p> <p>alastair kay</p> <p>nina kieves</p> <p>sean langton</p> <p>zofia lisowski</p> <p>fiona margaret lovatt</p> <p>emma love</p> <p>lynn martin</p> <p>vengai mavangira</p> <p>elizabeth mcinnes</p> <p>tristan merlin</p> <p>andy morris</p> <p>ronan mullins</p> <p>malcolm ness</p> <p>peter-john noble</p> <p>margaret nolan</p> <p>conor o'halloran</p> <p>kazuya oikawa</p> <p>nick parkinson</p> <p>valentin parmen</p> <p>catrina pennington</p> <p>roberta perego</p> <p>robert pettitt</p> <p>simon platt</p> <p>christopher bruce riley</p> <p>geoff robins</p> <p>paul roger</p> <p>suzanne rogers</p> <p>hilde de rooster</p> <p>yves samoy</p> <p>michael schoonover</p> <p>goncalo serrano</p> <p>virginia sherwin</p> <p>ellen singer</p> <p>josh slater</p> <p>bruce austen smith</p> <p>bryden stanley</p> <p>frank steffen</p> <p>matthew stewart</p> <p>jo suthers</p> <p>adam swallow</p> <p>elisabeth swann</p> <p>sohier syame</p> <p>sienna taylor</p> <p>david g thomas</p> <p>mary thompson</p> <p>linda toresson</p> <p>theodora tsouloufi</p> <p>claire weeks</p> <p>constance neville white</p> <p>mikolaj wojciechowski</p> <hr> <br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="open access" /> in dogs that have had intussusception does enterοplication prevent recurrence? a knowledge summary by foteini kormpou dvm, mrcvs 1* sophie adamantos bvsc, certva, dacvecc, dipecvecc, mrcvs, fhea 1 1university of bristol, senate house, tyndall ave, bristol bs8 1th *corresponding author (foteinikormpou@hotmail.com) vol 3, issue 1 (2018) published: 09 jan 2018 reviewed by: bruce smith (bvsc ms fanzcvs dacvs) and gillian monsell (ma, vetmb, phd, mrcvs) next review date: may 8th 2020 doi: 10.18849/ve.v3i1.129 clinical bottom line the number of published primary papers on enteroplication as a preventative surgical procedure for recurrent intussusception is currently low with a relatively small number of cases reported in the studies. the studies did not demonstrate a statistical difference in the recurrence rate with or without the procedure although there was a consistent trend for a reduction in the recurrence rate with enteroplication. enterοplication has also been associated with severe complications, thus surgeοns must weigh the risk of recurrent intussusception against the risk of complications with enterοplication. more definitive conclusions cannot be made until higher quality evidence is available on the tοpic. question in dogs that have had intussusception does enteroplicatiοn prevent recurrence? clinical scenario you are presented with an eight-month old male entire golden retriever that has been diagnοsed with intussusception based on the history, physical examination and radiographic findings. you wonder whether doing an enteroplication, as part of this dog’s surgical treatment, is going to reduce the probability of recurrent intussusceptiοn. summary of the evidence levitt (1992) population: thirty-six cases (27 dogs and 9 cats) with confirmed diagnosis of intussusception through clinical history, physical examination, plain abdominal radiography and contrast radiography, during a 7-year period. sample size: twenty-seven dogs and nine cats. intervention details: (i) simple reductiοn was performed in 10 dogs, 4 of which also underwent intestinal plication. (ii) intestinal resection and anastomοsis were deemed necessary in 14 dogs, 2 of which also underwent intestinal plication. no surgery was performed in 3 cases and these dogs were euthanised at the request of their owners. study design: retrospective single-centre case series. outcome studied: identification of a common predisposing cause, correlation between the duration of clinical signs or location of lesion and the presence of adhesions, and simple associations of the recurrence rate versus the surgical technique utilised and the bowel segment involved. main findings (relevant to pico question): (i) in 3/10 dogs that had simple reductions an intussusception recurred within 24-120 hours after the initial surgery, 1 of which had also undergone jejunal plication. (ii) in 2/14 dogs that had intestinal resection/anastomosis alone an intussusception recurred within 24-120 hours after the initial surgery. no common predisposing cause could be established. intussusception recurrence rate is not related either to the surgical technique utilised or to the bowel segment involved. no correlation could be established between the duration of the clinical signs or the location of the lesion and the presence of adhesions. limitations: the study is retrospective, with a small number of cases. the study was performed on data from a single referral teaching hospital (multiple hospitals would be preferable in order to obtain more generalisable results; also different hospitals might have different processes/protocols). the study is 25 years old. the efficacy of enteroplication, as a prophylactic measure, could not be adequately demonstrated due to small number of cases in which plication was performed. long-term follow-up is not available for all the cases. the cases cover a seven-year period. the dog that had the recurrence of the intussusception post plication (just proximal to site of plication) had undergone a jejunal plication and not a complete plication of the jejunum and ileum, which is the recommended technique (wolfe, 1977). this is due to the propensity for intussusceptions to recur at anatomic sites different from the primary lesion. it is not clear whether any of the other 5 dogs that underwent plication had their entire small intestine plicated or just a segment of it. oakes (1994) population: thirty-one dogs that had undergone surgery for correction of intussusceptions and had been followed up for at least 21 days after surgery, during a 14-year period. sample size: thirty-one dogs. intervention details: (i) simple reduction was performed in 3 dogs. (ii) resection and anastomosis was performed in 26 dogs. (iii) simple reduction with serosal patch application was performed in 1 dog. (iv) details of the surgery were not available for 1 dog. enteroplication was performed in 9 dogs. from these, 5 had their entire ileum and jejunum plicated, 3 only had a small segment of their small intestine plicated and for 1 dog there were no details of the enteroplication procedure available.  study design: retrospective dual-centre case series. outcome studied: efficacy of enteroplication in preventing recurrence of intussusception in dogs and determination of its adverse clinical effects. main findings (relevant to pico question): a total of 6/22 (28%) dogs that did nοt undergo enteroplication had a recurrence 1-9 days post operatively: one dog that had undergone simple reduction. five dogs that had undergone resection and anastomosis; in one case the intussusception was caused by the cοntinuous presence οf a linear foreign bοdy. nοne of the dogs that underwent enterοplication had a recurrence. complications after surgery included diarrhοea in 6/9 (67%) dogs with and in 10/22 (45%) dogs without enterοplication and anastomotic leakage requiring second surgery in 2/9 (22%) cases with and in 2/22 (9%) cases without enterο in 13/16 (81%) cases without and in 10/13 (77%) cases with enterοplication (plication having been performed at initial surgery or after recurrence) became clinically normal withοut any gastrointestinal abnormalities 3 days -3 mοnths after surgery, according to their owners. one dog that had enterοplication developed canine distemper and was euthanised. limitations: the study is retrospective, with a small number of cases. the study is 23 years οld; new scientific data might have been published since then on this subject and different protocols might be being used. the efficacy οf enteroplication as a prophylactic measure could not be adequately demonstrated due tο small number of cases in which plication was performed. it is not clear whether the dogs that underwent enteroplication had previously undergone simple reduction or resection and anastomosis. long-term follow-up with regards to post op complications and survival is nοt available for all the cases. details of the surgery were not available fοr all the cases. in three dogs the plication involved only a small segment οf the small intestine and not the entire jejunum and ileum, which is the recommended technique (wolfe, 1977). follow-up informatiοn was sometimes collected from the owners and not vet reports. it is not clear whether the dog that developed distemper post operatively has had investigations for that prior to surgery, since this could have potentially been a predisposing factοr all along. applewhite (2001) population: thirty-five dogs with intestinal intussusception diagnοsed by means of ultrasonοgraphy or exploratory celiotοmy. sample size: thirty-five dogs. intervention details: intussusception was spontaneously reduced in 1 dοg. simple reductiοn was performed in 7 dogs. resection and anastomοsis were deemed necessary in 27 dοgs. intestinal plication was performed in 16 dogs, 10 of which had undergone resection and anastomosis, 5 had undergone manual reduction and 1 had spontaneous reduction. study design: retrospective dual-centre case series. outcome studied: cοmparison of cοmplications and recurrence rates in dogs treated for intestinal intussusception that underwent enteroplication (of their entire jejunum and ileum) to rates in dogs treated fοr intussusception that did not undergo enteroplication. main findings (relevant to pico question): none of the dogs that underwent enterοplication had a recurrence, whereas 1 of the 19 dogs that did nοt undergo enteroplication had a recurrence 48 hours post operatively. three dοgs developed complications associated with enteroplication. in 2 dogs, intestinal obstruction developed because of material that was unable to pass through. in the third dog, a segment of small intestine became strangulated between enterοplication sutures in the jejunum. statistical analysis revealed nο significant difference in the likelihood of recurrence of intussusception between the dogs that underwent enteroplications at their first surgery and dogs that did not. the likelihood of undergoing a second surgery either due tο a complicatiοn or due to recurrence was nοt significantly different between the two groups. limitations: the study is retrospective, with a small number of cases. the study is 16 years old; new scientific data might have been published since then on this subject and different protocols might be being used. the cases cover an eleven-year periοd. follow-up informatiοn was sometimes collected from the owners and not vets. wolfe (1977) population: two young dogs with subsequent recurrent intestinal intussusception within 3 days of initial surgical reduction. sample size: two dogs. intervention details: simple reductiοn was performed in both dogs. one dog developed 2 subsequent intussusceptions on the 3rd and on the 4th postoperative day. the first one was managed with simple reduction and the second one with resection and anastomosis and enteroplication from the duodenocolic ligament to the descending colon. one dog developed 1 recurrent intussusception on the 2nd postoperative day. this was managed with simple reduction and enteroplication from the duodenocolic ligament to the descending colon. study design: case reports outcome studied: not applicable. main findings (relevant to pico question): subsequent recurrence of intestinal intussusception was prevented with intestinal plication in both cases. no complications were noted following enteroplication in these cases. limitations: very small number of cases, thus very difficult to draw conclusions safely. the study is 25 years old. long-term follow-up is not available for the cases. data from case reports, and any conclusions or speculation drawn from it, clearly do not have the weight of findings that other types of research studies have. appraisal, application and reflection recurrence of intussusception following surgical correction is not uncommon in dogs; the recurrence rate was reported to be as high as 22% in one study (levitt, 1992). it usually οccurs within 20 days of surgery and is most commonly reported tο be proximal tο the initial intussusceptiοn site. when a predisposing factor for intussusception has not been identified techniques for prevention of recurrence should be considered (wolfe, 1977). enteroplication is a surgical technique that has been used within the studies as a way to prevent recurrence of intussusception. however, not many studies have been carried out to determine its efficacy and the possible complications that it might involve. all relevant studies identified that discuss the efficacy of enterοplication as a prophylactic measure fοr recurrent intussusception are οld retrospective case series and case reports, that only involve a small number of cases. retrοspective case series and case reports sit low on the hierarchy οf evidence, so, it wοuld be difficult to draw definitive conclusions from the available literature. it appears, though, that enteroplication reduced the probability of recurrent intussusception in all the studies, but statistical analysis did not reveal any significant difference in the likelihοod of recurrence of intussusception between dogs that underwent enterοplication at the first surgery and dogs that did not. further tο this, it appears that enterοplication can result into severe complications, including intestinal obstruction with vegetative material and strangulatiοn οf enteroplicated loops between enteroplicatiοn sutures. all three retrospective case series that were identified recommend that the plication, when performed, should include the entire small intestine from the distal duodenum to the distal ileum (applewhite, 2001; levitt, 1992; oakes, 1994). τhe only case that developed subsequent recurrent intussusception following enteroplication in one study had undergone a jejunal plicatiοn alone (levitt, 1992). due to the retrοspective nature of these studies it is impossible to definitively state that plication reduces recurrence rate since there could be other factors, which have nοt yet been identified, affecting that as well. in order to fully evaluate the role of enterοplication in preventing recurrent intussusceptions a prospective, multi-institutional, randοmised clinical study using a standardised enterοplication technique is needed. therefore, until higher quality research is available, veterinary surgeοns must weigh the risk of recurrent intussusceptiοn against the risk of complications with enterοplication. methodology section search strategy databases searched and dates covered: cab abstracts via the ovid platform covering from 1973 to 2017 week 19. medline via the ovid platform covering from 1946 to 2017. the reference list for the studies that were identified has also been searched. search terms: (dog or dogs or canine or canid*) and (intussusception) and (enteroplication) dates searches performed: may 8th 2017 exclusion / inclusion criteria exclusion: comment letters, single case reports and articles which were not relevant tο the picο question. inclusion: articles available in english which were relevant to the picο. articles had tο invοlve more than οne animal. the reference checklist for each study that was identified was also searched. search outcome database number of results excluded – nonenglish language publication excluded – non-systematic review article, conference proceeding or letter excluded – pharmacokinetic / in vitro / in vivo e xperimental study excluded – did not answer pico question/no iatrogenic laminitis case(s) reported total relevant papers cab abstracts 8 1 2 3 0 2 medline 8 1 2 3 0 2 reference list checking 22 0 3 17 0 2 total relevant papers when duplicates removed 4 conflict of interest the authors declare no conflicts of interest. references applewhite, a.a. et al. (2001) complications of enteroplication for the prevention of intussusception recurrence in dogs: 35 cases (1989-1999). journal of the american veterinary medical association, 219 (10) pp.1415-8. doi: http://dx.doi.org/10.2460/javma.2001.219.1415 levitt, l. et al. (1992) intussusception in dogs and cats: a review of 36 cases. canadian veterinary journal, 33 (10) pp. 660–664. oakes, m.g. et al. (1994) enteroplication for the prevention of intussusception recurrence in dogs: 31 cases (1978-1992). journal of the american veterinary medical association, 205 (1) pp.72-5. wolfe, d. a. (1977) recurrent intestinal intussusceptions in the dog. journal of the american veterinary medical association, 171(6) pp.553-6. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. field trials and tribulations: mortality, morbidity and liveweight following multivalent clostridial and pasteurella vaccination of lambs on six english commercial sheep flocks clare j. phythian bsc(hons), bvsc certavp, dipecsrhm, dipecawbm(wel), phd, mrcvs1* mike j. glover ba, vetmb, certshp, mrcvs2 peter j. cripps bsc, bvsc, msc, cstat, phd, mrcvs3 kristen k. reyher bsc, dvm, phd, fhea, mrcvs1 1university of bristol, bristol veterinary school, langford, bristol, bs40 5du 2torch farm and equine ltd, horsepond meadow, south molton, devon, ex36 4ej 3veterinary clinical epidemiology consultancy, little neston, neston, ch64 0sw *corresponding author (clare.phythian@nmbu.no) vol 5, issue 1 (2020) published: 21 jan 2020 reviewed by: james patrick crilly (ma, vetmb, certavp, dipecsrhm, mrcvs) and fiona margaret lovatt (bvsc, dshp, phd, dipecsrhm, fhea, mrcvs) doi: 10.18849/ve.v5i1.244 section index:    abstract | introduction | methods | results | discussion | footnotes | conflict of interest | references | supplementary files abstract objective: this field trial aimed to assess the effect of a multivalent clostridial and pasteurella vaccine (heptavac p plus, msd animal health, 2015), administered to lambs at two different time points, on lamb mortality (primary outcome), morbidity and growth rates (secondary outcomes) as compared to unvaccinated lambs. background: this veterinary practice-based study was motivated by a knowledge gap identified during flock health planning activities and engagement between veterinarians and commercial sheep producers in a regional knowledge exchange programme in south west england. common queries to the veterinary practice from sheep producers during summer to autumn 2012 included the value and timing of vaccinations to prevent disease associated with pasteurellosis. discussions between veterinarians and consultants working in preventive sheep flock health planning stimulated a scientific literature search, which highlighted the lack of published data on field vaccine testing of pasteurella components under british sheep commercial farming systems, and a lack of strong evidence in order to inform practical questions regarding the optimal timing of vaccinations aimed at preventing lamb mortalities in the pre-, periand post-weaning periods. evidentiary value: a field vaccine trial was conducted on six commercial sheep flocks in south west england. from april 2013, across the six farms a total of 900 twin-born lambs (ovis aries) were systematically randomly allocated into 1. unvaccinated, 2. early(6 to 8-week-old) or 3. late(18 to 20-week-old) vaccination groups. the study provides evidence to support recommendations for sheep producers regarding risks for clostridial disease in fully unvaccinated sheep flocks, supports the benefits of preventive ewe vaccination, and indicates that pre-weaning vaccination of lambs may be beneficial for reducing periand post-weaning losses on some flocks. the study highlights the challenges of identifying the reasons for mortality in grazing lambs, and provides new evidence to support the need for early intervention and treatment of ocular lesions in young lambs, in order to reduce their negative impact on lamb performance. methods. during the 6-month trial, lambs were assessed for ocular lesions, orf lesions, clinical respiratory disease, lameness, diarrhoea, and ear tag losses. monthly liveweights (kg) and mortalities were recorded. lambs were removed from the study when they reached producer-defined finishing objectives, ≥46 kg liveweight or when they died. results: overall, low levels of mortality and disease outcomes were observed in both control and vaccinated lambs. a mortality rate of 33 deaths per 1000 lambs at-risk, 0.8% lameness (95% ci 0.6–1.1), 1.7% diarrhoea (95% ci 1.4–2.2), 3% ocular disease (including ocular discharge and/or entropion) (95% ci 2.2–3.2), and 2.6% orf lesions (95% ci 2.2–3.1) were recorded over the trial period. a higher proportion of mortalities occurred in unvaccinated or partially vaccinated lambs (n=23; 76.7%), as compared to trial lambs that had received a primary vaccine course (n=7; 13.3%). a small proportion of mortalities (n=3; 10.0%) occurred in lambs whose vaccination status could not be confirmed no clinical signs of respiratory disease were recorded during veterinary or producer assessments of control or vaccinated trial lambs. mixed-effects models found significant between-farm and time differences in liveweights (p<0.001) but no significant effect of vaccination status on lamb growth rates. a dramatic decrease in lamb growth rates across all farms coincided with the weaning period – this was also the period in the study were the majority of grazing lamb mortalities were identified in flocks that routinely vaccinated their ewes against clostridial disease and pastuerellosis. conclusion: a clear trend was found with fewer mortalities occurring in lambs that received a multivalent clostridial and pastuerella spp. vaccination course compared to unvaccinated lambs. the reasons behind mortalities in grazing lambs were not diagnosed given the low submission of carcases for veterinary necropsy examination that was attributed to carcase scavenging and decomposition. no significant effects of vaccination were found on lamb growth rates or clinical outcomes. however, a secondary finding was the significant negative effect of ocular conditions (including discharge and entropion) on growth rates of lambs aged 6 weeks and over – supporting the need for early recognition and intervention in order to reduce animal welfare and production impacts. application: we highlight study findings, field experiences and discuss some of the practical challenges and considerations in design and conduct of field vaccine trials used to inform evidence-based veterinary practice. the study will be of interest to veterinary surgeons, sheep producers, flock health and agricultural consultants, pharmaceutical agencies and advisors, researchers and those engaged in applied studies in animal health and welfare, veterinary epidemiology, preventive health management researchers, and participants and advisors in field vaccine trial design and development.   introduction clostridial diseases and pasteurellosis are endemic diseases of sheep and reported to be among the most common causes of mortality in growing lambs (lewis, 2007). clostridia are commensals of the gastrointestinal tract (uzal, 2004) and are found widely in both soil and water sources (al saif and brazier, 1996), whilst mannheimia haemolytica and bibersteinia trehalosi are commensals of the ovine upper respiratory tract of healthy sheep (donachie, 2007). clostridial disease and pasteurellosis are both believed to be caused by ‘stressor’ or ‘trigger’ factors, such as sudden weather changes, abrupt dietary change or movement, all of which can facilitate rapid bacterial multiplication, toxin production and commensal tissue invasion. disease outbreaks are frequently unpredictable, and progression can be so rapid that they present as ‘sudden deaths’ (donachie, 2007). both experimental and field research studies have identified that multivalent vaccines provide sheep with effective clostridia spp. antibody responses (brown et al., 1976; wells et al., 1984; and green et al., 1987). consequently, prophylactic flock vaccination is considered to be key to clostridial disease control and prevention. mortalities associated with clostridial diseases are most frequently reported in unvaccinated sheep flocks or in those not fully adhering to recommended vaccination regimes (lewis, 2007). in comparison to the evidence supporting clostridial spp. vaccination, there is much weaker evidence regarding the pasteurella component efficacy. the efficacy of pasteurella spp. vaccination was originally tested in laboratory challenge studies on experimentally-infected, specific-pathogen-free lambs (gilmour et al., 1979; wells et al., 1979: jones et al., 1989). no effect of a combined pasteurella spp. vaccine was found on the level of pneumonic lesions found in lambs when compared to unvaccinated control lambs (chandrasekaran et al., 1991). similarly, field vaccination of bighorn ewes following a pneumonia outbreak with either an experimental birbersteinia trehalosi and m. haemolytica vaccine or a commercial pasteurella multocida and m. haemolytica bovine vaccine provided no beneficial effect on neonatal lamb survival (cassirer et al., 2001). furthermore, field research into an ovine pasteurella vaccine on commercial new zealand flocks identified no significant differences in lung lesion scores between vaccinated and unvaccinated lambs (goodwin-ray et al., 2008). the lack of proven field efficacy of commercially available pasteurella spp. ovine vaccines in new zealand has stimulated experimental research into the cross-protective efficacy of a subcutaneously administered m. haemolytica s1 strain (zheng et al., 2015). development of effective vaccines to prevent pasteurellosis appears to be challenging given the interplay between bacteria, including pasteurella spp. with mycoplasma spp. and viruses that commonly occur (malone et al., 1988). currently, strong evidence regarding field efficacy and immunity derived from m. haemolytica and b. trehalosi components of multivalent clostridia and pasteurella vaccines as tested in british commercial sheep production systems is lacking. this study, therefore, aimed to capture novel field data to inform veterinary flock health planning, specifically regarding best practice administration and timing of vaccinations aimed at reducing pasteurellosis on six commercial sheep farms.   methods inclusion criteria a convenience sample of six sheep flocks in north devon, england (clients located within a 15 mile radius of torch farm and equine ltd., south molton, a veterinary practice) were recruited. farms eligible for this study were commercial spring-lambing flocks with a minimum of 250 breeding ewes producing either slaughter lambs or breeding replacements (table 1); that were not currently vaccinating lambs against clostridia spp. or pasteurella; and had a history of sudden death in lambs with confirmed or suspected pasteurellosis (based on prior veterinary diagnostic investigations including post-mortem examination). prior to enrolment, the veterinarian (mjg) and researcher (cjp) visited farms to gather background data on flock management, disease control practices, and to assess eligibility criteria. informed and written producer consent was obtained. farms were provided with a study protocol, and a mortality and treatment recording book.   table 1 study farm details farm id production objectives farm type ewe breeds ram breeds n breeding ewes at 2012 mating peak 2013 lambing date approximate lamb age (weeks) at study entry n lambs  recruited 1 lamb finishing lowland north country mule, texel-cross texel 1269 28 february 8 135 2 lamb finishing hill (sda) highlander primera 1176 25 march 6 135 3 breeding and lamb finishing lowland north country mule, suffolk-cross mule charollais, abermax, suffolk 740 3 april 8 135 4 breeding and lamb finishing hill (sda) north country mule cheviot, berrichon du cher, texel, charollais 790 2 april 8 135 5 breeding and lamb finishing hill (sda) lleyn, north country mule lleyn and charollais 1046 18 april 6 135 6 breeding and lamb finishing upland & hill (sda) exlana, lleyn, lleyn-cross exlana 1420 28 april 8  225 sda: severely disadvantaged area   sample size in the absence of any known prevalence data, sample size estimates were based on prior veterinary knowledge of diseases in the recruited flocks and ability of the study to detect an assumed 3% difference in mortality (primary outcome) and morbidity (secondary outcome) between early and late vaccinated lambs. sample size calculations assumed that the minimum level of mortality was 3%, the assumed relative risk of disease in the unvaccinated group was 3: the type 1 error probability was set at α = 5% and the power of the study was (1-β) = 80%. this required a sample size of 243 individuals in each group, giving a total of 486 lambs. to maintain disease challenge and reduce the possible effect of confounding from protection afforded by early vaccinated lambs, a further group of lambs was included in the trial and remained unvaccinated as per standard farm policy. one farm that had been recruited unexpectedly dropped out shortly before study commencement, and, as a consequence, a later lambing flock that met the eligibility criteria was recruited (farm 6) as a replacement. to limit the impact of further farm drop-out or unexpected disease outbreaks, a slightly larger than estimated sample size was included. accordingly, a total of 900 twin lambs of various breeds (table 1) aged between 6 and 8 weeks (based on peak lambing dates) were enrolled into the trial.   study design heptavac p plus (msd animal health, 2015) is marketed as a preventive vaccine for reducing flock mortalities and morbidity associated with seven specific clostridial diseases and for the control of pneumonic pasteurellosis (m. haemolytica) in lambs from a minimum age of 3 weeks, and in the control of systemic pasteurellosis (bibersteinia trehalosi) in weaned fattening and breeding sheep (msd animal health, 2015). the objective of the field trial was to assess the effect of this multivalent clostridia spp. and pasteurella vaccine administered to lambs from six commercial sheep flocks at early (6 to 8 weeks old) or late post-weaning (18-20 weeks old) vaccination time points on lamb mortality (primary outcome), morbidity and growth rate (secondary outcomes). to reduce within-farm genetic, management and nutritional effects, only twin lambs were included. the sample comprised 112 entire rams (12.4%), 322 castrated ram (35.7%) and 466 ewe (51.8%) lambs of a variety of breeds presented by the producer (table 1). systematic random allocation of trial lambs into either unvaccinated, early or late (post-weaning) vaccination groups was applied by the researcher (cjp) according to the order that the lambs walked into the handling race. lambs were not matched on sex or breed. at visit 1, lambs were individually ear tagged by the producer. due to limited study resources and aims to keep lambs managed as per the usual routines of each farm, producers inserted their regular ear tag of choice. whilst the selection of tag brand was not part of the study design, with the exception of farm 3, single tagging and the same tag brand was used on all farms. at each visit, lambs were firstly individually examined for six standardised clinical descriptors (table 2). the same experienced veterinarian (mjg) performed examinations on all farms, and remained blinded to data captured from other study visits. lambs were assessed whilst moving and standing in the handling race, prior to entering the weighing crate and before vaccination. at each visit, farm weighing scales were calibrated before individual liveweight data (kg) capture. the researcher maintained data entry. on each farm, all trial lambs (including early and late vaccinated lambs and unvaccinated lambs) were managed as a single management group until weaning, when they were separated into two same-sex management groups. trial lambs were managed as a separate group and did not graze with other (non-trial) lambs on the farm from the period of study, enrolment to end. lambs were selected for slaughter according to producer preference for weight, carcase conformation and fat class; if selected prior to the study visit, lambs were weighed the day before slaughter by the producer. all vaccinations were performed by the same veterinary surgeon following manufacturer (msd, 2015 and best practice guidelines on vaccine storage and administration industry (ruma, 2006). as illustrated in fig. 1, lambs were vaccinated with a primary course of heptavac p plus at two time points: ‘early’ (first vaccine administered when lambs were approximately 6 to 8 weeks-old) and ‘late’ (first vaccine administered when lambs were approximately 18 to 20-weeks-old). primary vaccination consisted of two doses (2 ml) of heptavac p plus injected subcutaneously 5–10 cm below the ear using a sterile vaccination system (sterimatic worldwide ltd, uk). dosing interval was 4 to 5 weeks. vaccine was stored at 4°c and transported to farms in insulated cool boxes. bottles were unopened until just before administration. a new vaccination bottle was used for each farm, and once opened, vaccine was used within 2 hours. the veterinarian who administered all vaccinations was not blinded to vaccine type or brand. no placebo was used. the researcher sprayed the fleece of all trial lambs with a colour mark based on allocation group; colours differed between study farms. the veterinarian and producer were not informed of fleece codes. due to the on-farm nature of the trial and their necessary involvement with handling and vaccinating lambs and need for informed consent and awareness of the vaccine treatment groups, they were not considered to be fully blinded. at each visit, farmer-maintained mortality and treatment records were collected. throughout the trial, farms were asked to present trial and non-trial lamb mortalities for necropsy examination.   table 2 standardised clinical descriptors for assessment of lamb health and morbidity (secondary outcome) scored on binary scale (absent/present) clinical outcome assessment criteria  clinical respiratory signs observed signs of mucopurulent nasal discharge, and/or persistent severe coughing, and/or dyspnoea and/or, tachypnoea facial and oro-nasal orf lesionsa observed active and healing facial and oro-nasal orf lesions: external lesions, with or without discharging pustules and/or associated signs of inflammation; significant swelling and hyperaemia, and/or without signs of keratinizationa ocular discharge/lesion/entropionb observed ocular discharge (purulent, or haemorrhagic, or tear staining) and/or keratitis, conjunctivitis, and/or corneal ulcer and/or entropion ear tag lesion observed external lesions (abscesses and/or purulent discharge and/or tears and/or rips) around site of ear tag lamenessb observed three-legged gait and/or holding a foot off the ground and/or stiff or stilted gait, and/or head-nod associated with gait diarrhoeab observed diffuse faecal perineal soiling a scored as per descriptors of lovatt et al. (2012) b scored as per descriptors of phythian et al. (2012)   trial time schedule is illustrated in fig. 1. early vaccinated lambs received their first primary dose (aged approximately 6 to 8 weeks-old) at visit 1 and the second 1 month later (visit 2). on farms 1 to 5, lambs were weaned prior to visit 4; late vaccinated lambs received their first primary dose at visit 4 (approximately 18 to 20 weeks old) and second dose at visit 5. due to management constraints and later recruitment, farm 6 lambs were weaned just prior to visit 3. late vaccination was conducted at visits 3 (when lambs were approximately 16 weeks old) and 4. due to the early slaughtering of lambs on farm 1, only two late vaccine group lambs received the full vaccine course. the study ended on 7 november 2013 before trial lambs reached finishing objectives and exclusion weight criteria on farm 6.   figure 1 schedule of timings for the first (1st) and second (2nd) vaccinations of the primary vaccine course for early and late vaccination groups, weaning and the end of trial on each of the six study flocks   ethical approval the study was part of recognised veterinary practice under the veterinary surgeons act of 1966. ethical approval was obtained from the university of bristol ethics committee (ethical review reference vin/13/021).   statistical analysis data was entered into excel (microsoft office) and analysed using stata version 13 (statacorp, texas). based on the study start date, study age (days) was assigned for each weight-recording session. since these commercial farms had slightly different finishing goals, if lambs had not already left the trial, the exclusion criteria and final visit liveweight was set as ≥46 kg. descriptive statistics explored the number of lambs, and proportion of mortality, morbidity, tag losses, and liveweights on each farm at each study period. one-way analysis of variance (anova) examined for significant differences in mean liveweight of each group at study entry, in order to assess for any systematic bias in allocation. differences in overall mortality rates between vaccinated and unvaccinated trial lambs were examined for significance using wilcoxon signed-rank (paired) test. growth rates (daily liveweight gain – dlwg, g/day) were calculated between successive paired visits as: difference in weight/number of days between successive weighings. overall, mean trial lamb dlwg (w0) was calculated as: (last recorded weight minus weight on visit 1 / number of days in trial)*1000. mean difference in liveweight gain (kg) between unvaccinated and early vaccinated lambs was examined from visit 1 up to visit 4 (weaning) using paired t-tests. statistical significance testing was set at p≤0.05. data modelling was supported by a statistician (pjc) blinded to vaccine status. firstly, using mixed effects multilevel linear regression models including farm identity and visit number (1 to 6) as fixed effects to assess the effect of vaccination status (unvaccinated, early or post-weaning vaccination) on mortality, liveweight and dlwg. the continuous predictor ‘study age’ was also forced into all models to assess the effect of vaccination status on dlwg. no significant interaction terms were identified. later, farm identity was included as a random effect, as individual lamb identity was nested within farm. visit period (1 to 6) was also examined as a random effect. residuals were modelled in an autoregressive structure with an order of one. effect of lameness, ocular condition, orf lesion, diarrhoea or ear tag lesion on liveweight were analysed in separate mixed-effects regression models. during analysis, farm 1 lambs originally allocated into the late group but that were not vaccinated were recoded as unvaccinated lambs. similarly, farm 6 entered the trial later, and the trial ended before lambs reached finishing objectives/exclusion criteria. therefore, two datasets – 1. entire dataset of all six farms and 2. dataset with removal of farms 1 and 6 – were compared to assess for significant differences in study findings. to assess the effect of vaccination up to the point of weaning (i.e. early vaccination versus no vaccination), lambs originally allocated to the late vaccination group were recoded as unvaccinated. fixed and mixed-effects multilevel linear regression models, as described above, were used to identify any differences between liveweight and dlwg of unvaccinated and early vaccinated lambs up to visit 4 on farms 1 to 6.   results farm management with the exception of farm 1, all other study flocks had at least a 5 year history of prophylactic administration of multivalent combined clostridial and pasteurella vaccine (heptavac p plus, msd animal health, 2015) to breeding animals (primary course and a booster 4 to 6 weeks prior to expected peak lambing date). no flocks had administered multivalent clostridial or pasteurella vaccines to pre-weaned lambs in the previous 5 years. all lambs were routinely tail-docked using rubber rings within the first week of life and, except for farm 6, routinely castrated with rubber rings. on farm 5, all lambs routinely received a live orf vaccine (scabivax forte, msd animal health, 2015) prior to turnout onto pasture. trial lambs received oral anthelmintics, on average five times (range 4–6) during the trial period. farm 1 employed a rotational grazing system; farm 2 moved stock every 3 days, whilst farms 3 to 6 used set-stocking. on all farms, trial lambs were maintained as a single management group. on each farm, all trial lambs were grazed together as a single management group until weaning, when male and female trial lambs were separated and managed as two same-sex trial groups. farm 1 provided creep feeding for lambs from visit 1; farms 2 to 5 provided supplementary creep feed from weaning onwards; and farm 6 provided no concentrates during the study.   animals between 23 april and 7 november 2013, the number of lambs assessed per visit decreased over time, reflecting cumulative effects of mortalities (table 3 and table 4), exclusion of three sick lambs between visits 4 and 5 (fractured limb, blind, and recumbent) and lambs reaching finishing or exclusion criteria from visit 3 onwards. overall, 72 tag losses (8.0%) were recorded (table 3). due to double ear-tagging on farm 4, only 52 replacement tags were inserted.   table 3 number of lambs recruited, recorded ear tag losses, lamb mortalities, earliest and latest finishing times and minimum weight of finished trial lambs on six sheep flocks farm id n lambs recruited to study n (%)  ear tag losses in live lambs n (%)  trial mortalities recorded n (%) mortalities confirmed in unvaccinated trial lambsa,b n (%) mortalities confirmed in vaccinated lambsb n (%) unconfirmed vaccination status c earliest finishing time from study entry (study age) minimum weight of finished trial lambs (kg) latest finishing time from trial entry (study age) farm 1 135 21 (15) 7 (5.2) 7 (100) 0 (0) 0 (0) 56 days 40 148 days farm 2 135 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 90 days 41.5 154 days farm 3 135 36 (26.7) 4 (3.0) 2 (50.0) 2 (50.0) 0 (0) 122 days 43 155 days farm 4 135 5 (3.7) 7 (5.2) 6 (85.7) 0 (0) 1 (14.3) 125 days 42 154 days farm 5 135 4 (3.0) 3 (2.2) 2 (66.7) 0 (0) 1 (33.3) 99 days 42.4 162 days farm 6 225 6 (2.7) 9 (4.0) 6 (66.7) 2 (33.3) 1 (11.1) d d d total 900 72 (8.0) 30 (3.3) 23 (76.7) 4 (13.3) 3 (10.0)       a unvaccinated lambs include those in the unvaccinated trial group and trial animals in early or late vaccination groups prior to completion of the primary vaccination course following vaccine datasheet guidance. b trial lambs were considered to be fully vaccinated two weeks following the correct administration of the primary vaccine course) in adherence with vaccine datasheet guidance. c due to timing of death occurring between visit dates and lack of an exact dead date it is unclear whether early vaccine group lambs were fully vaccinated according to datasheet guidance at the time of death. d lambs did not reach producer finishing target or reach study exclusion criteria before the end of the study period.   mortality a total of 30 mortalities (3.3%) were recorded in trial lambs, which was equivalent to a study mortality rate of 33 deaths per 1000 lambs at-risk. ear tags were retrieved by producers from 14 trial lamb carcases and presented to the researcher, allowing full confirmation of the individual lamb identity in these cases. for the remaining mortalities, trial group status was identified by examining database records and cross-checking the number of lambs at each farm visit. lambs were presumed dead if they were missing on at least two consecutive visits, and had not been slaughtered. this approach permitted confirmation of the group and vaccination status of all but three mortalities (table 3). mortalities arose in both vaccinated and unvaccinated trial lamb groups (table 3). a clear trend was found with a higher level of lamb losses recorded in unvaccinated lambs, compared to lambs that were considered to be fully vaccinated (p=0.052). overall, farms 1 and 4 experienced the highest levels of trial lamb mortality (5.2%). on farm 1, all mortality cases occurred in unvaccinated lambs or before primary vaccine course completion. due to the lack of an exact death date for some lambs, it was not possible to confirm whether three trial lambs in the early vaccinated group were considered to be fully vaccinated (table 3). overall, 14 trial lambs died pre-weaning and 16 trial lambs died in the period post-weaning. there was some between-farm variation in the timing of lamb deaths. all trial lamb losses (n=7) on farm 1 occurred from early june to early july, i.e. before weaning (fig. 1), although lambs on this farm were receiving concentrate feed at their time of death. by contrast, there were two main periods for the timing of lamb losses (n=23) on farms 3–6. deaths of grazing lambs on farms 3–6 mainly occurred in the week of and up to 1 month post-weaning (16/23, 69.6%), i.e. late july to late august. the remainder of trial deaths on farms 3–6 occurred pre-weaning and were concentrated in the late june to late july period (7/23, 30.4%). the reasons for mortalities in trial lambs was not fully elucidated due to the very low number (n=2) of animals presented for veterinary post-mortem examination; both lamb carcases examined came from a single study flock. on farm 1, one trial lamb from the unvaccinated group (approximately 4 months old) was presented for necropsy on 13 june 2013 at the veterinary practice, and an unvaccinated non-trial lamb (coinciding with reported ‘sudden deaths’ in eight non-trial lambs), was necropsied on 28 june 2013 (mjg) during a trial farm visit. both lambs were in good body condition. gross post-mortem findings in the trial lamb included the presence of blood-tinged frothy fluid present in the trachea and congestion of both lung lobes with frothy fluid. the thymus surface and thoracic fat surface were petechiated, pericardial capillaries were inflamed and generalised petechiation of the pericardium with haemorrhage on the internal surface of left ventricular wall was observed. gross findings of the non-trial lamb included tracheal hyperaemia, petechiation of diaphragm, sub-capsular renal petechiation, fibrinous pericarditis, and liquid small intestinal content. no further diagnostic testing was performed.   morbidity no adverse events associated with vaccine administration were recorded. no clinical respiratory disease was recorded during repeated assessments. relatively low mean levels of lameness, signs of diarrhoea, ocular discharge/entropion and orf lesions were recorded (table 4). no significant effect of ear or orf lesions on dlwg were found. orf was not observed on farms 4 and 6, nor in lambs that had received orf vaccination at pasture turnout (farm 5). whilst entire ram lambs had heavier liveweights than ewe lambs (p<0.001), no significant interaction was found between sex and clinical outcomes. compared to unaffected peers, those with signs of lameness or entropion/ocular discharge or diarrhoea were lighter (p<0.001).   table 4 number (n) and percentage (%) of trial lambs observed with specific clinical signs (secondary outcome) at each visit period on six sheep flocks clinical outcome score n (%) lambs observed across all farms with each outcome at each visit (n=6) total n (%) lambs assessments 1 2 3 4 5 6 ocular lesion no lesions observed 851 (94.6) 872 (99.4) 860 (97.6) 776 (95.2) 725 (98.1) 411 (99.8) 4513 (97.0) discharge 25 (2.8) 11 (1.24) 20 (2.27) 27 (3.31) 10 (1.35) 1 (0.24) 94 (2.0) entropion 24 (2.7) 4 (0.5) 1 (0.1) 12 (1.5) 4 (0.5) 0 (0) 45 (1.0) ear tag lesion no lesions observed 898 (99.8) 849 (95.7) 867 (98.4) 811 (99.5) 736 (99.6) 411 (99.8) 4590 (98.7) ripped or torn 0 (0) 2 (0.2) 6 (0.7) 4 (0.5) 2 (0.3) 1 (0.3) 15 (0.3) infection or abscess 2 (0.2) 36 (4.1) 8 (0.9) 0 (0) 1 (0.1) 0 (0) 47 (1.0) diarrhoea absent 881 (97.9) 883 (99.6) 861 (97.7) 800 (98.2) 720 (97.4) 408 (99.0) 4571 (98.3) present 19 (2.1) 4 (0.4) 20 (2.3) 15 (1.8) 19 (2.57) 4 (0.97) 81 (1.7) orf not observed 888 (98.7) 782 (88.2) 874 (99.2) 815 (100) 739 (100) 412 (100) 4521 (97.4) active or healing lesion 12 (1.3) 104 (11.6) 7 (0.8) 0 (0) 0 (0) 0 (0) 123 (2.7) gait sound 899 (99.9) 887 (100) 880 (99.9) 808 (99.1) 723 (97.8) 399 (96.8) 4592 (98.7) lame 1 (0.1) 0 (0) 1 (0.1) 7 (0.9) 16 (2.2) 13 (3.2) 38 (0.8)   liveweight trial group liveweights at study entry (visit 1) were not significantly different and showed no evidence of systematic allocation bias (table 5).   table 5 mean, standard deviation (sd) and range (min–max) in liveweight (kg) of unvaccinated, early and late vaccinated trial lambs at each of the six visits (v1 to v6) on six sheep flocks vaccination status   statistic visit v1 v2 v3 v4 v5 v6 unvaccinated   n 300 300 299 276 249 135 mean liveweight 16.6 25.0 30.3 34.3 37.3 41.8 sd 3.5 4.3 5.4 5.8 5.9 4.9 min–max 7.0–26.5 13–38 11.6–45.0 18.0–48.0 22.0–51.0 25.0–51.5 early vaccination n 300 298 293 269 250 143 mean liveweight 16.5 24.5 30.0 33.8 36.2 41.6 sd 3.2 4.1 5.5 5.7 19.0–49.0 4.8 min–max 8.0–25.0 13–27 16.0–46.0 15.0–51.0 6.2 24.0–51.5 late vaccination n 300 289 289 269 240 134 mean liveweight 16.4 24.9 30.2 34.5 36.8 41.8 sd 3.2 4.0 5.3 5.4 6.1 4.7 min–max 8.4–26.0 14.2–37.0 17.6–44.0 20.0–48.0 22.4–49.0 28.0–54.5   mean liveweight varied between farms (table 5). mean finishing weight (farms 1 to 5) was 44.9 kg. the trial ended before lambs on farm 6 reached finishing weights. mean dlwg generally decreased over time (w1 to w5), particularly after weaning and prior to visit 4 (table 6). mean time from study entry to finishing was 116 days (95% ci 112–120 days); i.e. on average lambs reached slaughter weight at 6 months old. farm identity and visit period had a significant effect on liveweight (p<0.001). when the full dataset and dataset excluding farms 1 and 6 were examined, and when farm identity, visit number, sex and animal identity were accounted for, no significant effect of vaccination on liveweight or dlwg was found. furthermore, there was no significant difference in dlwg between unvaccinated and early vaccinated lambs up to weaning.   table 6 mean, standard deviation (sd) and range (min–max) in daily liveweight gain (dlwg) for consecutive weight gained in the time between visits 1 to 2 (w1), visits 2 to 3 (w2), visits 3 to 4 (w3), visits 4 to 5 (w5), visits 5 to 6 (w5) and overall dlwg (w0) of trial lambs on six sheep farms   weight gain    statistic farm id farm 1 farm 2 farm 3 farm 4 farm 5 farm 6 w1 mean dlwg (g/day) 312.4 372.2 333.4 264.4 252.9 192.0 sd 54.4 73.0 78.0 58.0 63.5 57.7 min–max 162.2–459.5 189.7–569.0 71.43–535.7 115.4–423.1 -40.0–393.3 -86.2–362.1 w2 mean dlwg (g/day) 316.8 205.1 242.9 162.2 161.42 85.6 sd 69.9 69.8 78.2 70.74 85.9 49.5 min–max 74.1–555.6 55.56–388.9 -35.7–607.1 -112.9–451.6 -214.3–592.9 76.9–307.7 w3 mean dlwg (g/day) 278.6 270.10 212.2 153.9 119.3 64.7 sd 99.0 76.7 75.1 85.1 61.6 62.5 min–max 0–466.7 71.4–464.3 -111.11–388.9 -111.1–463.0 -73.17–419.5 -132.4–294.1 w4 mean dlwg (g/day) 182.9 167.4 71.7 190.8 66.6 28.8 sd 93.4 78.7 64.0 72.3 66.2 82.0 min–max 40.81–346.2 -42.86–382.4 -68.97–400.0 0–341.5 -137.9–324.1 -177.4–241.9 w5 mean dlwg (g/day) a 184.0 88.5 89.6 150.4 a sd a 73.25 68.5 101.08 54.14 a min–max a -42.9–328.6 -309.5–312.5 -166.7–344.8 -5.9–270.6 a w0 mean dlwg (g/day) 309.6 248.6 202.8 181.9 147.8 92.1 sd 50.2 45.36 69.23 35.49 33.1 27.0 min–max 155.4–414.1 159.1–357.1 71.4–482.1 90.9–307.7 3.5–282.8 17.2–224.1 a insufficient data for analysis: most lambs finished before visit 6 (farm 1) or the trial had already ended (farm 6)   discussion to the authors’ knowledge, following a literature search on the subject, no previous studies assessing field performance of multivalent clostridial spp. and pasteurella vaccines on british sheep flocks have been reported. in contrast to the medical sector, veterinary vaccine field trials are often considered inferior to challenge trials because of the lack of standardised conditions (knight-jones et al., 2014). however, vaccines need to perform under farming conditions where variation in individual animal immunity, pathogen exposure (knight-jones et al., 2014) and environmental and husbandry factors influence disease aetiology (emea, 2001). well-designed and well-conducted field trials are necessary for informing evidence-based management of livestock (sanderson, 2006; dean et al., 2015).   trial design and conduct the veterinary all trials initiative (www.vetalltrials.org) supports the open publication of all trial outcomes and veterinary clinical trial results in order to prevent duplication of unreported studies, improve animal welfare and improve the quality of studies used to inform evidence-based decision making (dean et al., 2015). this article serves to highlight trial results, and discuss planned study design and conduct considerations together with actual field experiences to inform and improve further studies. a ‘gold standard’ randomised controlled trial (rct) was not feasible due to limited personnel and financial resources. instead, we used the reflect guidelines (sargeant et al., 2010) to inform field trial design, conduct and reporting of study results. blinding of the veterinarian, researcher and producers was performed as far as possible. due to the nature of veterinary practice-based research and the need for producer involvement in animal handling, there were some practical limitations. participants and researchers were not blinded to the treatment administered (i.e. the type or brand of vaccine). producers presented a sample of twin lambs considered representative of the flock. systematic randomisation was performed to reduce introduction of sample selection bias. to reduce observer scoring and recall biases, lambs were assessed by the same veterinarian who was blinded to data recorded at previous trial visits. to minimise potential measurement errors, farm weighing systems were calibrated at each visit, before use. to minimise the effect of competitive maternally-derived antibodies (msd animal health, 2015), all early vaccine lambs received their first primary vaccine dose aged 6 weeks or above. expected ear tag losses in commercial systems were the reason for having both individual and group identification methods. the high level of tag losses (26.7%) on farm 3 may reflect the tagging technique, that a different brand of tag was used, or fencing type. fleece colour was sufficient for group identification, and colour codes were withheld from the veterinarian and producers. since fleece marks were clearly visible, trial participants were not fully blinded. up to weaning, all trial lambs on each farm were managed as a single group, and post-weaning were managed as a group of trial ewe lambs and a group of trial ram lambs. there was no evidence that lambs of different vaccination status were deliberately managed in a different way due to incomplete blinding. limited resources necessitated data entry by the researcher. modelling, however, was supported by a statistician (pjc) blinded to vaccine status.   generalisability trial farms were considered representative of farms and production types within the practice area and represented a convenience sample. therefore, mortality, liveweight and dlwg data must be interpreted in light of the approximate age and timing of visits. such data cannot be considered representative of all commercial english sheep flocks nor should it be used for benchmarking of flocks of a similar production type.   mortalities and necropsy findings the study identified a lower level of mortality in fully vaccinated lambs, however vaccination alone did not prevent lamb mortalities. 13.3% (n=4) of trial mortality cases occurred in lambs classed as fully vaccinated, and these mostly arose in the early vaccination group. aside from farm 1, the majority of grazing lamb losses occurred in the week immediately after weaning or in the month following weaning. this timing appears to coincide with the period 12–16 weeks after ewe vaccination when colostral antibodies to clostridal spp. are purported to wain in lambs which have received adequate passive transfer of immunity from correctly vaccinated ewes (msd animal health, 2015). however, due to the very low level of lambs presented for necropsy investigations, the causes of death in both vaccinated and unvaccinated trial lambs were not diagnosed. mortality data capture and necropsy were not undertaken during the field pasteurella spp. vaccine trial by goodwin-ray et al. (2008) due to the expected logistical difficulties for accurately monitoring on new zealand flocks. given the smaller english trial flock sizes in this study, accurate producer-recording of mortalities was considered feasible. all flocks were within a 15 mile radius of the veterinary practice, and participating producers were offered free-of-charge necropsies. despite this, only one study flock (farm 1) submitted lambs (one trial and one non-trial lamb) for necropsy during the study. the low level of necropsy uptake was disappointing. whilst producers recognised the value of necropsy for informing management decisions, a commonly reported issue was the extensive degree of scavenging and carcase decomposition when lambs were found dead, which concurs with the concerns of researchers in the earlier new zealand study. the present trial highlights the real logistical and practical issues with monitoring mortalities in grazing lambs, even when recruiting an engaged and committed group of producers to veterinary practice-based research. a total of 30 mortalities were registered but the lack of individual animal identity and poor recovery rate of ear tags from decomposed or scavenged carcases, and the loss of ear tags between visits, particularly on farm 3, initially presented some challenges for data analysis. however, since vaccine status was colour coded, applying the assumption that lambs missing for at least two visits and not slaughtered had died, these elements facilitated confirmation of the vaccination status of nearly all mortality cases. on farm 1, where no multivalent clostridia spp. or pasteurella preventive ewe vaccination was historically undertaken, all trial lamb deaths occurred pre-weaning in either unvaccinated lambs, or in partially vaccinated lambs prior to completion of their primary vaccination course. sudden deaths of prime lambs that were near to reaching slaughter weight were reported on farm 1, but did not occur in the trial lamb group. necropsies on farm 1 revealed gross signs suggestive of pasteurellosis, and enterotoxaemia due to clostridium perfringens d toxin (colloquially: ‘pulpy kidney’). further investigations, including bacteriology, brain histology and epsilon toxin testing, required for definitive diagnosis of clostridial enterotoxaemia (uzal et al., 2004) were not conducted due to limited study resources. therefore, these diseases and other causes of septicaemia could not be excluded. lambs on farm 1 may have been at a higher risk of clostridial disease and pasteurellosis prior to weaning since they were offered creep feeding throughout the trial period, whereas on farms 2–4 – where creep feeding was offered post-weaning – the change in diet and stress associated with weaning may explain the higher number of lambs that died post-weaning. evidence from this study and earlier clinical reports (lewis, 2007) support the value of preventive ewe vaccination as a means of reducing lamb mortality on farm 1 associated with preventable disease. lamb losses or clinical signs (respiratory disease) associated with pasteurella spp. were not definitively diagnosed in any of the trial groups, which may reflect the very low level of necropsy submissions and/or a low level of disease challenge during the study year. therefore, insufficient data were captured to give useful diagnostic information, specifically information regarding the prevention of pastuerellosis, which had been the background for this practice-based trial. future researchers might recruit housed lambs to improve capture of mortality cases for diagnostic investigations, which was not the approach used here since the aim was to capture data generalisable to pasture-reared lambs.   lamb growth rates significant between-farm and visit-period differences in growth rate (dlwg) were found, which likely reflect differing management practices (e.g. creep feeding of lambs). across all farms and irrespective of vaccination group, the highest mean dlwg (277.4 g/day) was recorded early on, between visits 1 and 2, when lambs were between 6 and 12 weeks old, and likely reflects peak milk production of ewes. with the exception of two flocks (farms 5 and 6), the mean dlwg over the study period was above 150 g/day. highest mean dlwg was recorded on farm 1 and may be explained in part by that farm’s earlier lambing period, which may be associated with reduced parasite and other disease challenges and, most likely, early concentrate feeding of lambs prior to weaning. by comparison, lambs born later in the season, grazed in severely disadvantaged areas (sda) (e.g. on farm 5 and 6) and that did not receive supplementary concentrate feeding had a lower mean dlwg. reduced lamb growth rates can have considerable impacts on flock performance associated with delays in finishing time to slaughter, missing the peak in market prices, submission of less-uniform lambs to slaughter, increased numbers of lambs kept as stores, and the subsequent effects on ewe lamb fertility and performance (gascoigne and lovatt, 2015). in this study, mean dlwg reduced over the trial period on all farms and decreased considerably post-weaning, prior to visit 4 (98.9 g/day), but improved by visit 5 (122.6 g/day). weaning is a stressful event, with changes to lamb nutrition, social stability and other factors. reduced immunity and increased host susceptibility to infectious and parasitic disease may explain reduced dlwg observed at visit 4. however, disease and parasite monitoring were not performed systematically across these flocks. further investigations, for example including dlwg recording of the wider flock, close monitoring of parasite burdens in grazing lambs, diagnosing the reasons behind mortalities, and understanding grazing management and disease control practices may identify multiple factors associated with reduced growth rates around weaning time. vaccination was not associated with a significant difference in lamb growth rate. sample size calculations were based on a priori assumptions on mortality differences between vaccinated and unvaccinated lambs. therefore, the lack of statistical significance in analysis of the secondary outcome (dlwg) may reflect a type i statistical error (inadequate sample size to identify a true effect) or a true effect. however, significantly reduced growth rates in finishing lambs with severe lung lesions associated with m. haemolytica or p. multocida have been identified in a trial with 259 lambs (daniel et al., 2006), so the sample size of 900 lambs presented here may have been sufficient to detect a meaningful effect. a lack of significant differences in dlwg was also found in a new zealand study that tested a multivalent pasteurella vaccine (ovipast p plus, msd animal health, 2015) on 9174 lambs from six commercial flocks (goodwin-ray et al., 2008). testing of the same pasteurella spp.-specific vaccine on english sheep flocks was considered but given the additional requirements for handling and vaccination costs, and in light of the current vaccine routines and producer identified knowledge gap, this trial was instead designed to examine an alteration in timing of commonly practiced (post-weaning) vaccination of lambs with a multivalent clostridia and pasteurella vaccine.   disease incidence an accepted a priori risk was that insufficient disease exposure to detect significant differences in study outcomes might occur. herd immunity (i.e. protection afforded from vaccinated animals within the same management group) can affect the ability of studies to detect meaningful between-group differences (dohoo et al., 2009). therefore, flocks that were not already vaccinating lambs against clostridial disease or pasteurellosis, and those with confirmed/suspected disease, were recruited. furthermore, unvaccinated lambs were left within each trial group with the aim of maintaining some disease challenge. remaining lambs in each flock were left unvaccinated as per standard farm practice. despite this, routine preventive breeding animal vaccination on five farms likely reduced disease challenge. following primary vaccination and pre-lambing boosters, datasheets suggest that the vaccine used offers lambs 12 to 16 weeks of colostral-derived antibody protection against some clostridial diseases; lamb dysentery, pulpy kidney and tetanus (msd animal health, 2015). based on the datasheet advice of unproven, but reported, duration of up to 4 weeks of pasteurella/mannheimia passive immunity derived from colostrum, it was assumed that pasteurellosis challenge was not markedly reduced for trial lambs. all producers participating in the trial perceived a lower level of respiratory disease outbreaks in lambs during 2013. lack of recorded clinical respiratory signs may support this view of low disease exposure, although clinical observation is not a sensitive tool. transthoracic ultrasonography is a more sensitive means of diagnosing ovine respiratory disease (scott and sargison, 2010), but was not applied here due to time and financial constraints. it is not possible to validate producer perceptions and trial findings with regional veterinary laboratory diagnostic data (supplementary material) due to the very low level of diagnoses, and unknown disease and vaccination status of submitting flocks. overall, there is no strong evidence that suggests 2013 was an unusually low year for pasteurellosis in the region. orf cases peaked (11%) at visit 2 and declined considerably 1 month later. reduced weight gain for up to 5 weeks after clinical orf lesions has previously been reported in three-week-old lambs (lovatt et al., 2012). however, lovatt et al. (2012) found no significant growth rate differences between orf affected and unaffected lambs aged 7 weeks and over, which concurs with our findings in lambs aged 6 weeks and over. lameness (0.9%) and ocular conditions (3.3%) were lower than those previously reported (2.1% and 6.6%, respectively) in younger lambs (phythian et al., 2013), which may reflect variation in sample age, pathogen exposure, management practices, and, potentially, greater veterinary involvement. gait was assessed as lambs moved through handling areas, most frequently mobile systems, at pasture. thus, lameness levels may represent only the most severe cases, and might underestimate true prevalence. lame lambs, or those with entropion/ocular discharge or diarrhoea scour were lighter than unaffected peers. this is the first report providing evidence of a significant impact of ocular lesions (including discharge and entropion) on the growth rate of lambs aged 6 weeks old and above, and highlights the need for early intervention in affected lambs to reduce the animal welfare and production impacts associated with these conditions.   future studies a single group of trial lambs was not maintained for both animal welfare and practical reasons. on all farms, male and female trial lambs were separated at weaning and remained in a same-sex group of trial lambs. since all farms managed all trial lambs in this way and the statistical methods were capable of taking account of individual farm differences, this effect was considered to be limited. trial timing was based on peak lambing dates, logistical considerations, and assumed time to slaughter. one farm unexpectedly dropped out shortly before study commencement, and, as a consequence, a later lambing flock was recruited that did not sell lambs to slaughter before the trial ended (farm 6). another flock (farm 1) had sold almost all lambs by the time the secondary course of the primary ‘late’ group vaccination was due. however, excluding farms 1 and 6 from the dataset made no significant difference to study findings. whilst a larger sample than suggested by sample size estimates had been included to limit the impact of unpredicted issues (e.g. drop-out or unexpected disease), selecting farms with closer lambing dates, more similar management practices, as well as recruiting a much larger sample, and considering alternative design (e.g. a clustered random trial), could be worthwhile for future trials on pasture-managed sheep. visits were not extended beyond 6 months due to flock management and trial financial resources. future studies might consider only enrolling breeding lambs to facilitate longer-term evaluation of post-weaning vaccination. although, findings of such studies may not be generalisable to commercial flocks rearing lambs for slaughter.   conclusions overall, there was a clear trend in reduced mortality rates in grazing lambs that received a multivalent clostridia and pasteurella spp. vaccine course, compared to unvaccinated lambs. no significant effects of preor post-vaccination on lamb growth rates were found. on one trial farm that did not undertake preventive clostridial and pasteurella breeding animal vaccination, there was strong clinical and gross pathological suspicion of pasteurella and clostridial disease in two lambs, which highlighted the disease risks for unvaccinated sheep flocks. carcase scavenging and decomposition resulted in a very low submission rate of lambs found dead at pasture. this lack of veterinary necropsy examination resulted in a loss of valuable data on the causes of mortality in grazing lambs, which are likely to vary between flocks and differ between years. whilst there may not be per se a cost benefit for ewe or lamb vaccination every year, best practice recommendations for maintaining an annual vaccination regime are based on maintaining ‘herd immunity’. a whole farm approach to veterinary flock health planning with specific risk assessment, cost-benefit analysis and farm-specific evidence from lamb mortality data, supported by necropsy and diagnostic testing, could help to inform the decision to implement a new regime, or to amend the timing of preventive vaccination programmes for lambs.   implications overall, there was evidence to support veterinary advice to implement preventive ewe vaccination on one unvaccinated flock (farm 1). this study cannot provide evidence to indicate the benefit of vaccination in flocks experiencing severe disease outbreaks associated with pasteurella spp. there were fewer mortalities in lambs that were vaccinated prior to weaning (‘early’ vaccination group). however, this trial cannot provide evidence for a ‘one-size fits all’ recommendation for implementing pre-weaning vaccination of lambs in flocks that already adhere to best practice preventive ewe vaccination.   conflict of interest acknowledgments: we gratefully acknowledge the six farmers for all their time and their considerable efforts in the field work involved and thank the staff at torch farm and equine ltd. for their logistical support. we are grateful to paul williams, ruminant veterinary advisor for msd animal health, for his support in acquiring funding for this evidence-based veterinary practice research. we also thank professor william browne of the centre for multilevel modelling and professor david barrett of the school of veterinary science, university of bristol, for earlier, helpful discussions and support on vaccine study design, and statistical analyses employed. funding: the study was financially supported by the msd animal health 2013 ruminant research bursary (£2000), which was used to purchase vaccines and supported some of the travel costs entailed. competing interests: msd animal health provided funding support but the funders played no role in the study design, conduct, analysis, interpretation or reporting of these findings.   references ahpa. animal health and plant agency sheep disease surveillance 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goats. anaerobe. 10: 2, 135–143. doi: http://dx.doi.org/10.1016/j.anaerobe.2003.08.005 wells, p.w., evans, h.b., burrells, c., sharp, j.m., gilmour, n.j., thompson, d.a. & rushton, b. 1979. inability of passively acquired antibody to protect lambs against experimental pasteurellosis. infection and immunity. 26: 1, 25–29. doi: http://dx.doi.org/10.1128/iai.26.1.25-29.1979 wells, p.w., robinson, j.t., gilmour, n.j., donachie, w. & sharp, j.m. 1984. development of a combined clostridial and pastuerella haemolytica vaccine for sheep. veterinary record. 114, 266–269. doi: http://dx.doi.org/10.1136/vr.114.11.266 zheng, t., gupta, s.k., mccarthy, a.r., moffat, j. & buddle, b.m. 2015. cross-protection study of a mannheimia haemolytica serotype 1 vaccine against acute pasteurellosis in lambs induced by a serotype 2 strain. veterinary microbiology. 177: 3-4, 386–393. doi: http://dx.doi.org/10.1016/j.vetmic.2015.02.019   supplementary files, images & tables table s1 sheep surveillance dashboard 2012–2017 data for number of sheep in devon submitted for necropsy to the regional animal plant and health agency (apha) veterinary investigation centre in which pasteurella spp. were diagnosed as cause of death year n sheep with specific diagnoses systemic pasteurellosis pasteurella  (non-respiratory) pneumonia – pastuerella multocida 2012 2 1 0 2013 1 2 1 2014 2 0 0 2015 1 0 0 2016 7 0 0 2017 5 4 1 data extracted directly from the publicly available sheep disease surveillance dashboard: https://public.tableau.com/profile/siu.apha#!/vizhome/sheepdashboard_/overview n.b denominator data on total number of sheep submitted for necropsy over these periods were not provided.   intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. a scoping review of the current literature exploring the nature of the horse-human relationship h.g.r. clough bvetsci1 j.h. burford ma, vetmb, phd, certva, certes, sfhea, frcvs1 a.l. roshier bsc (hons), phd, pgche, pgcert, ma (higher education), msc (behaviour counselling), sfhea1 g.c.w. england bvetmed, phd, dvetmed, dvr, dvrep, dipecar, dipact, pfhea, frcvs1 s.l. freeman bvetmed, phd, certva, certvr, certes, dipecvs, fhea, frcvs1* 1school of veterinary medicine and science, university of nottingham, college road, sutton bonington, leicestershire, le125rd *corresponding author (sarah.freeman@nottingham.ac.uk) vol 4, issue 4 (2019) published: 20 nov 2019 reviewed by: zofia lisowski (bvsc, phd, afhea, mrcvs), suzanne rogers (bsc(hons) chbc) and jo ireland (bvms, phd cert, avp(em), fhea, mrcvs) doi: 10.18849/ve.v4i4.240 section index:    abstract | introduction | methods | results | discussion | footnotes | conflict of interest | references | supplementary files abstract objective: to perform a scoping review of the current evidence on the horse-human relationship. background: the horse-human relationship has a significant impact on how horse owners care for and make decisions for their horse. evidentiary value: identification of consensus and gaps in current evidence. methods: a literature search was performed in cab abstracts and medline using search terms relating to the nature of the horse-human relationship in horses used for pleasure riding. publications were reviewed against inclusion and exclusion criteria. original qualitative or observational research studies relating to the relationship between a horse and owner were analysed. data were extracted on study method and population characteristics. results: there were 4,481 studies identified; 27 studies were included in the final data extraction. the studies covered 11 different areas, the most frequent were effect of humans on equine behaviour (5/27), equine training methods and behaviour (4/27) and horses within sport and leisure (4/27). a range of methodologies were used, with the most frequent being thematic analysis (6/27 studies), use of an instrument, tool or scale (3/27) and behavioural scoring (4/27). the majority of studies considered the human’s perspective (20/27), six considered the horse perspective and one considered both the horse and human perspective. no studies investigated the same or similar aims or objectives. conclusion: the current evidence on the horse-human relationship is diverse and heterogenous, which limits the strength of evidence for any particular area. application: future research should focus on developing reliable and repeatable tools to assess owner motivations and horse-human relationship, to develop a body of evidence.   introduction from its first domestication over 6,000 years ago, the horse – equus ferus caballus – has evolved from its primary role as working animal into additional roles as much-loved and reliable companions (endenburg et al., 1999). the evolution of their use has in turn influenced not only the way we interact with horses today, but also the relationships that are formed between horses and humans (hausberger et al., 2008). consequently, it is important to gain an understanding of horse-human relationships in today’s environment, and how these relationships influence decisions made at key stages within a horse’s life. there are currently around 100 million working equids (horses, donkeys and mules) across the world, predominantly located in poorer or developing countries, where they have a major role in rural economies and the lives of the families and communities that depend on them (world horse welfare, 2019). in the uk, the role of the horse is, however, very different. a recent survey carried out by the british equestrian trade association (2019) found that there are around 847,000 horses, and 374,000 horse-owning households in britain. it has also been reported that 96% of uk horse owners ride for pleasure and 53% of these have horses whose main role is for leisure riding and hacking, which represents a major change from a utility-based role, to a companion-based role important in sport and leisure (dashper, 2014). a review carried out by hausberger et al. (2008) explored the various areas of the horse-human relationship which included tools to assess horses’ relation to humans, exploration of the bond between a foal and a human, and matching of the horse and rider. this is only a single review and there are no comprehensive peer-reviewed studies of the topic. performing a scoping review to describe the current research available on the horse-human relationship may be beneficial prior to performing systematic reviews. it would enable us to identify and categorise which aspects of the horse-human relationship have previously been explored, and identify where there are existing bodies of evidence or current gaps in knowledge and research. for this study, the definition of ‘relationship’ described by hinde (1979) was used: ‘the emerging bond from a series of interactions: partners have, on the basis of the past experiences, and expectations on the other individual's responses’. a scoping review is similar to a systematic review and follows many of the methodological steps. the review type provides a preliminary evaluation of the size and scope of available literature in order to gauge the nature and extent of research evidence (grant and booth, 2009). arksey and o'malley (2005) described the motivations as to why a scoping review may be performed which included: to investigate the range, extent and type of research activity; to determine the value of performing a full systematic review; to summarise and distribute findings or to identify gaps in the existing literature. the aim of this scoping review is to investigate and categorise the current published literature regarding the nature of the horse-human relationship in horses used for pleasure riding.   methods protocol and registration this review has not been registered to an existing protocol. this scoping review was conducted using the methodological framework presented by arksey and o'malley (2005) and the results are presented using the prisma extension for scoping reviews (tricco et al., 2018). this project was reviewed and approved by the ethics committee, school of veterinary medicine and science, university of nottingham. eligibility criteria to be eligible for the review, papers needed to investigate the relationship, bond or interactions between horse and human for horses used for pleasure. papers were included if they reported on original research studies, and the full text of the paper was available and published in english. the study focused on the literature around pleasure horses, and therefore studies on animal-assisted therapy, working equids, and horses used for agricultural purposes were excluded (table 1). inclusion exclusion full text available non-english publications original research single cases/essays qualitative or observational studies with methodology capturing a two-way relationship between horse and human reviews   studies of use of equids for animal-assisted therapy1   studies of working equids in developing countries2   studies of equids for agricultural use3   experimental/quasi-experimental studies which did not investigate the horse-owner relationship using an owner/carer in the study design4 table 1: inclusion and exclusion criteria used to perform a scoping review of current publications exploring the horse-human relationship.   for the purposes of this study, the following definitions were used for the exclusion criteria: 1studies of use of equids for animal-assisted therapy: defined as a study, or person or people having intermittent access to an animal with the aim of improving specific physical, mental or social functioning. 2studies of working equids in developing countries: defined as studies of working equids in any countries listed by the development assistance committee (dac) of the organisation for economic co-operation and development (oecd) eligible for official development assistance, 2017 data (oda list). 3studies of equids for agricultural use: defined as equids that provide support to farmers in developing countries for example carrying feed and water for livestock and connecting farmers to cooperatives and markets (brooke, 2015). 4experimental/quasi-experimental studies: experimental studies defined as studies which compare different treatments, where the researcher controls treatments using a randomised controlled study or control groups. quasi-experimental studies defined as those that compare different treatments where the treatments are not randomised or are not controlled by the researcher (e.g. comparing responses pre and post-treatment in same patient). information sources and search strategy a literature search was performed on 13.11.17 and updated on 11.04.19 using cab abstracts (1910–present) and medline (1946–present), which have been reported as the two key databases for veterinary literature (grindlay et al., 2012). the following search terms were used: human, person, people, individual, horse, equine, equid, equus, equi, relationship, bond, interaction. all references were downloaded and managed in endnote reference manager (endnote x8.0.1). selection of sources of evidence any duplicate papers were removed and the titles were reviewed by the primary researcher (h. clough). publications were retained if the titles contained terms relating to the horse-human relationship. any titles that were ambiguous were retained for abstract review. abstracts were reviewed and retained if they related to studies of factors associated with the horse-human relationship and the search terms described above. any studies identified during the abstract review that did not have the full text available were excluded. any abstracts that were ambiguous were retained for full text review. the full text of included publications were then reviewed against inclusion and exclusion criteria (table 1) by two researchers (h. clough and s. freeman) to agree the final included studies (figure 1). data charting process and data items the included publications were analysed to generate data extraction tables for the methods and population characteristics of each of the publications. data extracted for study methods were: title; author; study methodology; aims; measures; and key outcomes as self-reported by the authors. data extracted on study populations were: author and date; location; study participants; population size; and study perspective. the study perspective was established by identifying the study population and objectives. no additional analysis was conducted. methodological quality or risk of bias of included studies was not appraised, consistent with guidance on scoping review conduct (arksey and o’malley, 2005; tricco et al., 2018).   results selection of sources of evidence a total number of 5018 studies were found on the initial database searches. there were 132 papers included after the abstract check, however only 112 of these had the full text available (figure 1). from these 112 full text publications, 85 studies were excluded from final analysis as they did not meet the final inclusion criteria (table 1); the excluded studies were 33 reviews (two of which were systematic reviews), 14 studies of animal-assisted therapies, six studies of working equids, 28 experimental or quasi-experimental studies and four studies which did not investigate the horse-human relationship (figure 1). there were 27 papers which met the final inclusion criteria and were therefore analysed and data presented in extraction tables comparing study, method and population characteristics.   figure 1: prisma flow diagram demonstrating the process used for a scoping review on the current literature exploring the horse-human relationship and how the final 27 included studies were identified. from: moher et al., the prisma group (2009).   characteristics of source of evidence the data regarding the study methodology for each of the 27 included studies are presented in table 2. a range of different study methods were used, including questionnaires (n=11), behavioural observational studies (n=7), focus groups (n=1), ethnographic studies (n=5), interviews (n=2) and mixed methods (n=1). the measures used in the studies included: thematic analysis (n=7); instrument, tool or scale (n=4); behavioural scoring (n=4); mixed measures (n=3); open and closed questions (n=4); interview scoring guide (n=1); likert/vas scale (n=1); component analysis of data (n=1); physiological parameters (n=1); and behavioural scoring and physiological parameters (n=1) (table 2). the aims of each of the studies were all individual. there were no studies investigating the same or similar aims and objectives, but there were some similarities between studies and the areas in which they explored. these areas included: the effect of humans on equine behaviour and reactions (n=5); equine training methodologies and behaviour (n=4); horses within sport and leisure (n=4); equine welfare (n=3); human attachments and bonds to horses (n=3); horse-human ecologies (n=2); the influence of human-animal relationship on psychological wellbeing (n=2); equine euthanasia (n=2); the importance of personality traits to breeders (n=1); and colic decisions (n=1) (table 2). publication title author methodology/study design aim of study measures important outcomes equine gatekeepers, animal narratives and foxhunting landscapes acton, a. ethnographic study exploration of the connection between mounted fox hunting packs and the landscape. narratives of past and present foxhunters to give an ethnographic account of the role of the horse in the fox hunting culture. using animals as ‘co-actors’ rather than subjects in ethnographic approaches promoted appreciation of the environment and the animals within it. living the 'best life' or 'one size fits all' – stakeholder perceptions of racehorse welfare butler, d. et al. focus groups exploring the perceptions of stakeholder in the british racing industry of factors influencing racehorse welfare. thematic analysis of three areas: ‘best life’ and minimum welfare standards; main welfare challenges; and innovative practices to improve welfare. overall consensus on minimum welfare standards and ‘best life’. important of tailoring plans for individuals highlighted. ‘best life’ scenario relies on horse-human relationship to implement, monitor and change as needed. companion animals as selfobjects brown, s.e. semi-structured interviews exploring if self-psychology can be systematically applied to human-animal relationships. scoring guide to selfobject type was developed and used on the interview transcripts. self-psychology could be successfully applied to the human-animal relationship. in this study, animals were found to rival or surpass humans in the ability to provide self-object needs. an investigation of human-animal interactions and empathy as related to pet preference, ownership, attachment, and attitudes in children daly, b. and morton, l.l. five instrument questionnaire investigation of the relationship between children and pets in regards to pet preference, ownership, attachment and attitudes. the pet ownership survey (daly and morton, 2003) the bryant index of empathy (1982) the pet preference inventory (daly and morton, 2003) the lexington attachment to pets scale (johnson et al., 1992) the pet attitude scale (templer et al., 1981). those who were highly attached to their pets were more empathetic than those who were less attached. girls were more empathetic than boys. empathy was higher for those who expressed a preference for horses and birds. tools of the trade or part of the family? horses in competitive equestrian sport dashper, k.   ethnographic study exploring horses in competitive equestrian sport and altering the horse-human relationship. loosely structured interviews around four broad themes: participants’ involvement in equestrian sport, how that involvement fits in with or clashes with other areas of life, goals and motivations within the sport, and attitudes to the horses they ride. the emerging key themes included: the changing nature of equestrian sport; the influence of owners and the feelings of mutual respect and affection that can develop between horses and humans. listening to horses: developing attentive interspecies relationships through sport and leisure dashper, k. ethnographic study considering some ways in which human participants try to develop attentive relationships with their equine partners. transcription and thematic analysis of interviews and field notes taken in a three-year period. participants were acutely aware of their horses as individuals with personalities, likes, dislikes and how this impacted owners’ decision making ability. horses were described by the participants as ‘persons’. emerging themes included: guardianship, affection and relationship building. "riding up forested mountain sides, in wide open spaces, and with walls": developing an ecology of horse-human relationships davis,d. et al. ethnographic study to demonstrate the complex ways in which riding terrains affect shared ecologies of horse-rider relations, identities, and psyches. analysis of narrative data using a grounded, practice theory. dressage riders were described as becoming attuned, focused and in touch with their horses. event riders described the importance of shared trust, fearlessness and their confidence in the horse. endurance riders were described as relating stamina, conditioning and stoic endurance for survival. overall finding that horse and human paired together, defined, distinguished, and identified by the environments that they were in. training methodologies differ with the attachment of humans to horses dearaugo ,j. et al. questionnaire using attachment theory to investigate whether the attachment between rider or handler and horse differed according to the preferred training method. nine items used to assess attachment using a seven point scale. scores were calculated for avoidance and anxiety and statistically analysed. behavioural training participants scored more highly on the attachment-avoidance scores. the behavioural and eclectic training methods were associated with higher levels of education. examining canadian equine industry participants' perceptions of horses and their welfare dubois,c. et al. questionnaire exploring the perceptions of horse sentience and welfare status of animals in the canadian equine industry. 39 questions on participants demographic and experience, and their opinions on sentience and welfare, including use of scenarios. horses were mainly considered companion animals, and most participants strongly believed horses could feel pain, fear and boredom. participants agreed that there were welfare issues within the issues, specifically horse that were unwanted, not trained appropriately, or there was a lack of knowledge by the owner/care giver. participants’ opinions were affected by the role they assigned to horses and how they were involved in the equine industry. importance of personality traits in horses to breeders and riders graf,p. et al. online questionnaire evaluating the importance of personality traits in horse to breeders and riders. 41 item web-based questionnaire containing open and closed questions and likert and ranking scales. temperament, character traits and willingness to work were assigned more weight. less weight was given to performance traits like quality of trot or show-jumping. the relative weighting of traits varied between the different groups of rider. ease of daily work, safer handling and horse-human relationship were commonly listed in answer to why personality traits are important. a brief note on some possible factors involved in the reactions of horses to humans hausberger,m. et al. behavioural observation assessing the possible factors involved in the reactions of horses to humans. observation and scoring of posture using waring and dark’s (1978) observations. more horses showed a friendly behaviour opposed to an aggressive behaviour towards an unfamiliar human. inter-individual variations in reaction were clear and had a good consistency. factors involved in those variations included the breed and the usual caretaker. horses depending on the same caretaker for their daily routine were found to have similar responses which differed from that of other groups. equipment and training risk factors associated with ridden behaviour problems in uk leisure horses hockenhull, j. and creighton, e. (a) questionnaire identifying risk factors associated with ridden behaviour problems in uk leisure horses from the training approaches and equipment used. 16 questions regarding the type of work undertaken with the horse, the types of equipment and training methods used on it and the regularity that professional services (farriers, saddlers and dentistry professionals) were employed. respondents were also asked to assess the frequency that their horse performed 15 different behavioural problems over the last week it was ridden using rating scales. risk factors associated with the ridden behaviour problems included: the design and fit of the saddle, with dressage and working hunter saddles associated with a reduced risk of ridden behaviour problems compared to general purpose saddles. the horse’s foot care and shoeing routine was associated with three of the four groups with behavioural problems. an increased time (7 weeks or more) between farrier visits was associated with an increased risk of discomfort behaviour. the use of artificial training aids was associated with an increased risk of behaviour problems. spending more time with the horse outside of training situations was associated with a reduced risk of problems. the strengths of statistical techniques in identifying patterns underlying apparently random behavioural problems in horses hockenhull, j. and creighton, e. (b) data analysis of an online questionnaire determining how principal components analysis has been used to identify relationships underlying individual behavioural problems in horses. principal component analysis of data from three linked cross-sectional questionnaires. 44 individual behavioural problems, including stable related and handling behavioural problems, pre-feeding behavioural problems, and ridden behavioural problems, were reduced to 12 behavioural problem components. each component was composed of groups with behavioural problems that may share a common underlying aetiology. the study findings demonstrated the value of statistical techniques in identifying associations between apparently random behavioural problems. stranger danger? an investigation into the influence of human-horse bond on stress and behaviour ijichi, c. et al. behavioural and physiological measures determining whether horses’ owners confer a ‘safe-base’ and improve horse behaviour and physiological stress response to novel handling tests. measures of behaviour, eye temperature and heart rate whilst navigating novel obstacles with owner or unfamiliar handler. there was no statistically significant difference in the behavioural or physiological measures of stress between when the horses were handled by their owner or an unfamiliar person. factors influencing the attitude of equestrians towards sport horse welfare ikinger, c. et al. online questionnaire assessing factors influencing the attitude of equestrians towards sport horse welfare. 150 questions with the majority using five point likert scale. the factors with the greatest impact on attitudes to horse welfare were the affection for animals, the attitude towards ‘classically organised’ equestrianism and the utility orientation. gender, income, agricultural background, tradition, brand orientation and the importance of breed and pedigree were also found to have a significant influence. age and involvement in horse-riding as a hobby were found to have no effect on attitudes to horse welfare. separating a horse from the social group for riding or training purposes: a descriptive study of human-horse interactions jorgensen, g.h.m. et al. behavioural observation determining the difficulty of haltering and separating a horse from a group for riding or trainer purposes and how horse-human interactions could affect this. in each group, the horse owner or keeper (handler) was asked to enter the group, approach his/her horse, halter it and lead it out through the gate, then keep the horse standing out of sight from other horses for 2 minutes. interactions were video recorded and behaviours were scored. only 1 out of 100 horses moved away from the handler when approached. 96% of the target horses followed their handler without showing any resistance. in 75% of the tests, the other horses did not interact with the target horse and/or handler. separating a horse from its group can be considered relatively safe and unproblematic if there are good management practices and trained handlers. investigating horse-human interactions: the effect of a nervous human keeling, l.j. et al. behavioural observation evaluating the effect of a nervous human on horse-human interactions. heart rates and direct behavioural observations made and scored on a three, four or five point scale. there was an increase in heart rate for both the person and the horse when walking past a potentially challenging situation. the findings indicate that analysis of heart rate recorded simultaneously from people and horses under different experimental handling or riding conditions presents a useful tool to investigate horse-human interactions. my horse is my therapist: the medicalization of pleasure among women equestrians lee davis, d. et al. ethnographic study exploring the role that horse-human interactions may play in well-being and impairment among a sample of everyday riders. thematic analysis of lifecycle narratives. the themes that were identified included: pleasure; fun; joy; benefits; and therapies. pet ownership and adolescent health: cross-sectional population study mathers, m. et al. questionnaire assessing whether adolescent health and wellbeing was associated with having a pet in the household. body mass index was measured by a trained researcher. the average daily physical activity level was measured using multimedia activity recall for children and adults, and self-report. blood pressure was measured using digital bp monitor. health status was measured by the paediatric quality of life (qol) inventory. qol measured using the kidscreen tool and self-report. owning a pet or time spent caring for/ playing with a pet was not related to adolescent health or well-being. having horse(s) was associated with slightly higher self-reported paediatric quality of life. euthanasia in aged horses: relationship between the owner's personality and their opinions on, and experience of, euthanasia of horses mcgowan, t.w. et al. questionnaire exploring the relationship between the owner’s personality and their opinions on, and experience of, euthanasia of horses. questionnaire on euthanasia of horses and a self-assessment five factor personality test. most owners considered euthanasia of a horse to be a difficult decision, which they based on the horse’s current health, anticipated future quality of life, and veterinary advice. owners reported the loss to be a distressing experience rather than providing a sense of relief. female owners who found it more difficult to make the decision were more likely to have neurotic personalities and based their decision more on their relationship with the horse and the horse’s quality of life. veterinarians play an important role in the diagnosis of health factors that influence the decision to euthanase. the personality of the owner may influence the extent to which they find euthanasia distressing, especially in female horse owners. survey of human-horse relationships and veterinary care for geriatric horses mueller, m.k. et al. questionnaire exploring the relationship between horse owners/lessees and geriatric (>20-years-old) or non-geriatric horses, and factors influencing veterinary care decision making. online questionnaire using human-horse attachment scale, and modified version of pet bereavement questionnaire, as well as owner and horse demographics and details of veterinary care. geriatric horses were more frequently consider to be companion animals, retired or part of a business compared to non-geriatric. no significant differences in degree of horse-human attachment between geriatric and non-geriatric horses. higher levels of bereavement associated with euthanasia compared to when horses died, and for geriatric horses compared to non-geriatric. participants made a number of accommodations for their care and management of geriatric horses. cross-modal perception of human emotion in domestic horses (equus caballus) nakamura, k. et al. behavioural observation investigating whether horses can cross-modally perceive human emotions. horses were shown human facial expressions on screen and voices from a speaker from their caretaker or stranger using positive (happy/gentle) or negative (angry/scolding) expressions. these were played in the congruent condition (both audio and visual positive or both negative) and incongruent (e.g. positive facial expression with negative voice) conditions. horses behavioural response measured by total looking time and response latency. horses looked at the screen for longer when the caretaker incongruency condition was used compared to the congruency condition. horses looked at the speaker faster with incongruent condition compared to congruent condition for both caretaker and stranger. study concluded that horses can cross-modally recognise emotions of both caretakers and strangers. could it be colic? horse-owner decision making and practices in response to equine colic scantlebury,c.e. et al. mixed-methods: interviews and cross sectional questionnaire assessing horse owner decision making in response to equine colic. 15 interviews were analysed to conceptualise the processes involved in horse-owner management of colic. cross sectional survey of 673 horse owners designed to test the concepts found. veterinary-client communication was important during a colic episode in assisting owners during the decision making process. from the interviews, the cost of veterinary assistance and treatment influenced the timing of the decision to call the veterinary surgeon and consenting to surgery. money was not an influencing factor in the survey. behaviour patterns of horses can be used to establish a dominant-subordinate relationship between man and horse sighieri, c. et al. behavioural observation investigating how humans can enter the social hierarchy of the horse by mimicking the behaviour and stance it uses to establish dominance. methods based on the three elements fundamental to the equilibrium of the herd: flight, herd instinct and hierarchy. the trainer–horse relationship was established in three phases: retreat, approach and association. response time was measured for each phase. all horses responded to their trainer. 4/5 completed the three phases (retreat, approach and association) on the same day. one horse took several days, however all phases were completed. observations suggest that it is possible to manage unhandled horses without coercion by mimicking their behavioural patterns. austrian veterinarians' attitudes to euthanasia in equine practice springer, s. et al. questionnaire examining austrian equine veterinarians attitudes to equine euthanasia in a range of scenarios and identifying factors affecting end of life decisions. online questionnaire with 56 questions covering demographic information, medical/technical, agreement with normative and descriptive statements, case scenarios and open-ended questions. veterinarians consider medical, social and economic factors to be of great importance on the decision making process and especially recognise the impact of the emotional bond between horse and owner. requests for ‘convenience’ euthanasia (including changed circumstances, last will of the owner and financial reasons) are typically rejected. participants’ gender, duration of working experience, and the proportion of their working time spent with horses was significantly associated with responses to euthanasia scenarios. over-riding concerns: developing safe relations in the high-risk interspecies sport of eventing thompson, k. et al. interviews developing safe human-horse horse-human relationships in eventing by understanding how risk perception and experience subjectively is implicated in through and by the horse-human relationship. immersion, coding, categorising and generation of themes. the analysis of the interviews was sensitised around the perceptions of risk, experience of risk, rider concerns and rider mitigation. findings were consistent with the following three theories of voluntary risk taking: edgework; sensation-seeking; and flow. further mixed methods research has been suggested to fully evaluate the use of existing risk theory for understanding participant experiences of high-risk sports like eventing. developing a horse welfare assessment protocol viksten, s.m. et al. behavioural observation development of a horse welfare assessment protocol. 15 animal based, 24 resource based and eight management based measures used. this was repeated after 16–­­25 days with the same horses. the ability to use this assessment tool for up to 22 horses a day. changes to draft protocol were made and include an ethogram to assess the human-animal relationship. table 2: data extraction table for method characteristics of 27 publications that met the final inclusion criteria for a scoping review of literature exploring the horse-human relationship.   population characteristics table 3 presents the population characteristics of these studies. all 27 studies were published within the last 17 years. fifteen studies were published within the last 5 years (2014–2019), eight studies were published between 2009 and 2013 and four studies were published before 2009. the majority of these studies were carried out in europe (n=15), with eight of these conducted in the uk. most studies focused on one perspective rather than the two-way interaction involved in the horse-human relationship; perspective of the human (n=20), perspective of horses (n=6), perspective of both (n=1) (table 3). author and year of publication location participants total population size (number relating to horse in multi-species studies) perspective acton (2014) england, uk horse, rider and landscape in foxhunting culture n/a human butler et al.  (2019) england, uk trainers, owners, vets, stable staff, equine charity, racing welfare and british horse racing authority staff 42 human brown (2007) alabama, usa members of a social media group for rescuing horses 24 (10 interviews pertained to horses) human daly and morton (2006) ontario, canada children aged 8–14 years 155 (58 stated preference for horse as a pet) human dashper (2014) england, uk elite horse riders 26 human dashper (2017) england, uk amateur horse riders and caregivers 17 human davis et al. (2013) midwestern, usa and northern norway horse people competing in different disciplines 60 human dearaugo et al. (2014) global horse riders and handlers 538 human dubois et al. (2018) canada canadian citizens, over 18 years of age, with an interest in horses 901 human graf et al. (2013) global sport riders, leisure riders, and breeders 1087 participants human hausberger and muller (2002) saumur, france adult horses 224 horses of mixed breeds horse hockenhull and creighton (2012a) uk   leisure horse owners and their horses 1326 owner reports on horses human hockenhull and creighton (2012b) uk leisure horse owners – component analysis of three studies stable related and handling – 1230 horses pre-feeding behaviour – 890 horses ridden behaviour – 791 horses human ijichi et al. (2018) gloucestershire, uk livery horses at equestrian establishment 46 horses of mixed breeds and experiences horse ikinger et al. (2016) germany riders 2947 human jorgensen et al. (2011) eastern norway   horses 20 groups of horses of mixed breeds horse keeling et al. (2009) sweden horses, handlers and riders leading – 10 horses of mixed breeds and 20 handlers riding – 17 horses and 17 riders horse and human lee davis et al. (2015) midwestern usa and arctic norway non-professional riders 60 interviewed, 52 lifestyle narratives reported (interviews from 8 men were not analysed) human mathers et al. (2010) victoria, australia students aged 13–19 928 students, 61 of which owned horses human mcgowan et al. (2012) queensland, australia horse owners of aged horses 111 owners human mueller et al. (2018) study conducted in usa – geographical location of participants not reported horse owners who owned/leased >1 horse 2395 participants human nakamura et al. (2018) tokyo, japan horses and caretakers from university equestrian teams 19 horses, their caretakers and strangers horse scantlebury et al. (2014) north west, uk horse owners with colic experience 15 interviewees 673 horse owners – questionnaire human sighieri et al. (2003) arezzo, italy unhandled mares five haflinger mares horse springer et al. 2019 austria member of the austrian equine veterinary association 64 veterinarians involved in equine work human thompson and nesci (2016) australia eventers 21 participants human viksten et al. (2017) sweden swedish riding school horses 37 horses of mixed breeds horse table 3: data extraction table of population characteristics from 27 publications that met the final inclusion criteria of a scoping review of literature exploring the horse-human relationship.   discussion the human animal relationship has become an increasingly popular area for scientific research (hosey and melfi, 2014; dashper, 2017). research in this area has predominantly explored the relationships that humans have with companion animals, and only more recently the relationship that humans have with horses. the exploration of the horse-human relationship through a scoping review identified a diverse and heterogeneous body of published literature. scoping reviews, unlike systematic reviews, do not strive for evidence synthesis or appraisal of research quality of the studies, but instead pose a transparent and thorough map of research areas identified (arksey and o'malley, 2005). heterogeneity across the 27 publications identified in this scoping review highlights the benefits of performing a scoping review prior to an extensive literature review. very limited comparisons of aims, objectives and methodologies could be drawn across the publications, but this study provides the framework to define more specific research questions and systematic reviews for future research, by extracting key information and grouping and categorising data. the research areas identified by this review as having the most studies were: equine behaviour and reactions towards humans (5/27); equine training methodologies and behaviour (4/27) and horses within sport and leisure (4/27). broad search terms and inclusion criteria were used for this scoping review to gain an understanding of the current scientific research involving the horse-human relationship and what, if any, specific research areas could be identified. this also raised challenges: it led to a large variability in the studies that were identified using the search terms, including literature on working equids and animal-assisted therapies. it was decided after the initial database search and categorisation of research areas that these research areas would be excluded from the final scoping review, allowing the focus to remain on the relationship between humans and horses applicable to the main horse owning population within the uk. it is important however, to appreciate that the relationship humans have with working equids and the use of equids in animal-assisted therapies, are important areas of research within the horse-human relationship. these require further investigation to gain a better understanding of the available research within the areas themselves, independent of this study. the results of the initial searches from the scoping review highlighted the numbers of publications in each area, which will be helpful to inform future systematic reviews. for this review, 27 studies met the inclusion criteria. only two databases were used for the literature search; these databases were deemed the most appropriate for veterinary literature (grindlay et al., 2012) and therefore most suitable for a scoping review. the searches used in this study did not identify some studies which would have met inclusions criteria for example; chamove et al. (2002) and maurstad et al. (2013), as the journals were not within the medline or cab abstracts databases. a more detailed systematic review would require inclusion of other databases that may be more inclusive of other social science journals and studies, such as the international bibliography of the social sciences. this scoping review has demonstrated the diversity of the publications in this area and therefore the challenges in defining databases and search strategies for an area that is currently ill defined and multi-disciplinary in nature. a systematic review investigating human-animal relationships, bonds and interactions performed by hosey and melfi (2014) identified 116 publications involving companion animals (dogs, cats and equids), of which 22 involved the human-animal relationship. this review did not state how many of these publications involved equids exclusively, however it suggests that 27 publications identified by this current review represents a reasonable body of the current evidence. there were however methodological differences, including the databases searched (proquest and google scholar) and the lack of defined inclusion and exclusion criteria in the study by hosey and melfi (2014). of the publications reviewed in the current study, only one involved the dyadic relationship of human and horse, with the majority focusing only on one perspective (horse or human). the lack of exploration of the two-way interaction between humans and animals was also identified by dwyer et al. (2006), subsequently leading to the development of the monash dog owner relationship scale (dwyer et al. 2006). further research into the two-way relationship between horses and humans may be beneficial to understand how best to match horses with owners or riders, and to prevent incompatibilities that may become detrimental to the horse or human. a diverse range of publication aims, objectives and methodologies were identified in this review, and there was significant diversity in the research areas and topics. some major gaps in the research and lack of evidence for a number of areas were identified, and these were used to identify areas which should be considered for future research: development of a reliable and repeatable tool for categorising horse owners’ motivations and reasons for being involved with horses. development of a reliable and repeatable system for categorising the different roles and activities that horses are used for. development of a tool for defining the different types of relationships people form with horses and other equids. identification of the horse factors and the owner factors that influence the horse-human relationship, and how these interact and affect owner decision making. it can be concluded that the research surrounding the relationships between horse and human is extremely diverse and heterogeneous, with a paucity of evidence in most areas. from this scoping review of the literature, key areas of current research evidence were identified and defined, but gaps within the research body exploring the nature and factors influencing the horse-human relationship were also documented. the main limitations were around the challenges in identifying suitable publications, and social science databases should be included in future reviews. this review highlights the need for further investigation (systematic reviews) into the main research areas defined by the review, but also the need for new studies to fill significant gaps within the research. gaining an understanding of the relationships we have with animals is important to help us understand how and why health and welfare may be compromised by inadequate or inappropriate decision making. the horse-human relationship is clearly a key component of this but is lacking a significant evidence-base. exploration into the relationships that horse owners have with their horses, and the influence this may have on their decisions was identified as an area with little published literature.   conflict of interest the authors declare no conflicts of interest. funding: this work was funded by the horse trust as part of a mres studentship for harriet clough.   references acton, a. 2014. equine gatekeepers, animal narratives and foxhunting landscapes. anthrozoos,27, 81–94. doi: https://doi.org/10.2752/175303714x13837396326459 arksey, h. & o'malley, l. 2005. scoping studies: towards a methodological framework. international journal of social research methodology, 8, 19–32. doi: https://doi.org/10.1080/1364557032000119616 beta national equine survey. 2019. brown, s. e. 2007. companion animals as selfobjects. anthrozoos,20, 329–343. doi: http://dx.doi.org/10.2752/089279307x245654 butler, d., valenchon, m., annan, r. & whay, h.r. 2019. living the 'best life' or 'one size fits all'-stakeholder perceptions of racehorse welfare. animals, 9(4), 134. doi: http://dx.doi.org/10.3390/ani9040134 chamove, a. s., crawley-hartrick, o. j. & stafford, k. j. 2002. horse reactions to human attitudes and behavior. anthrozoös, 15, 323–331. doi: http://dx.doi.org/10.2752/089279302786992423 daly, b. & morton, l. l. 2006. an investigation of human-animal interactions and empathy as related to pet preference, ownership, attachment, and attitudes in children. anthrozoos,19, 113–127. doi: http://dx.doi.org/10.2752/089279306785593801 dashper, k. 2014. tools of the trade or part of the family? horses in competitive equestrian sport.society & animals, 22, 352–371. doi: http://dx.doi.org/10.1163/15685306-12341343 dashper, k. 2017. listening to horses: developing attentive interspecies relationships through sport and leisure.society & animals, 25, 207–224. doi: https://doi.org/10.1163/15685306-12341426 davis, d., maurstad, a. & cowles, s. 2013. 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a knowledge summary by leo packham bvetmed pgdip(vcp) mrcvs 1* 1university of bristol, langford vets, langford, somerset, bs40 5du *corresponding author (lafpackham@outlook.com) vol 5, issue 4 (2020) published: 04 nov 2020 reviewed by: siddharth sudunagunta (bvetmed certavp(vc) mrcvs) and kieran borgeat (bsc bvsc mvetmed certvc mrcvs dipacvim dipecvim-ca (cardiology)) next review date: 20 feb 2022 doi: 10.18849/ve.v5i4.300 pico question in dogs with congestive heart failure, does the use of torasemide as a first line diuretic result in a superior survival time when compared to furosemide?   clinical bottom line category of research question treatment the number and type of study designs reviewed five studies were critically appraised, they were all prospective randomised controlled trials strength of evidence moderate outcomes reported there is currently a lack of studies looking at comparing furosemide directly with torasemide in patients with congestive heart failure. there are many similarly drawn conclusions from the studies: torasemide is not inferior to furosemide in the treatment of chf, torasemide is comparable to furosemide at one tenth the dose (or less) and that torasemide may be more effective at diuresis than furosemide with a prolonged duration of action conclusion there is currently no clear and obvious benefit for the use of torasemide, over furosemide, as a first line diuretic for dogs with congestive heart failure   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision-making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care clinical scenario a 6-year-old male neutered cocker spaniel presents to you as an emergency, with tachypnoea, dyspnoea, a grade iii/vi systolic heart murmur and a recent history of exercise intolerance. after initial stabilisation you have diagnosed stage c degenerative mitral valve disease and plan to start this patient on appropriate oral medication, which will include a diuretic. typically, furosemide will be used, but is there any evidence to suggest the use of torasemide carries any benefits as a first line diuretic? the evidence a search of the literature revealed five studies relevant to this pico. four out of five of these papers had a sample size of 10 or less and the populations were only studied generally for a few weeks. they were all prospective and randomised, though only one study was blinded. summary of the evidence chetboul et al. (2017) population: dogs ≥3 kg with congestive heart failure (chf) due to degenerative mitral valve disease (dmvd) sample size: 366 dogs intervention details: dogs were within one of two groups during each study. stratum 1 included dogs that presented with their first chf episode, needing a diuretic. or, dogs that had existing chf and needing a change in diuretic dose change due to deterioration. stratum 2 included dogs that had had a previous episode of chf that were now stable and without clinical or radiographic signs of chf. all dogs received either furosemide (n = 186) or torasemide (n = 180) for 3 months. doses for furosemide were chosen based on clinical signs, if a dog was placed into the torasemide the dose of furosemide was converted to torasemide via a conversion table. there were two complete studies in this paper, both followed the above protocol, but the second study changed the conversion method following safety results, ultimately reducing overall doses of torasemide. all dogs were examined by clinicians on day 0 (inclusion day and initiation of treatment), ± 2 days on days 7 and 28, then ± 4 days on days 56 and 84. at each of these visits dogs received a complete physical exam, a blood test was performed and radiographs were obtained of right lateral and dorsoventral projections. study design: prospective, multi-centre, multi-national, randomised control trial outcome studied: to demonstrate that torasemide is noninferior to furosemide for treating dogs with chf and to compare the two drugs on the time to reach a composite cardiac end point. outcome success of this study was based on the hypothesis that treatment of stratum 1 was expected to improve their clinical condition and treatment of stratum 2 was expected to be able to maintain their condition. treatment success was based on a composite clinical score which included assessment of dyspnoea, cough, exercise tolerance and ascites. chf was assessed through the radiographic findings and changes to a patients modified new york heart association classification. composite cardiac end point: spontaneous cardiac death, euthanasia due to heart failure, worsening of chf class. main findings (relevant to pico question): at the end of study 1 47/75 (63%) of dogs receiving torasemide had treatment success, over 42/76 (55%) of dogs receiving furosemide. at the end of study 2 63/105 (60%) of dogs receiving torasemide had treatment success, over 65/110 (59%) of dogs receiving furosemide. the composite cardiac end point was reached in a shorter period of time in the furosemide group than the torasemide group. this was significant. compared to the furosemide group, the torasemide group had a higher number of adverse effects that were significant. these included polyuria/polydipsia or urinary incontinence (as reported by the owner), hepatic enzyme elevation and renal adverse effects (including elevation in renal parameters to acute renal failure). limitations: the study was sponsored and monitored by the manufacturer of an oral torasemide product. 3 months follow-up was a relatively short time frame to collect data. there were two baseline variables that were significantly different between the two treatment groups. these were duration of heart disease (days) and dyspnoea score. however, pretrial treatment duration was similar between the two groups and not significant. the composite clinical scoring was semi-objective. peddle et al. (2012) population: dogs with stable chf due to dmvd sample size: seven dogs intervention details: all dogs enrolled in the study had already been receiving furosemide orally, twice daily, for the preceding 14 days. (other medication was permitted, though could not have had a dose adjustment within the preceding 7 days). at day 0 (enrollment), dogs were randomly assigned into two groups: either continue existing furosemide dose (n=4) or to change to torasemide at an equivalent dose (n=3). (equivalent dosing was calculated at one tenth that of their initial furosemide dose). on day 7 there was crossover of the two groups. and on day 14 the study ended. therefore, each patient received 7 days of each therapy. at days 0, 7 and 14 there was evaluation of each variable (clinical, laboratory, radiographic and quality of life). each dog was evaluated by the same clinician on all three visits. study design: prospective, double-blinded, randomised, crossover study outcome studied: in both groups the variables that were assessed were: clinical variables: body weight, resting heart rate and respiratory rate. laboratory variables: non-invasive systolic blood pressure, urine specific gravity, blood urea nitrogen (bun), creatinine, bun/creatinine ratio, phosphorus, calcium, sodium, potassium, chloride, carbon dioxide, albumin and anion gap. radiographic variables: a right lateral and ventrodorsal thoracic radiograph, evaluated by a board-certified cardiologist blinded to the patient’s treatment. vertebral heart size (vhs) was used to assess heart size. quality of life variables: as perceived by the owner, quality of life (qol) was assessed via a ‘functional evaluation of cardiac health’ questionnaire (freeman, et al., 2005). the owners were also asked to subjectively record any clinical side effects or changes in condition of their pet, though these were not included in the table of results. main findings (relevant to pico question): out of the entire study population, no dog in either group developed chf either clinically or radiographically at any time. there were increases in creatinine, bun, phosphorus, carbon dioxide, albumin and anion gap following the torasemide treatment that were all significant. there were decreases in urine specific gravity (usg) and chloride following the torasemide treatment that were both significant. there was no significance difference in clinical, radiographic or qol score variables between the two therapies. with regards to the subjective reports by the owners; there were three. two of which stated that the dogs urinated more frequently during torasemide therapy and one of which stated that the dog urinated less frequently during the furosemide therapy. limitations: small study sample size. only seven dogs were used in total. although using an evaluated and known questionnaire to assess patient qol, the assessment by owners carries an element of subjectivity with it. all dogs within the study were clinically stable and had received furosemide for at least 14 days prior to enrollment. the study was over such a short time period that it is extremely difficult to forecast any long-term benefits of one therapy over the other. visits to the vet did occur at different times of the day between patients. due to the pharmacodynamic nature of diuretics, this may affect the significance of some variables (for example time between tablet given and urine specific gravity). the authors do note this and advise that each individual dog was assessed at the same time for each of their three visits. lack of a washout period between therapies. uechi et al. (2003) population: clinically healthy dogs, 1 to 2 years old. (this study also looked at a population of cats, separately, that is not relevant to this pico question) sample size: 10 dogs intervention details: the dogs were split into two groups of five dogs. one group served as the control, the other underwent surgery to induce mitral regurgitation (mr). the study was performed 6 to 8 months postoperatively. each dog (from both groups) randomly received placebo, furosemide (2 mg/kg) and torasemide (0.2 mg/kg) for 7 days. each treatment period was separated by a 14 day interval. blood and urine samples were obtained at baseline and 1, 2, 4, 6, 8, 12 and 24 hours after each drug administration on days 1 and 7. urine samples were obtained with a urinary catheter. study design: prospective randomised crossover study outcome studied: in both groups the variables measured were: urine volume (ml/kg/hr) urinary sodium and potassium (mmol/kg) blood plasma analysed renin activity, angiotensin ii and aldosterone via radioimmunoassay main findings (relevant to pico question): no dog developed chf when compared to the placebo, mean analysis of urine revealed that furosemide lost its diuretic effect 6 hours after administration whereas torasemide continued past 12 hours. mean analysis of urine at day 7 revealed dogs receiving torasemide had a significantly decreased urinary potassium excretion compared to day 1 in both control and mr dogs. plasma renin activity did not differ between groups significantly. torasemide significantly increased plasma angiotensin ii concentrations in both the control and mr dogs compared to placebo. furosemide only significantly increased it in the mr dogs. dogs receiving torasemide had a significantly increased plasma aldosterone concentration compared to both the placebo and furosemide treatments in both the control and mr groups. limitations: the method was poorly written and hard to follow. ultimately no dog had chf. the only imaging performed were serial thoracic radiographs until the onset of venous congestion was seen and a single echocardiogram 1 month postoperatively. the description of surgery is not clear between the cat and dog population. the mr was surgically induced, the changes to the cardiovascular system may not be representative of acquired mitral valve regurgitation. hori et al. (2007) population: healthy dogs between 2 and 8-years-old sample size: eight dogs intervention details: dogs were randomised to receive either placebo, furosemide (2 mg/kg) or torasemide (0.2 mg/kg), orally twice daily, for 14 days. each dog received all three treatments for 14 days, with at least a 7 day interval between treatments. indwelling urinary catheters were placed in all dogs. baseline (pretreatment) data was obtained through blood and urine samples collected following complete urination on the first of each 14 day cycle. blood and urine samples were collected on day 1 and 14 at 1, 2, 4, 6, 8, 12 and 24 hours after diuretic or placebo administration. day 1 and day 14 gave shortand long-term results respectively. study design: prospective randomised crossover study outcome studied: in all three groups there were two main groups of variables measured: urine – urine volume (ml/kg/hr), urine specific gravity and urine creatinine concentration were measured. blood – haematocrit, plasma protein (via refractometry), electrolytes (sodium, potassium and chloride), plasma bun, creatinine and aldosterone were measured. body weight was also recorded. main findings (relevant to pico question): the author’s use of shortand long-term is to mean 1 and 14 days respectively. the following statements apply to all dogs: short-term administration of furosemide and torasemide significantly increased urine volume both compared to baseline (pretreatment) and placebo. long-term administration of both furosemide and torasemide decreased urine specific gravity significantly. compared to placebo, long-term administration of torasemide significantly increased urine volume. this was not the case with furosemide. with respect to furosemide, shortand long-term administrations of torasemide increased urine volume, which was significant. both furosemide and torasemide treatments significantly increased bun and plasma creatinine, after long-term administration compared to baseline. long-term administration of furosemide and torasemide significantly increased plasma aldosterone concentrations compared to baseline. it was significantly higher with torasemide compared to furosemide. limitations: small population size of only eight dogs, all of which were clinically healthy. therefore, assumptions made about the use of these diuretics and their actions in canine patients with cardiovascular disease may not be representative, especially for their use in the treatment of chf, their main indication for use. the authors do highlight this limitation in their discussion. the study quotes ‘long-term’ usage as 14 days. although the study demonstrated that there were significant differences found in variables between day 1 and day 14, in a clinical setting there is likely to be a much longer period spent on diuretics. especially in those patients with stable chf, such as the dmvd patients. the authors state that a relatively high dose of torasemide was used to exacerbate the therapeutic effects, demonstrating beneficial effects over furosemide in the study. this may not be present at lower doses, used more commonly in the clinical setting. the interval between groups was not specified, only stated as ‘at least 7 days’. it is unknown whether some dogs may have had a longer wash-out period than others. potter et al. (2019) population: healthy, middle-aged, purpose-bred laboratory beagles sample size: six dogs intervention details: there were three treatments within the study: placebo, furosemide (2 mg/kg) and torasemide (0.1 mg/kg). all three treatments were given per os (po), every 12 hours (q12), for 10 days and between each treatment there was a 10 day washout period. each dog was randomly placed into a treatment group and there were only two dogs on the same treatment at any one time. all dogs ultimately received all three treatments over the course of the study. day −1 was the day before each 10 day period started (there was no day 0) and on this day blood work, urinalysis and clinical parameters were recorded. it was used to reference ‘pretreatment’ data. blood was taken on days −1, 1, 5 and 9. urine was collected on days −1, 2, 6 and 10. water consumption was measured during the study in ml/kg/day. prior to urinary catheterisation the dogs were sedated. study design: prospective randomised crossover study outcome studied: to compare the magnitude of renin–angiotensin–aldosterone system (raas) activation between furosemide and torasemide. the authors hypothesised that the effect would be comparable. they also indirectly evaluated a purported anti-aldosterone effect of torasemide. during each treatment period multiple variables were recorded: clinical parameters (blood pressure, body weight and heart rate) blood (bun, creatinine, potassium, sodium, chloride, multiple angiotensin peptides (via liquid chromatography-tandem mass spectrometry) and aldosterone) urine (usg), creatinine, potassium, sodium, chloride, 24hr urine volume and aldosterone. electrolyte free water clearance main findings (relevant to pico question): the following statements apply to all dogs (unless where an average is indicated: throughout the study there was no significant differences within, or between, treatment groups for bun, sodium or potassium (as well as blood pressure, body weight and heart rate). hypochloraemia was present in both diuretic treatment groups when compared to placebo, and average serum chloride concentrations were lower in the torasemide group compared to the furosemide group. these were all statistically significant findings. average serum creatinine was significantly greater than placebo in both diuretic treatment groups. though it remained within reference range in all treatment groups. 24 hour urine volume was greater in both diuretic groups when compared to placebo. on day 10, the 24 hour urinary output of the torasemide group was significantly greater than that of the furosemide group. urinary excretion of potassium was not significantly different between treatment groups. regarding the raas values measured; there was no significant difference between diuretics. suggesting they achieved a similar level of raas activation, and torasemide was considered ‘equipotent’ at approximately one-twentieth the dose of furosemide. limitations: the study was funded by the manufacturer of an oral torasemide product. small study sample size of only six dogs. the population of dogs used in this study is not representative of those cases seen in clinic. the authors highlight this and state that because the subjects were ‘normal’ dogs, it does not replicate the derangements seen in heart failure. this is particularly true of raas activation during naturally occurring chf. the administration of treatment in the study does not mimic chf; the subjects only received treatment for 10 days (of any one product) which is not typically representative of the length of time animals are treated for chf. although the authors state that the risk of sequence effect would have been minimised by the 10 day washout period, there may still be some element of unevaluated sequence effect present. appraisal, application and reflection there were some case reports published within the literature that looked specifically at torasemide being used on canine patients with cardiovascular disease. these were excluded from the search results as not only were they a poorer quality evidence base, but they were not comparing furosemide and torasemide. of the five papers examined, following the literature search, only one paper (chetboul et al., 2017) had a reasonable population number; 366, the other four papers had only 10 dogs or less. even though all papers that were used for this knowledge summary were prospective, it may be preferable to have a large retrospective study comparing the use of torasemide and furosemide with much greater sample size. congestive heart failure due to degenerative mitral valve disease is typically a chronic disease that is managed over a far longer period than these studies sustained therapy for. chetboul et al. (2017) had a superior treatment time (3 months) compared to the other four papers studied; none of which had a treatment time greater than 14 days on either furosemide or torasemide. this detracts from the ability to relate these findings into real cases seen within the clinic. there are many similarly drawn conclusions from the above studies: torasemide is noninferior to furosemide in the treatment of chf, torasemide is comparable to furosemide at one tenth the dose (or less) and that torasemide may be more effective at diuresis than furosemide with a prolonged duration of action. within human medicine there are studies demonstrating that, compared to furosemide, torasemide can reduce morbidity and mortality associated with chf failure (cosín & díez, 2002). torasemide is often used as a rescue diuretic therapy (oyama et al., 2011). given some of the frequently suggested positive findings of torasemide in the above studies, such as reduced diuretic resistance, reduced cardiac remodelling and a potassium sparing nature new studies into the long-term safety of torasemide may be rewarding for the treatment of animals in chronic chf. in view of the strength of evidence and the outcomes from the studies, no clear and obvious benefit to the use of torasemide, over furosemide, as a first line diuretic for dogs with congestive heart failure can be drawn. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform (1973 – 2020 week 06) medline on ovid platform (1946 – february 2020) web of science (1900 – february 2020) search strategy: cab abstracts and medline: exp dogs/ (dog or dogs or canin* or canid*).mp (torasemide or torsemide or upcard).mp furosemide/ (furosemide or frusemide).mp (1 or 2) and 3 and (4 or 5)   web of science: dogs or dog or canin* or canid* torasemide or torsemide or upcard furosemide or frusemide 1 and 2 and 3 dates searches performed: 20 feb 2020 exclusion / inclusion criteria exclusion: conference proceedings, opinions, letters, case reports, articles not in english (or english translations unable to be located) and those articles not relevant to the pico or involving the wrong species. inclusion: all appropriate articles relevant to the pico. search outcome database number of results excluded – english version unavailable excluded – not relevant to pico question excluded – conference proceedings, opinion, letter or case reports total relevant papers cab abstracts 21 10 0 6 5 medline 15 0 9 1 5 web of science 27 0 22 1 4 total relevant papers when duplicates removed 5 conflict of interest the author declares no conflicts of interest. the author would like to thank the university of bristol, veterinary science library services. references chetboul, v., pouchelon, j.l., menard, j., blanc, j., desquilbet, l., petit, a., rougier, s., lucats, l., and woehrle, f. (2017). short-term efficacy and safety of torasemide and furosemide in 366 dogs with degenerative mitral valve disease: the test study. journal of veterinary internal medicine, 31(6): 1629–1642. doi: https://doi.org/10.1111/jvim.14841 cosín, j. & díez, j. toric investigators (2002) torasemide in chronic heart failure: results of the toric study. european journal of heart failure, 4(4): 507–13. freeman, l. m., rush, j. e., farabaugh, a. e. & must, a. (2005). development and evaluation of a questionnaire for assessing health-related quality of life in dogs with cardiac disease. journal of the american veterinary medical association, 226(11), 1864–1868. doi: https://doi.org/10.2460/javma.2005.226.1864 hori, y., takusagawa, f., ikadai, h., uechi, m., hoshi, f., and higuchi, s. (2007). effects of oral administration of furosemide and torsemide in healthy dogs. american journal of veterinary research, 68(10): 1058–1063. doi: https://doi.org/10.2460/ajvr.68.10.1058 oyama, m.a., peddle, g.d., reynolds, c.a., and singletary, g.e. (2011). use of the loop diuretic torsemide in three dogs with advanced heart failure. journal of veterinary cardiology, 13(4): 287–292. doi: https://doi.org/10.1016/j.jvc.2011.10.001 peddle, g.d., singletary, g.e., reynolds, c.a., trafny, d.j., machen, m.c., and oyama, m.a. (2012). effect of torsemide and furosemide on clinical, laboratory, radiographic and quality of life variables in dogs with heart failure secondary to mitral valve disease. journal of veterinary cardiology, 14(1): 253–259. doi: https://doi.org/10.1016/j.jvc.2012.01.003 potter, b.m., ames, m.k., hess, a., and poglitsch, m. (2019). comparison between the effects of torsemide and furosemide on the renin-angiotensin-aldosterone system of normal dogs. journal of veterinary cardiology, 26: 51–62. doi: https://doi.org/10.1016/j.jvc.2019.11.003 uechi, m., matsuoka, m., kuwajima, e., kaneko, t., yamashita, k., fukushima, u., and ishikawa, y. (2003). the effects of the loop diuretics furosemide and torasemide on diuresis on dogs and cats. journal of veterinary medical science, 65(10): 1057–1061. doi: https://doi.org/10.1292/jvms.65.1057 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in adult dogs, does feeding a raw food diet increase the risk of urinary calculi formation compared to feeding a complete dry kibble diet? a knowledge summary by emma taylor bsc (hons) 1 nieky van veggel msc cbiol fhea 1* 1writtle university college, lordship road chelmsford, essex, cm1 3rr, united kingdom *corresponding author (nieky.vanveggel@writtle.ac.uk) vol 3, issue 2 (2018) published: 17 apr 2018 reviewed by: morag moseley (rvn dms cert san) and sue badger (med, cert ed, rvn) next review date: 1 jun 2019 doi: 10.18849/ve.v3i2.155 pico question in adult dogs, does feeding a raw food diet alter urine composition compared to a kibble diet? clinical bottom line the evidence provided by the single study identified is weak and the outcomes can neither support nor challenge the hypothesis that a raw food diet increases the risk of urinary calculi compared to a kibble diet. therefore, professionals working within the veterinary science or nutrition field should proceed with caution when advising clients and rely on their professional experience until more evidence is generated. clinical scenario during consultation you are asked by a client if a raw food diet supports the prevention of kidney stone formation in dogs because they have read on an internet forum that a raw food diet is a healthy and natural alternative to kibble that alleviates a number of health issues. the client is now seeking additional advice from you. you decide to explore the available literature that investigates the effect of raw feeding is on urine composition in dogs. the evidence there is currently very little published evidence which studies the effect of raw feeding on urine composition. the literature search returned 129 records of which 120 records were excluded because they were not related to the pico.  a further 5 records were excluded because they investigated the use of meat-meal with carbohydrate biscuit rather than raw meat, 1 record was excluded as it was non-primary research and 1 record excluded for investigating non-urinary parameters. the study by dijcker et al., (2012) identified that currently, evidence is undetermined on whether a raw food diet maintains healthy urinary composition parameters or increases the risk or urolithiasis in adult canine dogs. the findings from this paper found that feeding a commercially available dry kibble diet was associated with a high urine calcium to creatinine (ca/cr) ratio compared to the raw diet which was associated with a lower ca/cr ratio.  summary of the evidence dijcker (2012) population: dogs aged between 1.3 to 16.1 years of age, 13 female (of which 4 entire), 10 male (of which 4 entire), bodyweight range 12-35 kg. sample size: 23 intervention details: treatment group 1 (n = 23): fed raw food over a 4-week period treatment group 2 (n = 23): complete and balanced dry extruded feed over a 4-week period. each diet started with a 3-day gradual diet change, and diets were provided by owners.   study design: cohort (study 1) and rct (study 2) in crossover design questionnaire from private owners outcome studied: uox and uca excretion rates and the dietary and animal related factors which are associated with these parameters. a single urine sample was collected in week 4 of the diet by the owner through natural voiding. urine sample was divided immediately between a non-acidified vial and an acidified vial containing 2n hcl. samples were stored at -20 °c until analysis. uox was measuring using isotope dilution mass spectrometry, whereas uca was measured atomic absorption spectroscopy. main findings (relevant to pico question): urinary creatinine concentration high in dogs fed raw meat diet (tg1) limitations: high degree of non-completers (38/64) with another 3 dogs excluded as outliers. small sample size (n = 23) questionnaire with high risk of bias. inconsistencies with urine sampling by owners inconsistences in urine storage by owners reliance on owners providing research diets appraisal, application and reflection the option to feed a raw diet to dogs has grown in popularity and is now readily available commercially.  historically, there has been concern regarding excessive protein intake and the potential increase of calculi promoting substances such as calcium and uric acid (robertson et al., 1979).  this concern has been steadily increasing (lulich et al., 1999) which has led to the association of a high protein diet with the increased risk of renal damage (singer, 2003). interest in the health benefits of a protein fed diet is increasing, however studies measure the relationship between protein and growth rather than welfare and health. studies are also based on results from comparatively brief studies of less than 6 months.  furthermore, the majority of research conducted focusing on raw feeding, assesses the transmission rate of zoonotic disease and the risk this poses to human health (joffe and schlesinger, 2002; strohmeyer et al., 2006; finley, et al., 2006; lefebvre et al., 2008). it was noted at the british small animal veterinary association (bsava) 2016 congress, that standardised information and advice is limited and not easily available to veterinarians, which reduces their ability to advise clients correctly. this lack of evidence-based peer reviewed research was addressed by goh (2016), who found that advice concerning a raw feed diet often stems from anecdotal evidence only. there is currently very little published evidence which studies the effects of raw feeding on urine composition and therefore on urinary calculus formation or urinary tract health. additionally, there is still little evidence-based scientific research and a lack of feeding trials which supports the hypothesis that raw diets are a healthier or more nutritionally balanced than other diets (michel, 2006; van veggel & armstrong, 2017). methodology section search strategy databases searched and dates covered: cab abstracts (1973-2017), pubmed (1950-2017) search terms: (dog or dogs or canine or canines or bitch or bitches) and (raw or barf or 'biologically appropriate raw feed' or natural or meat or 'raw food*' or 'raw diet*') and (urine and (composition or analysis or constituent)) dates searches performed: 1st june 2017 exclusion / inclusion criteria no limitations regarding study design, setting, sample size or study population were imposed. exclusion: review papers dogs under 1 year of age mixed diet non-urinary parameters non-peer reviewed publications inclusion: primary research papers dogs over 1 year of age urinary composition complete raw feed search outcome database number of results excluded – not related to pico excluded – non-primary research excluded – under 1 year of age excluded – not complete raw food excluded – non-urinary composition total relevant papers cab abstracts 32 29 1 0 1 0 1 pubmed 97 91 0 0 4 1 1 total relevant papers when duplicates removed 1 conflict of interest the authors declare no conflict of interest. references dijcker, j. c., hagen-plantinga, e. a., everts, h., bosch, g., kema, i. p. and hendriks, w. h. (2012) ‘dietary and animal-related factors associated with the rate of urinary oxalate and calcium excretion in dogs and cats.’ the veterinary record, 171(2) p. 46. doi: http://dx.doi.org/10.1136/vr.100293 finley, r., reid-smith, r., ribble, c., popa, m., vandermeer, m. and aramini, j. (2008) ‘the occurrence and antimicrobial susceptibility of salmonellae isolated from commercially available canine raw food diets in three canadian cities.’ zoonoses and public health, 55(8–10) pp. 462–469. doi: http://dx.doi.org/10.1111/j.1863-2378.2008.01147.x finley, r., reid-smith, r. and weese, j. s. (2006) ‘human health implications of salmonella-contaminated natural pet treats and raw pet food.’ clinical infectious diseases: an official publication of the infectious diseases society of america, 42(5) pp. 686–691. doi: http://dx.doi.org/10.1086/500211 goh, l.-m. (2016) ‘bsava congress 2016 raw food diets for dogs and cats: do we know enough?’ veterinary record, 178 pp. 549–550. joffe, d. j. and schlesinger, d. p. (2002) ‘preliminary assessment of the risk of salmonella infection in dogs fed raw chicken diets.’ the canadian veterinary journal = la revue veterinaire canadienne, 43(6) pp. 441–442. lefebvre, s. l., reid-smith, r., boerlin, p. and weese, j. s. (2008) ‘evaluation of the risks of shedding salmonellae and other potential pathogens by therapy dogs fed raw diets in ontario and alberta.’ zoonoses and public health, 55(8–10) pp. 470–480. doi: http://dx.doi.org/10.1111/j.1863-2378.2008.01145.x lulich, j.p., osborne, c.a., thumchai, r., lekcharoensuk, c., ulrich, l.k., koehler, l.a., bird, k.a., swanson, l.l. and nakagawa, y. (1999) ‘epidemiology of canine calcium oxalate uroliths.’ veterinary clinics of north america: small animal practice, 29(1) pp. 113-122. doi: http://dx.doi.org/10.1016/s0195-5616(99)50007-7 lunn, k. f. (2011) ‘raw food diets in dogs: concerns for canine and human health.’ advances in small animal medicine and surgery, 24(2) pp. 1–2. doi: http://dx.doi.org/10.1016/j.asams.2011.01.001 michel, k. e. (2006) ‘unconventional diets for dogs and cats.’ veterinary clinics: small animal practice, 36(6) pp. 1269–1281. doi: http://dx.doi.org/10.1016/j.cvsm.2006.08.003 robertson, w. g., heyburn, p. j., peacock, m., hanes, f. a. and swaminathan, r. (1979) ‘the effect of high animal protein intake on the risk of calcium stone-formation in the urinary tract.’ clinical science (london, england: 1979), 57(3) pp. 285–288. doi: http://dx.doi.org/10.1042/cs0570285 schlesinger, d. p. and joffe, d. j. (2011) ‘raw food diets in companion animals: a critical review.’ the canadian veterinary journal, 52(1) pp. 50–54. singer, m. a. (2003) ‘dietary protein-induced changes in excretory function: a general animal design feature.’ comparative biochemistry and physiology part b: biochemistry and molecular biology, 136(4) pp. 785–801. doi: http://dx.doi.org/10.1016/j.cbpc.2003.08.012 strohmeyer, r. a., morley, p. s., hyatt, d. r., dargatz, d. a., scorza, a. v. and lappin, m. r. (2006) ‘evaluation of bacterial and protozoal contamination of commercially available raw meat diets for dogs.’ journal of the american veterinary medical association, 228(4) pp. 537–542. doi: http://dx.doi.org/10.2460/javma.228.4.537 van veggel, n. and armstrong, m. (2017) ‘in dogs with periodontal disease is feeding a complete raw meat diet more effective than a complete kibble “dental” diet at reducing periodontal disease?’ veterinary evidence, 2(2). doi: http://dx.doi.org/10.18849/ve.v2i2.88 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. is a cross-match necessary before a cat’s first blood transfusion? a knowledge summary by ben safrany bvetmed, pgc(sam), mrcvs 1* sophie adamantos bvsc, certva, dacvecc, dipecvecc, mrcvs, fhea 1 1paragon veterinary referrals, paragon business village, paragon way, red hall crescent, wakefield, wf1 2df *corresponding author (ben.safrany@paragonreferrals.co.uk) vol 5, issue 2 (2020) published: 06 may 2020 reviewed by: nicolette joosting (bsc, bvsc) and conor o'halloran (bvsc, mrcvs) next review date: 11 nov 2021 doi: 10.18849/ve.v5i2.306 pico question in transfusion-naïve cats receiving a type specific blood transfusion is cross-matched blood (major and minor) associated with an increased haematocrit development and reduction in acute transfusion reactions when compared with those receiving non-crossmatched blood?   clinical bottom line category of research question treatment the number and type of study designs reviewed ten papers were critically reviewed. there were four retrospective case series, three prospective cross-sectional surveys, a retrospective cohort study, a prospective case series and a prospective randomised control trial. strength of evidence weak outcomes reported it would appear that in the united kingdom the incidence of non-ab transfusion reactions is low.  a single study suggests that cross-matching may result in a greater improvement in haematocrit, but this is unlikely to be clinically significant. there is evidence to support the hypothesis that non-ab antigens (for example the mik antigen) differ with geographic distribution. conclusion based on the information available it is it is challenging to establish a meaningful clinical conclusion on which to base a recommendation.   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.  clinical scenario you are presented with a 5-year-old, neutered male domestic shorthair cat with a 3 day history of progressive lethargy and hyporexia. a complete blood count reveals a severe, regenerative anaemia (packed cell volume (pcv) 11%). serum biochemistry identifies mild hyperbilirubinaemia. you are suspicious of immune mediated haemolytic anaemia and send blood to a reference laboratory for further analysis. survey imaging of the thorax and abdomen is normal. the cat is blood type a. you feel a blood transfusion is needed/required. the cat’s owners have another cat who is a suitable blood donor and is also type a. you wonder whether to proceed with transfusion of blood from this cat immediately, or whether to perform a cross-match first. the evidence the evidence available consists of predominantly retrospective descriptive studies, with some prospective experimental studies. the retrospective studies have inherent bias and are therefore low on the hierarchy of evidence. furthermore, type independent cross-match incompatibilities are not the primary outcome studied in most papers. this has led to inconsistency in areas of study design including methodology of blood typing and cross-matching, criteria for transfusion, blood product used (packed red blood cells versus whole blood), data collected and methods for calculating scaled haematocrit development (if used). as a result, it is challenging to establish a meaningful clinical conclusion.   hct – haematocrit pcv – packed cell volume prbc – packed red blood cells   summary of the evidence binagia et al. (2016) population: cats receiving a type specific blood transfusion at referral centres in arizona and michigan between 2012 and 2015. sample size: 126 cats receiving 102 transfusions intervention details: medical records were reviewed to select cats blood type in anticipation of a blood transfusion. cats receiving a cross-match were compared with those that did not. study design: retrospective dual-centre cohort study outcome studied: incidence of transfusion reactions. post transfusion pcv, survival, time to discharge. main findings (relevant to pico question): there was no difference in the rate of transfusion reactions, post-transfusion pcv, or survival between groups. the non-crossmatched group had a significantly longer duration of hospitalisation. limitations: this was a retrospective study and is therefore subject to more bias than an equivalent prospective study. accuracy relies on accurate record keeping, it is possible transfusion reactions could be under-reported, timings of pre and post-transfusion pcv may be inconsistent. only the abstract is available, so key information (for example the incidence of transfusion reactions) is not available for review. it is not stated whether cases were transfusion naïve. given the retrospective nature it is likely that the cats that received cross-matches were previously transfused. the method and type (major or minor) of cross-match is not stated. the criteria for reporting a transfusion reaction are not defined. goy-thollot et al. (2019) population: healthy, transfusion naïve domestic shorthair cats over the age of 1 year presenting at a hospital in lyon, france between october 2017 and march 2017. sample size: 49 cats intervention details: blood samples collected from healthy cats presenting for wellness examination or neutering. blood typing was performed using immunochromatographic and flow cytometric techniques. major cross-matching was performed using gel column (gc) (major cross-match only) and feline antiglobulin-enhanced gel column (agc). study design: single centre prospective cross-sectional survey outcome studied: the presence of naturally occurring alloantibodies in cats. the sensitivity of the agc compared with the gc method of cross-matching. the agreement between immunochromatographic and flow cytometric techniques of blood typing. main findings (relevant to pico question): incompatibilities outside of the major ab system were detected in 3/49 cats and were only detected using the agc test. there was a good agreement between the two cross-match methods, with additional incompatibilities detected by the agc method. limitations: there is only a small sample size. the study population is healthy and therefore different to clinically affected cats requiring transfusion. there is no gold standard cross-matching test to compare the results to, so it is not clear if additional incompatibilities were revealed but the agc method gives false positives, or if the gc technique underestimated the incidence of incompatible cross-matches. the agc technique has not been used in any of the other studies, making comparison difficult. hourani et al. (2017) population: hospitalised anaemic cats receiving a type specific whole blood transfusion at the university of berlin (dates not provided). sample size: 21 cats received 33 blood transfusions intervention details: medical records were reviewed to select cats receiving a transfusion of type specific whole blood. major, minor and recipient control cross-matches were performed before all transfusions and then every 2 days thereafter. cross-matching was performed in-house using standard and tube protocol. study design: prospective single centre case series outcome studied: major, minor and control cross-match status. hct development. main findings (relevant to pico question): no acute transfusion reactions were recorded. 15/21 cats’ major cross-matches remained compatible throughout. 5/20 [sic] cats developed major cross-match incompatibility 2–10 days after the first transfusion. no incompatible cross-matches in transfusion naïve patients. hct development as expected in 17/33 cross-match incompatible patients achieved a hct on average 1.04% less than expected. cross-match compatible patients achieved a hct on average 0.53% more than expected. limitations: cross-matches performed on stored samples, older samples may increase the occurrence of incompatible cross-matches. in-house cross-matching only. bilirubin not measured, may have aided the detection of delayed transfusion reactions. small sample size. klaser et al. (2005) population: cats receiving transfusion of type specific whole blood or prbcs at the animal medical centre, new york between january and december 1999. sample size: 126 cats receiving 148 transfusions intervention details: medical records were reviewed to identify cats receiving a blood transfusion. a cross-match was only performed in the event of a previous transfusion over 4 days earlier. study design: retrospective single centre case series outcome studied: number of and reasons for transfusions. incidence of acute transfusion reactions. volume of blood administered, change in pcv and clinical outcome. main findings (relevant to pico question): 127/148 whole blood transfusions, 21/148 prbc transfusions. a median increase in pcv of 6.4 ± 3.9% was observed in all cats. acute transfusion reactions occurred in 11/148 (7.4%) transfusions, of these, 10 were acute non-haemolytic transfusion reactions and one was an acute haemolytic reaction in a untyped cat, suspected to have been transfused with blood of an incompatible type. limitations: retrospective study design. the increase in hct, incidence of incompatible cross-matches and method of cross-matching were not reported. mcclosky et al. (2018) population: cats receiving a type specific rbc transfusion at the university of pennsylvania between january, 2013 and december, 2016. sample size: 300 cats (220 transfusion naïve) intervention details: medical records were reviewed to identify cats receiving a transfusion with or without a major cross-match. cross-matches were performed using the tube method. study design: retrospective single centre case series outcome studied: incidence of major cross-match incompatibilities. scaled increase in pcv. incidence of transfusion reaction. survival to discharge, 30 and 60 day survival. main findings (relevant to pico question): major cross-match incompatibilities in 23/154 (14.9%) transfusion naïve cats and 15/55 (27%) previously transfused cats. cross-matched blood was not associated with significant difference in scaled increase in pcv when compared with non-crossmatched blood (+0.76 ml/kg and +0.97 ml/kg respectively). febrile transfusion reactions occurred in 8/79 (10.1%) of non-crossmatched transfusions and 4/161 (2.5%) cross-matched transfusions. six cats were administered cross-match incompatible units (one transfusion naïve), no reactions were observed and the scaled increase in pcv was +0.86 ml/kg. cross-match not associated with improved survival to discharge or 30 and 60 day survival. two non-crossmatched cats developed suspected transfusion associated adverse effects and died. post-mortem compatibility testing or necropsy were not performed. limitations: this was a retrospective study and is therefore subject to more bias than an equivalent prospective study. accuracy relies on accurate record keeping, it is possible transfusion reactions could be under-reported, timings of pre and post-transfusion pcv may be inconsistent. although a reduction of transfusion reactions was observed in cats receiving a cross-match it is not clear if this applies to transfusion naïve cats. some (8%) cross-matches performed by case clinician rather than laboratory staff. a febrile transfusion reaction was defined as an increase in body temperature ≥ 2°f during or within 4 hours of the transfusion. it is possible that this criteria will overestimate the rate of febrile transfusion reactions. the two cats that died were not included in adverse event statistics, it is unclear if their deaths were transfusion related or related to an underlying disease. sylvane et al. (2018) population: transfusion naïve cats, older than 4 months, receiving type specific prbc transfusion at the animal medical centre, new york from january 2016 to august 2017. sample size: 48 cats intervention details: each cat was randomised to have a major cross-match or not before transfusion (24 cats in each group). 24/48 cross-matched cats received type specific cross-matched blood. 24/48 non-crossmatched cats received type specific non-crossmatched blood. blood transfusion was initiated 2 hours after the initial pcv measurement in both groups. when cross-matched, each cat was matched to at least 2 donor units. all cross-matches were performed at an external reference laboratory. donor blood was sourced from a commercial blood bank. study design: prospective randomised control trial outcome studied: incidence of acute transfusion reactions. scaled increase in pcv. main findings (relevant to pico question): cross-matched cats were cross-matched to at least 2 units of prbcs, 52 cross-matches were performed in total. 10/52 (19%) incompatible cross-matches. 4/24 transfusion reactions (7%) in cross-matched group, three were febrile non-haemolytic transfusion reactions (fnhtr), one was a suspected haemolytic transfusion reaction. 7/24 transfusion reactions (1%) in non-crossmatched group, all were fnhtr. there was no significant difference in the rate of transfusion reactions between groups. no significant difference in mean pcv post-transfusion scaled to the dose of prbc administered was detected between groups. limitations: this study has a relatively small sample size. the hct of transfused units of prbc were not recorded. fnhtr defined as an increase in body temperature by 1°c during the transfusion without evidence of haemolysis. there is a risk of this criteria over-reporting transfusion reactions. tasker et al. (2014) population: transfusion naïve cats presenting to the university of bristol, uk for clinical evaluation for ill health or as potential blood donors between january and october 2012. sample size: 112 cats intervention details: excess blood collected from cats presenting to the centre was used. the samples were phenotyped and genotyped for blood group type. the samples were cross-matched with a reference sample from a cat of the same ab phenotype. major and minor cross-matches were performed in a microtitration system. reference samples for cross-matches were provided by a blood bank and stored for up to 28 days. study design: single centre cross-sectional survey outcome studied: the agreement between ab blood phenotyping and genotyping. the incidence of incompatible cross-matches in type specific blood. main findings (relevant to pico question): no major cross-match incompatibility was detected. two incompatible minor cross-matches. no conclusive evidence of non-ab blood type incompatibilities. limitations: cross-matches performed with limited number of reference samples. reference samples were obtained from usa. this study only reports the incidence of incompatible cross-matches performed on type specific blood, not the outcome of transfusion. weingart et al. (2004) population: cats receiving a type specific rbc transfusion at the university of berlin between september 1998 and august 2001. sample size: 91 cats receiving 163 transfusions intervention details: medical records were reviewed to identify cats receiving a transfusion of type specific fresh whole blood. major and minor cross-matches were performed using the tube method. study design: retrospective single centre case series outcome studied: indications for transfusion. hct development. transfusion frequency and volume. survival rate. transfusion reactions. plasma bilirubin before and 1–5 after transfusion (29 transfusions). main findings (relevant to pico question): transfusion performed for a variety of reasons including blood loss, haemolysis, ineffective erythropoiesis, hypoproteinaemia and severe coagulopathy. a mild increase in serum bilirubin was detected in 11/29 (38%) cases. transfusion reactions were noted in 2/163 (1.2%) transfusions. both were compatible in type and cross-match and were receiving their second and third transfusions. there were 7/60 (11.7%) incompatible major cross-matches, one was in a transfusion naïve cat. transfusions were administered regardless, no clinical transfusion reactions were observed, hct development was as expected in five cases, but remained unchanged in two. limitations: this was a retrospective study and is therefore subject to more bias than an equivalent prospective study. accuracy relies on accurate record keeping, it is possible transfusion reactions could be under-reported, timings of pre and post-transfusion pcv may be inconsistent. the number of transfusion naïve cats was not reported. cross-matches were not performed in all cats prior to transfusion. it is not clear how many transfusion naïve cats were tested prior to transfusion. nearly half (44%) of cats included in the study had multiple transfusions, potentially increasing the risk of transfusion reactions. much lower reported incidence of transfusion reactions compared with other studies, it is possible transfusion reactions were under recognised and reported. weinstein et al. (2007) population: type a blood donor cats and a renal transplant recipient presenting at the university of pennsylvania (dates not stated). sample size: 66 cats intervention details: all cats blood-typed them major and minor cross-matches were performed. cross-matches performed using the tube and gel column methods. agglutinin titres then performed to characterise alloantibodies. study design: prospective single centre cross-sectional survey and case report outcome studied: incidence of incompatible cross-matches in type a blood. presence of auto and alloantibodies. main findings (relevant to pico question): there were incompatible cross-match results in type compatible erythrocytes in three blood donors. all three cats produced incompatible cross-matches with the same cat, suggesting all three cats produced an alloantibody against the same red cell antigen expressed by this cat. these findings suggest the presence of an alloantibody against a common red cell antigen, independent of the ab system, termed mik by the authors. all three cats had no transfusion history, suggesting the alloantibody was naturally occurring. the authors also include a case report of a severe haemolytic transfusion reaction in a cat receiving a type specific transfusion of prbcs. they mention two other mik negative cats identified at the institution but do not expand. limitations: data is only presented on a limited number of mik negative cats. data is needed on more mik negative cats to further understand their clinical relevance and prevalence. single centre report from a colony of research cats. weltman et al. (2014) population: cats receiving a type specific transfusion of prbcs between 2000 and 2010 at the cornell university teaching hospital. sample size: 209 cats receiving 233 transfusions intervention details: prbcs were administered with a major cross-match (43 transfusions in 36 cats) or without a major cross-match (190 transfusions in 173 cats). cross-matches performed in all patients that received a transfusion greater than 3 days previously or as requested by the clinician in transfusion naïve cats. cross-matches were performed using the tube method.   study design: single centre retrospective case series outcome studied: the change in pcv following packed red blood cell administration relative to dose of prbcs administered. main findings (relevant to pico question): the administration of type specific, cross-match compatible prbcs resulted in a significantly greater increase in pcv when compared to non-crossmatched packed red blood cell administration. limitations: this was a retrospective study and is therefore subject to more bias than an equivalent prospective study. accuracy relies on accurate record keeping, it is possible transfusion reactions could be under-reported, timings of pre and post-transfusion pcv may be inconsistent. non-crossmatched cats had a lower pretransfusion pcv, it is possible that they represent a cohort of cats too unwell to wait for a cross-match. most cross-matched cats were not transfusion naïve, reducing the relevance to the pico question. there is a difference in the aetiology of the anaemia between study groups. appraisal, application and reflection traditionally, it has been advised that a cross-match has only been required prior to administering type specific blood to cats if they had a previous transfusion more than 4 days previously. recently cross-match incompatibilities and transfusion reactions independent of the ab system have been reported. it has been hypothesised that naturally occurring alloantibodies to alternative red blood cell antigens are responsible, with particular interest paid to the mik antigen, first reported by weinstein in 2007. weltman et al. (2014) showed that administering cross-match compatible blood lead to greater haematocrit development when compared with non-crossmatched transfusions. binangia et al. (2016), hourani et al. (2017) and sylvane et al. (2018) failed to repeat these findings in more recent studies, but did identify a reduced frequency of pyrexic (non-haemolytic) transfusion reactions in cross-matched cats. however, weingart et al. (2007) reports two cases with an incompatible cross-match where transfusion did not increase pcv, suggesting treatment failure. it is noteworthy that all reports of non-ab transfusion reactions in transfusion naïve cats originate in the united states, raising the possibility that a geographical element exists. in 2014, tasker et al. were unable to demonstrate cross-match incompatibilities independent of the ab system in a cohort of cats from the united kingdom. a limitation of the papers reviewed were inconsistencies relating to the method of cross-match and whether only a major cross-match, or major and minor cross-matches were performed. in a major cross-match the donor’s erythrocytes are screened for incompatibility with the recipient’s plasma, whereas a minor cross-match tests for incompatibilities between donor plasma and recipient erythrocytes. goy-thollot et al. (2019) report an increased sensitivity of a feline antiglobulin-enhanced gel column method of cross-matching which was not used in any of the other studies. it is possible that such a technique is more sensitive that other techniques, however, the clinical significance of this is yet to be investigated.   the application of these studies to clinical cases is still debatable. the only prospective randomised study (sylvane et al., 2018) failed to show a difference in transfusion reactions between cross-matched and non-crossmatched cats and no difference in increase in haematocrit following transfusion. based upon the studies presented here it is challenging to establish a meaningful clinical conclusion on which to base a recommendation. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform; 1980–2019 pubmed on ncbi platform; 1973–2019 search strategy: cab abstracts and pubmed: (cat or cats or feline) and (transfusion or transfused) and (crossmatch or cross-match or crossmatched or cross-matched or cross match) or (non-ab) dates searches performed: 11/11/2019 exclusion / inclusion criteria exclusion: book chapters, articles not available in english, clinical review articles. inclusion: articles available in english which were relevant to the pico. articles had to involve more than one cat. search outcome database number of results excluded – book chapter excluded – clinical review article excluded – not relevant to pico excluded – full article not available total relevant papers cab abstracts 39 1 1 29 0 8 pubmed 117 0 9 96 2 10 total relevant papers when duplicates removed 10 conflict of interest the authors declare no conflicts of interest. references binagia, e., mattison, b. & koenigshof, a. (2016). ‘cross-matched vs non-crossmatched feline blood transfusions and effects on transfusion reaction rates, post-transfusion packed cell volume, duration of hospitalisation, and survival’, journal of veterinary emergency medicine and critical care, abstract presented september 7–11, 2016 in grapevine, tx, usa. doi: http://dx.doi.org/10.1111/vec.12516 goy‐thollot, i., nectoux, a., guidetti, m., chaprier, b., bourgeois, s., boisvineau, c., barthélemy, a., pouzot-nevoret, c. & giger, u. (2019). ‘detection of naturally occurring alloantibody by an in‐clinic antiglobulin‐enhanced and standard crossmatch gel column test in non‐transfused domestic shorthair cats’, journal of veterinary internal medicine, 33(2), pp. 588–595. doi: http://dx.doi.org/1111/jvim.15381 hourani, l., weingart, c. & kohn, b. (2017). ‘alloimmunisation in transfused patients: serial cross-matching in a population of hospitalised cats’, journal of feline medicine and surgery, 19(12), pp. 1231–1237. doi: http://dx.doi.org/10.1177/1098612x16688574 klaser, d. a., reine, n. j. & hohenhaus, a. e. (2005). ‘red blood cell transfusions in cats: 126 cases (1999)’, journal of the american veterinary medical association, 226(6), pp. 920–923. doi: http://dx.doi.org/10.2460/javma.2005.226.920 mcclosky, m. e., cimino brown, d., weinstein, n. m., taney, m. t., marryott, k. & callan, m. b. (2018). ‘prevalence of naturally occurring non-ab blood type incompatibilities in cats and influence of crossmatch on transfusion outcomes’, journal of veterinary internal medicine, 32(6), pp. 1934–1942. doi: http://dx.doi.org/10.1111/jvim.15334 sylvane, b., prittie, j., hohenhaus, a. e. & tozier, e. (2018). ‘effect of cross-match on packed cell volume after transfusion of packed red blood cells in transfusion-naïve anemic cats’, journal of veterinary internal medicine, 32(3), pp. 1077–1083. doi: http://dx.doi.org/10.1111/jvim.15120 tasker, s., barker, e.n., day, m.j. & helps, c. r. (2014). ‘feline blood genotyping versus phenotyping, and detection of non-ab blood type incompatibilities in uk cats’, journal of small animal practice, 55(4), pp. 185–189. doi: http://dx.doi.org/10.1111/jsap.12180 weingart, c., giger, u. & kohn, b. (2004). ‘whole blood transfusions in 91 cats: a clinical evaluation’, journal of feline medicine and surgery, 6(3), pp. 139–148. doi: http://dx.doi.org/10.1016/j.jfms.2004.01.005 weinstein, n. m., blais, m., harris, k., oakley, d. a., aronson, l. r. & giger, u. (2007). ‘a newly recognized blood group in domestic shorthair cats: the mik red cell antigen’, journal of veterinary internal medicine, 21(2), pp. 287–292. doi: http://dx.doi.org/10.1111/j.1939-1676.2007.tb02962.x weltman, j. g., fletcher, d. j. & rogers, c. (2014). ‘influence of cross-match on posttransfusion packed cell volume in feline packed red blood cell transfusion: influence of cross-match on feline transfusion efficacy’, journal of veterinary emergency and critical care, 24(4), pp. 429–436. doi: http://dx.doi.org/10.1111/vec.12204 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. the effects of biannual equine influenza vaccine on performance in adult horses a knowledge summary by emma shipman bvetmed, msc, dipacvim, certva, mrcvs1* 1school of veterinary medicine and science, university of nottingham, sutton bonington campus, leicestershire, le12 5rd *corresponding author (emma.shipman@nottingham.ac.uk) vol 4, issue 3 (2019) published: 26 jul 2019 reviewed by: polly compston (bsc (hons), bvm&s, msc, mrcvs) and margaret nolan (bsc, msc, phd) next review date: 01 may 2020 doi: 10.18849/ve.v4i3.196 pico question in three day event horses, does biannual routine influenza vaccination compared to annual routine influenza vaccination reduce performance levels? clinical bottom line there is no evidence that biannual equine influenza vaccination compared to annual booster vaccination in three day event horses is associated with reduced performance. a group of five studies published over an 11 year period from one were evaluated. in adult warmblood horses there is weak evidence that exercise in the 28 day period post booster vaccination for equine influenza and equine herpes virus 1 and 4 (ehv1&4), is associated with changes in physical and clinical pathophysiological parameters including total red blood cell (rbc) count, neutrophil and lymphocyte count, fibrinogen concentration and serum proteins. these changes occurred at variable time points in the 14 days post exercise and values were not outside the published reference ranges for the reporting laboratories where published. athletic performance of the horses was not evaluated. no recommendations for equine influenza vaccination protocols in three day event horses can be made from the evidence. the evidence there is no retrospective or prospective evidence examining performance in three day event horses after annual or biannual booster vaccination against equine influenza virus. there is no evidence examining performance levels in three day event horses after booster vaccination against equine influenza virus. there is a small amount of evidence, and the quality of the evidence is low, evaluating clinical and clinicopathological data that may relate to performance in adult warmblood horses undergoing booster vaccination and subsequent exercise. these five randomised controlled trials were conducted at one veterinary teaching hospital using a small number of adult warmblood horses over an 11 year period. the evidence evaluated may not be applicable outside the experimental group of 15 horses and some horses may have been included in more than one of the studies. summary of the evidence (a) gundasheva (2015) population: adult hanoverian geldings at one bulgarian veterinary hospital sample size: 15 horses intervention details: vaccinated for ehv1&4 and equine influenza virus (eiv) 12 months after initial vaccination [n=6] vaccinated for ehv1&4 and ei 12 months after initial vaccination and submitted to physical exercise for 4 days commencing 14 days after revaccination [n=6] control group of unvaccinated animals [n=3] study design: randomised controlled trial outcome studied: erythron parameters, heart and respiratory rates were determined 0h, 2h, and day 14 and 17 after booster vaccination and days 1, 2, 4 and 11 after commencement of exercise. results were presented as mean +/standard error of mean (sem) main findings (relevant to pico question): all erythron parameters of all groups remained within the published reference ranges for the study period heart rate and respiratory rate were significantly increased in the physical exercise group 0h and 2h post exercise rbc count was statistically different between vaccine and vaccine plus exercise groups, increasing in the vaccine and exercise group on day 4 after cessation of physical exercise but not on day 2 or 11 limitations: small group sizes whether horses in the intervention groups had received primary and/or booster vaccinations against ehv1&4 and eiv is not reported randomisation process was not described reported reference ranges are laboratory specific prior vaccination status of the horses was not discussed in detail level of preceding fitness prior to study inclusion was not reported sotirov et al. (2004) population: adult hannovarian horses (4–9 years old) at one bulgarian veterinary hospital sample size: 12 horses intervention details: vaccinated for ehv1&4 and ei 12 month after initial vaccination (control group) [n=6] vaccinated for ehv1&4 and ei 12 months after initial vaccination and exercised for 4 days commencing 14 days after booster vaccination [n=6] study design: randomised controlled trial outcome studied: serum lysozyme, and magnitude of alternate pathway complement activation and classical pathway complement activation were determined on days 17, 18, 19, 21 and 28 after booster vaccination, corresponding to days 0, 1, 2, 4 and 11 after cessation of exercise. values were reported as mean +/sem main findings (relevant to pico question): exercise post booster vaccination did not alter lysozyme concentrations at any time point alternate complement pathway activation was statistically higher in the exercise group on days 4 and 11 post cessation of exercise limitations: small group size randomisation process was not described level of preceding fitness prior to study inclusion was not reported for either group prior vaccination status of the horses was not discussed in detail goundasheva [sic] et al. (2005) population: adult hanoverian horses (4–9 years) at one bulgarian veterinary hospital sample size: 12 horses intervention details: vaccinated for ehv1&4 and eiv 12 month after initial vaccination (control group) [n=6] vaccinated for ehv1&4 and eiv 12 months after initial vaccination and exercised for 4 days commencing 14 days after booster vaccination [n=6] study design: randomised controlled trial outcome studied: white blood cells (wbc), band neutrophils, segmented neutrophils, eosinophils, monocytes and lymphocytes, cortisol and antibody titers against ehv1&4 and eiv were determined on days 17, 18, 19, 21 and 28 after booster vaccination, corresponding to days 0, 1, 2, 4 and 11 after cessation of exercise. results were presented as mean +/sem main findings (relevant to pico question): kinetics of antibody titers in response to booster vaccination were similar between groups lymphocyte counts increased in the vaccine only group on days 17, 18 and 28 after revaccination in the vaccine and exercise group band neutrophils counts increased and segmented neutrophils decreased on day 18 after revaccination (day 1 after cessation of exercise) limitations: no data was presented for serum cortisol concentration other than 0h and 2h after cessation of exercise in the exercise group randomisation process was not described small group size while trends in various leucocyte counts are reported, no comment is made as to whether these lie outside the published reference ranges for the appropriate laboratories level of preceding fitness prior to study inclusion was not reported (b) gundasheva (2015) population: adult hanoverian geldings (4–9 years of age) at one bulgarian veterinary hospital sample size: 15 horses intervention details: vaccinated for ehv1&4 and eiv 12 months after initial vaccination [n=6] vaccinated for ehv1&4 and eiv12 months after initial vaccination and submitted to physical exercise for 4 days commencing 14 days after revaccination [n=6] control group of unvaccinated animals [n=3] study design: randomised controlled trial outcome studied: albumin, alpha, beta and gamma globulin serum protein fractions were determined in all groups on days 14 and 17, 18, 19, 21 and 28 after booster vaccination corresponding with days 1, 2, 4 and 11 after cessation of the exercise program. results were reported as mean +/-sem main findings (relevant to pico question): statistically significant difference were noted for albumin, alpha 2 and beta 1 and 2 globulins between booster, vaccinated and booster, vaccinated and exercised horses at individual time points  but these differences did not persist over the timeframe of the  study. beta 2 globulins were reported as reduced in the exercise group at certain time points whereas all other parameters were increased in the exercising group. all parameters remained with the published reference ranges at all time points for the reporting laboratory. limitations: no data was collected during the first 14 days post booster vaccine small group size randomisation process was not described level of fitness of the horses included in this study prior to commencement of the trial was not discussed gundasheva and georgieva (2015) population: adult hanoverian geldings (4–9 years of age) at one bulgarian veterinary hospital sample size: 15 horses intervention details: vaccinated for ehv1&4 and ei 12 months after initial vaccination [n=6] vaccinated for ehv1&4 and ei 12 months after initial vaccination and submitted to physical exercise for 4 days commencing 14 days after revaccination [n=6] control group of unvaccinated animals [n=3] study design: randomised controlled trial outcome studied: haptoglobin, fibrinogen and erythrocyte sedimentation ratio were evaluated in all groups on days 14 and 17, 18, 19, 21 and 28 after booster vaccination, corresponding with days 1, 2, 4 and 11 after cessation of the exercise program. results were reported as mean +/-sem. main findings (relevant to pico question): plasma haptoglobin was not significantly different at any time point between the vaccinated, and the vaccinated and exercised groups. fibrinogen concentration was significantly different between the vaccinated, and vaccinated and exercised group at day 1 post cessation of exercise, increasing in the exercise group but not significantly different at any other time point during the study. haptoglobin and fibrinogen remained within the reference range for the laboratory in all horses throughout the study period. erythrocyte sedimentation rate (esr) were significantly different between the vaccinated only and vaccinated plus exercised group, increasing in the vaccinated plus exercised group on days 1, and 4 after cessation of exercise, but not day 2. reference ranges for haptoglobin and fibrinogen concentrations were not presented. limitations: randomisation process was not discussed for horses in the revaccination only and revaccination plus exercise groups, it was unclear whether the prior vaccination 12 months preceding the commencement of the study, was a primary course or booster vaccination small group size level of preceding fitness prior to study inclusion was not reported appraisal, application and reflection there is no evidence available comparing performance levels in three day event horses receiving either biannual or annual booster vaccinations against equine influenza virus. there is no evidence available evaluating performance levels in three day event horses receiving booster vaccination for equine influenza virus or placebo controls. only low quality evidence is available from a group of five papers from one veterinary teaching hospital evaluating a variety of physical and clinicopathological variables in adult warmblood horses after either booster vaccination against equine influenza virus and equine herpes virus and rest or booster vaccination followed by a controlled exercise program for 4 days commencing 14 days after vaccination. variables evaluated included: heart rate*, respiratory rate* and total red blood cell count * serum proteins (albumin*, alpha 1, alpha 2*, beta 1* and beta 2*, gamma globulins) fibrinogen*, haptoglobin erythrocyte sedimentation rate total white blood cell, eosinophil, neutrophil* and lymphocyte* counts lysozyme*, classical and alternate complement activation* statistically significant differences (p < 0.05) were noted in the above variables (*) at intermittent time points in the 14 days post exercise (corresponding to 18–31 days post booster vaccination.) values were reported as means in all cases with mean plus standard error of mean in some publications. confidence limits were not reported in any of the studies. reported values remained within the published reference ranges for the conducting laboratories at all time points when these were reported in the studies. while the above variables are commonly evaluated in horses with reduced performance, athletic performance was not directly evaluated. the study participants were reported as male , male entire geldings or not reported and previous level of fitness prior to study inclusion was not discussed in any study. in all trials an exercise period of 4 days was used, which is likely to vary greatly to training programs for competing three day event horses. while all study horse were reported as being previously vaccinated for equine influenza virus and equine herpes virus 1&4 a year prior to inclusion in the trial, whether this was a booster or primary vaccine course was not discussed. all trials involved booster vaccination with an oil adjuvanted intramuscular vaccine and therefore these finding may not be relevant to horses receiving intranasal/immune stimulating complex (iscom) vaccines/vaccines containing varying influenza strain or vaccines containing equine influenza only. conclusions: there is no evidence that biannual equine influenza vaccination compared to annual booster vaccination is associated with reduced performance in three day event horses. the quality of the data in adult warmblood horses in the 28 days period post booster vaccination where exercise occurred on days 14–17post vaccination is insufficient to determine whether athletic performance was affected during this period. more definitive conclusions on vaccination protocols in three day event horses cannot be drawn until higher quality evidence is available on the topic. methodology section search strategy databases searched and dates covered: pubmed ncbi platform 1973–2018 week 16 cab abstracts on ovid platform 1973–2018 week 16 search terms: pubmed equine* or horse* or equus or equid* or mare or mares or pony or ponies or exp equidae/ or exp equus/ or exp horses/ or exp mares/ 'three day event*' or 'show jump*' or dressag* or endur* or exercis* or sport* or compet* or athlet* or 'cross country' exp show jumping/ or exp horse riding/ (1 and 2) or 3 vaccin* or immunisation or immunization or inoculation or exp vaccination/ or exp immunization/ influenza or flu or exp influenza/ 4 and 5 and 6 cab abstracts equine or horse or mare or mares or broodmares or pony or ponies three day evening or show jumping or dressage or endurance or exercise or sport or sporting or competition or athlete or athletic or cross country influenza or flu vaccine or vaccination or immunisation or immunization or inoculation 1 and 2 and 3 and 4 dates searches performed: 01 may 2018 exclusion / inclusion criteria exclusion: non english language papers single case reports book chapters and literature reviews without novel information not relevant to the question inclusion: papers comparing physical or clincopathological data, in sports horses exercising after revaccination for equine influenza or equine influenza and equine herpes virus 1&4 were evaluated. due to the absence of published data in sports horses after biannual vaccination for ei, varying vaccination protocols were included. search outcome database number of results excluded – [non english language] excluded – [single case report] excluded – [narrative review/opinion pieces] excluded – [not relevant to pico] total relevant papers cab abstracts 188 37 2 5 139 5 ncbi pubmed 25 2 0 0 22 1 total relevant papers when duplicates removed 5 conflict of interest the author declares no conflicts of interest. references goundasheva[sic], d., chenchev, i., katsarova, r., karadiov, t., tsachev, i., barzey, g. (2005). "changes in leukocyte and antibody response following exercise in horses with booster vaccination against influenza and herpes virus 4/1." revue de medecine veterinaire 156(11): 527–532. (a) gundasheva, d. (2015). "effect of exercise on erythron, heart and respiratory rates in horses vaccinated against equine herpes virus 4/1 and equine influenza virus." comparative clinical pathology 24(6): 1565–1572. doi: http://dx.doi.org/10.1007/s00580-015-2117-9 (b) gundasheva, d. (2015). "electrophoretic analysis of serum proteins in strenuously trained horses revaccinated against equine herpes virus 4/1 and equine influenza virus." veterinarija ir zootechnika 69(91): 18–25. gundasheva, d., & georgieva, t. (2015). "changes in some acute phase response parameters after physical exercise in horses with booster vaccination against equine herpes virus 4/1 and equine influenza virus." veterinarija ir zootechnika 70(92): 22–28. sotirov, l., goundasheva, d., dzheleboy, p. (2004). "lysozyme and complement response to exercise in horses with booster vaccination against influenza virus and equine herpes virus 1 and 4." revue de medecine veterinaire 155(8/9): 449–452. acknowledgement rcvs knowledge was supported in producing this knowledge summary by an educational grant from petplan charitable trust. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in dogs with metaldehyde intoxication, are benzodiazepines more effective than methocarbamol in relaxing muscles and reducing tremors? a knowledge summary by theophanes liatis dvm (hons) mrcvs 1* 1small animal hospital, university of glasgow, 464 bearsden rd, bearsden, glasgow g61 1bd *corresponding author (theofanis.liatis@gmail.com) vol 5, issue 2 (2020) published: 26 jun 2020 reviewed by: luisa de risio (dvm (hons) phd decvn frcvs rcvs ebvs®) and simon platt (bvm&s dipecvn dipacvim frcvs) next review date: 02 jul 2021 doi: 10.18849/ve.v5i2.292 the term tremor used throughout the paper has been more recently replaced by the term twitches which is acknowledged by the author (lowrie & garosi, 2016). pico question in dogs with metaldehyde intoxication, are benzodiazepines (e.g. diazepam, midazolam) more effective than methocarbamol in relaxing muscles and reducing tremors?   clinical bottom line category of research question treatment the number and type of study designs reviewed five papers were critically reviewed. there were five retrospective case series strength of evidence weak outcomes reported currently, five retrospective case series exist in the literature which discuss metaldehyde intoxication cases treated mainly with benzodiazepines, a few of which had methocarbamol. there is not really any study to compare directly benzodiazepines with methocarbamol. in addition to that, factors such as commercial (e.g. the low availability of methocarbamol in the uk market compared to the us market), administrational (e.g. multiple administration routes of benzodiazepines) and pharmacological (e.g. lack of anticonvulsant function of methocarbamol), have played an important role in the treatment choice. several case reports exist as well conclusion currently, there is insufficient evidence to determine whether benzodiazepines are more effective than methocarbamol in relaxing muscles and reducing occurrence of muscle tremors   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision-making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a 4-year-old male neutered dog is presented to you as an emergency due to acute ongoing generalised muscle tremors. prior to the episode, the dog was out for a walk at the neighborhood. physical examination reveals hyperthermia (40.5oc), neurological examination reveals generalised muscle tremors, however the dog is bright, alert and responsive. based on generalised muscle tremors and absence of other neurological findings, you suspect that the hyperthermia is secondary to the tremors, and you neurolocalise forebrain, cerebellum, meninges (pyrexia), peripheral nerve or multifocal, as it is difficult to clinically establish the origin of  generalised muscle tremors. you observe some watery discharge of blue/green colour from the anus, compatible with the colour of the commercial form of slug bait, and thus you suspect metaldehyde intoxication. would you choose methocarbamol or benzodiazepines to relax the muscles and reduce the tremors of the dog? the evidence five studies of indirect relevance to the pico were reviewed, all of them being retrospective in nature. due to a lack of prospective or retrospective studies with direct correlation of benzodiazepines and methocarbamol treatment without administration of other medications (e.g. antiepileptic drugs), the strength of the evidence is extremely low. summary of the evidence firth (1992) population: dogs with snail bait poisoning (metaldehyde or methiocarb) and follow-up. this study was conducted in australia sample size: 56 dogs intervention details: 26/56 dogs were intoxicated by metaldehyde (30/56 dogs were intoxicated by methiocarb) there is no information whether the intoxicated dogs manifested epileptic seizures, tremors or both there is no information whether the dogs were amenable or not to administration of oral medications upon presentation treatment was achieved with sedatives, general anaesthetics and/or muscle relaxants including: diazepam premedication (9/26) diazepam/ketamine general anaesthesia (ga) (12/26) diazepam/ketamine/lidocaine ga (7/26) lidocaine/ketamine ga (1/26) methocarbamol (post-ga) (6/26) methocarbamol was given only after performing ga with either one of the above mentioned ga protocols, but not as sole medication two dogs were lost to follow-up study design: retrospective, single centre, case series outcome studied: different management protocols (including the use of premedication, general anaesthesia and post-general anaesthesia relaxants) the correlation between the treatment modality and patients’ response and outcome main findings (relevant to pico question): there was full recovery of 100% (24/24) metaldehyde intoxication cases using multimodal treatment, most of which included diazepam. however, there was no comparison between the usage of benzodiazepines and methocarbamol limitations: this is a retrospective, single centre, case series study with a low level of evidence. the usage of methocarbamol was additional to a ga protocol that might or might not include diazepam the outcome was not correlated with the specific treatment that each dog had yas-natan et al. (2007) population: dogs diagnosed with metaldehyde. this study was conducted in israel (school of veterinary medicine, the hebrew university of jerusalem) sample size: 18 dogs intervention details: all cases were intoxicated by metaldehyde and presented with a variety of clinical signs 16/18 dogs presented with epileptic seizures and 10/18 dogs presented with muscle tremors amongst other clinical signs only 2/18 dogs were amenable to administration of oral medications upon presentation as they were not presented with status epilepticus or altered mentation. nevertheless, only injectable medications were administered within the study monotherapy (6/18 dogs) or multimodal treatment was administered (12/18 dogs) including one, or more than one, of the medications below: diazepam (17/18) phenobarbital (7/18) pentobarbital (6/18) isoflurane (9/18) diazepam was administered in a dose of 0.28–6.3 mg/kg iv q24h study design: retrospective, single centre, case series outcome studied: clinical signs and clinicopathological findings different management protocols the correlation between the treatment modality and patients’ response and outcome main findings (relevant to pico question): dogs with metaldehyde intoxication which were mostly treated with multimodal treatment including diazepam had overall a good outcome (survival rate of 83%) limitations: this is a retrospective, single center, case-series study with a low level of evidence. this is a study which does not concentrate on the treatment. no information provided for the type of treatment in conjunction with the outcome the treatment of the dogs with metaldehyde intoxication is multimodal, and the majority of dogs were treated with barbiturates. as the barbiturates are successful antiepileptic drugs, this makes the conclusion of diazepam efficacy unreliable zimmermann et al. (2010) population: dogs with status epilepticus due to acute intoxications. this study was conducted in germany (ludwig maximilian university of munich) sample size: 14 dogs (three of them diagnosed with metaldehyde intoxication) intervention details: 3/3 cases were intoxicated by metaldehyde and presented with status epilepticus 0/3 presented with muscle tremors none of the dogs (0/3) were amenable to administration of oral medications as per status epilepticus upon presentation all metaldehyde intoxicated dogs were administered phenobarbital alone or with other medications, whilst two of them were treated with diazepam. specifically: dog 1: phenobarbital, pentobarbital dog 2: diazepam, acepromazine, atropine, phenobarbital, pentobarbital dog 3: lidocaine, diazepam, propofol, pentobarbital for dog 2, diazepam was administered initially 0.5–1.0 mg/kg im and then iv, whilst for dog 3 only iv study design: retrospective, single centre, case series outcome studied: describe intoxication aetiology for dogs with status epilepticus describe clinical presentation different management protocols the correlation between the treatment modality and patients’ response and outcome main findings (relevant to pico question): dogs with metaldehyde intoxication which were treated in hospital with phenobarbital (2/3), pentobarbital (3/3), diazepam (2/3) and other medications survived all dogs were discharged with oral antiepileptic treatment (phenobarbital), which was tapered gradually until discontinuation for a total period of 4 weeks post-discharge) telephone follow-up was done for all dogs in the study (median follow-up time 2.6 years); the three dogs with metaldehyde intoxication were alive with no further seizures all metaldehyde intoxicated dogs survived limitations: this is a retrospective, single centre, case series study with a low level of evidence. this study is a general intoxication study, which does not concentrate specifically on metaldehyde intoxication. thus, the case number is very low (n=3), where only 2/3 have been treated with diazepam the treatment of the dogs with metaldehyde intoxication is multimodal, and particularly all dogs are treated with pentobarbital or phenobarbital. as phenobarbital and pentobarbital are of the barbiturate family, they are very successful antiepileptic drugs, the conclusion of diazepam efficacy is unreliable the whole study does not provide detailed findings for every individual case (follow-up time, outcome, etc.) making the strength of evidence even lower jull et al. (2011) population: dogs with status epilepticus due to acute intoxications. this study was conducted in the uk (royal veterinary college, animal health trust) sample size: 20 dogs (17 cases were intoxicated by metaldehyde and presented with status epilepticus) intervention details: all dogs (17/17) had epileptic seizures (status epilepticus), however, it is not stated whether some of these dogs had muscle tremors as well none of the dogs (0/17) were amenable to administration of oral medications as per status epilepticus upon presentation metaldehyde intoxicated dogs received monotherapy or multimodal therapy. more specifically: 8/17: diazepam (monotherapy) 3/17: diazepam + phenobarbital 1/17: diazepam + propofol 1/17: midazolam (monotherapy) 2/17: midazolam + propofol 2/17: phenobarbital + propofol study design: retrospective, multi-centre (two centres), case series outcome studied: whether prolonged status epilepticus, secondary to a chemoconvulsant, can induce spontaneous recurrent seizures in dogs main findings (relevant to pico question): dogs with metaldehyde intoxication which were treated with benzodiazepine monotherapy (diazepam or midazolam) survived and did not manifest any post intoxication seizures 3/17 dogs of the metaldehyde intoxication group were discharged with oral antiepileptic treatment (phenobarbital) which was tapered gradually until discontinuation median follow-up time for the 20 dogs was 757 days. the 17 dogs with metaldehyde intoxication survived and none of them manifested any post intoxication seizures all metaldehyde intoxicated dogs survived limitations: this is a retrospective, multi-centre, case series study with a low level of evidence the multi-center nature of the study increases the possibility of non-standardised protocols between the centres, and thus the strength of the study there was no case treated with methocarbamol due to the nature of the study, no direct comparison between the different treatments can be reliably assumed bates et al. (2012) population: dogs with suspected metaldehyde intoxication (slug bait poisoning) with follow-up; cases reported to the veterinary poisons information service (vpis) through phone calls by veterinary practices. this study was conducted in the uk (1985–2010) sample size: 772 dogs intervention details: 597/772 dogs were symptomatic only 528/597 dogs developed increased muscular activity, such as tremor, twitching, muscle spasms or fasciculation, epileptic seizures or opisthotonos 290/597 dogs were presented with convulsions and 136/597 with tremors, whilst the rest had a variety of other neurological or extraneural signs there is no information whether the dogs were amenable or not to administration of oral medications upon presentation treatment, on either symptomatic or asymptomatic intoxicated dogs was achieved with one, or more than one, of the medications below: benzodiazepines (392/772) barbiturates (227/772) propofol (90/772) acepromazine (70/772) isoflurane (4/772) methocarbamol (2/772) ketamine (1/772) 496/597 dogs required more than one sedative or anaesthetic agent 18 of the responding veterinarians who used diazepam reported that diazepam appeared to be ineffective and an alternative sedative was required study design: retrospective, multi-centre, case series outcome studied: to analyse retrospectively telephone enquiries of referring veterinarians who confront dogs poisoned by metaldehyde describe clinical features the correlation between the treatment modality and patients’ response and outcome main findings (relevant to pico question): benzodiazepines remain a major option for metaldehyde intoxication treatment for the 50% of the cases, however there is evidence that refractory cases require further medications/anaesthetics the use of barbiturates and benzodiazepines remained fairly constant over the period examined benzodiazepines were given to half the dogs in this cases series methocarbamol was used only in two cases most likely as a result of the decreased availability in the uk limitations: this is a retrospective, multi-centre, case series study with a low level of evidence the multi-centre and questionnaire based nature of the study increases the possibility of non-standardised protocols between the centres, and thus the strength of the study there were only two cases treated with methocarbamol, with no detailed reference as to the outcome the outcome was not correlated with the specific treatment that each dog had, making any evaluation of the benzodiazepine or methocarbamol efficacy to each case impossible appraisal, application and reflection metaldehyde intoxication is a common intoxication in dogs attributed to ingestion of slug bait, which consists of the carbamate named metaldehyde. clinical signs include generalised muscle tremors and/or epileptic seizures, as well as a variety of other signs (dolder, 2003). among others (e.g. metabolic acidosis), one of the major causes of death in such cases is the hyperthermia secondary to the excessive generalised muscle tremors (dolder, 2003). consequently, one of the major therapeutic goals of the general practitioner is to decrease the muscle tremors, avoiding hyperthermia. as mentioned already, there are no prospective or retrospective studies in the literature to compare different treatments for metaldehyde intoxication in dogs focusing on benzodiazepines and methocarbamol. benzodiazepines bind to γ-aminobutyric acid (gaba) receptors of the brain resulting in increased gaba activity, which is the main neurotransmitter of the brain. consequently, they are used as centrally acting skeletal muscle relaxants, but also as anxiolytics, sedatives, hypnotics and anticonvulsants (podell, 1995; and van tulder et al., 2003). benzodiazepines are quite beneficial as most of them can be administered through different routes (intravenous [iv], intramuscular [im], per os [po], intranasal [in], intrarectal [ir]) (podell, 1995; and charalambous et al., 2017). diazepam reaches therapeutic plasma levels within 10 minutes when administered in or iv (musulin et al., 2011) or ir (papich & alcorn, 2007) or 30 minutes to 2 hours when administered po (plumb, 2008). diazepam im has a slower and incomplete absorption (plumb, 2008). the serum half-life of diazepam in dogs is 2.5–3.2 hours (plumb, 2008). diazepam’s major drawbacks include: (a) possible cause of contradictory response (central nervous system excitement) (plumb, 2008); (b) sedative inefficacy (plumb, 2008); (c) tolerance to its anticonvulsant effect in dogs (frey et al., 1984); and (d) inability to administer as a constant-rate infusion (cri) solution as its availability might be reduced within the plastic syringe (cloyd et al., 1980). midazolam’s unique solubility characteristics (water soluble injection but with high lipophilicity at body ph) give it a very rapid onset of action after injection (plumb, 2008). although midazolam iv provides the quickest onset of action (plumb, 2008), in route provides superiority when the time needed to place an iv catheter is taken into account and same efficacy (charalambous et al., 2019). midazolam im is rapidly and completely absorbed, in contrast with diazepam im. midazolam po is not commercially available, whilst midazolam ir is not clinically useful due to very low rectal bioavailability. compared to diazepam, midazolam is nearly 3 times as potent, and has a faster onset of action (in humans 30–97 seconds), but a shorter duration of effect. midazolam can also provide sedation if used with opioids, in contrast to diazepam (plumb, 2008). as a take-home medication, recently, midazolam in revealed to be superior to diazepam ir for status epilepticus (charalambous et al., 2017). midazolam’s major drawbacks include: (a) dose-dependence on plasma protein concentrations (as it is protein binding); (b) shorter serum half-life (within almost an hour) compared to diazepam, and therefore necessity for a cri; and (c) respiratory depression when used with other narcotics (e.g. opioids) (plumb, 2008). methocarbamol is a centrally acting muscle relaxant that selectively blocks polysynaptic reflex pathways in the spinal cord without any effect on monosynaptic pathways, whilst it has no direct effect on the contractile mechanism of the striated muscle, the nerve fibre or the motor end plate (van tulder et al., 2003; and nielsen et al., 2005). it has been used in veterinary medicine in traumatic myopathies or intoxications (including tetanus) (nielsen et al., 2005). oral tablets are the only commercially available form of methocarbamol, although it can be prepared in an off-label enema in hospital. methocarbamol has an onset of action of about 30 minutes after oral administration. its peak levels in humans occur approximately 2 hours after dosing, and its serum half-life is about 1–2 hours (plumb, 2008). in the us, methocarbamol iv is available as well, and successful management of tremors has been reported with methocarbamol cri in cats (draper et al., 2013). methocarbamol’s major drawbacks include: (a) limited routes of administration in combination with availability limited to the oral form in europe; (b) delayed onset of action compared to benzodiazepines iv; and (c) central nervous system depressant effects as a carbamate (sedation, salivation, lethargy, weakness, ataxia) (plumb, 2008). most of the above mentioned retrospective studies include benzodiazepines and particularly diazepam as one of the most common first-line drugs for the treatment of metaldehyde intoxication. firth (1992) reported metaldehyde intoxicated dogs treated with diazepam or methocarbamol. both canine groups were treated with diazepam or methocarbamol as a part of a multimodal treatment which included additionally a general anaesthetic. all dogs recovered, but no comparison between the groups can be made for the efficacy of either diazepam or methocarbamol. yas-natan et al. (2007) described cases of metaldehyde intoxication treated with benzodiazepines, most of which were accompanied by barbiturates (phenobarbital or pentobarbital). due to the administration of the above mentioned antiepileptic drugs, no conclusion can be made about the diazepam only efficacy to these patients, whilst no case with methocarbamol treatment is described. zimmerman et al. (2010) treated all three metaldehyde intoxication cases with diazepam followed by barbiturates amongst other medications, with an aim to control the status epilepticus. all cases recovered, however due to the multimodal nature of treatment, no conclusion could be made for the diazepam only efficacy. jull et al. (2011) described similar therapeutic protocols. bates et al. (2012) described that general practitioners preference to use of benzodiazepines (392/772 cases) among other treatment protocols as either monotherapy or multimodal therapy, with barbiturates being used frequently (227/772 cases). only 2/772 cases were reported to have used methocarbamol in the therapeutic protocol. in practice, the vast majority of dogs suspected to be intoxicated by metaldehyde are presented with epileptic seizures (e.g. status epilepticus) and/or generalised muscle tremors. at the time of presentation, the general practitioner is not able to distinguish the origin of the clinical signs, and given the emergency nature of these cases, injectable benzodiazepines (and specifically diazepam) are the first choice. injectable benzodiazepines offer rapid onset of action and have both antiepileptic and muscle relaxant properties. additionally, both generalised muscle tremors and epileptic seizures usually include motor activity of the facial and masticatory muscles and thus jaw movements, which makes any oral administration unsafe for the veterinary surgeon. therefore, these reasons, as well as the restricted administration routes of methocarbamol, could probably explain why the vast majority of studies include primarily benzodiazepines rather than methocarbamol.     conclusions in conclusion, there is not enough evidence to define whether benzodiazepines (e.g. diazepam, midazolam) or methocarbamol is better for the control of muscle tremors during metaldehyde intoxication, thus the answer of the current pico remains open. although it is reported that the availability of methocarbamol is limited in the uk (bates et al., 2012) and there are no prospective studies describing its efficacy on tremors, it is suggested that methocarbamol is very successful in reducing muscle tremors during this intoxication (dolder, 2003). due to possible manifestation of epileptic seizures concurrently with the generalised muscle tremors and in the light of their anticonvulsant activity, their broader availability, their multiple administration routes and their rapid action when given iv, benzodiazepines are preferred for the initiation of the treatment in cases of metaldehyde intoxication by many vets; and they carry on with an antiepileptic drug (e.g. phenobarbital) or general anaesthesia (firth, 1992; yas-natan et al., 2007; zimmermann et al., 2010; jull et al., 2011; and bates et al., 2012). it is important to note that in the decision-making process, apart from the pharmacological features of each medication, all points of care should be taken into consideration such as: (a) best practice: each patient should be treated with the best practice that would be to treat the dog immediately with the faster acting drug; (b) the patient stress factor: that is no oral medications should be administered in a patient with risk of regurgitation or distress; and (c) safety of the staff: that is risks that could arise from administration of oral medications in a dog with generalised muscle tremors (including the jaw). further studies are necessary to provide information on the efficacy of benzodiazepines or methocarbamol in patients with metaldehyde intoxication. methodology section search strategy databases searched and dates covered: cab abstracts, 1973 to 2019 week 25 pubmed, 1966 to current search strategy: cab abstracts: (dog or dogs or canine or canines or canis or bitch or bitches or puppy or puppies or pup or pups) or exp dogs/ or exp bitches/ or exp puppies/ or exp canidae/ or exp canis/ metaldehyde.mp. or exp metaldehyde/ or 'slug bait'.mp. or tremorgenic (intoxication or toxic* or poison* or toxicosis) or exp toxicity/ or exp poisoning/ 1 and 2 and 3   pubmed: dog or dogs or canine or canines or canis or bitch or bitches or  puppy or puppies or pup or pups metaldehyde or slug bait or tremorgenic intoxication or toxic* or poison* or toxicosis 1 and 2 and 3 dates searches performed: 2 july 2019 exclusion / inclusion criteria exclusion: articles not available in english, articles which were not relevant to the pico question. book chapters, literature reviews, single case reports, conference proceedings inclusion: original peer-reviewed articles in english language with more than one dog intoxicated by metaldehyde and treated with benzodiazepines and/or methocarbamol search outcome database number of results excluded – non-english language excluded – not relevant with the pico excluded – book chapters excluded – reviews excluded – case reports excluded – conference proceedings total relevant papers cab abstracts 113 16 71 2 11 5 3 5 pubmed 52 0 36 0 10 1 0 5 total relevant papers when duplicates removed 5 conflict of interest the author declares no conflicts of interest. references bates, n.s., sutton, n.m. & campbell, a. (2012). suspected metaldehyde slug bait poisoning in dogs: a retrospective analysis of cases reported to the veterinary poisons information service. veterinary record, 171(13): 324. doi: http://dx.doi.org/10.1136/vr.100734 charalambous, m., bhatti, s.f.m., van ham, l., platt, s., jeffery, n.d., tipold, a., siedenburgh, j., volk, h.a., hasegawa, d., gallucci, a., gandini, g., musteata, m., ives, e. & vanhaesebrouck, a.e. (2017). intranasal midazolam versus rectal diazepam for the management of canine status epilepticus: a multicenter randomized parallelâ€�group clinical trial. journal of veterinary internal medicine, 31(4): 1149–1158. doi: https://doi.org/10.1111/jvim.14734 charalambous, m., volk, h.a., tipold, a., erath, j., huenerfauth, e., gallucci, a., gandini, g., hasegawa, d., pancotto, t., rossmeisl, j.h., platt, s., de risio, l., coates, j.r., musteata, m., tirrito, f., cozzi, f., porcarelli, l., corlazzoli, d., cappello, r., vanhaesebrouck, a., broeckx, b.j.g., van ham, l. & bhatti, s.f.m. (2019). comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs: a multiâ€�center randomized parallel group clinical study. journal of veterinary internal medicine, 33(6): 2709–2717. doi: https://doi.org/10.1111/jvim.15627 cloyd, j.c., vezeau, c. & miller, k.w. (1980). availability of diazepam from plastic containers. american journal  of hospital pharmacy, 37(4): 492–496. doi: https://doi.org/10.1093/ajhp/37.4.492 dolder, l.k. (2003). metaldehyde toxicosis. veterinary medicine, march: 213–215. draper, w.e., bolfer, l., cottam, e., mcmichael, m. & schubert, t. (2013). methocarbamol cri for symptomatic treatment of pyrethroid intoxication: a report of three cases. journal of the american animal hospital association, 49(5): 325–328. doi: https://doi.org/10.5326/jaaha-ms-5835 firth, a. (1992). part 2: treatment of snail bait toxicity in dogs: retrospective study of 56 cases. journal of veterinary emergency and critical care,2(1): 31–36. doi: https://doi.org/10.1111/j.1476-4431.1992.tb00021.x frey, h.h., philippin, h.p. & scheuler, w. (1984). development of tolerance to the anticonvulsant effect of diazepam in dogs. european journal of pharmacology, 104(1–2): 27–38. doi: https://doi.org/10.1016/0014-2999(84)90365-0 jull, p., horton, c., volk, h.a. & de risio, l. (2011). effect of prolonged status epilepticus as a result of intoxication on epileptogenesis in a uk canine population. veterinary record, 169(14): 361. doi: http://dx.doi.org/10.1136/vr.d4750 lowrie, m. & garosi, l. (2016). classification of involuntary movements in dgs: tremors and twitches. the veterinary journal, 214: 109–116. doi: https://doi.org/10.1016/j.tvjl.2016.05.011 musulin, s.e., mariani, c.l. & papich, m.g. (2011). diazepam pharmacokinetics after nasal drop and atomized nasal administration in dogs. journal of veterinary pharmacology and therapeutics, 34(1): 17–24. doi: https://doi.org/10.1111/j.1365-2885.2010.01186.x nielsen, c. & pluhar, g.e. (2005). diagnosis and treatment of hind limb muscle strain injuries in 22 dogs. veterinary and comparative orthopaedics and traumatology, 18(4): 247–253. doi: https://doi.org/10.1055/s-0038-1632962    papich, m.g. & alcorn, j. (1996). absorption of diazepam after its rectal administration in dogs. american journal of veterinary research, 56: 1629–1636. plumb, d.c. (2008). plumb’s veterinary drug handbook. 6th ed.  iowa: blackwell publishing. podell, m. (1995). the use of diazepam per rectum at home for the acute management of cluster seizures in dogs. journal of veterinary internal medicine, 9(2): 68–74. doi: https://doi.org/10.1111/j.1939-1676.1995.tb03275.x van tulder, m.w., touray, t., furlan, a.d., solway, s., bouter, l.m. (2003). muscle relaxants for non-specific low-back pain. cochrane database of systematic reviews,doi: https://doi.org/10.1002/14651858.cd004252 yas-natan, e., segev, g. & aroch, i. (2007). clinical, neurological and clinicopathological signs, treatment and outcome of metaldehyde intoxication in 18 dogs. journal of small animal practice, 48(8): 438–443. doi: https://doi.org/10.1111/j.1748-5827.2007.00360.x zimmermann, r., steinberg, t.a., raith, k., hulsmeyer, v. & fischer, a. (2010). canine status epilepticus due to acute intoxication. tierärztliche praxis, 38(5): 285–294. doi: https://doi.org/10.1055/s-0038-1622862 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in dogs bitten by the european adder (vipera berus), do corticosteroids and supportive treatment improve clinical outcome compared to supportive treatment alone? a knowledge summary by hannah harjen bvetmed, mrcvs 1* 1department of companion animal clinical sciences, norwegian university of life sciences (nmbu), ullevålsveien 72, 0454 oslo, norway *corresponding author (hannah.harjen@nmbu.no) vol 3, issue 3 (2018) published: 08 aug 2018 reviewed by: nicola bates (bsc, msc, ma) and tiffany blackett (bsc (brunel), bsc (open), msc, ma) next review date: 08 aug 2020 doi: 10.18849/ve.v3i3.178 pico question in dogs bitten by the european adder (vipera berus), do corticosteroids and supportive treatment improve clinical outcome compared to supportive treatment alone? clinical bottom line there is currently insufficient strength of evidence to either support or reject the use of glucocorticoids in dogs bitten by the european adder (vipera berus) and further controlled trials are needed to fully answer this question. glucocorticoids may be indicated in cases of adverse reaction to antivenom treatment although there is not enough evidence to conclude whether there is a benefit to prophylactic administration prior to antivenom treatment. clinical scenario many dogs are bitten by the european adder (vipera berus) between april and october each year. treatment has often included administration of glucocorticoids and, in some countries, owners have traditionally carried glucocorticoid tablets to administer as an emergency treatment prior to seeking veterinary help (lund et al., 2013, turkovic et al., 2015). through their anti-inflammatory effects, glucocorticoids may reduce the pain and inflammation associated with snakebites in dogs as well as treating adverse reactions following antivenom administration (lund et al., 2013, armentano and schaer, 2011). potential disadvantages of glucocorticoid administration in these patients may include dose-dependent immunosuppression and increased catabolism (leisewitz et al., 2004). the potential for delay in seeking veterinary help when owners administer glucocorticoids as an emergency treatment is also a concern. a client comes into your practice and requests prednisolone tablets to administer to their dog in case of a bite by the european adder (vipera berus). you wish to know whether there is any evidence that giving glucocorticoids will improve clinical outcome in dogs bitten by the european adder, compared to supportive treatment alone. the evidence one double-blinded randomised placebo-controlled trial (brandeker et al., 2015) and two prospective case series (lervik et al., 2010, lund et al., 2013) were identified as relating to this question. the studies by lund et al. (2013) and lervik et al. (2010) had a relatively low sample size (n= 54 and n= 53, respectively). the largest sample size studied was 75 (brandeker et al., 2015). sample size was reduced by loss to follow-up in all three studies. two studies were identified (brandeker et al., 2015, lervik et al., 2010) as specifically considering the effect of glucocorticoids on outcome in dogs bitten by the european adder. no studies of time to recovery in relation to glucocorticoid treatment were found. the study by brandeker et al. (2015) was a double-blinded randomised controlled trial and thus ranks highly in term of evidence hierarchy. it does have some limitations which somewhat reduce its value and applicability to general first opinion practice. findings in the prospective case series by lervik et al. (2010) are in accordance with those of brandeker et al. (2015); however, the evidence is weaker due to study design. lund et al. (2013) focused on adverse effects of antivenom in a prospective case series. this study is not directly related to the pico question and is of lower evidentiary value but was accepted after full review, based on the inclusion of dogs treated with glucocorticoids. no studies found a beneficial effect of corticosteroid treatment in these patients apart from in one case of adverse reaction to antivenom (lund et al., 2013). no detrimental effect of corticosteroid administration was identified by the current evidence. two retrospective case series by turkovic et al. (2015) and sutton et al. (2011) provided the lowest ranking evidence considered. these were of limited use and provided statements relating to the use of glucocorticoids, which appeared to be based on conjecture, or findings relating to other snake species. these two studies are therefore not included in the evidence summary. summary of the evidence brandeker et al. (2015) population: dogs bitten by vipera berus between april 2011 and september 2012 and presenting to evidensia södra djursjukhuset or evidensia specialistdjursjukhuset strömsholm, within 24 hours of the bite. inclusion criteria: reported snake bite (observed snake bite, fang marks or a high suspicion of snake bite) and clinical signs typical of envenomation (local swelling and pain) exclusion criteria: pregnancy vaccination within last two weeks renal disease diabetes mellitus hyperadrenocorticism on-going treatment with glucocorticoids for pre-existing medical conditions treatment with non-steroidal anti-inflammatory drugs (nsaids) antivenom treatment sample size: n=75  (hospital one n= 51, hospital two n= 24) intervention details: two treatment groups: pred (n= 38) and placebo (n= 37) one subcutaneous injection of 1mg/kg prednisolone (pred) or 0.1ml/kg 0.9%nacl (placebo) at admission, following envenomation by the european adder supportive treatment: all dogs received iv fluids (type not specified) and opioid analgesics (methadone or buprenorphine – dose rates not specified) double blinded: the intervention treatment was administered by a technician study design: randomised controlled trial (double-blinded) outcome studied: data collected at three timepoints: day one = admission day two = 24h +/5h (hospital one) or 24h +/-12h (hospital two) day three = 10-28 days primary variables: mental status oedema: measured and then classified as absent, mild, moderate or severe secondary variables: appetite (subjective) vomiting diarrhea cardiac arrhythmia death blood analysis: c-reactive protein (crp), cardiac troponin i (ctni), haematology variables, prothrombin time (pt) main findings (relevant to pico question): no significant difference was found between pred and placebo groups in terms of: mental status extent of oedema appetite vomiting cardiac arrhythmia diarrhea duration of hospitalisation crp, prothrombin time, total leucocyte count statistically significant differences found between pred and placebo groups: higher monocyte count (within reference range) in pred group on day two higher ctni concentration (within normal reference range) in pred group on day one, no difference on day two limitations: the exclusion of dogs who were deemed to require antivenom after inclusion in the study is a potential source of bias. these dogs may have been more severely affected the randomisation method is not sufficiently described and hence it is unclear whether the study can truly be classified as a randomised controlled trial. a few of the outcome variables were recorded restrospectively, leading to questions of the blinding process variation in treatment following administration of prednisolone or placebo leading to a confounding effect of a non-standardised intervention protocol 21 dogs were lost to follow-up thus reducing the sample size. it is not specified which treatment group these originated from statistical analysis does not appear to account for confounders lack of standardisation of measurement of outcome parameters such as oedema and mental status, and multiple observers, leads to a lack of objectivity when comparing the two treatment groups presence or absence of cardiac arrhythmia not based on ecg and may therefore be under-estimated due to the referral setting, dogs with mild and only local signs may have been under-represented thus creating a bias towards more severely affected dogs wider range of time from bite to presentation in the prednisolone treated group (1-24 hours) versus the placebo group (0.5-11.5 hours) and non-standardised timing of steroid administration and data collection in relation to time of bite a sample size calculation is not described in the methods lervik et al. (2010) population: dogs bitten by vipera berus between april and august 2006 and presenting to södra djursjukhuset in stockholm or the university animal hospital in uppsala, within seven hours of the bite. inclusion criteria: strong suspicion of viper bite (bite witnessed or viper seen close to the dog) and/or clinical signs of a viper bite (lethargy, swelling) exclusion criteria: ongoing treatment with glucocorticoids for reasons other than the viper bite known history of liver disease sample size: n=53 ( from two hospitals – individual numbers not stated) intervention details: crystalloid fluid therapy (40-60ml/kg/hr to 40-60ml/kg/day): (n=53) colloid fluid therapy (5-20ml/kg/10min to 0.8ml/kg/day) : (n= 28) analgesics – buprenorphine, methadone or transdermal fentanyl (dose rates and routes not specified): (n= 36) antibiotics: (n=10) (drugs, dosage and route not specified) glucocorticoid treatment: no glucocorticoids: n=31 glucocorticoids prior to admission (owner of referring veterinary surgeon): n = 7 1-0.25mg/kg betamethasone per os, once (n= 5) 6mg/kg prednisolone injection (route not stated) (n= 1) 1mg/kg prednisolone per os, once (n=1) glucocorticoids on admission: n= 16 1-2 mg/kg prednisolone injection (route not specified), once (n=11) 0,2-2mg/kg prednisolone injection (route not specified) for 2-5 days (n= 2) 1-1.25mg/kg prednisolone per os, once (n=3) study design: prospective case series outcome studied: data collected at four timepoints: arrival (n=53) 24 hours (n=52) day 4-10 (n=46) day 9-23 (n=33) variables recorded: degree of swelling – mild, moderate or severe mental status – alert, slightly, moderately or severely depressed serum biochemistry (n=34): alanine aminotransferase (alt) alkaline phosphatase (alp) bile acids glutamate dehydrogenase (gldh) creatine kinase (ck) creatinine presence/absence of cardiac arrhythmia on auscultation ecg characterisation of arrhythmias detected on auscultation (n=5) main findings (relevant to pico question): no significant differences were found between the glucocorticoid treated group and non-glucocorticoid treated group in terms of: degree of swelling mental status day two alt was significantly higher than day one alt in the glucocorticoid treated group compared to the untreated group treatment with glucocorticoids did not have any clear positive or negative effect on clinical signs and mortality limitations: the distribution of cases between the two hospitals is not described and is therefore a source of potential bias due to possible differences in treatment and assessment of patients several observers and non-standardised measurement of subjective variables such as degree of oedema lead to a lack of objectivity when comparing the glucocorticoid-treated and untreated groups confounding effect of non-standardised treatment protocols is not accounted for 20 dogs lost to follow up and serum analysis not included for 19 dogs, thus decreasing the sample size different numbers of samples at the different timepoints; missing data oedema measurement not standardised in some cases (17%) – this outcomes was measured after steroid administration four dogs had known concurrent disease. a justification of the inclusion of these individuals is not provided. it is unclear why a dog with hyperadrenocorticism was included when dogs with pre-existing liver disease or receiving long-term steroids were excluded bias due to dogs receiving glucocorticoids being likely to have shown more severe clinical effects following the adder bite discussion states that no difference was found in recovery time between the two groups although this measurement is not clearly described or stated in materials & methods or results lack of statistical analysis; poor reporting of statistical analysis makes it difficult to fully assess the results variation in dosage and timing of steroid administration leading to a non-standardised intervention conclude that no positive or negative effect on mortality but no dogs died so difficult to conclude this sample size calculation is not provided lund et al. (2013) population: dogs presenting to private small animal clinics and the department of companion animal clinical sciences at the norwegian school of veterinary medicine in oslo between 2006 and 2009, with clinical signs consistent with vipera berus envenomation. inclusion criteria: snake or bite witnessed by the owner or wounds consistent with fang marks found by veterinary surgeon exclusion criteria: lack of clinical signs consistent with envenomation uncertainty with regards to whether clinical signs were caused by an adder bite sample size: n= 54 intervention details: administration of equine derived f (ab)’â‚‚ antivenom (1000mg) once: n=53 twice, four hours apart (2000mg total): n=1 supportive treatment: ivft, predominantly crystalloids (dose rate not specified): all dogs n= 54 antimicrobials (route and dose not specified): n= 51 amoxicillin or amoxicillin clavulanate (n = 39) enrofloxacin (n = 9) clindamycin (n = 3) corticosteroids: n= 21 prednisolone (0.5-4mg/kg po) administered by owner (n = 9) prednisolone (po, sc or iv, dose not specified) administered by veterinary surgeon (n = 7) dexamethasone (po, sc or iv, dose not specified) administered by veterinary surgeon (n = 6) hydrocortisone (po, sc or iv, dose not specified) administered by veterinary surgeon (n = 1) non-specified steroid (n =1) control group: dogs bitten by vipera berus but not administered antivenom study design: prospective case series outcome studied: data collected during two periods: period one: 2006-2007: questionnaire (parts 1-4) period two: 2008-2009: questionnaire (parts 1-4) and blood and urinalysis questionnaire: part 1: information from owner signalment date and time of bite snake or bite itself witnessed medical treatment administered prior to seeking veterinary attention part 2: information from veterinary surgeon (patient registry) time from bite to admission mental and physical status and clinical signs at admission location of bite presence of fang marks typical of adder bite type, dosage and effects of treatments administered part 3: antivenom treatment time from bite to antivenom treatment dose infusion rate pulse rate at five minute intervals resolution of clinical signs development of adverse effects (type, onset and duration) part 4: progression in mental and physical status and clinical signs 24 hours after admission and 1-2 weeks following admission (where available) blood and urinalysis: blood and urine samples collected at admission and 1-2 weeks following treatment (where possible) serum globulin and albumin urine protein main findings (relevant to pico question): non-self-limiting facial swelling secondary to antivenom administration responded to corticosteroid therapy in one dog two dogs developed adverse reactions to antivenom despite prior glucocorticoid treatment it was uncertain whether glucocorticoids prevented the development of adverse reactions in the remaining 20 dogs who received both glucocorticoids and antivenom limitations: many observers and non-standardised treatment protocols resulted in a number of confounders a control group is used only for blood and urinalysis and is not adequately described proportions of patients from referral versus first opinion practice are not documented, leading to a potential bias in severity of clinical symptoms and timing of treatments the intervention is not standardised: need for antivenom treatment was made subjectively by a number of different veterinary surgeons. dogs receiving antivenom may therefore have been more severely affected than the control group subjectivity of a number of the outcome variables and multiple observers results in a lack of objectivity and comparability of results response rate to questionnaires is not reported. it is possible that questionnaires at the university were more likely to be responded to as the investigator was on site to chase up. there is therefore a possible further bias towards those dogs presenting to the referral center and thereby potentially more severely affected lack of randomisation or matching of study and control groups appraisal, application and reflection evidence pertaining to this pico question is limited and of variable evidentiary value. the quality of evidence available is generally limited by bias due to non-standardised treatment and intervention protocols as well as potential bias towards more severely affected dogs and a reliance on measurement of subjective outcome variables. confounders such as the amount of venom per bite, non-homogenous venom in different adder populations, location of bite, body size of dog and time to presentation are present in all three studies and are difficult to control for in a clinical research setting. routine investigations are relatively insensitive for detecting cardiac arrhythmia and renal injury and, as such, these potential markers of clinical outcome are difficult to fully assess in these studies (palviainen et al., 2013, vestberg et al., 2017).these factors limit the conclusions that can be drawn from these studies regarding effects of glucocorticoids in envenomated patients. the study by brandeker et al. (2015) reports no difference in mental status, extent of oedema, appetite, vomiting and diarrhea, cardiac arrhythmias, c-reactive protein (crp), prothrombin time (pt), total leucocyte count or duration of hospitalisation between prednisolone and placebo-treated groups. these findings are relevant to answering this pico question since many of these parameters could influence clinical outcome. this study ranks highly in terms of evidence hierarchy. however, there are a number of limitations which do influence the quality of the evidence produced and its applicability in general small animal practice. the randomised and double-blinded status of this study is questioned by a lack of adequate description of the methods used and the fact that one of the outcome parameters was recorded retrospectively. there is a bias towards earlier treatment in the placebo group as demonstrated by a wider distribution of time from bite to presentation in the prednisolone-treated group compared to the placebo group. non-standardisation of the treatment protocol beyond the initial prednisolone or placebo injection and of treatment within the prednisolone-treated group also creates problems with comparability. dogs requiring antivenom were excluded. whilst this eliminates this confounding factor, another source of bias is created since the patients requiring antivenom may have been more severely affected. furthermore, information regarding the proportional group allocation of dogs excluded once they were deemed to require antivenom is not provided. many of the outcome parameters are subjective variables with multiple observers involved, again leading to objectivity problems when comparing the two groups. a sample size calculation is not described and statistical analysis does not appear to account for confounders. twenty-one dogs were lost to follow up and the exact proportions of cases lost to follow-up between the two groups is not described. milder cases may have been under-represented in this study and as such the applicability to first opinion practice is limited. lervik et al. (2010) also compared glucocorticoidtreated dogs to non-glucocorticoid treated dogs. this study can be considered of some use in answering this pico. findings of no significant difference in degree of oedema and mental status between glucocorticoid-treated and non-glucocorticoid treated untreated dogs are consistent with those of brandeker et al. (2015). this study does however suffer similar limitations to the study by brandeker et al. (2015), in addition to its lower ranking evidentiary status due to design. bias due to lack of randomisation, non-standardised intervention and treatments as well as the confounding effects of concurrent disease make comparisons difficult. sample size calculation is lacking and statistical analysis is poorly reported, thus hindering interpretation of significance. there is a greater bias towards most severely affected dogs in this study since the decision to administer glucocorticoids was based on the individual clinician’s opinion. the authors discuss the fact that no difference was found in mortality rates or time to recovery between the two groups. however, this should be interpreted with caution given the fact that these parameters are not defined in the materials and methods or reported in the results. the mortality rate of dogs bitten by the european adder is reported to be between 3% and 4.8% (sutton et al., 2011, kängström, 1989). it is therefore possible that the lack of observed difference found in this study is due to small sample size rather than lack of effect. the study by lund et al. (2013) is at first glance not related to the pico question. however, on more thorough review, it does provide some useful insights and thoughts to base further research on despite not being able to provide direct conclusive evidence specifically regarding glucocorticoid treatment and outcome. approximately 39% of dogs in this study received steroids; two dogs developed adverse reactions to antivenom despite prior treatment with steroids. corticosteroid administration was of benefit to one dog in this study during an adverse reaction to antivenom treatment but did not prevent adverse reaction to antivenom in two dogs. a further 19 dogs received corticosteroids in this study and did not suffer an adverse reaction to subsequent antivenom treatment. causation cannot be established but it does suggest that further studies regarding glucocorticoid use and adverse reactions following antivenom administration would be useful. this study also suffers a number of limitations including a lack of matching of the control group, subjective outcome measures and non-standardised treatments. confounding effects of antivenom treatment and time of glucocorticoid administration in relation to antivenom treatment are also present, which limit the study’s value. the studies by brandeker et al. (2015) and lervik et al. (2010) refer to the finding of a negative association between steroid  administration and survival in dogs bitten by vipera palaestinae (segev et al., 2004). whilst this finding is interesting, viper venom varies between species and individuals (malina et al., 2017, white, 2005) and findings from this study are subject to bias due to more severely affected dogs being more likely to be administered steroids. the study by segev et al. (2004) also fails to specify route of corticosteroid administration, dose rates and timing of administration in relation to bite. therefore, statements basing contraindications for steroid administration on the treatment of vipera berus envenomation, on this evidence, should be interpreted with caution.  controlled, randomised studies involving injecting venom in canine patients could help to answer this question more fully but are very unlikely to obtain ethical approval. in summary the main findings of this review are that extent of oedema, mental status and duration of hospitalisation are not significantly different in vipera berus envenomated dogs treated with glucocorticoids compared to dogs receiving supportive treatment alone. hence, there is currently no evidence that glucocorticoids improve clinical outcome in these patients. however, these findings are largely from one randomised controlled trial subject to some limitations and largely apply to dogs presenting with more severe symptoms. little evidence exists regarding the use of glucocorticoids in dogs with mild symptoms after envenomation. further studies are needed to fully answer the question of whether glucocorticoids should be indicated or not in these patients. whilst there is also currently no conclusive evidence to suggest that steroids are contraindicated in dogs bitten by the european adder, clinicians should consider that administration of glucocorticoids by an owner may delay them seeking veterinary help. given the suggestion by the current evidence that glucocorticoids are unlikely to have a large beneficial effect, and the possibility of consequent delays in seeking expert help, steroids cannot currently be recommended as an emergency treatment for owners to administer or as a necessary part of a clinical treatment protocol, other than possibly in cases of adverse reaction to antivenom. these findings are in accordance with the human literature. studies in humans have failed to demonstrate improvement in clinical outcome following glucocorticoid administration in snake-envenomated patients other than in cases of adverse reaction to antivenom (karlson-stiber et al., 2006, boels et al., 2012). glucocorticoid administration following vipera berus envenomation in humans is limited to cases of acute or delayed hypersensitivity to antivenom treatment. further high-quality evidence through randomised controlled trials with greater standardisation of treatment protocols would be helpful in answering this question fully. it would also be of use to study dogs presenting to first opinion practice. studies comparing time to presentation between dogs administered glucocorticoids by the owner and dogs who do not receive glucocorticoids at point of bite,  could also be helpful in building a more convincing body of evidence, for or against the use of glucocorticoids in this scenario. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform 1973 week 20 2018 web of science (clarivate analytics) 1945 2018 medline on ovid platform 1902 present scopus (elsevier) 1960 present search terms: dog* or cani* 'european adder' or 'european viper' or 'viper* berus' or adder treatment or steroid* or corticosteroid* or glucocorticoid* or glucocorticosteroid* or predni* or corticoid* 1 and 2 and 3  the same search terms were used for each database. related terms and synonyms were allowed. dates searches performed: 27.05.2018 exclusion / inclusion criteria exclusion: envenomation by snake species other than vipera berus non-english language. letters, book chapters, short communications. reviews of available treatments. inclusion: studies regarding the use of glucocorticoids in canine patients envenomated by vipera berus. search outcome database number of results excluded – non-english language publication excluded – did not meet pico question excluded – conference proceeding or letter excluded – book chapter excluded – duplicate excluded – after full review did not meet pico question total relevant papers cab abstracts 30 9 13 3 1 0 1 3 web of science 13 3 5 1 0 4 0 0 medline 15 2 7 1 0 4 0 0 scopus 3 0 1 0 0 2 0 0 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflicts of interest. references armentano, r. a. & schaer, m. 2011. overview and controversies in the medical management of pit viper envenomation in the dog. j vet emerg crit care (san antonio), 21, 461-70.available from: https://www.ncbi.nlm.nih.gov/pubmed/22316194 boels, d., hamel, j. f., bretaudeau deguigne, m. & harry, p. 2012. european viper envenomings: assessment of viperfav and other symptomatic treatments. clin toxicol (phila), 50, 189-96.available from: https://www.ncbi.nlm.nih.gov/pubmed/22372786 brandeker, e., hillstrom, a., hanas, s., hagman, r. & holst, b. s. 2015. the effect of a single dose of prednisolone in dogs envenomated by vipera berus--a randomized, double-blind, placebo-controlled clinical trial. bmc vet res, 11, 44.available from: https://www.ncbi.nlm.nih.gov/pubmed/25886633 karlson-stiber, c., salmonson, h. & persson, h. 2006. a nationwide study of vipera berus bites during one year-epidemiology and morbidity of 231 cases. clin toxicol (phila), 44, 25-30.available from: https://www.ncbi.nlm.nih.gov/pubmed/16496490 kängström, l. e. 1989. adder bite (vipera berus) in the dog and cat. svensk veterinartidning, 41, 38-46. leisewitz, a. l., blaylock, r. s., kettner, f., goodhead, a., goddard, a. & schoeman, j. p. 2004. the diagnosis and management of snakebite in dogs--a southern african perspective. j s afr vet assoc, 75, 7-13.available from: https://www.ncbi.nlm.nih.gov/pubmed/15214688 lervik, j. b., lilliehook, i. & frendin, j. h. 2010. clinical and biochemical changes in 53 swedish dogs bitten by the european adder--vipera berus. acta vet scand, 52, 26.available from: https://www.ncbi.nlm.nih.gov/pubmed/20416040 lund, h. s., kristiansen, v., eggertsdottir, a. v., skancke, e. & ranheim, b. 2013. adverse reactions to equine-derived f(ab')2 -antivenin in 54 dogs envenomated by vipera berus berus. j vet emerg crit care (san antonio), 23, 532-7.available from: https://www.ncbi.nlm.nih.gov/pubmed/24102941 malina, t., krecsak, l., westerstrom, a., szeman-nagy, g., gyemant, g., m, m. h., rowan, e. g., harvey, a. l., warrell, d. a., pal, b., rusznak, z. & vasas, g. 2017. individual variability of venom from the european adder (vipera berus berus) from one locality in eastern hungary. toxicon, 135, 59-70.available from: https://www.ncbi.nlm.nih.gov/pubmed/28602828 palviainen, m., raekallio, m., vainionpaa, m., lahtinen, h. & vainio, o. 2013. evaluation of renal impairment in dogs after envenomation by the common european adder (vipera berus berus). vet j, 198, 723-4.available from: https://www.ncbi.nlm.nih.gov/pubmed/24103867 segev, g., shipov, a., klement, e., harrus, s., kass, p. & aroch, i. 2004. vipera palaestinae envenomation in 327 dogs: a retrospective cohort study and analysis of risk factors for mortality. toxicon, 43, 691-9.available from: https://www.ncbi.nlm.nih.gov/pubmed/15109890 sutton, n. m., bates, n. & campbell, a. 2011. canine adder bites in the uk: a retrospective study of cases reported to the veterinary poisons information service. vet rec, 169, 607.available from: https://www.ncbi.nlm.nih.gov/pubmed/21868437 turkovic, v., teichmann, s. & dorfelt, r. 2015. european adder bites in dogs in southern germany. a retrospective study over a 6.5-year period. tierarztl prax ausg k kleintiere heimtiere, 43, 221-30.available from: https://www.ncbi.nlm.nih.gov/pubmed/26152480 vestberg, a. r., tidholm, a. & ljungvall, i. 2017. twenty-four-hour ambulatory electrocardiography characterization of heart rhythm in vipera berus-envenomed dogs. acta vet scand, 59, 28.available from: https://www.ncbi.nlm.nih.gov/pubmed/28468664 white, j. 2005. snake venoms and coagulopathy. toxicon, 45, 951-67.available from: https://www.ncbi.nlm.nih.gov/pubmed/15922768 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. are bisphosphonates a more effective treatment than intra-articular steroids in horses with distal hock osteoarthritis? a knowledge summary by hannah greene ma 1* 1washington state university college of veterinary medicine, bustad hall, pullman, wa 99163 *corresponding author (hannah.greene@wsu.edu) vol 5, issue 1 (2020) published: 11 mar 2020 reviewed by: janny de grauw (dvm, phd dip., ecvaa) and alastair kay (bvsc, ms, dipacvs, mrcvs) next review date: 21 may 2020 doi: 10.18849/ve.v5i1.235 pico question in horses that are lame due to osteoarthritis of the distal tarsal joints (bone spavin), is intra-articular medication with corticosteroids compared to systemic bisphosphonate treatment more effective in long-term lameness reduction?   clinical bottom line category of research question treatment the number and type of study designs reviewed three papers were critically reviewed. two were randomised controlled trials, and one was a retrospective study. strength of evidence weak outcomes reported there is insufficient evidence to support the use of systemic bisphosphonates over intra-articular corticosteroids to treat distal hock osteoarthritis in horses. conclusion horses with distal hock osteoarthritis should not be treated with systemic bisphosphonates until further blinded randomised controlled trials are completed. additionally, supportive evidence for the use of intra-articular corticosteroids as a treatment for degenerative hock osteoarthritis is limited to a retrospective study where modest, short-term improvements are reported: 58% of horses improved after an average of 56 days (labens et al., 2007). evidence does not support significant improvement in long-term outcomes: 50% of horses improved after 4 months (watts et al., 2016) and only 38% of horses improved after a mean follow-up period of 787 days (labens et al., 2007).   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.  the evidence labens et al. (2007) is a retrospective study that followed the outcomes of 51 horses treated with intra-articular (ia) corticosteroids for distal hock osteoarthritis (oa). the authors used lameness scores, radiographs and scintigraphy to assess the outcomes of treatment with ia corticosteroids in either the tarsometatarsal (tmt) or distal intertarsal (dit) joints. the authors concluded that after a single treatment with an ia corticosteroid, lameness improved in 34/59 (58%) of treated limbs at a median of 56 days post-treatment. at telephone follow-up a mean of 787 days after treatment, 38% of horses had a positive outcome: they were used as intended, had no detectable lameness according to the owner and were not receiving nonsteroidal anti-inflammatory drugs (nsaids). this study provides the strongest experimental design in absence of a randomised controlled trial among studies that examine ia corticosteroids as the sole treatment in chronic, degenerative oa. while the treatments were not uniform between cases, they do reflect the day-to-day clinical treatment of distal hock oa. this study reports a positive correlation between treatment with ia corticosteroids for distal hock oa and a modest, improved outcome. gough et al. (2010) is a randomised controlled trial that compared two treatment groups of horses with distal hock oa. the first group was treated with a 1 mg/kg tiludronate iv infusion and the second group was given an iv placebo infusion. the study used lameness scores, level of exercise and radiographs to assess outcomes at day 60. the authors concluded that the lameness scores for the tiludronate group were significantly lower than the placebo group at day 60 (p=0.0318). furthermore, they concluded that 60% of horses in the tiludronate group improved by 2 or more lameness scores at day 60. despite the type of experimental design (randomised controlled trial), there were significant limitations to the quality of the evidence such that a wholescale change to clinical practice is not recommended based on this trial alone. these limitations are further addressed in the appraisal section below. watts et al. (2016) is a randomised controlled trial of resveratrol supplementation and ia triamcinolone to treat distal hock oa. resveratrol is a compound with anti-inflammatory properties that is naturally found in grape skins. in this study the placebo group was treated with ia triamcinolone and a placebo powder (fermentation solubles, s. cerevisiae 1026, diatomaceous earth) 2 scoops fed every 12 hours. additionally both groups were treated with 2 g phenylbutazone iv immediately after ia injection and 2 g phenylbutazone po every 24 hours for the next 3-7 days. there was no control group (i.e. ia saline) to assess the efficacy of triamcinolone as a sole intervention, as the authors did not wish to withhold standard ia triamcinolone treatment from lame horses. to eliminate the majority of effects from ia triamcinolone, the authors chose to assess outcomes at 2 and 4 months post-treatment. at 2 months post-treatment, lameness was expected to recur in 90% of horses (labens et al., 2007) and at 3 months post-treatment 50% of horses were expected to be lame (de grauw et al., 2016). in effect, the authors assumed that treatment with ia triamcinolone alone will fail by either 2 or 4 months post-treatment and the outcome of resveratrol supplementation can be interpreted without ia triamcinolone treatment effects. the authors conclude that horses injected with ia triamcinolone and supplemented with resveratrol had better performance than horses injected with triamcinolone alone at 2 and 4 months post-treatment. while the efficacy of the resveratrol intervention is not the subject of this pico question, watts et al. (2016) found that 4 months after ia corticosteroid (triamcinolone) injection, only 35% of horses had returned to full work, confirming that long-term outcome of ia triamcinolone treatment is not favourable for distal tarsal oa. further study limitations are outlined in the appraisal section below. summary of the evidence labens et al. (2007) population: horses treated at the university of glasgow veterinary school for oa of the tmt and/or dit joint between 1998 and 2005 sex: 35 geldings, 15 mares, one stallion age: median = 9 years (range 4–18 years) breed: 28 thoroughbreds (tb), warmbloods (wb) or tb x wb crosses; 23 undisclosed breeds use: 29 general purpose, 10 showjumping, four dressage, two eventing, two hunting, four unknown use sample size: n=51 intervention details: case selection horses were identified by a database search of horses treated at weipers centre equine hospital, university of glasgow veterinary school. the study included horses treated for distal tarsal joint oa between 1998 and 2005. horses accepted into the study met each of the following conditions: analgesia of the tmt and/or dit joint reduced lameness by 50% or more based on the aaep 5 point lameness score there was radiographic evidence of tmt and/or dit joint oa the horses received an ia injection of methylprednisolone acetate (mpa) or triamcinolone acetonide (triamcinolone) with or without hyaluronic acid (ha) into the tmt and/or dit joint horses with bilateral hindlimb lameness (25/51 at first examination) were also included in the study if they met the following criteria: ia analgesia reduced lameness by 50% or more in one hindlimb there was increased uptake of a radiopharmaceutical by the dit and/or tmt joint in the other hindlimb on scintigraphic examination horses were split into two groups: group 1 = moderate or severe radiographic evidence of oa of dit and tmt joints group 2 = mild or no radiographic evidence of oa of dit and tmt joints   intervention dose: mpa median = 55 mg (range 20-120 mg) triamcinolone median = 9.8 mg (range 5–20 mg) first treatment: 49/51 horses (59 hindlimbs) were treated once with an ia corticosteroid specific joint treated not identified choice of ia corticosteroid was determined by the attending clinician’s preference: triamcinolone only in four hindlimbs triamcinolone with ha in 17 hindlimbs mpa only in 38 hindlimbs median interval between first treatment and second exam = 56 days (range 18-1436 days) median interval between the first and second treatment = 69 days second treatment: 14/51 horses were treated two or more times with an ia corticosteroid 12 of these horses (13 hindlimbs) were treated twice and re-examined by the same clinician mpa only in 12/13 hindlimbs triamcinolone with ha in 1/13 hindlimbs joints treated: dit and tmt 5/13 hindlimbs tmt only in 8/13 hindlimbs median interval between second treatment and re-examination = 50 days (range 25-194 days) study design: retrospective study outcome studied: subjective assessment: lameness scores difference between lameness scores at initial and follow-up examinations was calculated if the clinician was the same for both exams the horse was classified as ‘lame’ or ‘sound’ if two different clinicians performed initial and follow up examinations positive outcome = horse fulfilled intended use without the owner detecting lameness and without receiving oral nsaids negative outcome (excluded from analysis) = horse developed unrelated problems that prevented its return to exercise and/or horse received surgical treatment follow up information was obtained for 42/51 horses at a mean of 787 days after the last appointment (range 114–1942 days) lameness variables assessed at initial and follow-up exam based on aaep lameness score (0 = not lame, 5 = not weight bearing; including half-point scores) during initial exams lameness was assessed in the following conditions: walk and trot, straight line, hard surface walk and trot, right and left circles on the lunge, hard and soft surfaces during follow-up exams lameness was assessed only in the condition which exacerbated the lameness in the initial exam.   objective assessment: radiographic examination radiographs were available at time of inclusion and were not repeated after treatment standing dorsoplantar, dorsolateral-plantaromedial oblique, dorsomedial-plantarolateral oblique and lateromedial radiographs of all affected tarsi blinded assessment of radiographic signs of oa by first author signs included: irregular subchondral bone, subchondral bone sclerosis, narrowed joint, osteophytes, bony bridge formation, subchondral bone lysis and ankylosis each sign was graded as absent, mild, moderate or severe   objective assessment: scintigraphy 12/51 horses underwent scintigraphy (lateral and plantar views) only included horses with bilateral lameness six veterinary surgeons experienced in scintigraphic interpretation conducted a blind assessment of the images main findings (relevant to pico question): after a single treatment with mpa or triamcinolone (+/-ha) lameness improved in 34/59 (58%) of treated limbs. the median improvement was 0.75 grades (range 1.5–3 grades) on the 0–5 lameness scale (p<0.001) 15/59 (25.4%) of limbs were sound at the first re-examination 46/51 (90.2%) of horses remained lame at the second examination horses treated twice showed no improvement when assessed at a median of 50 days after the second treatment (p=0.141) none of the horses that improved by two or more grades of lameness had radiographic evidence of oa in the proximal intertarsal (pit) joint no significant differences observed between horses with varying degrees of radiographic severity no significant differences observed between effects of mpa and triamcinolone (p-value or raw numbers not provided) no significant differences observed between horses in which only the tmt joint or both the dit and tmt joint were treated at telephone follow-up (on average 787 days after the last exam): 38.2% of horses had a positive outcome (used as intended with no nsaids) the horses with a positive outcome tended to have moderate to severe oa more frequently than horses with a negative outcome 12/12 horses showed significant radiopharmaceutical uptake in the distal tarsal joints scintigraphy was available at time of inclusion and not repeated after treatment the horses with diffuse uptake showed significant improvement in their lameness score after one treatment (p=0.032). the horses with focal uptake did not show significant improvement there was no significant association between the type of uptake (i.e. focal or diffuse) and the outcome of treatment at telephone follow-up limitations: as a retrospective study, this study lacks a control group and cannot prove causation; i.e., differences between treatments cannot be causally linked to treatment alone, as disease status may have influenced treatment allocation to mpa or triamcinolone. further limitations include: lameness grading was subjective and not blinded the horses were from a wide age range (4–18 years) and effect between age and outcome was not calculated the intervention (mpa or triamcinolone +/-ha, and dose) was not uniform between groups no information on ancillary treatment/chondroprotective supplements etc. follow-up exams and treatments did not occur within a uniform date range and were not performed by the same observer the inclusion criteria for distal hock oa (positive response to ia analgesia) did not rule out other conditions such as psd and intertarsal ligament enthesopathy. these other differentials respond differently to treatment and scintigraphic examination insufficient power for radiographic and scintigraphic evidence. imaging was not conducted following treatment gough et al. (2010) population: horses in the uk and ireland with a clinical diagnosis of distal hock oa sex: 35 non-pregnant mares, 73 geldings (108 initially included) age: mean 11 years (range 5–20 years) use: pleasure horses, event horses, showjumpers or other sample size: n=108 initially included; only 87 met the final inclusion criteria intervention details: case selection horses with a clinical diagnosis of distal hock oa that met each of the following conditions: clinical signs of spontaneous lameness from 6 weeks–1 year in duration decreased level of performance according to owner a lameness score 3/10 or greater on the lamest limb after ia analgesia of tmt and/or dit joint of the least lame limb a 50% or greater improvement in lameness score after ia analgesia of tmt and/or dit joint of the lamest limb radiographic assessment that included signs of oa on one of four standard views of the lamest limb. horses were excluded from the study for any of the following reasons: less than 3 years of age pregnancy lameness less than 6 weeks duration or more than 1 year duration feed additives with chondroprotective substances given within 4 weeks of the study treated with nsaids or chondroprotective drugs (i.e. ha, chondroitin, glucosamine, polysulfated glycosaminoglycan) within 14 days prior to the study treated with corticosteroids within 60 days prior to the study treated with ia medications within 60 days prior to the study a history of two or more hock joint injections in the past year a change in pattern of shoeing within 4 weeks prior to the study underwent nuclear scintigraphy within 60 days prior to the study a lameness score of 2/10 or less after ia analgesia was administered to the least lame limb level of exercise was not significantly reduced (8/10 or greater) a less than 50% improvement in lameness score following ia analgesia of tmt and/or dit joint of the lamest limb no radiographic evidence of distal hock oa a possible diagnosis of psd confirmed by a high metatarsal 4 point block, local infusion or tibial block with ultrasonographic evaluation initially included horses were excluded for any of the following reasons (n=108 at initial inclusion, 21 horses excluded, n=87 at final inclusion): when concomitant disease interfered with the assessment of the efficacy of treatment any event occurred with potential influence on clinical outcome prescription of forbidden treatments horses were diagnosed with another orthopedic problem on day 60 that was not apparent on day 0 horses were split into two groups (n=87): group 1 = tiludronate group, 42 horses group 2 = placebo group, 45 horses imbalanced groups not addressed 40 horses needed in each group for 80% power to evidence an average of one lameness grade difference   intervention dose: group 1 = 1 mg/kg tiludronate diluted with normal saline to 1 litre by iv infusion over 30 minutes group 2 =1 mg/kg placebo powder diluted with normal saline to 1 litre by iv infusion over 30 minutes first treatment, day 0: treatments were determined by a biometrician-generated randomisation list horses were divided into blocks with four horses in each block. (“in each list, treatments were randomly allocated by blocks of four horses (two tiludronate treated and two placebo horses per block).” whether or not there was a group of three is unspecified.) double blinded: neither the owner nor the veterinarian knew if the infusion was the treatment or the placebo at day 0 all horses were given iv sedation before infusion (20 mcg/kg bwt detomidine hydrochloride or 40 mcg/kg bwt romifidine) second treatment, day 60: horses with an inadequate response at day 60 were given 1 mg/kg bwt tiludronate diluted with normal saline by iv infusion over 30 minutes day 60 treatments were not blinded so there was no placebo administered during the trial horses could receive the following treatments: hoof trimming or reshoeing. the type of shoe could not be altered horses with lameness were treated with nsaids if deemed necessary (e.g. phenylbutazone or flunixin). horses with a concomitant disease such as colic or trauma were also treated with nsaids (e.g. phenylbutazone, flunixin meglumine), butylscopolamine or metamizole but not anti-microbials in each case there had to be 15 days between treatment and the next control visit feed additives. horses who had been receiving chondroprotective feed additives in the four weeks prior to the study continued to receive these additives at the same dose throughout the studyno other treatments were allowed study design: randomised controlled trial outcome studied: subjective assessment: lameness scores lameness was assessed on a 10 point scale based on clinician observation. not specified if same or different clinician lameness was assessed on a straight line on hard ground lameness was monitored at days 0, 60 and 120 on days 60 and 120 critical lameness scores were obtained: lameness was assessed on the most lame limb after the least lame hock was given ia analgesia   subjective assessment: level of exercise exercise was graded on a 10 point scale exercise grading scores were specific to the horse’s discipline (e.g. racing, trotters, showjumpers and eventers, dressage, pleasure and endurance)   objective assessment: radiographs radiographic findings were compared between the treatment and control group. radiographic findings were not graded by severity of disease findings noted included: thickening of subchondral bone, subchondral bone lysis, subchondral bone sclerosis, narrowing or loss of joint space, periarticular osteophytes, periosteal new bone main findings (relevant to pico question): the lameness scores for the tiludronate group were significantly lower than the placebo group at day 60 (p=0.0318) tiludronate group lameness score group mean 2.6/10 (s.d. 1.7) placebo group lameness score group mean 3.3/10 (s.d. 2.0) approximately 60% of horses in the tiludronate group improved by 2 or more lameness scores at day 60 (distribution not provided) the number of horses in the placebo group that improved by 2 or more lameness scores is not provided lameness grading varied significantly between investigators (covariate investigator effect p=0.0395) horses with a higher lameness score at day 0 had a higher lameness score at day 60 (covariate baseline effect p=0.0007) in horses with periarticular osteophytes there was a significant improvement in lameness scores in the tiludronate group as compared to the placebo group (p=0.006). number of horses with periarticular osteophytes or subchondral bone thickening not given limitations: the 60 day outcome of the placebo group is not provided from day 60, the study was no longer blinded the study was funded by the makers of tildrenò (ceva) as part of the regulatory licensing trial. two authors work for ceva and the third author was paid by ceva for his clinical expertise. because the study was not double blinded past day 60, this could introduce bias the study relies on the investigator’s clinical experience to eliminate horses with psd. it was also assumed that the majority of horses with psd would not have a greater than 50% positive response to tmt ia analgesia within 10 minutes (dyson and romero, 1993 and dyson, 1994) outcomes were assessed with subjective lameness grading that varied significantly between investigators there was a significant interaction between investigator (p=0.0083) and treatment (p=0.0223) in the exercise results. the authors suggest this was due to differences in at home exercise protocols between investigators, but other biases could be responsible. as a result, improvement in exercise scores could not be associated with treatment the statistical results on lameness did not include a p-value for a possible interaction between treatment and investigator. including this p-value would provide more evidence that the treatment effect on lameness was not due to differences in investigator there was a significant difference in bodyweight between the two groups. the placebo group had a mean weight of 568 kg, while the tiludronate group had a mean weight of 521 kg (p=0.01). differences in bodyweight are difficult to interpret without breed information and likely clinically irrelevant results were only presented in percentages, means, standard deviations and p-values. frequencies (e.g. 5/9 horses) were not supplied the radiographic evidence exclusion criteria was based on investigator’s clinical experience alone and did not include a standardised, objective grading scale of radiographic lesions the paper does not address potential side effects of tiludronate. the authors do not specify that adverse events were monitored or reported watts et al. (2016) population: horses in the southern us with hindlimb lameness or poor performance sex: 12 non-pregnant mares, 28 geldings, one stallion breed: 10 warmbloods, 21 quarter horses or paints, nine thoroughbreds, one arabian mean age: 12.4 (+/6.5) in treatment group; 10.7 +/6.0 in placebo group use: dressage (8), eventing (7), jumping (5), western performance (11), pleasure or trail riding (3) and western show (7). use not-specified for four horses lost to follow up. sample size: n=45 intervention details: case selection horses with a hindlimb lameness or poor performance that met each of the following conditions: ≥ 3 years old primary hindlimb lameness localised to distal tarsal joints with diagnostic anesthesia horses were excluded for any of the following reasons: treated with ia medication in any tarsal joint in the previous 6 months treated with nsaids in the previous 7 days pregnant lameness > 4/5 required additional lameness treatments (e.g. shoeing changes, other ia injections) horses were split into two groups (n=45): 20 horses needed in each group to detect an improvement from 50% (placebo group) to 90% (resveratrol group) with 80% power and a=0.05 5% predicted loss 45 horses enrolled group 1 = resveratrol group, 23 horses group 2 = placebo group, 22 horses   intervention group 1 = 1,000 mg microencapsulated resveratrol in powder (70% resveratrol, 30% microencapsulant, fermentation solubles, saccharomyces cerevisiae 1026, diatomaceous earth) two scoops fed every 12 hours group 2 = placebo powder (fermentation solubles, cerevisiae 1026, diatomaceous earth) 2 scoops fed every 12 hours all enrolled horses received 4.5 mg of triamcinolone acetonide in each of the centrodistal and tmt joint of both hindlimbs four horses also received 62.5 mg of amikacin in each joint (this was a single clinician’s preference, it was not specified in which group these horses were enrolled) ia injection confirmed by either 1) joint fluid in needle hub or 2) radiography or fluoroscopy to confirm needle placement all horses were treated with 2 g phenylbutazone iv after ia injections owners instructed to give 2 g phenylbutazone po q 24 h for 3–­7 days and return to full work in 3–7 days depending on clinician instructions. diet, turnout and exercise programs maintained as before study enrollment owners recorded medications or supplements added or stopped during treatment period study design: randomised controlled trial outcome studied: subjective assessment: lameness scores lameness was assessed on a 5 point scale based on clinician observation. lameness was also noted to be unilateral or bilateral lameness was assessed on a 40 m straight line and in a 20 m half circle on hard ground in both directions lameness was monitored at enrollment and 4 months post-enrollment diagnostic anesthesia was only performed at enrollment   subjective assessment: level of exercise owner questionnaire at 2 and 4 months clinician asked owner or rider about horse’s perceived performance   objective assessment: inertial sensor system parameters measured were pelvic asymmetry (maxdiff and mindiff) and vertical pelvic movement vs. expected pelvic movement (a1:a2 ratio) main findings (relevant to pico question): two horses in each group (four total) lost to follow-up at 2 months; 41 horses analysed 2 months after enrollment, the percentage of horses whose performance was better, compared with worse or the same, was significantly (p=0.04) higher for the resveratrol group (20/21 [95%]) than for the placebo group (14/20 [70%]) 4 months after enrollment, the percentage of horses whose performance was better, compared with worse or the same, was still significantly (p=0.02) higher for the resveratrol group (18/21 [86%]) than for the placebo group (10/20 [50%]). 2 months after enrollment 70% (14/20) of riders reported that the horse’s performance was better in the ia triamcinolone only group compared to baseline 4 months after enrollment 50% (10/20) of horses improved in the ia triamcinolone only group compared to baseline 4 months after treatment, 35% of horses had returned to full work in placebo group 2 (vs 38% of horses in treatment group 1; not significant) limitations: many key performance indicators in the rider questionnaire were not significantly different between groups. these included: whether the horse had returned to full work (yes vs no), whether signs of lameness were present (yes vs no), performance compared with expectations (at/above vs below) and whether the owner/rider was satisfied with how the horse was doing (yes vs no) there was no difference in pelvic asymmetry from inertia sensor between the two groups confidence intervals were not provided to substantiate changes in a1:a2 ratio (only scatterplots and p-values given) other differentials for distal tarsal lameness (e.g. proximal suspensory desmopathy) were not excluded radiographic evidence was not considered appraisal, application and reflection labens et al. (2007) provides the strongest experimental design in support of ia corticosteroids as the sole treatment in chronic, degenerative oa. there is no randomised controlled trial to support the use of ia corticosteroids as a treatment for degenerative hock oa. this study reports a positive correlation between treatment with ia corticosteroids for distal hock oa and a modest, improved outcome. the limitations of the study include non-uniform treatments (doses, site of injection and choice of corticosteroid varied), non-uniform time to follow-up, and non-uniform time between subsequent exams and treatments. another weakness was that the cases studied did not conclusively rule out other disease processes that would not respond to ia corticosteroid treatment (e.g. proximal suspensory desmitis and intertarsal ligament enthesopathy). one strength of this study is that it uses a moderately large sample size (n=51). more importantly, it provides the strongest experimental design in absence of a randomised controlled trial among studies that examine ia corticosteroids as the sole treatment in chronic, degenerative oa. while the treatments were not uniform between cases, they do reflect the day-to-day clinical treatment of distal hock oa. the modest therapeutic success in this study indicates that clinicians can expect about half of horses to have a positive outcome 2 months after treatment, but only 34/59 (58%) of horses to have a long-term positive outcome. these outcomes are restricted to ia corticosteroid treatment as a sole intervention and do not consider other treatments for distal hock oa. gough et al. (2010) is a randomised controlled trial that evaluated efficacy of tiludronate as a treatment for distal hock oa. the authors concluded that the lameness scores for the tiludronate group were significantly lower than the placebo group at day 60 (p=0.0318). furthermore, they concluded that 60% of horses in the tiludronate group improved by 2 or more lameness scores at day 60. finally, the authors report that for the subset of horses with periarticular osteophytes in both groups, lameness scores were lower in the tiludronate group as compared to the placebo group (p=0.006). there are a number of limitations associated with this study, the main ones are highlighted here. first, the distribution of lameness scores for both the placebo group and the treatment group was not reported. second, the study became unblinded at/after day 60. the study was also funded by the makers of tildrenò (tiludronate disodium). while this funding source was clearly disclosed, it may have introduced bias. third, lameness grading varied significantly between investigators (covariate investigator effect p=0.0395), which may have impacted outcome assessment. there was also a significant effect of investigator (p=0.0083) and an interaction between investigator and treatment (p=0.0223) in the exercise results. this suggests that differences in at home exercise protocols were significant between investigators and centres. as a result, improvement in exercise scores could not be utilised as a treatment outcome as this was more likely to be associated with investigator rather than treatment. a final limitation is that this study does not address potential side effects of tiludronate. despite the type of experimental design (randomised controlled trial), there were significant limitations to the quality of the evidence such that a wholescale change to clinical practice is not recommended based on this trial alone. watts et al. (2016) is a randomised controlled trial of resveratrol supplementation and ia triamcinolone to treat distal hock oa. the authors conclude that horses injected with ia triamcinolone and supplemented with resveratrol had better performance than horses injected with triamcinolone alone at 2 and 4 months post-treatment. better performance was indicated subjectively by owner reported performance improvement and objectively by vertical pelvic movement measured by inertial sensor system (the a1:a2 ratio is calculated for each hindlimb and compares the horse’s actual vertical pelvic movement with an expected vertical pelvic movement). yet certain key performance indicators did not vary between the treatment and placebo groups: subjective lameness scores by a clinician, pelvic asymmetry from inertial sensor, and the owner/rider’s perception that the horse had returned to full work. while the efficacy of the resveratrol intervention is not the subject of this pico question, watts et al. (2016) found that 4 months after ia corticosteroid (triamcinolone) injection, only 35% of horses had returned to full work, confirming that long-term outcome of ia triamcinolone treatment is not favourable for distal tarsal oa. evaluating the comparative efficacy of treatments for distal hock oa comes with many challenges. one challenge is that to date, there is no published randomised controlled trial to directly compare the efficacy of ia corticosteroids with systemic bisphosphonates. the strongest evidence for either treatment comes from randomised controlled trials where each intervention is examined separately. watts et al. (2016) is a randomised controlled trial of resveratrol supplementation and ia triamcinolone to treat distal hock oa. while the efficacy of the resveratrol intervention is not the subject of this pico question, watts et al. (2016) does provide evidence that long-term outcome of ia triamcinolone treatment for distal tarsal oa is suboptimal: at 2 months post ia triamcinolone treatment, 70% (14/20) horses' performance improved while at 4 months post ia triamcinolone treatment, only 50% (10/20) of horses’ performance improved. de grauw et al. (2016) conducted another randomised controlled trial that compared efficacy of ia triamcinolone with ia triamcinolone + hyaluronate acid (ha). it was excluded from this knowledge summary because oa was not confirmed radiographically and no tarsal joints were included in the study; therefore, conclusions about the intervention relative to tarsal oa cannot be drawn. but this study does shed light on ia triamcinolone efficacy at various intervals post-treatment. at 3 weeks post-treatment, 88% of patients treated with ia triamcinolone had improved by 2 lameness grades. at 3 months post-treatment, owners reported only 50% of horses were back in full work, which is very similar to the proportion found by watts et al. (2016). again, there was no placebo control group due to ethical implications of withholding treatments from lame horses. de grauw et al. (2016) also note that the 3 week improvement in lameness may in part have been due to the resting protocol they implemented. another prospective case series, although investigating the outcomes of a different treatment (ia ethanol injection) in cases of distal tarsal joint oa (lamas et al., 2012), is also relevant to the pico question at hand, given the study’s population and inclusion criteria: of the 24 horses included, all horses had lameness recur within 4 months of receiving ia corticosteroids (triamcinolone or mpa) in the tmt joint (lamas et al., 2012). this suggests that failure of ia corticosteroids for long-term management of distal tarsal oa is certainly not uncommon. while ia corticosteroids are commonly used in everyday practice, prospective, randomised controlled trials with adequate power are necessary to assess their efficacy in treating distal hock oa. while it may not be ethically feasible to include a control group treated with ia saline in these studies, a non-treated group with controlled exercise should be included at a minimum. additionally, placement of ia treatments should be confirmed radiographically as injection into distal tarsal joints — especially the dit joint — is not always accurate (seabaugh et al., 2017 and hoaglund et al., 2019). additional blinded randomised controlled trials are needed to assess efficacy of bisphosphonate treatment for distal hock oa, as various shortcomings for gough et al. (2010) were noted above. regardless of the intervention studied, a combination of subjective and objective outcomes should be assessed. these may include (blinded) lameness scores, rider reported performance improvement, and ideally some form of quantitative motion analysis (e.g. vertical pelvic movement from inertial motion unit sensor systems). methodology section search strategy databases searched and dates covered: cab abstracts on the ovid platform 1973 to 2018 week 19 pubmed accessed via the ncbi website 1910 to may 2018 search strategy: cab abstracts (equine* or horse* or equus or equid* or mare or mares or broodmare* or 'brood mare*' or pony or ponies or filly or fillies or colt or colts or yearling* or stallion* or thoroughbred* or standardbred* or racehorse* or 'race horse*').mp. or (exp horses/ or exp equus/ or exp equidae/ or exp mares/ or exp colts/ or exp foals/ or exp stallions/ or exp thoroughbred/ or exp racehorses/) and (arthropat* or arthrit* or osteoarthrit* or osteo-arthrit* or synovitis or tenosynovitis or 'joint disease*' or oa or djd or osteoarthrosis or lame or lameness or spavin or gait).mp. or (exp osteoarthritis/ or exp arthritis/ or exp joint diseases/) and (tarsal* or tarsus* or carpus* or carpal*).mp. or exp tarsus/ or exp carpus/ and ((corticosteroid* or glucocorticoid* or corticoid* or dexamethason* or methylprednisolon* or triamcinolon* or tmc or betamethason* or prednisolon* or prednison* or prednicare* or steroid*).mp. or (exp prednisolone/ or exp prednisone/ or exp glucocorticoids/ or exp steroids/) or (bisphosphonat* or biphosphonat* or bisphosponat* or biphosponat* or disphosponat* or diphosphonat* or diphosponat* or disphosphonat* or tiludron* or clodron*))   pubmed (horse or equine or equus or equidae or equid or mare or broodmare or “brood mare” or pony or filly or colt or yearling or stallion or thoroughbred or standardbred or racehorse or “race horse”) and (arthropathy or arthritis or osteoarthritis or osteo-arthritis or synovitis or tenosynovitis or “joint disease” or oa or djd or osteoarthrosis or lame or lameness or spavin or gait) and (tarsal or tarsus or carpal or carpus) and ((corticosteroid or glucocorticoid or corticoid or dexamethasone or methylprednisolone or triamcinolone or tmc or betamethasone or prednisolone or prednisone or prednicare or steroid) or (bisphosphonate or biphosphonate or bisphosphonate or biphosponate or disphosponate or diphosphonate or diphosponate or disphosphonate or tiludronate or tiludronic or clodronate or clodronic)) dates searches performed: 21 may 2018 exclusion / inclusion criteria exclusion: papers that did not answer the pico question were excluded for the following reasons: the therapeutic intervention was not a corticosteroid or a bisphosphonate (e.g. gold, resveratrol, nsaids, surgery, ethanol, polysulfated glycosaminoglycans, hyaluronic acid, dimethyl sulphoxide), or the therapeutic interventions were not administered according to the pico requirements (i.e. corticosteroids were not given intra-articularly or bisphosphonates were not given systemically), or the study was based on a non-osteoarthritic disease (e.g. osteochondrosis, infection, hemoarthrosis, tarsal sheath effusion, stringhalt), or a non-equine model was used. also excluded were non-english language, non-systematic review articles, case reports, conference proceedings or duplicates inclusion: either ia corticosteroids or systemic bisphosphonates were studied in horses with distal tarsal joint lameness due to oa search outcome database number of results excluded – did not answer pico question excluded – conference proceedings, case report or non-systematic review articles total relevant papers cab abstracts 81 55 23 3 pubmed 36 32 1 3 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflicts of interest. the author would like to thank dr. suzanne fricke for introducing evidence based veterinary medicine into the curriculum at washington state university college of veterinary medicine and encouraging students to utilise this methodology. references dyson, s. & romero, j. (1993). an investigation of injection techniques for local analgesia of the equine distal tarsus and proximal metatarsus. equine veterinary journal. 25(1), 30–35. doi: http://dx.doi.org/1111/j.2042-3306.1993.tb02897.x dyson, s. (1994). proximal suspensory desmitis in the hindlimb: 42 cases. british veterinary journal. 150(3), 279–291. doi: http://dx.doi.org/1016/s0007-1935(05)80008-9 de grauw, j., visser-meijer, m., lashley, f., meeus, p. and van weeren, p. (2016). intra-articular treatment with triamcinolone compared with triamcinolone with hyaluronate: a randomized open-label multicenter clinical trial in 80 lame horses. equine veterinary journal. 48(2016), 152–158. doi:http://dx.doi.org/10.1111/evj.12383 gough, m., thibaud, d. and smith, r. (2010). tiludronate infusion in the treatment of bone spavin: a double blind placebo-controlled trial. equine veterinary journal. 42(5), 381–387. doi: http://dx.doi.org/10.1111/j.2042-3306.2010.00120.x hoaglund, e., selberg, k., seabaugh, k., hess, a. and bass, l. (2019). comparing the clinical success rate of the dorsolateral approach to the medial approach for injection of the centrodistal joint in the horse. equine veterinary journal. electronic version march 10, 2019. doi: http://dx.doi.org/10.1111/evj.13095 labens, r., mellor, d. & vouì‚te, l. (2007). retrospective study of the effect of intra-articular treatment of osteoarthritis of the distal tarsal joints in 51 horses. veterinary record. 161(18), 611–616. doi: http://dx.doi.org/1136/vr.161.18.611 lamas, l., edmonds, j., hodge, w., zamora-vera, l., burford, j., coomer, r. & munroe, g. (2012). use of ethanol in the treatment of distal tarsal joint osteoarthritis: 24 cases. equine veterinary journal. 44(4), 399–403. doi: http://dx.doi.org/10.1111/j.2042-3306.2011.00512.x seabaugh, k., selberg, k., mueller, p., eggleston, r., peroni, j., claunch, k., markwell, j. & baxter, g. (2017). clinical study evaluating the accuracy of injecting the distal tarsal joints in the horse. equine veterinary journal. 49(5), 668–672. doi: http://dx.doi.org/10.1111/evj.12667 watts, a., dabareiner, r., marsh, c., carter, g. & cummings, k. (2016). a randomized, controlled trial of the effects of resveratrol administration in performance horses with lameness localized to the distal tarsal joints. journal of the american veterinary medical association. 249(6) 650–659. doi: http:dx.doi.org/10.2460/javma.249.6.650 acknowledgement rcvs knowledge was supported in producing this knowledge summary by an educational grant from petplan charitable trust. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. use of intravenous lipid emulsion in dogs with suspected tremorgenic mycotoxicosis: 53 cases foteini kormpou dvm, pgcert(cvp) mrcvs1* aoife o’sullivan mvb certavp(ecc) mrcvs2 laura troth bvmedsci bvm bvs mrcvs2 sophie adamantos bvsc certva dacvecc dipecvecc mrcvs fhea1 1langford vets, university of bristol, langford, bs405du 2vets now, penguin house, dunfermline, ky11 8sg *corresponding author (fwteini2008@hotmail.com) vol 3, issue 2 (2018) published: 24 may 2018 reviewed by: tiffany blackett (bvetmed mrcvs) and nicola bates (bsc (brunel), bsc (open), msc, ma, srcs) doi: 10.18849/ve.v3i2.166 section index:    abstract | introduction | results | discussion | methods | conflict of interest | references | supplementary files abstract objective: the purpose of this study is to report the use of intravenous lipid emulsion (ile) in dogs presenting with suspected tremorgenic mycotoxicosis based on signs of intoxication and known ingestion of mouldy food or compost. background: ile is being used for toxicoses associated with fat soluble agents. as tremorgenic mycotoxins are lipophilic in nature, the use of ile may be of benefit in these patients.  methods: medical records of all dogs examined at any vets now clinic between november 2012 and november 2016, in which ile had been used, were reviewed and 53 cases were included in the study. results: in 96% of cases there was clinical improvement recorded post ile administration within a median time of 4 hours. no adverse effects were seen during the infusion or up to the time of discharge. conclusion: the administration of ile seems to be associated with a beneficial effect in the short term in dogs. prospective evaluation of this therapy is warranted to further evaluate the use of ile in these cases. introduction tremorgenic mycotoxicosis is a common intoxication in dogs, due to their indiscriminate eating habits. a presumptive diagnosis is made in most cases based upon history and clinical findings. known ingestion of, or possible access to, mouldy food, garbage, or compost is highly suggestive (barker et al., 2013). signs usually occur within 30 minutes of ingestion, although rarely, can be delayed for several hours (talcott, 2013). the most common signs of tremorgenic mycotoxin exposure reported to the veterinary poisons information service (vpis) include ataxia, tremors, restlessness, hyperaesthesia, tachycardia and vomiting. in severe cases opisthotonus, seizures and coma can be seen. signs can sometimes progress to hyperthermia, exhaustion, rhabdomyolysis, dehydration and hypoglycaemia. clinical signs usually resolve gradually within 24-96 hours. approximately 20 mycotoxins have been identified as tremorgens. those most frequently reported to affect dogs are penitrem a and roquefortine c, which are produced by penicillium spp (eriksen et al., 2010). after ingestion, the tremorgenic mycotoxins present in contaminated food are thought to cross the blood-brain barrier due to lipophilic properties (schell, 2000). multiple mechanisms of action have been suggested for tremorgenic mycotoxins. rats injected with penitrem a show marked increases in the release of gamma-aminobutyric acid gaba, glutamate, and aspartate at cerebrocortical synapses (norris et al., 1980). a similar interference with neurotransmission within the cerebellum is thought to be the reason behind the characteristic tremor in dogs (eriksen et al., 2010);however, it is generallybelieved that the mechanism of action differs for each toxin involved in the exposure. further researchis warranted to identify specific mechanisms of action. treatment is symptomatic and supportive and usually involves gastrointestinal decontamination, management of neurological signs with muscle relaxants,anti-seizure drugs and management for hyperthermia as required. due to the rapid absorption of mycotoxins and rapid onset of clinical signs, the window of opportunity to safely induce emesis is generally limited (boysen et al., 2002; crandell, 2006).therefore, once clinical signs are appropriately controlled, gastric lavage should be considered in these cases. activated charcoal with or without a cathartic may then be instilled through the gastric tube before it is removed to reduce toxin exposure. there is evidence that the common mycotoxins are excreted in bile, suggesting the likelihood of hepatic recirculation (puschner et al., 2009) and the need for repeated doses of activated charcoal over 2 to 3 days. ile was initially used to treat local anaesthetic overdoses in people. in recent years, reports of the use of ile in veterinary medicine has increased (fernandez et al., 2011; epstein et al., 2013; bates et al., 2013) and is advocated by the vpis and the animal poison control center (apcc) for toxicoses associated with fatsoluble agents. the exact mechanism of action for ile has yet to be determined. the “lipid sink” theory has been proposed as a possible mechanism as well as direct cardiovascular effects (fettiplace et al., 2015; rothschild l et al. 2010). during infusion of ile, a lipid phase in the aqueous portion of the blood is created, acting as a sink for lipophilic drugs, preferentially pulling them out, or keeping them out, of the tissues (fettiplace et al., 2015). its direct cardiovascular effect involves providing a source of energy to the myocardial cells. the use of ile for the treatment of lipophilic drug toxicity is increasing. french et al., 2001, suggested that lipid soluble toxicants with a partition coefficient (logp) greater than 1 or 2 and a high volume of distribution (vd) will respond better to ile therapy. however, ile’s efficacy in non-local anaesthetic toxicity appears to be heterogenous and the quality of evidence to support its use in these cases remains low (levine et al., 2016). the authors are aware of anecdotal reports of itsuse in mycotoxicosis, however, there is only one published case report of the use of ile in dogs with tremorgenic mycotoxin intoxication (parratt, 2014). in this report, although the dog improved with lipid, it was not sufficient to withdraw additional treatment. roquefortine was confirmed in vomitus in this case. the purpose of this study is to report the use of ile in dogs presenting with suspected tremorgenic mycotoxicosis, based on signs of intoxication and known ingestion of mouldy food or compost; with the hypotheses that, as tremorgenic mycotoxins are lipophilic in nature(puschner, 2009), the use of ile may be beneficial in these patients. results fifty-three dogs met the criteria for inclusion in the study. dogs were a median of 3.8 years old (range 0.5-13). there were 28 males and 26 females. common breeds represented included labrador retrievers (n = 7) and beagles (7). nineteen other breeds were represented by less than 4 dogs each. there were 7 mixed-breed dogs.  historical complaints and clinical abnormalities at the time of presentation included tremors (n=48), ataxia (n=17), vomiting (n=15), hyperthermia (n=15), seizures (n=13), hyperaesthesia (n=8), tachycardia (n=7), diarrhoea (n=4), collapse (n=2), abdominal pain (n=1). all dogs were presented primarily for neurological signs.  duration of signs prior to presentation was not consistently recorded in the medical records, but for the 25/53 cases that the duration had been recorded it was a median of 2 hours (range 16 minutes to 8 hours). treatment varied between individuals. ile was used for all the cases included in this study, but never as the sole agent. the exact dose and rate of ile administered was recorded in 46 dogs (87%). in 34/46 (73%) cases an intravenous bolus of 1.5ml/kg of a 20% solution of intralipid followed by 0.25-0.5 ml/kg/min constant rate infusion for 30-60 minutes was administered. the remaining 12 cases had a variety of doses with 7 treated with a bolus followed by infusion, 3 treated with a bolus only and 2 treated with an infusion only. seven cases (15%) had one repeated dose and four (9%) had two repeated doses. the repeated doses ranged from 0.25ml/kg to 1.5 ml/kg and were always the same as the initial bolus dose that was administered in each case. benzodiazepines (diazepam or midazolam) were administered in 38/53  (71%) cases, intravenous fluid therapy in 31/53 (58%) cases, methocarbamol in 22/53 (42%) cases, activated charcoal in 21/53 (40%) cases, phenobarbital in 10/53 (19%) cases, propofol in 10/53 (19%) cases, maropitant in 5/53 (9%) cases, medetomidine in 5/53 (9%) cases, apomorphine in 4/53 (8%) cases, opioids in 4/53 (8%) cases, glucose in 2/53 (4%) cases, mannitol in 1/53 (2%) case and co-amoxiclav in 1/53 (2%) case. the timing that ile was given in relation to the timing of other drugs or intravenous fluid therapy ranged and was not consistently recorded. in most cases where diazepam was used, this was the first drug to be administered. however, it appeared that diazepam alone was never sufficient to control the signs and, as a result, administration of additional drugs was deemed necessary. this agrees with previous reports suggesting that diazepam alone is not usually effective in mycotoxicosis cases (boysen et al., 2002; young et al., 2003). hospitalisation time at the clinic was a median of 12 hours (range 3-72). in 51/53 (96%) cases there was clinical improvement recorded in the clinical notes following ile. the time that clinical signs took to improve or resolve after ile was a median of 4 hours (range 30 minutes to 36 hours). in 23/53 (43%) there was complete resolution of the signs; 12 of these cases were discharged to their primary care vets and 11 of them were discharged home. from the cases with complete resolution of signs, five had a repeated dose of ile. in total, 19 dogs (36%) were discharged home, 33 dogs (62%) were transferred back to the primary care vet and one dog was euthanased due to the lack of improvement and financial restrictions. in one dog, no clinical information was recorded in the clinical records after administration of ile. this dog was discharged to its primary care vet. for the 33 dogs that were discharged to the primary care vet, no follow up information is available. discussion the results of this study suggest that the median time to clinical improvement in dogs with suspected tremorgenic mycotoxicosis treated with ile is 4 hours. this compares favourably with previous reports which suggest that signs resolve completely within 24 – 96 hours (barker et al., 2013). there is limited information about the natural progression of this disease, and clinical experience suggests that signs improve over variable periods of time.  the improvement seen in these cases may have been natural progression of disease. the prognosis for dogs treated for tremorgenic mycotoxins is reportedly excellent and this was confirmed in this study with only one dog being euthanased. the administration of ile seems to be associated with a beneficial effect in the short term in this population of animals; it appears that treatment with lipid resulted in reduced recovery time in dogs with tremorgenic mycotoxicosis, compared to expected recovery time based on literature reports (barker et al., 2013; young et al., 2003).  no adverse effects were recorded during the infusion or up to the time of discharge. there are a number of considerations that need to be taken into account for this study.  due to the retrospective nature of the study some of the data were not consistently recorded in the medical records. importantly long-term follow-up was not available, however all dogs, except for one, were considered to have improved and were clinically stable at the time of discharge. the timing ofthe ile administration in relationtothe timing ofthe other drugs or intravenous fluid therapy ranged and was not always recorded; hence it would be hard to confirm that it was solely the ile that resulted in the clinical improvement in these cases. further to this, interactions between ile and standard treatments are not currently known, but it is likely that any lipophilic drug, including diazepam, phenobarbital and propofol, will have minimal action during infusion of ile. the dosage of ile used varied between the cases and was not always recorded. however, in most cases standard protocols were followed and included an intravenous bolus of 1.5 ml/kg of a 20% ile, followed by a constant rate infusion cri of 0.25-0.5 ml/kg/min for 30-60 minutes, which was repeated as necessary. reported dose ranges in the literature include boluses of 1.5 ml/kg-2.0 ml/kg over 2-15 minutes, then as a cri 0.06 ml/kg/min to 0.5 ml/kg/min for multiple hours (gwaltney-brant, 2012). no maximum daily dose has been determined in veterinary patients (kuo et al., 2013). methocarbamol was used in 40% of cases to control the tremors. the beneficial use of methocarbamol in suspected mycotoxicosis cases has been reported previously (schell, 2010). as tremors may last for several days, oral doses of methocarbamol may be continued after the dog is discharged from the hospital. onset of its action is reportedly 30 minutes and its peak effect is 1-2 hours post oral administration. it is possible that the improvement seen in some of the dogs was due solely to methocarbamol administration. finally, the diagnosis of mycotoxicosis in these cases was presumptive and was based on the history and clinical signs. definitive diagnosis is difficult and not commonly reached. this is mainly due to the fact that the results cannot be obtainable in a clinically relevant timeframe and that tremorgenic mycotoxicosis is always treated empirically. definitive diagnosis involves analysis of vomitus or stomach contents, blood, urine, or the suspected contaminated material. analytic methods include identification of the mould through culture of the organism or detection of the toxins themselves (eriksen et al. 2010; rundberget et al., 2002; young et al., 2003). liquid chromatography has also been used to screen for the specific toxins penitrem a and roquefortine in serum (puschner, 2009) and urine samples (tiwary, 2009). these tests are available from some specialised diagnostic laboratories. on necropsy, penitrem a has been isolated from the liver, kidney, and brain (eriksen et al., 2010). even though no acute adverse effects of this therapy were reported in any of the dogs included in this study, these have been rarely reported. potential complications that have not been reported in dogs include sepsis secondary to bacterial contamination and thrombophlebitis (kirsten et al., 2012). in people, lipaemia, hepatosplenomegaly, jaundice, haemolysis, coagulopathy, fat emboli, and thrombocytopenia are potential concerns (kirsten et al., 2012). in addition, hypersensitivity reactions and possible interference with other drugs can be seen (gwaltney-brant, 2012). in a case series, one dog had swelling and pain associated with extravasation of the ile (bates et al., 2013).there is a single case report of a cat which presented with persistent gross lipaemia and suspected corneal lipidosis following treatment for ivermectin toxicity with ile (seitz et al., 2016). since there are no current studies evaluating the safety of ile use in acute toxicities (kuo et al., 2013), owners should be informed of its off-label use (haworth et al., 2012). the results of this study indicate that ile may be a valuable addition to the clinician’s treatment options for suspected exposure to tremorgenic mycotoxins. prospective evaluation of this therapy is warranted to clarify whether clinical signs are more rapidly resolved through the use of ile versus standard therapies. the use of a scoring system to quantify severity of signs such as that reported for use in cats with permethrin toxicity by peacock et al., 2015, would be useful to allow comparison of therapies as well as evaluating the clinical course of disease. further research needs to be conducted in a standardised manner in order to determine specifics for ile dosing, most effective time period for administration, length of administration, and which patients are most likely to respond. as this is a toxicity that is most commonly seen in first opinion practice creating methods by which randomised clinical trials are easily performed is required. methods criteria for selection of cases medical records of all dogs treatedat a vets now (out-of-hours emergency-care service provider) clinic between november 2012 and november 2016, in which ile had been used, were reviewed. cases were eligible for inclusion in the study if the dog had been treated with ile and had a highly suspicious diagnosis of mycotoxicosis from the history and the physical examination findings. cases were considered to be highly suspicious for mycotoxicosis if the following criteria were met: peracute onset of neurological signs with or without gastrointestinal signs and known ingestion of mouldy food/ compost according to the owner. for the purposes of this study, when duration of signs prior to presentation is recorded as “few hours”, this is considered to be less than 6 hours.  procedures data obtained from the medical records included age, breed, presenting signs, duration of signs prior to presentation, treatment, progress during hospitalisation, hospitalisation time and outcome at the time of discharge (dead, alive and discharged home or alive and discharged to primary care veterinary practice). due to the nature of out-of-hours veterinary care in the uk, long-term follow-up information was not available, since all dogs were discharged either to the owners careor to their primary care veterinary practice by the end of the shift, if they were considered to be stable enough to travel. data was entered into a spreadsheet and cases were evaluated by two of the authors (fk and lt) data were extracted into a statistical package (spss v 23.0). data are presented descriptively. conflict of interest the authors declare no conflicts of interest. references barker, a.k. et al. (2013). tremorgenic mycotoxicosis in dogs. compendcontineduc vet 35(2):e2. bates, n. et al. (2013). lipid infusion in the management of poisoning: a report of 6 canine cases. veterinary record 172, 339. doi: http://dx.doi.org/10.1136/vr.101036 boysen, s., rozanski, e., chan, d., grobe, t., fallon, m. and rush, j. (2002). tremorgenic mycotoxicosis in four dogs from a single household. journal of the american veterinary medical association, 221(10), pp.1441-1444. http://dx.doi.org/10.2460/javma.2002.221.1441 crandell d. toxicological emergencies. in: mathews ka, ed. veterinary emergency and criticalcare manual. 2nd ed. guelph: lifelearn publishers; 2006:630-640. epstein, s.e. and hollingsworth, s.r. (2013). ivermectin-induced blindness treated with intravenous lipid therapy in a dog. journal of veterinary and emergency critical care 23, 58-62. doi: http://dx.doi.org/10.1111/vec.12016 eriksen, g.s. et al. (2010). poisoning of dogs with tremorgenic penicillium toxins. med mycol 48(1):188-196. fernandez, a.l., lee ja, rahilly l, hovda l, brutlag ag, engebretsen k. (2011). the use of intravenous lipid emulsion as an antidote in veterinary toxicology. j vet emergcrit care. 21: 309-320. doi: http://dx.doi.org/10.1111/j.1476-4431.2011.00657.x fettiplace mr, weinberg g. past, present and future of lipid resuscitation therapy. j parenter enteral nutr 2015; 39(1 suppl):72s-83s. doi: http://dx.doi.org/10.1177/0148607115595979 french d, et al. partition constant and volume of distribution as predictors of clinical efficacy of lipid rescue for toxicological emergencies. clinical toxicology (2011), early online, 1–9. doi: http://dx.doi.org/10.3109/15563650.2011.617308 gwaltney-brant, s. and meadows, i. (2012) use of intravenous lipid emulsions for treating certain poisoning cases in small animals. veterinary clinics of north america: small animal practice 42, 251-262. doi: http://dx.doi.org/10.1016/j.cvsm.2011.12.001 haworth, m.d. and smart, l. (2012) use of intravenous lipid therapy in three cases of feline permethrin toxicosis. journal of veterinary emergency critical care 22, 697-702. doi: http://dx.doi.org/10.1111/j.1476-4431.2012.00804.x kirsten e. waratuke, dvm aspca animal poison control center, what’s the take-home? / navc clinician’s brief / october 2012. pp:49-50. kuo, k. and odunayo, a. (2013) adjunctive therapy with intravenous lipid emulsion and methocarbamol for permethrin toxicity in cats. journal of veterinary emergency critical care 23, 436-441. doi: http://dx.doi.org/10.1111/vec.12070 levine, m. et al. (2016) "systematic review of the effect of intravenous lipid emulsion therapy for non-local anesthetics toxicity", clinical toxicology, 54(3), pp. 194-221. doi: http://dx.doi.org/10.3109/15563650.2015.1126286 norris pj, smith cct, de belleroche j, et al. actions of tremorgenic fungal toxins on neurotransmitter release. j neurochem 1980;34:33-42. 10. doi: http://dx.doi.org/10.1111/j.1471-4159.1980.tb04618.x parratt c. (2014) intravenous lipid rescue for tremorgenic mycotoxicosis: assessment of response to therapy using a smart phone [abstract]. 13th eveccs annual meeting, 12-15 june, prague, pp272-273. peacock, r. e., hosgood, g., swindells, k. l. and smart, l. (2015), a randomized, controlled clinical trial of intravenous lipid emulsion as an adjunctive treatment for permethrin toxicosis in cats. journal of veterinary emergency and critical care, 25: 597–605. doi:10.1111/vec.12322. puschner b (2009) penitrem a and roquefortine. in: plumlee kh, ed. clinical veterinary toxicology. st. louis, mo: mosby. pp:258-259. rothschild l et al (2010) intravenous lipid emulsion in clinical toxicology scand j trauma resuscemerg med. 2010; 18: 51. rundberget t, wilkins al (2002) determination of penicillium mycotoxins in foods and feeds using liquid chromatography-mass spectromectry. j chromatog a 2002;964;189-197. schell mm: tremorgenic mycotoxin intoxication. vet med 95(4):283-286, 2000. seitz ma, burkitt-creedon jm. persistent gross lipemia and suspected corneal lipidosis following intravenous lipid therapy in a cat with permethrin toxicosis. j vet emergcrit care 2016 nov-dec;26(6):804-8. doi: http://dx.doi.org/10.1111/vec.12440 talcott, p. (2013) "mycotoxins", small animal toxicology, pp. 677-682. doi: http://dx.doi.org/10.1016/b978-1-4557-0717-1.00063-6 tiwary ak et al (2009) using roquefortine c as a biomarker for penitrem a intoxication. j vet diagn invest 21(2):237-239. doi: http://dx.doi.org/10.1177/104063870902100210 veterinary poisons information service (vpis) [online] available from: https://vpisglobal.com/ [accessed: 22nd may 2018] young kl et al (2003) tremorgenic mycotoxin intoxication with penitrem a and roquefortine in two dogs. j am vet med assoc 222(1):52-53. doi: http://dx.doi.org/10.2460/javma.2003.222.52 intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. in mares with placentitis does the duration of antibiotic treatment affect foal outcome? a knowledge summary by elizabeth barter bvsc (hons) mvm 1* 1scone equine hospital, 106 liverpool street, scone, nsw 2337, australia *corresponding author (elizabeth.barter@sconeequine.com.au) vol 5, issue 3 (2020) published: 03 jul 2020 reviewed by: margaret nolan (phd) and kayleigh barker (bvetmed(hons) cert avp stud med mrcvs) next review date: 09 aug 2019 doi: 10.18849/ve.v5i3.309 pico question in mares with placentitis does treatment with long-term antibiotics result in improved foal viability when compared to repeated short courses of 7 to 10 days?   clinical bottom line category of research question treatment the number and type of study designs reviewed the literature search identified six publications that included length of antibiotic treatment and foetal outcome. the publications consisted of four non-randomised non-blinded controlled trials and two randomised non-blinded controlled trials strength of evidence collectively there was weak evidence to support either an intermittent or continuous antibiotic protocol in the treatment of placentitis in mares outcomes reported the literature involved experimental induction of ascending placentitis with foal survival or viability as the outcome conclusion further research is required into the diagnosis of placentitis, length of treatment and choice of antibiotic/s to penetrate the uterus in a diseased state   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision-making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario placentitis in mares is typically characterised by premature udder development or vaginal discharge from mid to late gestation and carries a high risk of abortion or birth of a compromised foal (macpherson et al., 2013; and waldridge & pugh, 2001). the cause of placentitis and agent/s involved however are often unknown and treatment, regardless of cause, usually involves antibiotics, anti-inflammatories, and progesterone (cummins et al., 2008; and waldridge & pugh, 2001). microbial agents thought to be involved in placentitis include bacterial species such as streptococcus equi subsp. zooepidemicus,(s. zooepidemicus) and escherica coli (canisso et al., 2015; and curcio et al., 2017). fungal infections have also been reported including aspergillosis (canisso et al., 2015). when mares are diagnosed with placentitis antibiotics may be prescribed either for the remaining length of pregnancy or in a pulsatile manner (leblanc, 2010; christensen et al., 2010; curcio et al., 2017; bailey et al., 2010; and ryan et al., 2008). pulsatile therapy frequently recommends mares to receive antibiotics for 10 consecutive days a month starting at 7 months gestation (leblanc, 2010). no scientific data is currently available to confirm the efficacy of this treatment protocol (leblanc, 2010). some evidence suggests that prolonged treatment is unable to eliminate bacteria and intermittent use may support suppression of bacterial growth (bailey et al., 2010). clinicians are reliant on experimental models and anecdotal evidence in making appropriate decisions regarding antibiotic choice and antibiotic length. there are currently a lack of studies comparing shortand long-term antibiotic use as a direct measurement of foal survival from mares with placentitis. abbreviation ccfa – ceftiofur crystalline free acid cfu – colony forming units ctup – combined thickness of the utero-placental unit iv – intravenous administration po – oral administration tms – trimethoprim/sulphonamide im – intramuscular the evidence the literature search identified six publications that included antibiotic length of treatment and foetal outcome. the publications consisted of four non-randomised non-blinded controlled trials of level 4 (lower quality controlled trials) (ocebm levels of evidence working group) (macpherson et al., 2013; christensen et al., 2010; murchie et al., 2006; and ryan et al., 2008). this included one pilot study (ryan et al., 2008) and one short report presented at a conference (christensen et al., 2010). two publications were randomised non-blinded controlled trials of level 2b (lower quality randomised controlled trials) (bailey et al., 2010; and curcio et al., 2017). all studies involved experimental induction of ascending placentitis with s. zooepidemicus. pony mares were used in 4/6 studies with one study involving light bred horses (christensen et al., 2010) and one study using criollo type mares (curcio et al., 2017). all horses were in late gestation either unspecified gestational days (christensen et al., 2010) or between 269 to 300 days gestation (macpherson et al., 2013); 280–295 days; (ryan et al., 2008) 290 days; (bailey et al., 2010) 280–295; (murchie et al., 2006) 269–288; and (curcio et al., 2017) 300 days. the number of mares included in the studies were low ranging from five (murchie et al., 2006) to 33 (christensen et al., 2010) with number of mares per treatment group ranging from two (murchie et al., 2006) to 12 (bailey et al., 2010) limiting clinical extrapolation. the outcome consistently measured between studies was ‘foal viability’, however the parameters determining viability varied between studies. foal viability was described by macpherson et al. (2013) and bailey et al. (2010) as a foal able to right themselves, breathe without assistance, respond to stimuli and suckle. low risk foals were determined by curcio et al. (2017) as those able to breathe without assistance in less than 2 minutes, attain sternal recumbency in less than 5 minutes, a normal suckle reflex in 20 minutes, and able to stand with little or no assistance. foal viability parameters were not defined in two studies (christensen et al., 2010; and murchie et al., 2008) and live foal rate was used in a single study (ryan et al., 2008). in studies with positive control (infected and not treated) any treatment improved foal outcome compared to no treatment at all (bailey et al., 2010; and curcio et al., 2017). the exception is macpherson et al. (2013) that showed no difference in foal viability in untreated mares and mares receiving ccfa. there was no evidence to support that continuous antibiotics improved foal viability with similar foal viabilities seen in mares treated with tms for 10 days in curcio et al. (2017) at 93% (26 viable foals from 28 infected mares that received antibiotics) compared to antibiotics prescribed until abortion or parturition in ryan et al. (2008) 64% (nine viable foals from 14 mares infected and received antibiotics), christiansen et al. (2010) 71% (17 viable foals from 24 infected and treated pregnancies), and bailey et al. (2010) at 83% of viable foals (10 viable foals from 12 infected and treated pregnancies). these findings support the need for ongoing research into identifying mares at risk of placentitis and once diagnosed monitoring clinical progression. summary of the evidence macpherson et al. (2013) population: pony mares 280–295 days gestation sample size: n = 12 pony mares intervention details: all 12 mares were inoculated with s. zooepidemicus cervically. treatment was initiated at onset of clinical signs (evidence of increase ctup, placental separation, change in fluid character on ultrasound. clinical signs of mammary gland development or vulvar discharge) group 1 (n = 3): administered ccfa 6.6 mg/kg im q96h group 2 (n = 6): administered ccfa 6.6 mg/kg im q96h, altrenogest and pentoxifylline (dose and scheduling not included) group 3 (n = 3): no treatment was given treatment was continued until abortion or parturition study design: prospective non-blinded, non-randomised controlled trial outcome studied: length of gestation was determined from time of inoculation until parturition. a viable foal was defined as one that had the ability to right themselves, breathe without assistance, respond to stimuli, and suckle main findings (relevant to pico question): ccfa alone (group 1), or in combination with altrenogest and pentoxifylline (group 2) did not improve foal survival or lengthen gestation group 1: no foals were viable and mean delivery occurred from 15 +/0.2 days after inoculation group 2: two of the six foals were viable. mean delivery was 15 +/10 days after inoculation group 3: two of the three foals were viable. mean delivery 34 +/16 days after inoculation limitations: unknown number of cfu installed into the cervix unknown if strain of zooepidemicus was sensitive in vitro to ccfa small sample size unable to extrapolate to other forms of ccfa such as short acting intravenous administration ryan et al. (2008) population: pony mares (unspecified breed) approximately 290 days gestation sample size: n = 18 ponies intervention details: mares were infected intra-cervically with approximately 2 x 106 cfu of s. zooepidemicus tested sensitive to tms in vitro. all horses commenced treatment upon signs of vaginal discharge and or placental changes (within 36 hours of inoculation). treatment was maintained through to delivery and 7 days post-partum experiment 1 (n = 6): group 1 (n = 3): trimethoprim/sulfamethoxazole (30 mg/kg body weight q12h) group 2 (n = 3): as group 1 combined with altrenogest (2.0 mg/50 kg body weight q24h) experiment 2 (n = 12): group 3 (n = 4): as group 1 group 4 (n = 4): as group 1 plus dexamethasone once a day over 6 days starting at 40 mg, then decreasing after 2 days to 35 mg for 2 days, then 25 mg for 2 days group 5 (n = 4): non-infected controls study design: prospective non-blinded, non-randomised controlled trial, pilot study outcome studied: live foal macrophage cytokine mrna, relaxin and progesterone by serial blood examinations collected prior to infection and at 12, 24, 48, and 72 hours post infection. blood samples were then taken 3 times a week until delivery transrectal ultrasound of foetal and placenta well-being (unspecified) main findings (relevant to pico question): experiment 1: group 1 (n = 3): two aborted at 11, and 12 days post inoculation. one carried a near-term viable foal group 2 (n = 3): one aborted at 14 days post inoculation. remaining two carried near-term viable foal experiment 2: group 3 (n = 4) and 4 (n = 4): one mare from each group aborted a dead fetus. remaining six produced live pre-term foals group 5 (n = 4): control mares all delivered normal viable foals limitations: small sample size the strain of zooepidemicus used was tested sensitive to tms and may not be known in a clinical setting no positive control of inoculated and not treated no specifications to foal viability christensen et al. (2010) population: pregnant light breed horses sample size: n = 33 horses intervention details: group 1: (n = 27) inoculated intra-cervically with streptococcus equi subsp zooepidemicus (2–10 x 106 cfu). all treatments were commenced on signs of vaginal discharge or placental changes (within 48 hrs of inoculation) and continued until delivery group 1a (n = 6): tms 30 mg/kg bid po group 1b (n = 6): as group a and dexamethasone given over 6 days with decreasing doses every 2 days 40 mg, 35 mg, 25 mg qd iv group 1c (n=6): as group a and acetylsalicylic acid 50 mg/kg bid po for 6 days group 1d (n = 6): as group c and altrenogest 2.2 mg/50 kg qd po group 1e (n = 3): infected controls group 2: (n = 6) non-infected controls study design: prospective non-blinded, non-randomised controlled trial, short report outcome studied: delivery of a viable foal main findings (relevant to pico question): all infected mares that did not receive treatment aborted within 9 days of inoculation. all mares not infected delivered viable foals group 1a (tms): 4/6 foals survived group 1b (tms and dexamethasone): 4/6 foals survived group 1c (tms and acetylsalicylic acid): 5/6 foals survived group 1d (tms, acetylsalicyclic acid, and altrenogest): 4/6 foals survived group 1e (infected controls): no foals survived out of three group 2 (uninfected controls): 6/6 foals survived mean gestational age at delivery was shorter in all infected mares than control negative mares. antibiotic therapy substantially improved pregnancy outcome limitations: limited number of horses makes statistical power poor between groups limited details provided in short study viability of foals not defined bailey et al. (2010) population: normal pregnant pony mares 280–295 days gestation. normal determined by systemic parameters, ctup, echo density of foetal fluids, foetal activity, and foetal heart rate sample size: n = 17 ponies intervention details: all mares inoculated with 107 cfu s. zooepidemicus known sensitive to tms in vitro group 1 (n = 5): infected untreated controls group 2 (n = 12): infected and given trimethoprim/sulfamethoxazole (tms 30 mg/kg body weight bid po), altrenogest (alt 0.088 mg/kg body weight qd po) and pentoxifylline (ptx 8.5 mg/kg body weight bid po). treatment continued until abortion or parturition study design: prospective non-blinded, randomised controlled trial outcome studied: delivery of a viable foal defined as a foal able to right themselves, breathe without mechanical assistance, respond to stimulation and suckle main findings (relevant to pico question): mares that were treated (group 2) were significantly more likely to deliver a viable foal (10/12 deemed viable) than mares that were not treated (group 1 no viable foals) 10 of the foals in group 2 had negative blood cultures whilst all foals in group 1 (untreated group) had positive cultures from either blood, stomach contents or thoracic fluid tms combined with pentoxifylline and altrenogest may improve the viability of foals with experimentally induced placentitis limitations: bacteria tested sensitive to tms supraphysiologic dose of bacteria administered intra-cervically to induce disease limited number of horses in study randomisation method not described murchie et al. (2006) population: late gestational pony mares aged 4–15 years, weighing 190–290 kgs, with gestation age 269–288 days sample size: n = 5 ponies intervention details: study 1 (n = 5): all mares had microdialysis probes inserted into their allantoic fluid. all mares received penicillin g 22,000 u/kg, every 6 hrs gentamicin 6.6 mg/kg body weight qd and flunixin meglumine 1 mg/kg body weight qd. all treatments were given intravenously. samples were taken serially immediately before injection then 5, 15, 30, 45, 60, 90 minutes then 2, 4, 6, 12, 18, 20, 22, and 24 hours after drug administration study 2 (n = 2): experimental placentitis was induced by intracervical inoculation with s. zooepidemicus 1 x 107 cfu 10 days after study 1. mares were treated 4 days after inoculation as described above for 7 days study design: prospective non-blinded, non-randomised controlled trial outcome studied: objective to monitor drug concentrations in allantoic fluid of pregnant pony mares using in vivo microdialysis and establish if this method is useful for determining allantoic concentrations of drugs in normal mares and those with placentitis foal viability after allantoic fluid samples in both infected and non-infected mares main findings (relevant to pico question): study 1: penicillin g and gentamicin were detected in allantoic fluid study 2: placental drug transfer may be altered if active placental infection is present potential for increased dose intervals for penicillin g and increased dose rate of gentamicin to effectively combat placental infections in mares both mares that were infected aborted non-viable foals one at 291 days and one at 307 days gestation limitations: small sample size of two mares in study 2 make conclusions regarding efficacy of 7 days treatment difficult to surmise intervention procedure of allantoic sampling may also have compromised foetal well-being with only two out of five viable foals born at 32 and 45 days after experimentation, whilst one mare that had allantocentesis performed and was not inoculated aborted at 315 days gestation curcio et al. (2017) population: 27 multiparous criollo or criollo type mares approximately 300 days gestation, 10 +/2-years-old, parity of 3 +/0.5, body weight 437 +/22 kg with no history of subfertility or late term pregnancy abnormality sample size: n = 46 pregnancies from 2012 to 2014 intervention details: group 1 (n = 8): control not infected group 2 (n= 38): infected with 107 cfu s. zooepidemicus group 2a (n = 8): tms 30 mg/kg body weight bid intravenously and flunixin (1.1 mg/kg qd iv) group 2b (n = 8): as group a with altrenogest 0.088 mg/kg intramuscular every 7 days for two treatments group 2c (n = 6): as group a with estradiol cypionate (ec) 10 mg/mare intramuscular every 3 days for three treatments group 2d (n = 6): as group a with altrenogest as described in group b and ecp as described in group c group 2e (n = 10): infected no treatment all treatments were initiated 48 hours after inoculation and continued for 10 days study design: randomised non-blinded controlled trial outcome studied: time of induction to delivery serum steroid concentrations in response to treatment foal viability was separated into low and high risk foals defined as low risk if: able to breathe without assistance in under 2 minutes assume sternal recumbency in less than 5 mins exhibit normal suckle reflex in 20 minutes stand with no or minimal assistance foals defined as high risk if: signs of immaturity (silky hair coat, floppy ears, delayed sucking) evidence of sepsis main findings (relevant to pico question): time from inoculation to delivery was not significantly different between group 1 control mares and group 2d mares receiving supplemental ec (mean 35 and 46 days respectively) time from inoculation to delivery was significantly shorter in mares receiving other treatments in groups 2b, 2c, and 2d compared to control mares. however, delivery was shortest in mares not receiving any treatment (group 2) foal survival at parturition and 7 days of age were similar amongst treated groups 2a–2e to control (group 1) ranging between 66.7–100% there was no significant difference in the number of high risk foals in group 2d compared to control mares (group 1) there was a significant difference in the number of high risk foals in groups 2a–2c and 2e compared to control (group 1) mares in group 2e had significantly higher number of dystocia’s and premature parturitions limitations: unknown if the same mares were used over multiple seasons, which order of treatments were received, and if those inoculated were known to no longer be infected unknown if strain cultured was sensitive to tms in vitro small treatment groups appraisal, application and reflection placentitis is a common condition estimated to affect 3–5% of thoroughbred pregnancies and can be challenging for the clinician to diagnose and treat (canisso et al., 2015). current treatment protocols recommend a multifactorial approach involving antibiotics, anti-inflammatories and progesterone (murchie et al., 2006; and waldridge & pugh, 2001). two different antibiotic regimes have been proposed in the treatment of placentits; 1) pulse antibiotics involving 10 consecutive days each month until parturition; and 2) continuous antibiotics until parturition. the purpose of this knowledge summary was to evaluate the evidence comparing the treatment length of antibiotics and foal viability as no studies reported the use of pulse antibiotic therapy. six studies met the inclusion criteria and all the studies involved experimental induction of ascending placentitis using s. zooepidemicus. two studies curcio et al. (2017) and bailey et al. (2010) provide the most comparable in terms of length of antibiotic treatment. curcio et al. (2017) treated for 10 days with an average time from inoculation to parturition of treated mares 23.7 days and foal survival of 93% (26/28). bailey et al. (2010) treated until abortion or delivery with average time from inoculation to parturition 31 days with 83% (10/12) of treated mares producing viable foals. treatment commenced later in the study by curcio et al. (2017) with the average gestation of mares approximately 300 days, whilst mares in the study by bailey et al. (2010) were 280–295 days gestation. viability of the foals and mean gestational lengths were similar between the studies, regardless of duration of antibiotics (both over 320 days gestation). clinically it is recognised that chronic insidious placentitis carriers a better prognosis compared to acute disease as the foal has time to mature. the aim of placentitis treatment may be to delay parturition and allow foetal maturation as opposed to eliminating bacteria. all the studies used supraphysiological doses of s. zooepidemicus to initiate placentitis. the amount of colony forming units were unspecified in two studies (murchie et al., 2006; and bailey et al., 2010) whilst the remaining studies varied. ryan et al. (2008) inoculated 2 x 106 cfu, whilst christiansen et al. (2010) had a variable dose between 2–10 x 106 cfu, macpherson et al. (2013) and curcio et al. (2017) used a higher dose of 1 x 107 cfu. clinical ascending placentitis is thought to be insidious in onset and reflective of mare perineal or cervical conformation (waldridge & pugh, 2001) and experimental inoculation may limit clinical extrapolation of results. the strain used was tested sensitive to the antibiotics prescribed in vitro (tms) in ryan et al. (2008) and bailey et al. (2010), however was not specified if it was sensitive to the antibiotics prescribed in the other studies. no studies commented on culture and sensitivity of vaginal discharge post inoculation or uterine fluid post foaling/aborting. when and how antibiotics were prescribed varied between studies. two studies used tms at 30 mg/kg body weight po every 12 hours (christensen et al., 2010; and bailey et al., 2010). curcio et al. (2017) used the same dose rate, however delivered the tms iv every 12 hours and ryan et al. (2008) did not specify dose rate or administration route of tms. a single study used penicillin g (22,000 u/kg), and gentamicin (6.6 mg/kg) (murchie et al., 2006) and a single study evaluated ccfa the active metabolite of ceftiofur at 6.6 mg/kg im repeated after 96 hours (macpherson et al., 2013). four studies specified that antibiotics were commenced when clinical signs of placentitis occurred which varied between 36 hours (ryan et al., 2008) to 48 hours (christensen et al., 2010) or was not specified (macpherson et al., 2013; and bailey et al., 2010). clinical signs attributed to placentitis included vaginal discharge (christensen et al., 2010; and ryan et al., 2008) or elevated ctup (christensen et al., 2010).  murchie et al. (2006) initiated antibiotics 4 days post inoculation regardless of clinical signs observed, and curcio et al. (2017) initiated antibiotics 48 hours after inoculation regardless of clinical signs observed. the length of antibiotic treatment varied amongst the studies with four of the studies continuing antibiotics until parturition (christensen et al., 2010, bailey et al., 2010, macpherson et al., 2017; and ryan et al., 2008), whilst murchie et al. (2006) treated for 7 days and curcio et al. (2017) treated for 10 days. no studies evaluated examined physical, chemical, or ultrasonographic parameters of mares or foals whilst the mares were on antibiotic treatment. the study by ryan et al. (2008) additionally evaluated the use of antibiotics in mares with placentitis after abortion or foaling. post mortem investigation of the non-viable foals found evidence s. zooepidemicus in foal lungs from mares that were treated with antibiotics and those that were not. the majority of foals in the study by ryan et al. (2008) born from treated mares had negative blood cultures (10/12 foals treated with antibiotics had negative blood cultures). uterine cultures taken from mares immediately post foaling or aborting that were on antibiotics were less predictable, with two thirds of mares (8/12 mares) returning a positive uterine culture to s. zooepidemicus despite the administration of antibiotics for over 4 weeks. it was proposed by ryan et al. (2008) that early initiation of treatment was able to inhibit bacterial growth and subsequent inflammation. as treatment was initiated at onset of clinical signs, delayed antibiotic administration may only suppress bacterial growth. further research is required into when to start antibiotic treatment and improve detection of mares with suspected placentitis. methods to monitor foetal well-being to aid in determining when to treat placentitis is limited. curcio et al. (2017) noted that 4/10 mares that were inoculated failed to develop vaginal discharge and 3/10 mares failed to show an increase in ctup or evidence of placental separation on rectal ultrasound. further studies into the correlation of foetal circulation including heart rate, cord pressure (vincze et al., 2019) and thickness of the placenta measured both abdominally and rectally may aid in earlier identification of mares with placentitis (curcio et al., 2017). decreasing progesterone and rising oestrogen levels have been correlated with poor prognosis of foetal survival (curcio et al., 2017). allantocentesis samples have also been used to assess foetal health, however further investigation is warranted into the technique (murchie et al., 2008). all studies involved a multi-model approach to treatment with combined therapeutic regimes. 5/6 studies included altrenogest (macpherson et al., 2013; christensen et al., 2010; curcio et al., 2017; bailey et al., 2010; and ryan et al., 2008), single studies evaluated flunixin (murchie et al., 2006), acetylcystine (christensen et al., 2010), and estradiol cypionate (curcio et al., 2017). two studies examined pentoxifylline (bailey et al., 2010; and macpherson et al., 2017), and two studies examined dexamethasone (christensen et al., 2010; and ryan et al., 2008). the evaluation of these agents into the treatment of placentitis is beyond the scope of this article. the use of antibiotics in a pulsatile manner has been explored in dogs with chronic pyoderma (carlotti et al., 2004). in the canine model cephalexin (15 mg/kg twice a day) was prescribed for 2 days of the week and was compared against a placebo. the study found that pulse ‘weekend’ therapy was effective in reducing the time between relapses in canine idiopathic pyoderma and no resistance was noted in the 12 month period. it has been proposed that bacterial resistance to antibiotics may be limited in pulse antibiotic therapy as it minimises the time microbes are exposed to antibiotics and the selection of resistance (baker et al., 2018). it was noted that in pulse therapy a bactericidal drug is advised with high concentrations to minimise pathogen abundance (baker et al., 2018; and carlotti et al., 2004). more research is required into what drugs and clinical scenarios pulse antibiotic therapy may be implemented. multiple types of placentitis have been described in the literature including ascending, focal mucoid (nocardioform), diffuse (haematogenous) and multifocal (canisso et al., 2015). all the above studies involved an experimental model to induce ascending placentitis and the extrapolation to other forms is limited. placentitis treatment remains frustrating for the clinician to treat with limited ability to perform culture and sensitivity against the potential organism/s involved. current literature supports the use of antibiotics in the combined treatment of placentitis but does not provide evidence of the length of time they should be prescribed for. further investigation of placentitis may involve correlating foetal and placental well-being to foal survival to be used as a measure of ceasing or altering treatment regimes. methodology section search strategy databases searched and dates covered: search terms were applied in pubmed central accessed on ncbi website (1910–2019), cab abstracts database accessed on ovid platform (1973–2019) search strategy: cab abstracts: (equine* or horse* or equus or equid* or mare or mares or broodmare or broodmares or 'brood mare' or 'brood mares' or pony or ponies).mp. or exp equidae/ or exp equus/ or exp horses/ or exp mares/) (placentitis or placenta or pregnancy or fetus or foetus).mp. or exp placentitis/ or exp pregnancy/) (antibiotic or antibiotics or antimicrobial or antimicrobials or anti-microbial or anti-microbials or antibacterial or antibacterials or 'antiinfective agent' or 'antiinfective agents' or 'anti-infective agent' or 'anti-infective agents' or penicillin or gentamicin or ceftiofur or excede).mp. or exp antibacterial agents/ or exp antibiotics/ or exp antiinfective agents/) 1 and 2 and 3 pubmed: (equine or horse or mare or mares or broodmare or brood mare or pony or ponies) (placentitis or placenta or pregnancy or fetus or foetus) (antibiotic or antibiotics or antimicrobial or antimicrobials or anti-microbial or anti-microbials or antibacterial or antibacterials or 'antiinfective agent' or 'antiinfective agents' or 'anti-infective agent' or 'anti-infective agents' or penicillin or gentamicin or ceftiofur or excede) 1 and 2 and 3 dates searches performed: 9 august 2019 exclusion / inclusion criteria exclusion: non-english language, narrative or non-systematic review articles, unpublished data, pharmacokinetic, or in vitro experimental studies inclusion: any reported use of antibiotics in the treatment of placentitis in mares search outcome database number of results excluded – nonenglish language publication excluded – systematic review or non-equine excluded – did not state duration of antibiotic excluded – single case report total relevant papers cab abstracts 285 18 214 4 38 11 pubmed 263 10 216 2 30 5 total relevant papers when duplicates removed 6 conflict of interest the author declares no conflicts of interest. references bailey, c. s., macpherson, m. l., pozor, m. a., troedsson, m. h., benson, s., giguere, s., sanchez, l. c., leblanc, m. m. & vickroy, t. w. (2010). treatment efficacy of trimethoprim sulfamethoxazole, pentoxifylline and altrenogest in experimentally induced equine placentitis. theriogenology, 74(3), 402–12. doi: http://dx.doi.org/10.1016/j.theriogenology.2010.02.023 baker, c. m., ferrari, m. j. & shea, k. (2018). beyond dose: pulsed antibiotic treatment schedules can maintain individual benefit while reducing resistance. scientific reports, 8(1). doi: http://dx.doi.org/10.1038/s41598-018-24006-w canisso, i. f., ball, b. a., cray, c., squires, e. l. & troedsson, m. h. (2015). use of a qualitative horse-side test to measure serum amyloid a in mares with experimentally induced ascending placentitis. journal of equine veterinary science, 35(1), 54–59. doi: http://dx.doi.org/10.1016/j.jevs.2014.11.007 carlotti, d. n., jasmin, p., gardey, l. & ssanquer, a. (2004). evaluation of cephalexin intermittent therapy (weekend therapy) in the control of recurrent idiopathic pyoderma in dogs: a randomized, double-blinded, placebo-controlled study. veterinary dermatology, 15(s1), 1–19. doi: http://dx.doi.org/10.1111/j.1365-3164.2004.00410_2-4.x christensen, d. l., moulton, k., hopper, r., walters, f. k., cooley, a. j., leblanc, m. & ryan, p. (2010). evidence-based medicine approach to develop efficacious therapies for late-gestation mares presenting with uterine infections using and experimentally induced placentitis model. animal reproduction science, 121, 345–346. cummins, c., carrington, s., fitzpatrick, e. & duggan, v. (2008). ascending placentitis in the mare: a review. irish veterinary journal, 61(5), 307–313. doi: http://dx.doi.org/10.1186/2046-0481-61-5-307 curcio, b. r., canisso, i. f., pazinato, f. m., borba, l. a., feijo, l. s., muller, v., finger, i. s., toribio, r. e. & nogueira, c. e. w. (2017). estradiol cypionate aided treatment for experimentally induced ascending placentitis in mares. special issue: the david e. bartlett award for lifetime achievement in theriogenology., 9, 454. doi: http://dx.doi.org/10.1016/j.theriogenology.2017.03.010 leblanc, m. m. (2010). ascending placentitis in the mare: an update. reproduction in domestic animals, 45, 28–34. doi: http://dx.doi.org/10.1111/j.1439-0531.2010.01633.x macpherson, m. l., giguere, s., hatzel, j. n., pozor, m., benson, s., diaw, m., sanchez, l. c., vickroy, t. w., tell, l., wetzlich, s. & sims, j. (2013). disposition of desfuroylceftiofur acetamide in serum, placental tissue, fetal fluids, and fetal tissues after administration of ceftiofur crystalline free acid (ccfa) to pony mares with placentitis. journal of veterinary pharmacology therapeutics, 36(1), 59–67. doi: http://dx.doi.org/10.1111/j.1365-2885.2012.01392.x macpherson, m. l., giguere, s., pozor, m. a., runcan, e., vickroy, t. w., benson, s. a., troedsson, m. h. t., hatzel, j. n., larson, j., vanden berg, e., kelleman, a. a., sanchez, l. c. & leblanc, m. m. (2017). pharmacokinetics of ceftiofur sodium in equine pregnancy. journal of veterinary pharmacology therapeutics, 40(6), 656–662. doi: http://dx.doi.org/10.1111/jvp.12399 murchie, t. a., macpherson, m. l., leblanc, m. m., luznar, s. & vickroy, t. w. (2006). continuous monitoring of penicillin g and gentamicin in allantoic fluid of pregnant pony mares by in vivo microdialysis. equine veterinary journal, 38(6), 520–525. doi: http://dx.doi.org/10.2746/042516406x156136 murchie, t. a., macpherson, m. l., leblanc, m. m., luznar, s. & vickroy, t. w. (2008). detection of gentamicin and penicillin concentrations in allantoic fluid of pregnant pony mares by in vivo microdialysis. havemeyer foundation monograph series, 33. ryan, p., crouch, j., sykes, d., moulton, k., christiansen, d., hopper, r., read, r., bennett, w. & leblanc, m. m. (2008). experimentally induced placentitis in late gestation mares with streptococcus equi zooepidemicus: prevention of pre-term birth. havemeyer foundation monograph series, 35–36. vincze, b., baska, f., papp, m. & szenci, o. (2019). introduction of a new fetal examination protocol for on-field and clinical equine practice. theriogenology, 125, 210–215. doi: http://dx.doi.org/10.1016/j.theriogenology.2018.11.004 waldridge, b. m. & pugh, d. g. (2001). equine placentitis. compendium on continuing education for the practicing veterinarian, 23, 573–575. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. healing of equine heel bulb lacerations: evidence behind casting compared to bandaging alone a knowledge summary by jonathan ruiz bvetmed sci (hons), bvm, bvs, mrcvs 1 julia dubuc dmv, dés, dacvs-la, m.sc, mrcvs 1* 1university of nottingham, sutton bonnington campus, sutton bonnington, leicestershire, le12 5rd *corresponding author (julia.dubuc@nottingham.ac.uk) vol 5, issue 2 (2020) published: 03 apr 2020 reviewed by: josh slater (phd, dip eceim) and debbie archer (bvms, phd certes(soft tissue), dipecvs, frcvs, fhea) next review date: 07 dec 2020 doi: 10.18849/ve.v5i2.255 pico question in horses with heel bulb lacerations, does casting the distal limb compared to bandaging result in increased speed of healing and functional outcome?   clinical bottom line category of research question treatment the number and type of study designs reviewed a single retrospective study was found to be relevant to the topic along with one case report and two case series, including one tutorial article strength of evidence the majority of the current recommendations come from expert opinions, making the level of evidence low outcomes reported there are currently insufficient data to compare the effect of foot/slipper casts versus bandaging alone on the rate of healing of equine heel bulb lacerations conclusion based on the information from these three publications, it is not possible to recommend the use of a foot cast over a bandage alone at this time   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are called out to a 10-year-old cob gelding which has sustained a heel bulb laceration after jumping into the neighbouring field over a fence covered in barbed wire. the laceration is located on the lateral heel bulb of the right hindlimb and is 5 cm long. it extends from the lateral hoof wall, across the coronet and reaches 2 cm proximal to the coronet in a lateroproximal to mediodistal direction. the horse is consistently lames at the trot in a straight line (3/5 aaep) on that limb and the laceration appears very contaminated with soil. the evidence the literature comprises several non-peer reviewed publications, such as cpd material and tutorial articles. only one retrospective case study, including a large number of horses treated with bandaging and/or casting, was found. based on the publications currently available, there is sparse evidence that casting is superior to bandaging for healing of heel bulb lacerations in the horse and the quality of the evidence is considered low. summary of the evidence janicek et al. (2005) population: horses 75 quarter horses, six thoroughbreds, five tennessee walking horses, five quarter horses appendix, three paint horses, three appaloosas, two arabians, two unknown 11 stallions, 32 mares and 58 geldings age: mean 7 ± 4 years old (yo) (range, 1 to 23 years) medical records (1988–1994) of horses presented for lacerations of the heel bulb and distal portion of palmar and plantar aspects of the pastern sample size: n=101 intervention details: work-up laceration cleansing and lavage with an antiseptic solution radiographs to identify foreign bodies and bone involvement wound examination to determine involvement of: navicular bursa (nb), distal interphalangeal joint (dipj), proximal interphalangeal joint (pipj), digital flexor tendon sheath (dfts) deep digital flexor tendon (ddft) collateral cartilages of third phalanx n=1 horse euthanised at admission treatment if synovial structure involvement identified, through-and-through needle lavage 14–16 g needle placed remote to the wound lavage with 1–2 l polyionic solution (pump used) egress through wound itself infusion of amikacin in synovial structure repeat the above (standing) every other day until cytologic and bacteriology results indicate resolution antimicrobials: n=56 – broad-spectrum antibiotic therapy for 2 weeks minimum n=36 – trimethoprim-sulfadiazine, 15 mg/kg, orally (po), q12h n=20 – enrofloxacin, 5 mg/kg, po or intravenously (iv), q24h n=44 – no antibiotic treatment multiple protocols for wound treatment: < 8 hours duration or minimal contamination primary closure foot cast* or bandage > 8 hours duration second intention healing foot cast or bandage severe and contaminated with debris foot bandage for 7–10 days casting after foot bandage *foot cast = double layer 3–4 inches stockinette + 3 rolls of 3 inches/7.5 cm fiberglass cast tape up to middle of proximal phalanx follow-up information acquired by telephone interview with the owner or the trainer or both study design: retrospective case series outcome studied: successful outcome: sound horse able to be used at a level of performance that equaled or exceeded the level achieved before surgery foot cast versus foot bandage synovial involvement versus no synovial involvement main findings (relevant to pico question): wound treatment: n= 30 – primary closure (polydioxanone or polypropylene sizes 1 or 2) n=70 – second intention healing immobilisation: n= 52 foot cast (duration: 2.8 ± 1 weeks) and n= 76 foot bandage (duration: 3.2 ± 2.2 weeks) n= 24 – cast only duration: 3.1 ± 0.9 weeks n= 28 – cast followed by bandage duration cast + bandage: 5.1 ± 2.1 weeks n=48 – bandage only duration: 4.1 ± 1.3 weeks duration of cast immobilisation alone significantly shorter than bandaging alone. significant difference in outcome for primary wound closure versus second intention healing (latter failed more often). follow-up available for 61/100 horses mean time to follow-up after discharge: 37 ± 26 months 51/61 (84%) judged to have a successful outcome by owner/trainer 10/61 (16%) had unsuccessful outcome: remained persistently lame or unable to be used as intended 15/61 were managed with a cast alone 2/15 (13.3%) had cast complications (pressure necrosis of skin) 11/61 (18%) hoof wall defect developed after injury limitations: no control group and no random allocation of wound treatment (cast vs bandage) choice of foot dressing was at attending clinician’s discretion very little detail on complications for bandaging group and bandaging + casting together unclear how many horses: with second intention healing or primary wound closure were treated with a foot cast alone or bandage alone and if this is a confounding factor with synovial involvement were treated with a foot cast versus a bandage alone and which one would lead to faster healing in such cases limited outcome information and very subjective as assessed by trainer/owner booth & knottenbelt (1999) population: horses (one arab, one irish draft and two unknown) sample size: n=4 intervention details: location of wounds: coronet (n=1) heel bulb laceration (n=2) laterodistal aspect one forelimb (n=1) surgical debridement in all cases wounds sutured (n=2) bandage daily for 5 days (n=1 horse, prior to cast application) foot cast applied in all cases 4 weeks duration (n=3) 8 weeks duration (n=1) study design: tutorial article with small case series as examples outcome studied: mainly wound healing: soundness hoof wall defect main findings (relevant to pico question): all wounds healed n=1: cast sore (cast on for 4 weeks) of no apparent clinical significance n=1: hoof wall defect (noticed at 4 years follow-up) limitations: very small case series with limited details for each no bandage group to compare unclear why one cast was left in place for 8 weeks heel bulb laceration case unclear how many cast were placed under general (versus regional anaesthesia) and if difference in cast complications affected limb not always identified unclear if difference in healing between fore and hind limbs very limited long-term follow-up (available for one case only) ketzner et al. (2009) population: horses 27 quarter horses, six paints, five mixed breeds, three warmbloods, two arabians, two thoroughbreds, one appaloosa, one saddlebred, one belgian, one unknown breed three stallions, 26 mares and 20 geldings age: mean 7.2 ± 5.5 years old (yo) (range, 1 to 25 years) medical records (1995–2007) of horses with wounds of the pastern and foot region, presented to three university equine hospitals. sample size: n=49 horses with 50 wounds (cases) intervention details: work-up under general anaesthesia or after perineural analgesia skin around laceration scrubbed with povidone-iodine (pi) or chlorhexidine wound bed cleaned with 1.0% pi sterile palpation of wound bed to determine: synovial structure involvement if suspected, structure distended using sterile ringer’s lactate solution (rl) in site distant from wound bone involvement instability treatment if synovial structure involvement identified, synovial lavage performed with 1 l of sterile lrs injection of 500 mg of amikacin in synovial structure antimicrobials systemically for 42/50 wounds (84%) 19/42 (45.2%) penicillin and gentamicin 19/42 (45.2%) oral trimethoprim-sulfadiazine 4/50 (8%) [sic] other antimicrobials 6/50 (12%) received no antimicrobials 2/50 (9.5%) had no antimicrobials information in record if severely contaminated wounds or involvement of synovial structure, antimicrobials locally prior to casting for synovial infections: all had intra-articular (ia) amikacin (two of which also had timentin ia), one also had 5 intravenous injections with gentamicin in the regional limb wound closure for acute or minimally contaminated wounds primary closure, tension relieving patterns size 2 united states pharmacopeia (usp), polypropylene phalangeal cast: double layer stockinette + 3–4 layers of 3 inches/7.5 cm fiberglass cast tape from sole to mid-pastern + polymethylmetacrylate under the sole if cast placed standing, pastern region layed first in weight-bearing position and then foot including heel wedge, once pastern hardened if cast placed under general anaesthesia, foot done first, with toe extended, followed by pastern region. follow-up information acquired by telephone interview with the owner or during re-evaluation study design: retrospective case series outcome studied: soundness: sound if no lameness and back to previous level wound appearance excellent (no scaring), very good (minimal scaring), excessive scaring complications main findings (relevant to pico question): injuries 26/50 (52%) forelimb wounds and 23/50 (46%) hindlimb wounds 20/49 (40.8%) horses presented < 24 hours after injury and 29/49 (59.2%) presented > 24 hours after injury no overt lameness in 14/43 (32.6%), lameness in 29/43 (67.4%) lameness not recorded in seven horses (14%) 8/50 wounds (16%) had synovial involvement casting overall, average duration of treatment prior to casting 3.7 ± 6.6 days (range 0–29 days) if synovial involvement, average of 6 ± 5.8 days (range 0–14 days) total cast duration of 17.2 ± 5.9 days (range 9–36 days) wound repair 33/42 (78.6%) repaired under general anaesthesia versus 9/42 (21.4%) under standing sedation not recorded in eight horses 28/44 (63.6%) wounds were sutured versus 16/44 (36.4%) left unsutured not recorded in six horses follow-up between 2–93 months following hospital discharge (mean 33.3 ± 25.1 months) lost 3 horses to follow-up overall, 41/46 (89.1%) horses sound, 4/46 (8.7%) still lame, 1/46 (2.2%) euthanised as non-response to treatment of synovial involvement cases, 6/7 (85.7%) sound, 1/7 (14.2%) with residual lameness lost one horse with septic coffin joint to follow-up cosmetic appearance of wounds 8/38 (21.1%): excellent 26/38 (68.4%): good 4/38 (10.5%): excessive scarring involving the coronary band and hoof for four horses, owners had no recollection if there was scarring or not three horses lost to follow-up one horse was euthanised limitations: specific location of wounds non-identified (unknown how many involved the coronary band, heel bulb, pastern, etc.) no group treated with bandaging only for comparison/control type of synovial lavage non-specified (arthroscopic versus through-and-through needle lavage) incoherent information on systemic antibiotics no details on regional antimicrobials for contaminated wounds doses for intra-articular medication and intravenous regional limb perfusions are not specified little detail regarding complications, namely none on cast sores milner (2008) population: 13-year-old cob gelding sample size: n=1 intervention details: crescent shape full-thickness laceration of medial heel bulb in left forelimb no synovial involvement identified exposure of proximomedial edge of medial ungular cartilage wound lavage and foot bandage changed daily until day 4 on day 4, hydrosurgical (versajettm) and sharp debridement under general anaesthesia 1.25 mm cerclage wires (x2) used to retain the medial hoof wall in place foot cast (to mid-proximal pastern) for the following 14 days after cast removal, shoe with central support and polyurethane infiller in the sole for 4 weeks removal of wires at 4 weeks re-shod with central support shoe at 8 weeks study design: case report outcome studied: no specific outcome studied: presence or not of a hoof wall defect soundness laceration healing main findings (relevant to pico question): good apposition of wound edges and medial hoof wall at cast removal at 2 months after presentation: sound good healing and apposition of the heel bulb laceration limitations: case report (n=1) very little detail on how the cast was made and applied no long-term follow-up appraisal, application and reflection there are very few studies evaluating the efficacy of using distal limb casts when treating heel bulb lacerations compared with bandages alone in horses. based on the publication from janicek et al. (2005), casting as opposed to bandaging may reduce the treatment duration of heel bulb lacerations. however, the length of treatment and the success of wound healing are both directly related to the way these wounds are approached, namely if they are treated by primary or secondary closure (janicek et al., 2005). since the number of horses in each group (bandaging versus casting) treated with primary closure versus delayed primary or second intention healing was not specified, the conclusion that distal limb casting results in faster healing of heel bulb laceration remains questionable. janicek et al. (2005) recommended all heel bulb wounds which are minimally contaminated with debris and of short duration following injury (< 8 hours) be managed by primary closure and physical support of the site with either a bandage or a cast. in cases of wounds severely contaminated or traumatised, the authors recommended a foot bandage for 7–10 days prior to cast immobilisation. while these recommendations are very logical and allow more frequent monitoring of the wound healing and care, the study results are inconclusive when it comes to favour bandaging or casting to speed up wound healing. on the other hand, burba et al. (2013), an expert opinion article aimed at veterinary surgeons, stated that heel bulb lacerations were best treated by primary closure when possible and with the use of a foot cast. as this is an opinion piece rather than an original study, no compelling evidence in favour of using foot casts over bandaging was found for these cases. the potential involvement and treatment of synovial sepsis appears to be an important factor influencing outcome in cases of heel bulb laceration. janicek et al. (2005) reported that lacerations involving a synovial structure had a significantly poorer outcome than those without. synovial involvement also influences the approach to the wound. in the study by janicek et al. (2005), all wounds communicating with synovial structures were left to heal by second intention following surgical management of sepsis. the authors recommended that all lacerations involving synovial structures are considered contaminated and recommended delayed primary closure after repeated synovial lavages and natural sealing of the communication between the synovial structure and the wound itself. in the small case series from booth and knottenbelt (1999), 50 % of the lacerations were sutured, although the reason for this is not stated in the paper. in a similar publication from ketzner et al. (2009), 63.6% of wounds were sutured and the authors found no significant difference in outcome between cases involving or not involving a synovial structure. in a more recent publication on wounds of the lower limb eggleston (2018), recommends that a wound communicating with a synovial structure be managed with replaceable bandages until it can be confirmed that synovial communication is sealed and the infection resolved. celeste and szöke (2005) also recommended bandaging until infectious complications are resolved, after which casting the distal limb in successive periods of 2–3 weeks should be performed. whilst these recommendations are logical, they constitute expert opinion and we have failed to find corroborating evidence in the literature gathered for this knowledge summary. prospective studies comparing horses with heel bulb lacerations sutured (or not) in the same fashion, with and without synovial involvement, and divided into two separate groups (bandage versus ‘slipper cast’) are lacking. if such studies were performed, a standardised treatment plan prior to casting or bandaging would need to be implemented to allow direct comparison of the efficacy of the supportive dressing. the incidence of cast sores with all types of cast is reported to be anywhere between 45% to 81% (eggleston, 2018). however, if the cast is applied properly and is monitored regularly, the potential for serious complications is significantly reduced and are uncommon (booth & knottenbelt, 1999; and eggleston, 2018). janicek et al. (2005) reported that 2/15 horses managed with a cast alone developed pressure necrosis of the skin, which was of limited clinical significance. to further reduce this risk, a ‘slipper cast’ can be used for casting the foot. it reduces the risk of deep skin erosions if the cast material does not end in the mid-pastern region (celeste and szöke, 2005). closure of heel bulb lacerations can be challenging due to skin tension and the production of excessive granulation tissue (egt) is a concern if these wounds are left to heal by second intention (eggleston, 2018). booth and knottenbelt (1999) stated that when properly applied, distal limb casts improve the functional and cosmetic outcome of distal limb injuries. indeed, since a cast is by definition sturdier than a bandage, is it thought to provide better immobilisation of the distal limb. this led to the clinical impression that casting prevents movement of the foot and wound dehiscence (janicek et al., 2005; milner, 2008; and booth & knottenbelt, 1999) as well as decreasing the production of egt (smith, 1993). we have failed to find evidence to support this assertion in the available literature and believe this should be considered as expert opinion as well. in the case series from ketzner et al. (2009), 68.4% of wounds treated with casting healed with minimal scarring compared to 21.1% which healed without scarring. while this study includes wounds located to the pastern and hoof area, the number involving heel bulbs is not specified and all horses were treated with a casting, none with bandaging. an in vitro study comparing the immobilisation provided by both types of external coaptation would provide more information. casting is also potentially beneficial in cases of heel bulb laceration involving the coronet. when the coronary band is involved in the laceration, reconstructive surgery is paramount to decrease the risk of permanent deformation of the hoof wall and other complications such as hoof cracks and horn spurs (celeste and szöke, 2005). of the 61 horses available at follow-up in the janicek et al. (2005) study, 18% developed a hoof wall defect, but the number of horses treated with a foot cast compared to bandaging alone or a combination of the two is not stated. in the study from ketzner et al. (2009), 10.5% of all wounds healed with excessive scarring at the coronary band and hoof. as previously mentioned, all horses in that cases series were treated with casting and the number of wounds involving the coronary band/hoof remains unclear. it is therefore not possible to determine if this excessive scarring of the coronet and hoof is the result of a cast complication or of to original injury. the duration of the casting period is also controversial and the ideal timeframe for this immobilisation method is currently unknown. while some authors (janicek et al., 2005; and o'neill & o'meara, 2010) recommend that casts remain in place for 2–4 weeks in order to allow healthy granulation tissue to cover the wound, the publications identified in this submission each used casting for different periods of time, making it difficult to compare the benefit of shorter versus longer periods in casts.   methodology section search strategy databases searched and dates covered: cab abstracts 1973 to week 48 2018 pubmed ncbi 1910 to december 2018 search strategy: cab: (equine or equines or horse or horses or equus or equid or equids or mare or mares or broodmare or broodmares or pony or ponies or filly or fillies or colt or colts or yearling or yearlings or stallion or stallions or thoroughbred or thoroughbreds or standardbred or standardbreds or racehorse or racehorses or "race horse" or "race horses").mp. or exp horses/ or exp equus/ or exp equidae/ or exp mares/ or exp colts/ or exp foals/ or exp stallions/ or exp thoroughbred/ or exp racehorses/ (162478) ((heel or heels) and (bulb or bulbs)).mp (84) (immobilisation or immobilise or immobilised or immobilises or immobilization or immobilize or immobilized or immobilizes or (stabilisation or stabilise or stabilised or stabilises or stabilization or stabilize or stabilized or stabilizes) or (coronet or coronets or "robert jones" or rjb or "coronary bands" or "coronary band") or (bandages or bandaging or bandaged or bandage or binding or bind or bound or binds or dresses or dressing or dressed or dressings or cast or casts or casting or phalangeal cast or fix or fixed or fixing or fixes or wrap or wraps or wrapped or wrapping)).mp. or exp bandages/ (419534) (1 and 2 and 3 (13)   pubmed: (horse or horses or equine or equines or equus or equidae or equid or mare or mares or broodmare or broodmares or brood mare or brood mares or pony or ponies or yearling or yearlings or filly or fillies or colt or colts or stallion or stallions or thoroughbred or thorougbreds or standardbred or standardbreds or racehorse or racehorses or “race horse” or “race horses”) ((heel or heels) and (bulb or bulbs)) (immobilisation or immobilise or immobilised or immobilises or immobilization or immobilize or immobilized or immobilizes or stabilisation or stabilise or stabilised or stabilises or stabilization or stabilize or stabilized or stabilizes or coronet or coronets or "robert jones" or rjb or "coronary bands" or "coronary band" or bandages or bandaging or bandaged or bandage or binding or bind or bound or binds or dresses or dressing or dressed or dressings or cast or casts or casting or cast or fix or fixed or fixing or fixes or wrap or wraps or wrapped or wrapping) (#1 and #2 and #3)   hand search: paper identified outside of original search. dates searches performed: 7/12/2018 and 11/12/2018 exclusion / inclusion criteria exclusion: articles not relevant to pico question treatment other than casting or bandaging species other than equine conference papers/proceedings not published inclusion: relevant to pico question foot bandage or hoof cast/slipper cast correct wound type (heel bulb/coronet laceration) search outcome database number of results excluded – duplicates excluded – not published excluded – not relevant to pico question excluded – wrong species treated total relevant papers cab abstracts on the ovid interface 13 0 3 6 1 3 pubmed accessed via the ncbi website 5 4 0 1 0 0 hand search 1 0 0 0 0 1 total relevant papers 4 conflict of interest the authors declare no conflicts of interest. references booth, t. m. & knottenbelt, d. c. tutorial article: distal limb casts in equine wound management. equine veterinary education; 1999. 11(5):273–280. doi: https://doi.org/10.1111/j.2042-3292.1999.tb00962.x  burba, d. j. traumatic foot injuries in horses: surgical management. compendium continuing education for veterinarians; 2013. 35(1). celeste, c. j. & szöke, m. o. management of equine hoof injuries. veterinary clinics equine practice; 2005. 21:167-190. doi: https://doi.org/10.1016/j.cveq.2004.11.009  eggleston, r. b. equine wound management bandages, casts, and external support. veterinary clinics equine; 2018. 34:557–574. doi: https://doi.org/10.1016/j.cveq.2018.07.010 janicek, j. c., dabareiner, r. m., honnas, c. m. & crabill, m. a. heel bulb lacerations in horses: 101 cases (1988–1994). journal of the american veterinary medical association; 2005. 226(3):418–423. doi: https://doi.org/10.2460/javma.2005.226.418  ketzner, k. m., stewart, a. a., byron, c. r., stewart, m., gaughan, e. m., vanharreveld, p. d. & lillich, j. d. wounds of the pastern and foot region managed with phalangeal casts: 50 casesin 49 horses (1995–2006). australian veterinary journal; 2009. 87 (9): 363–365. doi: https://doi.org/10.1111/j.1751-0813.2009.00471.x milner, p. case history heel bulb laceration in a horse. uk vet: companion animal; 2008. 13(8):4-6. doi: https://doi.org/10.1111/j.2044-3862.2008.tb00519.x  o'neill, h. & o'meara, b. diagnosis and treatment of penetrating injuries of the hoof in horses. in practice; 2010. 32:484–490. doi: https://doi.org/10.1136/inp.c6671  smith, r. w. bandages and casts. equine veterinary education; 1993. 5:108–112. doi: https://doi.org/10.1111/j.2042-3292.1993.tb01012.x  acknowledgement rcvs knowledge was supported in producing this knowledge summary by an educational grant from petplan charitable trust. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. do oral or minimally invasive cheek tooth extraction techniques reduce the incidence of post-operative complications in the horse when compared to repulsion methods? a knowledge summary by victoria. a. colgate ma vetmb mrcvs 1* claire. e. wylie bvm&smsc (equine science) msc (vet epi and public health) phd mrcvs 2 timothy p. barnett bsc(hons) bvm&s msc certavp dipecvs mrcvs1 1rossdales equine hospital, cotton end road, exning, newmarket, suffolk, cb8 7nn 2university of sydney, sydney, new south wales, australia *corresponding author (vicky.colgate@rossdales.com) vol 3, issue 3 (2018) published: 18 jul 2018 reviewed by: russell parker (bvsc, msc, mrcvs, ecvs) and james carmalt (ma, vetmb, mvetsc, phd, frcvs, dabvp(eq), davdc(eq), dacvsmr(eq), dacvs professor equine surgery) next review date: 18 jul 2020 doi: 10.18849/ve.v3i3.158 pico question do oral or minimally invasive cheek tooth extraction techniques reduce the incidence of post-operative complications in the horse when compared to repulsion methods? clinical bottom line there is evidence that both oral and minimally invasive cheek tooth extraction techniques may reduce the incidence of post-operative complications in the horse when compared to repulsion methods. however, the published literature covering equine cheek tooth extraction techniques is sparse and of low evidential quality, so a definitive answer on the optimal methods available is not easily determined. bearing this in mind, the results of this pico suggest the use of oral extraction, after periodontal stretching, as the first line treatment due to its apparently more favourable success rate. where an alternative approach is required, such as with fractured teeth or loss of clinical crown, which can prevent the use of routine oral extraction methods, results indicate that minimally invasive extraction techniques may result in a better outcome, with fewer complications, than repulsion methods. further research that accurately categorises the various minimally invasive techniques available and compares them to repulsion and conventional oral extraction methods is needed. clinical scenario a 7-year old thoroughbred (tb) mare presents with a recent history of right facial swelling, which is painful and warm on palpation. after examination with an oral speculum, oral endoscopy and radiography you make a diagnosis of periapical infection of cheek tooth triadan 107 (2nd premolar, upper right arcade). you discuss treatment options with the owner: one of which is to extract the affected tooth. however, the owner is concerned by reports online that cheek tooth removal is associated with a large number of potential complications. what evidence is there to inform the owner that the oral or minimally invasive cheek tooth extraction techniques you have at your disposal are associated with less post-operative complications compared to repulsion techniques carried out under general anaesthesia (ga)? the evidence cheek tooth exodontia is a common procedure in equine practice, yet it is often a complex surgery that has the potential to cause serious short and long-term complications for the horse (casey and tremaine, 2010; ramzan, 2009). cheek teeth have previously been removed with a punch and hammer by repulsion through an osteotomy or by lateral buccotomy, both of which often require a ga.  the traumatic nature of repulsion means that damage to the alveolus, surrounding teeth, as well as the maxillary and mandibular bones is common (dixon, hawkes and townsend, 2008). this can lead to serious post-operative sequelae including: alveolar bone sequestrae, localised osteomyelitis and orosinus fistula with subsequent sinusitis. the clean-contaminated nature of both the repulsion and buccotomy techniques additionally increase the risk of incisional dehiscence and infection to the extent that lillich (1998) described complications of dental surgery to be ‘inevitable’. with the advent of effective sedatives and regional anaesthetic techniques, more advanced surgeries have become possible in the standing horse (dixon et al., 2005) and oral extraction is now the treatment of choice for cheek tooth exodontia. uncomplicated oral extraction should leave the supporting bones intact and the less traumatic nature of the technique means that post-operative complications are comparatively uncommon and, when they do occur, are much easier to treat (dixon, hawkes and townsend, 2008).  an 89% success rate for oral extraction was recorded by dixon et al (2005)  in younger horses with a long reserve crown. additionally ramzan, dallas and palmer (2011) reported an 87% success rate for complete removal of fractured cheek teeth using a dental pick elevation and oral forceps extraction technique under endoscopic guidance. suggested difficulties of the oral extraction technique include low patient compliance, the presence of teeth with advanced disease that cannot withstand forces of extraction or teeth that have too small a crown to be grasped by instruments (langeneckert et al., 2015). even in cases where reversion to a surgical approach is required it has been documented that an initial attempt at oral extraction significantly loosens the periodontal ligament to allow repulsion techniques to be carried out with less force, potentially resulting in fewer complications (dixon et al., 2012). where a surgical approach is required initial evidence suggests that methods, such as minimally invasive transbuccal screw extraction (mitse) and minimally invasive repulsion may provide a superior alternative to traditional repulsion (langeneckert et al., 2015). at the very least, these techniques can be performed under standing sedation thus negating the costs and potential morbidity and mortality associated with a ga.  although there is currently little literature on the minimally invasive techniques it seems that these are also not without complication. the transbuccal surgical approach still risks causing damage to the parotid salivary duct, facial vessels and nerves (langeneckert et al., 2015). reichert et al, (2014) suggested that pre-operative antibiotics were required in all cases as repeated introduction of instruments through the cannula in the cheek led to contamination of the incision, predisposing to infection and dehiscence. removal of cheek teeth causes disruption of the mastication unit that, in turn, can lead to wear abnormalities and tooth drift with subsequent adverse long-term effects on the chewing process (vlaminck et al., 2008). these long-term effects of tooth loss and the complications associated with ga will not be discussed here. rather, this patient/population-intervention-comparison-outcome (pico) question focuses on the benefits and complications directly associated with the technique chosen for cheek tooth exodontia. a total of 10 papers were found to fit the pico criteria and the evidence gained from these is reported below. summary of the evidence langeneckert (2015) population: equids (38 warmbloods (wb), 6 draft horses, 3 tbs, 3 quarter horses, 2 ponies, 1 miniature horse and 1 mule) presented to 4 referral centres (3 in switzerland and 1 in the uk) between 2010 and 2014 for attempted cheek tooth removal by the mitse technique. animals ranged in age from 3 to 23 years (mean 11 years) at the time of treatment. reasons for cheek tooth exodontia included 50 teeth with apical infection, 48 fractures, 4 neoplasia, 2 displacements and 1 supernumerary cheek tooth. sample size: 54 equids on which 58 separate mitse procedures were carried out. intervention details: medical records between 2010 and 2014 were searched for equids that had undergone a mitse procedure.  in each case identified, the following information was recorded from the medical history: signalment affected tooth preoperative clinical findings and imaging modalities used history of prior oral extraction attempts and reasons for their failure. complications encountered during mitse and hospitalisation additional surgical procedures after mitse duration of hospitalisation mitse was carried out on 49 maxillary and 9 mandibular cheek teeth. a small stab incision was used to create a transbuccal approach and a commercial, purpose built instrument set with a trocar-cannula unit, used to perform the procedure. follow up information obtained 6-46 months after hospital discharge by telephone interview with the owner or referring vet. specific information regarding nasal discharge, facial asymmetry and signs consistent with surgical site infection was requested. study design: multi-centre case series with follow-up. outcome studied: outcome of mitse (success or failure), where extraction was defined as successful if the entire dental structure was removed with no need for further intervention. frequency and type of intraoperative, short and long-term complications were recorded.  main findings (relevant to pico question): the paper reports that: 55/58 (95%) cases had previously experienced failed oral extraction. subsequent mitse successfully removed the entire dental structure in 47/58 cases (proportion = 0.81, 95% ci of proportion = 0.70-0.90). success was seen in 41/49 (84%) maxillary and 6/9(67%) of mandibular cases. mitse failed to remove the entire dental structure in 11 cases: 9/11 of these teeth were then successfully removed by a minimally invasive repulsion technique and 1/11 by traditional repulsion. in 1/11 mitse failed to completely remove a supernumerary molar but no further efforts were made to extract the residual dental material. 54/58 mitse procedures were carried out under standing sedation. four equids received a ga due to dangerous behaviour. 83 intraoperative difficulties were recorded during 44/58 procedures: extraction screw pullout occurred in 32 procedures due to friable tooth material (n=19) or mechanical lockage of the target tooth in the extraction pathway (n=13). 4/58 cases (7%) developed significant haemorrhage from the trocar incision leading to post-operative swelling of the cheek and transient facial nerve paralysis in 2 cases. 1/58 cases developed an oroantral communication. 3/58 cases developed temporary (24 hour) loss of facial nerve motor function due to diffusion of local anaesthetic. long-term follow-up was available in 41/44 cases where mitse was successful: all transbuccal approaches healed without scarring or facial asymmetry. 98% of owners satisfied with cosmetic and functional outcome. no long-term complications reported after mandibular mitse. in 6/17 maxillary cases with pre-operative nasal discharge mitse failed to resolve this with 5/6 cases requiring further surgical treatment and 1/6 left with intermittent nasal discharge. limitations: retrospective study with follow-up being obtained up to 46 months post-surgery, introducing potential for recall bias and loss of cases prior to follow-up. no control or comparison group. limited statistical analysis. some horses had multiple teeth removed each extraction counted as a separate procedure even though it was the same horse. most but not all cases had previously undergone oral extraction, which had failed, causing conversion to mitse. reichert (2014) population: horses (12 wbs, 3 ponies, 2 haflingers, 1 arabian, 1 morgan, 1 tb and 1 standardbred) with fractured clinical crown of a cheek tooth admitted to a single german clinic between july 2012 and january 2014 for removal of the tooth by a method other than oral extraction. mean age of study horses was 11.7 years (range 4-26 years). sample size: 21 horses from which 23 cheek teeth were independently removed. intervention details: medical records of all horses admitted to the clinic between july 2012 and january 2014 were reviewed. inclusion criteria: horses that underwent cheek tooth removal by a method other than oral extraction due to presence of an existing clinical crown fracture or that developed idiopathic fracture during attempted oral extraction. cheek teeth were removed by a variety of techniques: minimally invasive buccotomy with and without screw extraction (n=20) traditional repulsion (n=1) combination of repulsion and traditional lateral buccotomy (n=1) combination of repulsion and minimally invasive buccotomy (n=1) short term complications (<14 days post-surgery) were recorded from the clinical records. long term complications (>14 days post-surgery) and outcome obtained by telephone questionnaire with the owner. study design: single centre case series with follow-up. outcome studied: outcome of alternative techniques for cheek tooth removal when oral extraction has failed. type and frequency of complications encountered. complications were divided into intraoperative, short and long term as well as being further categorised as related to surgery or not. main findings (relevant to pico question): all 23 teeth were successfully removed(100% success rate): 5/23 intact 18/23 in multiple fragments intraand post-operative complications occurred in 15/23 procedures (65.2%) with 7 of these suffering multiple complications. 12 intraoperative complications were related to surgical technique: development of oro-maxillary fistula after minimally invasive buccotomy (n=6) fragments left in the alveolus after minimally invasive buccotomy(n=3) haemorrhage from the buccotomy site with haematoma formation (n=2) laceration of the palatine artery with resultant haemorrhage during minimally invasive buccotomy (n=1). the only short-term surgery related complication recorded was incisional infection at the buccotomy site (n=2). long-term surgery related complications included: development of an alveolar sequestrum following piecemeal tooth extraction by minimally invasive buccotomy (n=2). development of necrotic tissue at the buccotomy site (n=1). facial nerve paralysis was not observed after any surgical procedure. limitations: retrospective study at a single clinic with a small sample size. the technique for cheek tooth removal was not the same in all cases but results presented together. largely descriptive with minimal statistical analysis. the paper defines fragments left in the alveolus to be an intraoperative complication related to the surgical procedure. long term complications and outcome obtained by telephone questionnaire with the owner, giving potential for reporting bias. o’neill (2011) population: horses (42 wbs, 26 tb crosses, 13 tbs, 11 ponies, 4 miniature ponies and 18 miscellaneous breeds) admitted to 2 referral centres (1 in belgium and 1 in the uk) between 1999 and 2009 for removal of a cheek tooth by lateral buccotomy. included horses had an average age of 8.09 years at admission (range 2-25 years) and consisted of 54 geldings, 51 mares and 9 intact males. 52% of buccotomies were carried out due to fractured cheek teeth and just 34% due to periapical infection. sample size: 114 horses from which 134 cheek teeth were removed. intervention details: case records from 114 horses undergoing lateral buccotomy for cheek tooth removal obtained and the following information recorded: history presenting signs diagnostic tests performed intraoperative complications post-operative outcomes short (<2 months) and  (> 2 months) outcome obtained by re-examination or telephone interview with the owner/trainer. in all cases where a clinical crown was present oral extraction was initially attempted under standing sedation. if unsuccessful, lateral buccotomy was carried out under ga 24 hours later. study design: multi-centre case series with follow-up. outcome studied: success rate (not clearly defined) of lateral buccotomy for cheek tooth removal and frequency of procedure-related, short and long-term complications.  chi-squared test used to compare the incidence of wound dehiscence for maxillary and mandibular extractions. significance set at p<0.05. main findings (relevant to pico question): the paper reports that lateral buccotomy had a success rate of 70% in the short term and 92% in the long term. 34/114 (30%) horses suffered a procedure-related complication: 16 horses (14% of total horses) suffered partial wound dehiscence at the lateral buccotomy site, which healed by secondary intention within 6 weeks post-surgery. 13 of these incisions were maxillary and 3 mandibular. 3 horses (3%) developed permanent facial paralysis with drooping of the lower lip. this was not reported to impair prehension of food or ridden exercise in the long term. 6 horses (5%) showed signs of temporary paresis of the buccal branch of the facial nerve that resolved within 1 week. 4 horses (4%) developed an oroantral fistula. 4 horses developed myositis post ga. in 3 horses this resolved within 48hrs but a 19yr old horse was euthanased due to severe myositis. (average ga time was 124 minutes, range 29-200 minutes). 5 horses developed persistent sinusitis after surgery. 8/114 horses (7%) required further surgical procedures, mostly to treat ongoing sinusitis. in 16% of horses the complications of lateral buccotomy led to long-term sequelae or further surgical intervention in the short term. 92% of the 112 horses available for follow-up (1horse euthanased and another lost to follow-up) returned to their previous level of work >2 months after surgery. there was no significant difference in incidence of wound dehiscence between maxillary and mandibular extractions. (p = 0.55) limitations: retrospective study. success rates are reported but the definition of a ‘success’ is not given. authors conclude that ‘no long-term complications were noted’ yet 3 horses suffered permanent facial nerve paralysis. no control or comparison group. most horses had undergone attempted oral extraction, which had failed. in the methodology the paper claims to compare the incidence of wound dehiscence for maxillary and mandibular extractions but a proportion, rather than an incidence rate, is what is actually calculated. the lack of a statistically significant difference between these proportions, as calculated by the chi-squared test, is not evidence of lack of a real difference due to the small sample size and lack of a power calculation giving the statistical test low validity. ramzan (2011) population: horses (15 tb or tb crosses, 7 wb or wb crosses and 8 pony or mixed breed horses) that underwent standing oral extraction of fractured cheek teeth under endoscopic guidance at a single uk hospital between april 2007 and april 2010. 16 mares and 14 geldings were included with an average age of 11.5 years (range 5-23 years). all horses had clinical signs or fracture configurations that were considered to warrant exodontia. sample size: 30 horses from which a total of 31 fractured cheek teeth were removed. intervention details: medical records of horses admitted to the hospital for cheek tooth removal between april 2007 and april 2010 were reviewed. inclusion criteria: horses that underwent oral extraction of a fractured cheek tooth under endoscopic guidance. exclusion criteria: horses where extraction of the entire tooth was not the aim. in each included case the endoscopic video was reviewed and the following details recorded from the medical history: signalment tooth location fracture configuration outcome variables under standing sedation and endoscopic guidance, dental picks were used to progressively disrupt the periodontal attachments before elevators and forceps were used to complete the oral extraction.  use of cheek tooth ‘separators’ was avoided to prevent further breakdown of the clinical crown. study design: single centre case series outcome studied: the outcome was recorded as a binary categorical variable of ‘successful or unsuccessful’, where a success was defined as the complete removal of the fractured tooth from the alveolus. median age of horses in the success and failure group was compared using a mann-whitney u-test. main findings (relevant to pico question): 27/31 fractured teeth (87%) were successfully removed by standing oral extraction with endoscopic guidance. for 4/31 fractured teeth, oral extraction was unsuccessful due to: fragmentation of the clinical crown prior to sufficient periodontal loosening (n=2) poor access to tooth (n=1) poor patient compliance (n=1) median age of horses in the extraction failure group was 7 years, which was significantly younger than the median age in the extraction success group (median 12 years, p= 0.01, mann-whitney u-test) limitations: retrospective study with a small sample size. study performed at a single hospital, thus limiting generalisability of the results obtained to the wider equine population. no control or comparison group. solely reports success or failure of extraction technique with no details of any complications and no follow-up. all teeth removed were fractured so representing a very specific clinical situation. coomer (2011) population: horses (n=12) and ponies (n=6) undergoing standing cheek tooth repulsion following failed oral extraction in a single uk hospital between 2006 and 2009. breeds and sexes are not reported but median age of included horses was 7 years (range 1-30 years). all horses had maxillary (n=15) or mandibular (n=5) cheek tooth disease that necessitated exodontia. sample size: 12 horses and 6 ponies from which a total of 20 cheek teeth were successfully removed. intervention details: medical records of 82 horses that underwent attempted oral extraction of a cheek tooth were reviewed. inclusion criteria: horses where oral extraction failed and the tooth was subsequently removed by standing repulsion (n=18). for included horses the following information was recorded from the medical notes: signalment results of clinical, oral, radiographic and endoscopic examinations surgical technique post-operative complications long-term (>6month, range 6-41 month) follow-up was obtained by: repeat clinical examination (n=9) telephone interview with owner (n=8). telephone interview with referring vet (n=1). repulsion in this study is an adaption of the traditional approach: for intact teeth a 16mm galt trephine and dental punch were used to create an osteotomy. for root fragments a carbide metal drill bit was used to remove bone in preparation for a 5mm dental punch. intraoperative radiographs were obtained periodically to check punch position and hammering was continued until the tooth was loose enough to be manually removed from the mouth. all surgeries were carried out under standing sedation with maxillary and/or infraorbital nerve blocks to provide regional anaesthesia. study design: single centre case series with follow-up. outcome studied: proportion of cases where standing repulsion was successful and type and frequency of post-operative complications. main findings (relevant to pico question): the paper reports that: all 20 cheek teeth (100%) successfully removed by standing repulsion. in 8 horses the infraorbital nerve block failed to provide sufficient desensitisation, requiring a maxillary nerve block to be additionally performed. 10/17 horses (59%)(1 horse euthanased for an unrelated reason and lost to follow-up) showed resolution of the presenting clinical signs following repulsion. 41% required additional medical or surgical treatment to resolve the clinical signs. only complication after repulsion of mandibular cheek teeth was ongoing discharge in one horse that resolved after antibiotic treatment. the authors report that after maxillary cheek tooth removal sinusitis was the only complication encountered (6/13 horses, 46%). sinusitis was due to: displacement of the alveolar plug (n=2) cause not reported (n=1) on-going sinusitis (n=3). this should not really be regarded as a surgical complication but more an observation that the procedure failed to resolve one of the presenting clinical signs. minimal haemorrhage reported during repulsion most likely due to the elevated head position afforded by standing surgery. limitations: small retrospective study performed on data from a single hospital. no control or comparison group. all horses had initially undergone oral extraction, which failed. some whole teeth and some dental fragments removed but results not separated. largely descriptive results. some follow-up gained by questionnaire up to 41 months after the procedure introducing the potential for recall bias and loss of cases to follow-up. no definition of success or calculation of proportion of successful procedures just implied by the statement that 20 cheek teeth were successfully extracted. as presented above, numerical proportions and percentages used interchangeably throughout the text, often without qualification of the denominator. tremaine (2010) population: horses (2 tbs, 1 arab, 2 friesians, 1 appaloosa, 1 irish draft cross, 1 connemara cross, 1 welsh and 1 welsh cob) presenting to a single uk clinic between 2002 and 2008 for removal of impacted cheek teeth. study horses included 4 geldings, 5 mares and 1 intact male with a median age of 5 years (range 2-11 years). all horses had clinical signs of dental disease, including maxillary or mandibular swelling. sample size: 10 horses from which 11 incompletely erupted, impacted cheek teeth were removed. intervention details: medical records of horses requiring removal of incompletely erupted, impacted cheek teeth were reviewed and the following information collected: signalment results of clinical and ancillary diagnostic examinations i.e. radiography and oral endoscopy treatment response to treatment long term (> 6 months, range 6-48 months, median 9 months) follow-up information was obtained by: re-examination (n=4) telephone questionnaire with owner (n=5) cheek tooth removal was carried out by: transcortical osteotomy and buccotomy (n=9) repulsion assisted by ventral osteotomy (n=1) both procedures were performed under ga with additional regional nerve blocks. fluoroscopy was used to confirm position of the osteotomy which was made using a sharp osteotome or air-powered drill. periodontal attachments were disrupted and the tooth sectioned before dental fragments elevated and removed through the osteotomy or repulsed into the oral cavity. study design: single centre case series with follow-up. outcome studied: descriptive report of the procedures carried out, complications encountered and long term outcome. main findings (relevant to pico question): 2 horses (18% of procedures) developed incisional dehiscence after the alveolar packing was removed. 2 horses (18% of procedures) had a prolonged discharging tract post-surgery due to a fissure in the alveolus. both eventually resolved after curettage of the alveolus. no facial nerve deficits were seen post-operatively. all 10 horses were reported to have developed a marked, non-painful mandibular swelling after surgery that gradually remodeled, but was still present 6 months later in 3 horses (3/11 (27%) of procedures). (it seems unlikely that a mandibular swelling would have occurred in the single horse having a maxillary tooth removed, so it is likely this proportion should only be out of 10 but a percentage out of 11 is what the paper reports.) at median 9 month follow-up all horses had returned to work and no longer showed any clinical signs of dental disease. limitations: retrospective study carried out at a single hospital with a small sample size. some follow-up information obtained by questionnaire up to 48 months after surgery introducing potential for recall bias and loss of cases to follow-up. largely descriptive with no definition of a successful procedure or proportion calculated. not all cases received the same treatment yet data interpreted together. all cases of incompletely erupted, impacted cheek teeth yet in reality exodontia may be performed for many reasons. presentation of results is confusing as the paper presents numbers of horses combined with percentages of the total teeth removed/procedures carried out. dixon (2005) population: younger horses (median age 8 years, range 2-18 years) presenting to a single uk clinic between 1998 and 2003 for oral extraction of rigidly attached cheek teeth. study horses included 34 tbs, 20 tb crosses, 26 ponies, 5 draught horses, 5 wbs and 10 miscellaneous breeds. horses presented with a variety of disorders: 54 primary apical abscesses, 21 fractured cheek teeth, 13 displacements, 8 diastema, 2 supernumerary cheek teeth and 2 wear abnormalities. sample size: 100 horses from which 111 cheek teeth were extracted. intervention details: data collected from 100, mainly younger horses, consecutively undergoing standing oral extraction of rigidly attached cheek teeth by the first author. to be included, long-term post-operative evaluation had to be available. cases of oral cheek tooth extraction in older horses with short reserve crowns or advanced periodontal disease were excluded. oral extraction was carried out using the following technique: dental pick used to separate the gingiva from the cheek tooth. cheek tooth separator (molar spreader) then pushed into each interdental space and left in place for 3-5 minutes. cheek tooth extraction forceps (molar extractors) placed on the clinical crown and moved gently in a horizontal plane until foamy blood seen at the gingival margin. once the tooth was digitally loose a fulcrum was used to lever it vertically into the oral cavity. follow up was obtained by postal questionnaire sent to owners/trainers at a median of 16 months post-surgery. study design: single centre case series with follow-up. outcome studied: outcome of oral extraction reported as a binomial categorical variable of ‘success or failure’. type and frequency of post-operative problems encountered. largely descriptive report of long-term outcome. main findings (relevant to pico question): oral extraction of cheek teeth was successful in 89% of younger horses. in 11/100 horses oral extraction failed to remove the affected tooth intact. intraoperative fracture of the clinical crown was the most common cause of oral extraction failure (9/11 horses). 5/9 (56%) horses had existing pathological changes to the clinical crown that predisposed to fracture. in 18/21 horses with pre-existing cheek tooth fracture (86%) oral extraction was successful, indicating value as the initial line of treatment in these cases. 3/21 horses with existing fracture developed idiopathic clinical crown fracture during extraction, necessitating later removal by repulsion. 8 cases suffered post extraction complications; mainly alveolar sequestration (n=4) and localised osteitis. 7/49 cases with primary apical infection where the tooth was successfully extracted (14%), developed post-operative complications compared to 2.5% of cases without apical infection. local trauma to the hard palate was common after maxillary extraction. 1 horse developed haemorrhage as a result of damage to the greater palatine artery during extraction. this was controlled and led to no further complications. the paper reports that when extraction failure and post-operative complications are combined, 12/54 cases with apical infection (22%) developed extraction related problems compared to 7/46 (15%) of other cases.in the statistical analysis section, comparison of present results of oral extraction of 54 horses with apical cheek tooth infections (22% failures or post-operative problems) is made with the results of repulsion in 71 cases of apical cheek tooth infection also at this clinic, but reported in a previous study (49 % of post-operative problems) (dixon et al 2000b). when pearson’s chi-squared test for proportions was used this showed a significantly lower level of surgical failures and post-operative problems with oral extractions compared to repulsion (x2 =8.46, p=0.003). comparing just post-operative problems the level of significance increases (x2=14.12, p<001). limitations: no contemporaneous or randomised control group with comparisons made to a previously published historical control group of repulsion in 71 cases of apical cheek tooth infection at the same clinic. comparisons of success are drawn between techniques of oral extraction (this study) and repulsion (previous study at same clinic) for removal of cheek teeth. largely descriptive data, with application of a chi-squared test as a test of association for the proportion of surgical failures and post-operative problems combined in the oral extraction and the historical control group. no further analysis of outcome data performed. study based at a single hospital. long-term follow-up data displayed in the results table but not sufficiently discussed. duncanson (2004) population: horses (6 tbs, 27 tb crosses, 6 arabs, 5 arab crosses, 1 shire, 1 irish draught cross, 3 hunters, 5 cobs, 4 welsh ponies, 1 highland pony, 23 shetland ponies, 1 connemara pony and 42 cross bred ponies) requiring cheek tooth removal consecutively treated by the author in uk general practice, between september 1997 and february 2001. reasons for cheek tooth exodontia included: loose tooth/teeth (n=91) iatrogenic fractured tooth (n=8) displaced tooth (n=6) (1 supernumerary) maxillary tooth apical infection with secondary sinusitis causing malodorous nasal discharge (n=8) rostral maxillary tooth apical infection with external discharging sinus tract (n=2) mandibular tooth apical infection with external discharging sinus tract (n=7) diastema (n=3) the study horse population consisted of 68 mares, 55 geldings and 2 intact males. sample size: 125 horses (71 ponies and 54 horses) from which 155 cheek teeth were removed. intervention details: 125 horses consecutively undergoing cheek tooth removal by the author were included in the study: 68 primary cases and 57 referrals from other vets or equine dental technicians. for each horse the following details were recorded: sex, size, estimate of breed history body condition score as determined by visual assessment where 1=cachectic and 10= obese. clinical signs attributable to dental pathology. horses age was recorded as one of the following groups: birth6 months (age of erupting deciduous teeth) (n=0) 6 months2.5 years (age of deciduous teeth in wear) (n=0) 5-5 years (age of shedding of deciduous teeth) (n=2) 6-11 years (age of disappearing cups) (n=12) 12-18 years (age of disappearing stars) (n=28) 19 years and older ( age of v-shaped mandible, no stars) (n=83) cheek teeth were removed by: standing oral extraction with instruments (n=117). digital manipulation (n=8).  no regional anaesthesia used to aid extraction in any case. study design: single centre case series outcome studied: time taken for completion of extraction. nature and frequency of any complications encountered. main findings (relevant to pico question): oral extraction of cheek teeth under standing sedation was successful in all 125 horses. in 91/125 horses (73%) extraction was completed in <20 minutes (all these teeth were digitally loose on initial palpation) average time for extraction in old horses (group 6 n=83 and group 5 n=28) was just over 20 minutes, range 3-49 minutes. average time for extraction in young horses (group 4 n=12 and group 3 n=2) was 74 minutes, range 60-122 minutes. author suggests that difference in average length of the procedure is a good indicator in the difference in difficulty level of extracting a cheek tooth from an old, compared to a young horse. 3/125 horses suffered fracture of the tooth root during extraction but all fragments were eventually removed. alveolus was not packed post-extraction and no horses required additional surgery as a result. limitations: results collected from a single ambulatory practice. results mainly descriptive with little statistical analysis. no comparison or control group. study in general practice of mainly older horses, which limits its comparability with alternative extraction techniques investigated in different studies carried out on young horses in the referral setting. no follow-up carried out. body condition score recorded but data not interpreted.  dixon (2000b) population: horses suffering from primary apical infection of their cheek teeth referred to a single uk equine clinic. in 92 horses (median age 7 years) a maxillary cheek tooth was affected and in 70 horses (median age 5 years) a mandibular tooth was affected. specific breed and sex details are not reported but ponies made up 35% of the entire group of study equids and 54% of mandibular cases. sample size: 162 horses suffering from primary apical cheek tooth infection, of which 96 had the infected tooth removed by repulsion under ga and 26 by oral extraction under standing sedation. intervention details: records of 400 horses suffering from dental disease and admitted to edinburgh vet school for treatment by the first author were analysed.  this included: 353 consecutive cases seen between 1984 and 1998. 47 documented cases with follow up information seen prior to this period(dixon et al 2000a). of the 400 horses referred, 162 suffered primary apical infection of the cheek teeth and were included in this part 4 paper (the same study has produced results that have been published in 4 separate papers this paper being the 4th of the series) of relevance to the pico are those that had the infected tooth removed: mandibular tooth repulsed under ga via a ventral mandibular osteotomy beneath the apex of the affected tooth (33 cases). standing oral extraction of a mandibular tooth without regional or local anaesthesia (14 teeth from 12 cases). oral extraction of a mandibular tooth under ga (3 cases). maxillary tooth repulsed under ga via a 2-3cm trephine hole for rostral maxillary teeth or via a 5-6cm maxillary flap for caudal maxillary cheek teeth (69 teeth from 63 cases). standing oral extraction of maxillary teeth (10 cases). oral extraction of maxillary tooth under ga (4 cases). for each case, records, dental specimens and radiographs were re-examined.  (due to advances in knowledge during the study period this sometimes led to alteration of the initial diagnosis.) follow up information was usually obtained by repeat examination. if this was not possible information was obtained by telephone or written questionnaire with the owner/trainer/referring vet. study design: single centre case series with follow-up. outcome studied: outcomes studied that are relevant to the pico: frequency of successful extraction with different techniques. frequency and nature of shortand long-term complications encountered. all outcomes are discussed separately for extraction of mandibular and maxillary cheek teeth. main findings (relevant to pico question): for mandibular cheek teeth extracted by repulsion (n=33): affected apex and distal reserve crown usually disintegrated due to concussive forces before the tooth was palpably loose per os. in some cases displacement of the dental punch led to mandibular fracture. fracture replaced by digital compression without long-term consequence. 28/33 cases were available for follow-up, of which: 5/28 cases showed food at the surgical site due to displacement of the wax plug, however, this did not lead to any long-term problems. 1/28 developed quidding of feed months after surgery when food became trapped beneath a loose acrylic plug. 6/28 cases (21%) had chronic post-operative sinus tracts. for mandibular cheek teeth removed by oral extraction (n=12): all 14 teeth successfully removed intact. 9/12 cases available for follow up (median 1.5years) and all showed complete resolution of clinical signs. the study concluded that oral extraction was the method of choice for removal of most mandibular cheek teeth. oral extraction resulted in fewer post-operative complications with 9/12 cases (75%) responding to initial treatment, compared to 18/28 (64%) with repulsion. for maxillary cheek teeth removed by repulsion (n=63): 4 cases with dental sinusitis at presentation developed an oromaxillary fistula due to premature loss of the alveolar plug after surgery. 43/63 cases were available for follow-up: 19/43 cases were cured from dental infection after initial treatment, but 4/19 developed non-dental related post-operative complications such as pyrexia and severe sinus haemorrhage. 24/43 cases showed continuation or recurrence of clinical signs following repulsion. 3 cases showed chronic sinusitis with low-grade nasal discharge for > 6 weeks post-operatively. for maxillary cheek teeth removed by oral extraction (n=14): all 10 cases with rostral cheek teeth extracted healed quickly with no further complications. the paper concludes that when oral extraction and repulsion results are combined; initial surgery had a cure rate of 84% for rostral maxillary and 68% for mandibular cheek teeth. horses presenting with secondary dental sinusitis had a poorer prognosis with just 33% cured with initial treatment. limitations: retrospective study carried out at a single clinic over >14 year period, during which time (as the paper admits) diagnostic and surgical techniques were altered/updated. this means individuals in each group did not all receive exactly the same treatment, limiting their direct comparability. yet conclusions were made about differences between groups without statistical validity. comparison drawn between 96 horses undergoing repulsion and 26 undergoing oral extraction of cheek teeth but no randomised control group included in the study. largely descriptive analysis of results and comparison of proportions between treatment groups. cheek tooth removal is not the entire focus of the paper. data on success of technique difficult to interpret as results from maxillary and mandibular teeth are sometimes separated and sometimes grouped. prichard (1992) population: horses undergoing repulsion of diseased cheek teeth in a single american hospital. the 36 horses (12 tbs, 6 quarter horses, 5 standardbreds, 4 belgians, 3 arabians, 3 grade horses and 3 of other breeds) undergoing maxillary repulsion had a median age of 5 years (range 2-27 years) and consisted of 21 mares, 8 geldings and 7 intact males. the 25 horses (7 tbs, 4 standardbreds, 3 quarter horses, 3 grade horses, 2 arabians, 2 morgans and 4 of other breeds) undergoing mandibular repulsion had a median age of 4 years (range 1-14 years) and consisted of 12 mares, 9 geldings and 4 intact males. sample size: 61 horses from which 50 maxillary and 27 mandibular cheek teeth were removed. intervention details: hospital records searched to identify horses that had undergone cheek tooth repulsion for treatment of alveolar periostitis.  61 cases were reviewed and the following information recorded: signalment clinical presentation methods of therapy complications encountered during surgery and hospitalisation all teeth were removed by repulsion under ga with varying surgical approaches. for maxillary teeth: 19 flap sinusotomies 11 trephinations 3 windows created by motorised burrs 2 windows created by enlarging the draining tract with rongeur forceps 1 approach unrecorded for mandibular teeth: 13 ventral windows created with a motorised burr 7 trephinations 4 using an osteotome and mallet 1 approach unrecorded long-term follow up (> 5 months post-op) obtained by re-examination or telephone interview with the owner/trainer. study design: single centre case series with follow-up. outcome studied: type and frequency of intraand post-operative complications following surgical repulsion of a diseased cheek tooth under ga. main findings (relevant to pico question): 36/61 horses underwent maxillary tooth repulsion (50 teeth): 4/36 horses suffered intraoperative complications: repulsion of the incorrect tooth (n=1) fracture of lateral alveolar wall (n=1) fracture of medial alveolar wall and palatine bone (n=1) extensive osteomyelitis causing the bone flap to be discarded (n=1)   17/36 horses (47%) suffered serious post-operative complications with 8 horses requiring further intervention. (usually due to development or recurrence of nasal discharge). 30 horses were available for long-term follow up. (2 died and 4 were lost to follow-up) 6/30 (20%) horses suffered chronic nasal discharge +/oro-maxillary fistula. 24/30 (80%) healed with no further complications.   25/61 horses underwent mandibular tooth repulsion (27 teeth): 3/25 horses suffered intraoperative complications: fracture of medial alveolar wall (n=2) fracture of lateral alveolar wall and incorrect tooth repelled (n=1) 8/25 horses (32%) suffered serious post-operative complications with 4 requiring additional surgery. eventually: 3/8 recovered fully 3/8 developed chronic discharging tracts 2/8 died before long-term follow up 2/3 horses with chronic draining tracts additionally developed mandibular swelling. 1 case of mandibular swelling developed an odontogenic carcinoma at the surgical site. 14/17 horses available for long term follow up (82%) healed with no further or mild problems such as swelling or mild scarring. the paper concludes that although serious post-operative complications were common following repulsion. however, long-term outcome was good with approximately 80% of horses with available follow-up resolving the complication and having no further problems 5 months or more after surgery. limitations: retrospective study carried out at a single centre. different surgical approaches are used for repulsion but all outcome results interpreted together. horses only treated by repulsion so no direct comparison to other methods of cheek teeth removal can be made. nature of serious post-operative complications are mentioned in the abstract but not explained or discussed in the paper. with some follow-up information obtained by telephone questionnaire up to 5 months post-surgery there is potential for introduction of recall bias and loss of cases to follow-up. appraisal, application and reflection ten case-series studies were identified to be relevant to the pico, largely reporting descriptive data on a single surgical technique, with minimal statistical analyses. due to the lack of control groups in the published studies comparisons of techniques have to be drawn between different studies, as demonstrated in dixon et al (2005). there are inherent differences between all these studies in terms of the signalment of the equine population included, the reason for cheek tooth exodontia and the definition and type of complications recorded. whilst the heterogeneous nature of the study designs, population of horses and recorded data preclude direct comparisons of their results with each other, this pico has presented clear evidence in the differing populations for the benefit of oral extraction, in terms of reduced complication rates, over repulsion for extraction of equine cheek teeth. in line with our scenario, and often the case clinically, most of the studies include referral cases of cheek tooth exodontia in fairly young horses. however, duncanson (2004) carried out a case series of 125, mainly older horses, undergoing standing oral extraction in general practice. 66% (83/125) of horses included in the study were >19 years old, often with the teeth requiring extraction being digitally loose on palpation. this represents a very different horse population to the young horses with firm periodontal attachments referred to a hospital for exodontia. as such this study is of limited relevance to the pico and findings should be compared to those of the other studies with caution. cheek tooth removal could be indicated for a number of reasons, as demonstrated by the variation and scope of inclusion criteria between studies. the initial clinical presentation is likely to affect the extraction method used and, in turn, the outcome of the surgical procedure and any potential complications encountered. for example,  tremaine and mccluskie (2010) carried out a study on a very small population of horses all requiring exodontia due to incompletely erupted, impacted cheek teeth.  however, it has been reported that idiopathic apical infection is the most common indication for cheek tooth removal in the young horse (dixon et al, 2005). therefore, the results of these two population may not be directly comparable, and any conclusive comparisons need to be made with caution.  while making up part of the population in other studies, ramzan, dallas and palmer, (2011) and reichert et al (2014) report on methods for extraction of cheek teeth solely with fractured clinical crowns. a fractured clinical crown has previously been reported as a reason to preclude oral extraction (boutros and koenig, 2001) and the fragility and likelihood of fragmentation of these dental tissues complicates exodontia (ramzan, dallas and palmer, 2011). as such, studies including fractured teeth could be reporting a falsely high frequency for complication that actually is not associated with the procedure but the presenting complaint. although potentially lacking definitive evidence, there is almost universal agreement amongst the published authors that oral extraction under standing sedation should be the treatment of choice for equine cheek tooth exodontia, but when this fails a viable alternative is required. coomer, fowke and mckane (2011), o’neill et al (2011) and langeneckert et al (2015) report on methods of extraction used when initial oral extraction has failed. this accurately represents the clinical situation but the disruption of the periodontal ligaments that occurs during oral extraction may have aided subsequent surgical removal (dixon et al., 2012) to improve the success and reduce the complication rates reported. how the outcome of the surgical procedure and complications encountered is reported also shows great variation amongst the papers studied. the outcome of surgery is reported as a binomial categorical variable but only ramzan, dallas and palmer (2011) and langeneckert et al (2015) clearly define what is regarded as a ‘success’ or ‘failure’: for the other studies we must just assume that a ‘success’ was removal of the affected tooth. all of the studies report a calculated proportion for outcome and occurrence of complications when an incidence rate is what is needed to answer our pico. complications encountered are largely reported in a descriptive nature with little categorisation or standardisation between studies. indeed, tremaine and mccluskie (2010) reported a long-term complication of non-painful, mandibular swellings  that developed post-surgery in all cases and were still present 6 months later in 27% (3/11) of cases. prichard and hackett (1992) also noted post-operative swelling but discounted it as a minor long-term problem.  this lack of uniformity indicates an overarching need for standardisation of recording, and definition of surgical procedures, to allow more accurate comparisons to be drawn between studies. despite these limitations, the low quality of evidence and absence of any randomised controlled clinical trials that means a definitive answer to the pico cannot be provided; the evidence available indicates certain trends that should be investigated further in future studies. evidence on repulsion techniques suggests that long-term outcome is generally good albeit with some cosmetic imperfections and significant short-term morbidity. intraand short-term post-operative complications are common and often serious, to the extent that further surgery may be required. this would be unacceptable to many owners and indicates the need for a more reliable and successful first line of treatment. with lower incidence of complications compared to repulsion techniques, oral extraction should be used as the initial technique of choice for equine exodontia. however the success rate is not 100% so in cases where it fails an alternative cheek tooth removal technique may still be required. the evidence suggests that minimally invasive techniques may have a higher initial success than repulsion but they have, so far, failed to prevent some serious post-operative sequelae. in conclusion, analysis of the available evidence indicates a need for further research to conclusively answer the pico. such approaches could include a large, multi-centre, prospective cohort study, utilising a strict inclusion criteria to minimise the presence of confounding variables, or a gold-standard randomised, controlled clinical trial. these epidemiological approaches would elucidate whether oral or minimally invasive cheek tooth extraction techniques do significantly reduce the incidence of post-operative complications in the horse when compared to repulsion methods. methodology section search strategy databases searched and dates covered: cab abstracts on the ovid platform (1973 to 2017 week 23) pubmed accessed via the ncbi website (1910-2017, filtered for veterinary science) search terms: pubmed search: #1 (horse or equine or equidae or equus or colt or pony or mare or filly or gelding or stallion or yearling or thoroughbred or warmblood) filters: veterinary science #2 (tooth or dental or dentistry or mouth or oral or buccal or bucco) filters: veterinary science #3 (extract or extracts or extraction or extractions or extracted or extracting or remove or removes or removal or removed or removing or removement or surgical or surgical or surgically or surgery or surgeries or exodontia or exodontics or exodontic or endodontic or endodontics or peridontics or periodontics or peridontal or periodontal or repulse or repulses or repulsed or repulsing or repulsion or trephination or trephined or trephine or trephines or trephining or mte or mitr or transbuccal) filters: veterinary science #4 (#1 and #2 and #3) filters: veterinary science cab abstracts search: 1     (equine or equines or horse or horses or equus or colt or colts or pony or ponies or mare or mares or donkey or donkeys or filly or fillies or gelding or geldings or stallion or stallions or yearling or yearlings or thoroughbred or standardbred or warmblood).mp. or equidae/ or equus/ or horses/ or foals/ or colts/ or mares/ or stallions/ or thoroughbred/ or donkeys/ 2     (tooth or teeth or dental or dentistry or mouth or oral or buccal or bucco).mp. or teeth/ or tooth diseases/ 3     (extract or extracts or extraction or extractions or extracted or extracting or remove or removes or removal or removed or removing or removement or surgical or surgical or surgically or surgery or surgeries or exodontia or exodontics or exodontic or endodontic or endodontics or peridontics or periodontics or peridontal or periodontal or repulse or repulses or repulsed or repulsing or repulsion or trephination or trephined or trephine or trephines or trephining or mte or mitr or transbuccal).mp. or surgical techniques/ or surgical operations/ or periodontal diseases/ 4     1 and 2 and 3 *************************** mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes dates searches performed: 22nd june 2017 exclusion / inclusion criteria exclusion: pre-defined exclusion criteria included: not in the english language, book chapters, review articles, single case reports and articles from non-peer reviewed journals. additionally studies where cheek tooth removal was not the main focus and that reported on complications of loss of teeth from the arcade (i.e. tooth drift), rather than complications arising as a result of the extraction procedure were excluded. inclusion: any primary evidence study in which cheek teeth removal from equidae was the main focus and that reported on the surgical techniques used and the complications encountered. search outcome database number of results excluded – not in english language excluded – did not address the pico question excluded – book chapter, review article, single case report or non-peer reviewed publication excluded – could not be sourced excluded – duplication total relevant papers ncbi pubmed 753 20 700 24 1 0 8 cab abstracts 911 164 642 51 2 50 2 total relevant papers when duplicates removed 10 conflict of interest the authors declare 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(2010) removal of 11 incompletely erupted, impacted cheek teeth in 10 horses using a dental alveolar transcortical osteotomy and buccotomy approach, veterinary surgery. blackwell publishing inc, oct; 39(7), pp. 884–890. doi: http://dx.doi.org/10.1111/j.1532-950x.2010.00724.x vlaminck, l. et al (2008) radiographic evaluation of tooth drift after cheek tooth extraction and insertion of an intra-alveolar prosthesis in ponies, the veterinary journal, feb; 175(2), pp. 249–258. doi: http://dx.doi.org/10.1016/j.tvjl.2006.12.016 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in dogs with chronic enteropathies, can oral b12 tablets be used to treat hypocobalaminaemia? a knowledge summary by avril mcginn ba(hons) bvm&s certavp(sam) pgcert(vps)1* 12 caragh heights, caragh, naas, co. kildare, ireland *corresponding author (amcginn@tcd.ie) vol 4, issue 3 (2019) published: 30 aug 2019 reviewed by: linda toresson (phd, dvm) and peter-john mäntylä noble (bsc, bvm&s, phd, mrcvs) next review date: 12 may 2021 doi: 10.18849/ve.v4i3.202 pico question in dogs with chronic enteropathy does treatment with oral cobalamin compared to parenteral cobalamin provide serum cobalamin levels greater than 270 ng/l? clinical bottom line the evidence provided by block randomised controlled clinical trials indicates that oral dosing of cobalamin results in normocobalaminaemia, with levels similar to that achieved with parenteral dosing. these studies provide veterinary professionals with dosing schedules, and monitoring serum cobalamin levels is recommended to ensure normocobalaminaemia is achieved. it has been shown that supplementation with both oral and parenteral cobalamin correlates with increased intracellular cobalamin levels. future studies are needed to investigate the outcome of oral cobalamin dosing in dogs with extra-gastrointestinal disease. clinical scenario you are treating a dog with chronic enteropathy and have identified hypocobalaminaemia. you recommend commencing a course of parenteral cobalamin but the owner is reluctant. they are concerned about the discomfort of frequent injections, the stress of visits to the hospital, and the cost. the client asks if cobalamin tablets, otherwise known as vitamin b12, can be given instead of a course of injections. you decide to explore the literature to give advice on the subject. the evidence there is little published evidence comparing oral and parenteral administration of cobalamin in dogs with chronic enteropathy one case series and two block randomised clinical trials were used to answer the question. protocols for parenteral doses of cobalamin are based on expert opinion and clinical experience and are not validated protocols (ruaux, 2013). serum cobalamin of 252–908 ng/l is considered the normal range for a dog (vaden et al., 2009). toresson et al. (2016) produced a retrospective study based on a review of medical records of dogs that had been treated with oral cobalamin; the study concluded that dogs treated with oral cobalamin had normal cobalamin blood serum levels (>270 ng/l). a randomised clinical trial was later performed by toresson et al. (2018). this experimental trial concluded that both oral and parenteral cobalamin supplementation in dogs provided a significant increase in serum cobalamin concentrations >285 ng/l. this was followed by a study to show that both oral and parenteral supplementation of cobalamin resulted in decreased methylmalonic acid (mma) levels, with no significant difference between the two groups (toresson et al., 2019). a cobalamin deficiency leads to accumulation of mma, and mma is indicative of the cellular cobalamin level. this indicates that both oral and parenteral cobalamin supplementation provide effective cellular cobalamin levels, and that oral supplementation in dogs is an effective treatment option for hypocobalaminaemia in chronic enteropathies. summary of the evidence toresson et al. (2016) population: client owned dogs with signs of chronic enteropathy and hypocobalaminaemia treated with oral cobalamin tablets. an electronic search of a hospital database for dogs with chronic enteropathy treated with oral cobalamin between jan 2012–march 2014, sweden. cases were excluded if they had extra-gastrointestinal disease, were not compliant with the dose or had concurrent cobalamin parenteral supplementation. dogs included had initial serum cobalamin levels <270 ng/l, mean 223 +/33 ng/l sample size: 51 dogs: 34 male, 17 female intervention details: cyanocobalamin 1 mg tablets were used, once daily dosing for 20–202 days (median 72 days): body weight: 1 kg–10 kg = ¼ of a tablet, 10 kg–20 kg = ½ a tablet and >20 kg = 1 tablet. study design: retrospective case series outcome studied: objective assessment of serum cobalamin concentration. blood samples were taken between 20–202 days (mean 73) after initiation of daily oral tablets. main findings (relevant to pico question): no dogs were hypocobalaminaemic at the time of post treatment blood sampling, mean serum cobalamin: 1,017 ng/l (range 557–1477 ng/l) there was a significant difference between the starting cobalamin concentration and cobalamin after oral tablets (p<0.0001) mean increase in serum cobalamin was 794 ng/l (range 332–1256 ng/l) limitations: retrospective, uncontrolled study incomplete diagnostic work ups and dogs on different treatments for chronic enteropathy and different diets empiric dosing and range of doses given owners administering tablets may have compliance issues; tablets were not counted at blood sampling to check compliance. offering dogs’ tablets does not ensure they ingest it two giant schnauzers included – this breed has known inherited cobalamin malabsorption (fyfe et al., 1991) follow up serum cobalamin levels were not standardised, repeat blood samples were taken from 20–202 days post treatment. blood serum cobalamin concentration assessed – unsure if this correlates with intracellular levels toresson et al. (2018) population: client owned dogs with signs of chronic enteropathy and serum cobalamin <285 ng/l (interval 244–959 ng/l) sample size: 53 dogs intervention details: dogs allocated to treatment group in block randomised schedule design and all dogs had baseline serum blood cobalamin concentration samples. parenteral group: one subcutaneous injection of 0.25–1.2 mg per dog depending on body weight (weight range 3.1–49 kg). hydroxycobalamin once weekly for 6 weeks and an additional injection 4 weeks later (ruaux, 2013). oral group: each dog received 0.025–0.05 mg/kg cyanocobalamin daily for 90 days (+/15days). owners withheld tablets on the day of blood sampling, and tablets were counted to check compliance. study design: prospective open randomised controlled study on client owned dogs outcome studied: objective assessment of serum blood cobalamin concentration before treatment, day 28 (+/-5 days) after treatment and day 90 (+/-15 days) after treatment main findings (relevant to pico question): both the oral group and parenteral group had significantly increased serum cobalamin level at day 28 and day 90 compared to baseline (p<0.001) showing normocobalaminaemia in dogs that completed the study the parenteral group median showed higher levels at day 28 than the oral group (p< 0.001) the oral group showed higher levels at day 90 than the parenteral group (p<0.001) oral group median at day 28: 955 ng/l (range 564–2385 ng/l) parenteral group median at day 28: 1799 ng/l (range 575–9827 ng/l) oral group median at day 90: 1244 ng/l (range 768–4999 ng/l) parenteral group median at day 90: 600 ng/l (range 38–997 ng/l) limitations: this study was not blinded, the authors were aware of the treatment allocation to each dog when collecting serum samples. the reference interval provided at the start of the study for normocobalaminaemia is not justified or referenced owner compliance was an issue in terms of administering pills, and three dogs dropped out due to non-compliance with parenteral group, and one dog was lost to euthanasia all dogs were on different diets and diet changes occurred during the study, diets with a known cobalamin level had a range from 0.046–0.35 mg/kg, however authors did not account for the different cobalamin levels in diets between the groups the weekly dosing schedule, up to 4 weeks, has been shown to normalise mma concentrations after 4 weekly injections in cats (ruaux, 2005), beyond this, dosing is empirical and based on expert opinion and clinical experience (ruaux, 2013). it is commonly followed in practice not all dogs had a complete diagnostic work up and dogs were on different treatments one border collie was included in the study, this breed has known inherited cobalamin deficiency (lutz et al., 2013) power calculation not performed to indicate significance due to small sample size blood serum levels evaluated, this may not reflect cellular cobalamin levels (berghoff et al., 2012) loss to follow-up occurred in the parenteral group toresson et al. (2019) population: client owned dogs with clinical signs of chronic enteropathy and serum cobalamin concentrations of ≤285 ng/l (interval 244–295 ng/l) (normocobalaemia 244–959 ng/l) sample size: 36 dogs: oral group n=18. parenteral group n=18 intervention details: dogs were allocated to groups in block randomised schedule design. all dogs had baseline serum blood cobalamin, methylmalonic acid (mma) and homocysteine (hcy) concentration samples. parenteral group: one subcutaneous injection of   0.25–1.2 mg per dog (depending on body weight, weight range 3.1–49 kg) of hydroxycobalamin once weekly for 6 weeks and an additional injection 4 weeks later (ruaux, 2013). oral group: each dog received oral daily cyanocobalamin (behepan® 1 mg, pfizer). dogs less than 10 kg body weight received ¼ of a tablet, 10 kg–20 kg body weight ½ a tablet, and if >20 kg received one tablet. owners were told to withhold tablets on the day of follow-up examination. study design: prospective open, block randomised controlled study outcome studied: objective assessment of serum blood cobalamin, mma and hcy concentration before treatment. assessment of serum blood mma and hcy concentration day 28 ± 5 days after treatment and day 90 ± 15 days after treatment. main findings (relevant to pico question): mma: significant decrease in both oral and parenteral group from day 0 to day 28 (p<0.0001). there was no further decrease in mma after day 28. there was no significant difference between the oral group and parenteral group at day 28 and day 90. hcy: there was no significant difference in the hcy concentrations at any time point, and no significant difference between the two groups. limitations: this study was not blinded, owners and authors were aware of which treatment group the dog was in., this study had a small sample size, with thirty-six dogs at the start of the study and thirty one on completion, one dog was lost to euthanasia, one sample lost in shipment, and three did not comply with the protocol. no confidence intervals or effect sizes were calculated. samples were shipped twice within sweden and once to usa. this is acknowledged by the authors. human studies show mma and hcy are stable for up to 8 days at room temperature (hustard et al., 2012), but no studies are available for canine mma and hcy. samples included in this study were refrigerated within two hours of collection, and frozen within 1–3 days. they were transported to usa within 12–18 months. the authors do not state how long it took for samples to be tested. 13 samples were accidentally left at room temperature for 13 days and excluded from the study. owners were instructed not to give tablets on the day of sampling, while the parenteral group were sampled 5–7 days after cobalamin supplementation. the fluctuations of mma concentrations after tablet administration and subcutaneous injection of cobalamin are unknown. three of the authors work for the laboratory used in this study, however this is declared, and reports no personal or financial relationship. the weekly dosing schedule, up to 4 weeks, has been shown to normalise mma concentrations after 4 weekly injections in cats (ruaux, 2005), beyond this, dosing is empirical and based on expert opinion and clinical experience (ruaux, 2013). however despite the small sample size, this study demonstrates significant decreases in mma. appraisal, application and reflection dogs with chronic enteropathy (ce) display signs of ‘vomiting, diarrhea, borborygmus, hyporexia, abdominal pain, nausea and/or weight loss’ (dandrieux, 2016). hypocobalaminaemia has been shown to be a negative prognostic indicator in dogs with ce (craven et al., 2004) and serum cobalamin <200ng/l has an increased risk of poor outcome (allenspach et al., 2007. normocobalaminaemia has been described as serum levels between 252–908 ng/l, (vaden et al., 2009). however, in the studies described cobalamin is supplemented once levels are below 285 ng/l as this level represents the lowest 5% of the reference range (toresson et al., 2018). cobalamin is necessary for the methylmalonyl coa mutase (mcm) system (solomon, 2007) and deficiencies can result in the production of methylmalonic acid (stabler et al., 1986). berghoff et al. (2013) showed that the prevalence of hypocobalaminaemia in dogs with ce was 36%, while a quarter of these dogs had increased levels of methylmalonic acid. it has been recommended that all dogs showing signs of chronic gastrointestinal disease should have cobalamin levels assessed (dossin, 2011). the current protocol used most commonly in practice has been suggested by ruaux (2013) and the gastrointestinal laboratory at texas a&m university. this protocol involves an injection of cobalamin once weekly for 6 weeks, and a follow-up injection 4 weeks later of hydroxycobalamin, 0.25–1.25 mg/dog depending on boady weight (ruaux, 2013) (subcutaneously). these doses have not been validated, and are based on clinical experience and expert opinion (ruaux, 2013). some dogs with gastrointestinal disease need long-term management, and ruaux (2013) reports using up to weekly injections in these cases. this requires frequent visits to veterinary clinics, can be distressing for both owners and dogs, and costly. toresson et al., (2018) found that one dog was hypocobalaminaemic (38 ng/l) at day 90 after following this parenteral protocol. this suggests that the parenteral protocol was not adequate at supplementing cobalamin in this case. intrinsic factor mediates the absorption of cobalamin in the intestines and human studies have shown that one percent of cobalamin was absorbed separately from intrinsic factor by passive diffusion (berlin et al., 1968). this led to doctors treating patients with oral cobalamin and a cochrane review indicates that ‘high oral doses of b12 could be as effective as intramuscular administration’ (vidal-alaball et al., 2005). in our veterinary patients, tablets are more cost effective, convenient and cause the dog less discomfort. the paper by toresson et al. (2016) is a retrospective review of cases that suggests oral cobalamin provides serum cobalamin concentrations above the reference range (mean serum level increase of 794 ng/l +/462). this was followed by a block randomised controlled clinical trial (toresson et al., 2018). dogs were split into two groups by random allocation and either treated with cobalamin orally or parenterally, block randomization is used to reduce bias by assigning equal numbers to each treatment group. while dogs were given a range of doses and sample sizes were small; this study showed promising results that the oral group had similar results to the parenteral group. this study was not blinded as both owners and authors were aware of the treatments provided to each group; however the authors were collecting objective data so this may not have influenced results greatly. one limitation of the study was owner compliance, and in some instances owners did not fully comply with the protocol; however these cases were included in the results and still had normocobalaminaemia. in the randomised controlled clinical trial (toresson et al, 2018) the parenteral cobalamin protocol was taken from ruaux (2013). as mentioned already this is not a validated protocol and while cobalamin levels were higher at day 28 than the oral groups, levels dropped at day 90. this suggests that monthly injections of cobalamin may not be sufficient at maintaining cobalamin levels in some dogs. it has been mentioned above that ruaux (2013) has used weekly injections to maintain cobalamin levels in some cases. further studies may be needed to determine frequency of injections after the initial course. serum cobalamin levels from the oral group were increased at day 90; suggesting daily oral supplementation may be preferable long-term than the current parenteral protocols. serum cobalamin levels in these studies post treatment surpass’ the reference range provided, for example in toresson et al., (2018), the median serum cobalamin level of the oral group at day 90 is 1244 ng/l (768–4999 ng/l). toresson et al., (2018) address this as ‘signalling a satisfactory response to oral supplementation in most dogs’. the origin of the reference range for ‘normocobalaminaemia’ in all the studies is not referenced. the interval provided at the start in all the studies for normocobalaminaemia is not justified or referenced. the normal range is >251ng/l (berghoff et al., 2012) and hypocobalaminaemia in the studies described is considered once serum cobalamin levels are <270-285ng/l, as it represents the lowest 5% of the reference range. finally, the paper by torresson et al. (2019) demonstrates a reduction in mma levels, indicating that oral and parenteral supplementation are effective at a cellular level. this supports the use of oral cobalamin supplementation in dogs with chronic enteropathy, however, there was no significant change in hcy levels, suggesting the need for further studies in breeds with congenital or familial cobalamin malabsorption. recent reports have shown that both cobalamin and mma concentrations have normalised in dogs with congenital hypocobalaminaemia treated with oral supplementation (mccallum & watson, 2018 and kook & hersberger, 2019). holotranscobalamin is used as a marker for hypocobalaminaemia in humans (herrmann & obeid, 2012 and devalia et al., 2014), further studies are needed to determine the use of this marker in our canine patients.   methodology section search strategy databases searched and dates covered: cab abstracts (1989–2019), accessed via the ovid platform and pubmed (1910–2019), accessed on the ncbi website search terms: cab abstracts: (dog or dogs or canine or canines or bitch) (cobalamin or b12) (enteropath* or ibd or inflammatory bowel disease) (oral or parenteral) pubmed: ((((dog or dogs or canine or canines or bitch)) and (cobalamin or b12)) and (enteropath* or ibd or inflammatory bowel disease)) and (oral or parenteral) dates searches performed: 12/05/2019 exclusion / inclusion criteria no limitations regarding study design, setting, sample size or study population were imposed. exclusion: papers not written in english, did not answer the pico question, book chapter inclusion: original research papers investigating oral treatment or comparing oral to parenteral treatment search outcome database number of results excluded – not written in english excluded – book chapter excluded – did not answer pico question total relevant papers cab abstracts 5 0 0 2 3 pubmed 5 1 0 1 3 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflict of interest. references allenspach, k., wieland, b., grone, a., & gaschen, f. 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(2005) oral vitamin b12 versus intramuscular vitamin b12 for vitamin b12 deficiency. cochrane database of systematic reviews, 20. cd004655. doi: https://doi.org/10.1002/14651858.cd004655.pub2 acknowledgement rcvs knowledge was supported in producing this knowledge summary by an educational grant from petplan charitable trust. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. does meniscal release confer similar clinical benefits to meniscal tear treatment when compared to meniscectomy? a knowledge summary by ben garland bvetmed certavp(gsas) mrcvs 1* 1christchurch veterinary referrals, tuddenham road business park, tuddenham road, ipswich, suffolk, ip4 3qn *corresponding author (ben.veterinary@gmail.com) vol 5, issue 4 (2020) published: 21 dec 2020 reviewed by: duncan barnes (ma vetmb certsas dsas(orth) mrcvs) and catrina pennington (bvm&s mrcvs) next review date: 02 apr 2020 doi: 10.18849/ve.v5i4.339 pico question in adult dogs with naturally occurring medial meniscal tears concurrent to cranial cruciate ligament disease does meniscal release confer the same benefits in lameness resolution as meniscectomy?   clinical bottom line category of research question treatment the number and type of study designs reviewed a single prospective cross-sectional study was reviewed, that fulfilled the criteria strength of evidence none outcomes reported meniscal release, meniscectomy (partial, hemior complete), or the two combined performed for concurrent medial meniscal pathology at time of surgery for naturally occurring cranial cruciate ligament (ccl) rupture resulted in an acceptable long-term outcome. difference in outcome between the techniques was not reported conclusion there is no evidence that meniscal release provides an equal or superior treatment option for medial meniscal injury treated at the time of surgery for ccl rupture when compared to meniscectomy. the study critically reviewed performed meniscal release via radial transection through the meniscotibial ligament, and therefore does not represent mid-body abaxial radial release. neither is this summary appropriate for considering prophylactic meniscal release of the normal meniscus. in addition, the surgical treatments for cranial cruciate ligament rupture were either ‘tightrope’ or tibial plateau levelling osteotomy (tplo) procedures. further studies are required to compare clinical outcome between meniscal release or meniscectomy for treatment of concurrent meniscal tears   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a 3-year-old male neutered labrador retriever presents for investigation of a moderate right pelvic limb lameness localising to the right stifle with positive tibial compression and cranial drawer tests. you recommend radiographic investigation, exploratory arthrotomy, and surgical stabilisation to confirm and then treat suspected cranial cruciate ligament rupture. during an exploratory arthrotomy you confirm rupture of the cranial cruciate ligament and note a ‘bucket handle’ tear of the medial meniscus. you are aware that meniscal release is anecdotally used to treat this injury, but are uncertain this would provide a clinical outcome equal to partial meniscectomy. the evidence a single study was reviewed for this knowledge summary. there are no studies that directly compares the two treatment techniques investigated in this review making it impossible to perform systematic review or meta-analysis. to the author’s knowledge, there are no prospective randomised or blinded studies that directly compare the outcome of meniscal release and meniscectomy surgeries for the treatment of meniscal injury at the time of surgical treatment of cranial cruciate ligament rupture. the evidence presented as part of this summary compares the outcome of the two techniques grouped together with no meniscal treatment. meniscal treatment performed was selected based on intra-operative assessment and a surgeon’s clinical judgement for each patient. clinical outcomes were assessed at medium and long-term follow-up utilising subjective owner assessment. these results suggest that either surgical intervention for concurrent meniscal tears provides a high level of acceptable patient function when meniscal treatment was selected based upon surgeon assessment and clinical judgement. criteria for surgical decision making has not yet been defined to determine if and when meniscal release may confer similar clinical benefits to meniscectomy techniques. summary of the evidence ritzo et al. (2014) population: adult dogs with naturally occurring cranial cruciate ligament disease sample size: 163 adult dogs, encompassing 223 stifles intervention details: intra-articular stifle assessment, followed by surgical stabilisation for cruciate insufficiency by one of: arthroscopy and ‘tightrope’ 134/223 (60%); arthroscopy and tlpo 26/223 (12%); or arthrotomy and tplo 63/223 (28%) meniscectomy technique included ‘partial’ in 93/160 (85%), ‘hemi’ in 14/160 (13% and ‘complete’ in 2/160 (2%) study design: prospective cross-sectional study outcome studied: incidence and type of meniscal pathology, and the effect of meniscal pathology and its overall treatment on outcome in dogs managed for cranial cruciate ligament rupture. medium (6–12 months) and long-term (>1 year) functional outcome as assessed by owner questioning of: function pain postoperative complications current use of non-steroidal anti-inflammatory drugs or other analgesics (associated with cranial cruciate ligament disease). based on the results outcome was graded ‘full’, ‘acceptable’, or ‘unacceptable’. these were then grouped as successful (full and acceptable) or unsuccessful (unacceptable) outcome. main findings (relevant to pico question): of 223 cases, 160 (72%) had concurrent meniscal tear diagnosed at the time of inspection and stabilisation surgery. of these 159 were of the medial meniscus. all tears were treated with either meniscectomy 109/160 (68%), meniscal release (caudal) 81/160 (51%), or a combination of both 30/160 (19%). overall 51/160 (32%) meniscal release, 79/160 (49%) meniscectomy, 30/160 (19%) both. (this had to be extrapolated from the data presented). at medium term follow-up (6–12 months): owners of 94/163 dogs contacted, 68 dogs had concurrent tears treated, of which 65 (96%) had successful outcome at long-term follow-up (>1 year): owners of 87/160 dogs contacted, 62 dogs had concurrent tears treated of which 60 had a successful outcome (97%) limitations: outcome assessed meniscal intervention overall and does not differentiate between treatment types meniscectomy included partial, hemi-, or complete comparison and outcome were not grouped based on type of meniscal surgical intervention meniscal intervention was based on surgeon preference, with surgeon number and skill level not clearly defined meniscal treatment elected is not stated to be based on pathology encountered concurrent surgery for ccl rupture was not randomised nor its impact on outcome assessed with respect to meniscal surgery population of dogs limited to patients referred to a single referral centre outcome was owner centric, subjectively assessed, and grouped into broad categories non-blinded non-randomised confidence intervals were performed as per methods, but are not stated no statistical analysis is performed to consider the significance of outcome achieved a large proportion of treated dogs were lost to follow-up at both 6–12 months and >1 year appraisal, application and reflection only a single study was identified from this literature review where meniscal release was used to treat meniscal tears identified at the time of surgery for cranial cruciate ligament rupture. the study identified was observational, of prospective cross-sectional design, utilising a prospectively maintained database to retrospectively obtain data. importantly, this study design was not intended to directly compare the effect of meniscal release with meniscectomy in a cohort of dogs. instead, meniscal release and meniscectomy (partial, hemi-, or complete) were grouped together when considering clinical outcome. whilst this study provides evidence in relation to disease prevalence (as per the intentions of the study’s authors), when considering the impact of meniscal surgical techniques overall the evidence would be considered weak [class iii] (aragon & budsberg, 2005; and dean, 2013). furthermore, when considering the impact between meniscal interventions this study does not provide evidence that meniscal release confers the same clinical outcome as meniscectomy. when considering this study in the context of the clinical question posed several confounding factors can be identified. randomisation was not performed for either meniscal intervention or the surgical procedure used to treat ccl rupture. as such bias is introduced by the surgeon, when considering outcome against intervention performed. surgeon experience was recorded; however, this was not stratified to the differing interventions with surgeon skill or confidence open to influencing outcome. meniscal assessment method was not standardised, with arthrotomy or arthroscopy used. this could impact the detection sensitivity of meniscal pathology between treatment groups (pozzi et al., 2008a; and plesman et al., 2012). as undiagnosed meniscal pathology is recognised as a potential factor for suboptimal clinical outcome following surgery for cranial cruciate ligament rupture, utilising techniques of different sensitivity could confound outcome (fitzpatrick & solano, 2010; and thieman et al., 2006). similar rates of subsequent meniscal tears were obtained between all treatment groups reported (range 6.3–7.7%) and are within previously reported values (mcready & ness, 2016a). meniscal treatment selection was not linked to the type of pathology encountered, which may have unrecognised implications upon outcome given the breadth of concurrent medial meniscal pathology diagnosed (cook & pozzi, 2010). this could have clinical significance if outcome is linked to pathology encountered and surgical technique performed. the cohort of dogs included in this study consisted exclusively of a wide range of individuals referred to a single centre. patients factors such as bodyweight, body condition score, and co-morbidities are reported but not linked to outcome obtained. when addressing outcome, medium and long-term follow-up was available for a proportion of patients. a considerable number were lost to follow-up, with 42% and 39% of all 223 cases achieving medium and long-term follow-up respectively. outcome was based subjectively on owner assessment without the use of objective measures or a validated metrology instrument (mccoll et al., 2002; and muller et al., 2016). outcomes were broadly grouped into ‘full function‘,’acceptable function‘, and ‘unacceptable function‘ based on previously defined criteria in veterinary orthopaedics (cook et al 2010). a successful outcome was considered to be either 'full‘ or ‘acceptable’ function, therefore successful outcome should be regarded cautiously. statistical analysis to consider the significance of findings presented are not given within the study. whilst confidence intervals were discussed in the methodology, these were not expressed further in the results, nor are power calculations presented to determine group sizes. most importantly in relation to the clinical question, outcome was not separated between meniscal interventions or status at primary examination but instead grouped together. therefore, when considering this, regardless of limitations this paper only demonstrates successful outcome for the reported meniscal interventions for concurrent tears as a whole. as such, in relation to the clinical question posed here, this knowledge summary is unable to provide evidence that meniscal release confers the same benefits as meniscectomy in the clinical outcome obtained. the amount of available literature to consider this question is sparse, with very limited reference to meniscal release as a therapeutic technique for meniscal pathology. meniscectomy procedures are the most widely adopted technique for meniscal pathology treatment (cook & pozzi, 2010), with meniscal repair methods described for select meniscal tears (rovesti et al., 2018, and thieman et al., 2010). notably, the most robust evidence in this field is a recent meta-analysis by mccready & ness (2016a and b) investigating both cranial cruciate ligament treatment surgery and meniscal pathology diagnosis and treatment; however meniscal release as a treatment for concurrent tears did not feature in their analysis. anecdotally, some surgeons utilise meniscal release as their preferred treatment option for concurrent meniscal tears. meniscal release is relatively less technically demanding than meniscectomy, is faster, and can be performed via blind or minimally invasive methods (austin et al., 2007). given the commonality of cranial cruciate ligament disease in the canine population (wilke et al., 2005) with reported rates of 10–77% concurrent meniscal tears (cook & pozzi, 2010), successful meniscal treatment via the least invasive method possible may prove beneficial for patients and surgical efficiency considering the similar biomechanics reported between techniques (pozzi et al., 2008b, 2010a, and 2010b). however, it is therefore important to determine if meniscal release confers the same well documented benefits to patients in lameness resolution as meniscectomy procedures before considering this an evidence based surgical technique. from this knowledge summary there is no evidence to support meniscal release as equal to meniscectomy in clinical outcome achieved when treating concurrently diagnosed medial meniscal tears at the time of index surgery for naturally occurring cranial cruciate ligament rupture. other significant limitations include the unknown effect of the index surgery used to treat ccl rupture on the efficacy of meniscal treatment. furthermore, the meniscal release utilised was exclusively axial (also known as ‘caudal’ or ‘menisco-tibial’) which should be borne in mind when considering clinical application. a well designed, standardised prospective randomised control study would be required with objective long-term outcome measures to investigate this clinical question. methodology section search strategy databases searched and dates covered: cab abstracts on ovid interface; 1973 to april 2020 pubmed on ncbi platform; 1981 to april 2020 reference lists for chapter 31 (surgical treatment of concurrent meniscal injury) in: muir (ed) advances in the canine cranial cruciate ligament, wiley-blackwell. paper and reference list for mccready, d.j. and ness, m.g., (2016). systematic review of the prevalence, risk factors, diagnosis and management of meniscal injury in dogs: part 2. journal of small animal practice. 57(4). search strategy: cab abstracts: (dog or canine or canid or canis) (meniscal injury or meniscal tear or meniscal* or *meniscal) meniscal release 1 and 2 and 3 pubmed: ((((meniscal injury or meniscal tear or meniscal* or *meniscal)) and meniscal release)) and (dog or canine or canid or canis) dates searches performed: 02 apr 2020 exclusion / inclusion criteria exclusion: experimental studies; where meniscal release was used only to treat a normal meniscus; where meniscal inspection was not performed; ex vivo or biomechanical studies; papers not available in english; papers that could not be accessed inclusion: where meniscal release was used as a therapeutic treatment for meniscal tears search outcome database number of results excluded – after reading title excluded – after reading abstract excluded – after reading materials and methods excluded – paper could not be accessed or was not in english total relevant papers cab abstracts 36 6 10 13 6 1 pubmed 33 12 12 8 0 1 muir 15 6 4 2 3 0 mccready & ness 104 63 13 25 2 1 total relevant papers when duplicates removed 1 conflict of interest the author declares no conflicts of interest. the author would like to thank ms clare boulton at the rcvs knowledge library service for her assistance in searching the literature references aragon, c. and budsberg, s. (2005). applications of evidence-based medicine: cranial cruciate ligament injury repair in the dog. veterinary surgery. 34, 93–8. doi: http://dx.doi.org/10.1111/j.1532-950x.2005.00016.x austin, b., montgomery, r.d., wright, j., bellah, j.r. and tonks, c. (2007). evaluation of three approaches to meniscal release. veterinary and comparative orthopaedics and traumatology. 20(2), 92–97. doi: http://dx.doi.org/10.1160/vcot-06-04-0033 cook, j.l., evans, r., conzemius, m.g., lascelles, b.d.x., mcilwraith, c.w., pozzi, a., clegg, p., innes, j., schulz, k., houlton, j., fortier, l., cross, a.r., hayashi, k., kapatkin, a., brown, d.c. and stewart, a. (2010). proposed definitions and criteria for reporting time frame, outcome, and complications for clinical orthopedic studies in veterinary medicine. veterinary surgery. 39, 905–908. doi: https://doi.org/10.1111/j.1532-950x.2010.00763.x cook, j.l. and pozzi, a. (2010).  surgical treatment of concurrent meniscal injury. in: muir, p. ed., advances in the canine cranial cruciate ligament 1st edition. wiley-blackwell, 217–222. dean, r. (2013). how to read a paper and appraise the evidence. in practice. 35, 282–285. doi: http://dx.doi.org/10.1136/inp.f1760 fitzpatrick, n. and solano, m.a. (2010). predictive variables for complications after tplo with stifle inspection by arthrotomy in 1000 consecutive dogs. veterinary surgery. 39, 460–474. doi: https://doi.org/10.1111/j.1532-950x.2010.00663.x mccoll, e., jacoby, a., thomas, l., soutter, j., bamford, c., steen, n., thomas, r., harvey, e., garratt, a. and bond, j. (2002). design and use of questionnaires: a review of best practice applicable to surveys of health service staff and patients. health technology assessment. 5(31). doi: https://doi.org/10.3310/hta5310   mccready, d.j. and ness, m.g. (2016a). diagnosis and management of meniscal injury in dogs with cranial cruciate ligament rupture: a systematic literature review. journal of small animal practice. 57(2), 59–66. doi: https://doi.org/10.1111/jsap.12433 mccready, d.j. and ness, m.g. (2016b). systematic review of the prevalence, risk factors, diagnosis and management of meniscal injury in dogs: part 2. journal of small animal practice. 57(4), 194–204. doi: https://doi.org/10.1111/jsap.12462 muller, c., gaines, b., gruen, m., case, b., arrufat, k., innes, j. and lascelles, b.d.x. (2016). evaluation of clinical metrology instrument in dogs with osteoarthritis. journal of veterinary internal medicine. 30(3), 836–846. doi: https://doi.org/10.1111/jvim.13923 plesman, r., gilbert, p. and campbell, j. (2013). detection of meniscal tears by arthroscopy and arthrotomy in dogs with cranial cruciate ligament rupture: a retrospective, cohort study. veterinary and comparative orthopaedics and traumatology. 26(1), 42–46. doi: http://dx.doi.org/10.3415/vcot-11-10-0153 pozzi, a., hildreth, b.e. and rajalaâ€�schultz, p.j. (2008a). comparison of arthroscopy and arthrotomy for diagnosis of medial meniscal pathology: an ex vivo study. veterinary surgery. 37, 749–755. doi: https://dx.doi.org/10.1111/j.1532-950x.2008.00442.x pozzi, a., litsky, a.s., field, j., apelt, d., meadows, c. and johnson, k.a. (2008b). pressure distributions on the medial tibial plateau after medial meniscal surgery and tibial plateau levelling osteotomy in dogs. veterinary and comparative orthopaedics and traumatology. 21, 8–14. doi: https://doi.org/10.3415/vcot-06-12-0099 pozzi, a., kim, s. e. and lewis, d.d. (2010a). effect of transection of the caudal menisco-tibial ligament on medial femorotibial contact mechanics. veterinary surgery. 39, 489–495. doi: https://doi.org/10.1111/j.1532-950x.2010.00662.x pozzi, a., tonks, c.a. and ling, h.y. (2010b). femorotibial contact mechanics and meniscal strain after serial meniscectomy. veterinary surgery. 39, 482–488. doi: https://doi.org/10.1111/j.1532-950x.2010.00668.x rovesti, g.l., devesa, v., bertorelli, l. and rodriguez-quiros, j. (2018). facilitation of arthroscopic visualization and treatment of meniscal tears using a stifle joint distractor in the dog. bmc veterinary research. 14(1), 212. doi: https://doi.org/10.1186/s12917-018-1534-9 ritzo, m.e., ritzo, b.a., siddens, a.d., summerlott, s. and cook, j.l. (2014). incidence and type of meniscal injury and associated longâ€�term clinical outcomes in dogs treated surgically for cranial cruciate ligament disease. veterinary surgery. 43(8), 952–958. doi: https://doi.org/10.1111/j.1532-950x.2014.12220.x thieman, k.m., tomlinson, j.l., fox, d.b., cook, c. and cook, j.l. (2006). effect of meniscal release on rate of subsequent meniscal tears and ownerâ€�assessed outcome in dogs with cruciate disease treated with tibial plateau leveling osteotomy. veterinary surgery. 35, 705–710. doi: https://doi.org/10.1111/j.1532-950x.2006.00214.x thieman, k.m., pozzi, a., ling, h.â€�y. and lewis, d. (2010). comparison of contact mechanics of three meniscal repair techniques and partial meniscectomy in cadaveric dog stifles. veterinary surgery. 39, 355–362. doi: https://doi.org/10.1111/j.1532-950x.2010.00661.x wilke, v.l, robinson, d.a., evans, r.b., rothschild, m.f. and conzemius, m.g. (2005). estimate of the annual economic impact of treatment of cranial cruciate ligament injury in dogs in the united states. journal of the american veterinary medication association. 227, 1604–1607. doi: https://doi.org/10.2460/javma.2005.227.1604 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. an assessment of the impact of educational interventions on hand hygiene compliance a knowledge summary by carla husband bsc(hons) rvn 1* abbie mcmillan bsc(hons) rvn 1 lauren sweeney bsc(hons) rvn 1 1university of bristol, senate house, tyndall ave, bristol bs8 1th *corresponding author (ch16490@bristol.ac.uk) vol 5, issue 3 (2020) published: 16 jul 2020 reviewed by: myra forster-van hijfte (certvr certsam dipecvim-ca frcvs) and adam swallow (bvsc mrcvs) next review date: 15 oct 2021 doi: 10.18849/ve.v5i3.320 pico question in small animal veterinary professions, does implementation of an educational intervention, when compared to no intervention, improve hand hygiene compliance?   clinical bottom line category of research question treatment the number and type of study designs reviewed three papers were critically appraised. they were all prospective observational cohort studies strength of evidence weak outcomes reported two out of the three papers did not find educational implementation to have a statistically significant positive effect on hand hygiene compliance (hhc) in small animal veterinary professionals conclusion the veterinary evidence reviewed does not provide strong justification for the use of education in the improvement of hhc in small animal practice. this contrasts with extensive human evidence which supports the use of educational interventions (helder et al., 2010).  however, a limited veterinary knowledge base in the field of hh, combined with the flawed methodologies of the appraised literature, suggests that this finding is not representative of the effect education could have on hhc. the conclusion drawn from the evidence assessed within this knowledge summary is that educational interventions are not significantly linked to an improvement in hhc within a small animal veterinary setting. when considering the volume of human evidence which supports education as a tool to improve hhc, the authors suggest this knowledge summary should be repeated in the future when additional veterinary evidence is available to reassess the conclusion drawn   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision-making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario the head nurse in a small animal veterinary practice has noticed a decline in hand hygiene compliance (hhc) within the team and wants to implement a strategy to improve this. they are unsure whether further education will influence hhc within the team. they have seen from human medicine studies that education increases compliance significantly and wants to see whether there is appropriate literature in the veterinary field to support the findings. the aim of this knowledge summary is to appraise and consolidate veterinary research, so that veterinary professionals can understand the impact of educational interventions on hhc. the evidence all three articles, generated from scientific database searches, were retrieved from peer-reviewed and respectable scientific journals. two studies, conducted by smith et al. (2013) and shea & shaw (2012), were based in teaching hospitals and focused on multimodal educational approaches. shea & shaw (2012) provided a holistic representation of hhc throughout various departments in the hospital, whereas, smith et al. (2013) based the study in an intensive care unit. similarities within methodology allowed for in-depth comparison of the two studies. anderson et al. (2014) utilised first opinion clinics as the sample population, therefore the results could be easily transferred into general practice, such as the clinical scenario. this study utilised recommended hand hygiene protocols to promote objective data collection at a recognised standard. the study methodology produced robust results that could be replicated further to aid protocol changes within practice. all three studies demonstrated independent merits and limitations, however, the evidence provided by the articles collectively is not strong enough to recommend a change in clinical practice. summary of the evidence anderson et al. (2014) population: veterinary professionals in primary care companion animal clinics (south west and east ontario, canada). practices were recruited via two of the authors contacts, or via search on google maps. sample size: 38 clinics; including 449 individuals (veterinarians, technicians, receptionists, students, volunteers). no power calculations used to estimate sample size. intervention details: two video cameras installed: one in a consultation room and one in the “most likely” hand hygiene location in the backroom. baseline data of hand hygiene opportunities collected for 9–13 days after which, posters were mounted. two different posters were used that were easily visible for staff. poster a was placed in every consultation room, and poster b was placed in three locations in the backroom. post intervention data was collected for up to 8 days or 40 appointments, depending on which happened first. videos were assessed and coded according to world health organization’s (who, 2009) and a technique score was awarded. an anonymous survey looked at individual perception, response to the posters and perception of general hand hygiene practice. study design: prospective observational study outcome studied: primary variable related to pico was poster implementation and its impact on hhc. objective who guidelines were followed. mixed logistic regression and mixed linear regression were used to perform statistical analysis. main findings (relevant to pico question): no significant effect of posters on hhc. odds ratio = 1.04, 95% confidence interval and p-value = 0.5 (p<0.05). appropriate hand hygiene conducted in 14% of opportunities. survey: 272/289 (94%) of individuals noticed the posters. individuals stated the posters improved their hand hygiene awareness and practices (no figure given). limitations: only one coder, which could result in observer bias, providing subjective measurements. the coder could not be blinded to the presence or absence of the posters. clinics were not randomly selected, which could lead to inherent bias. no standardised time point when posters were installed, instead a time range, therefore the data set was not consistent. informed consent of filming gave potential rise to the hawthorne effect (eckmanns et al., 2006). two different poster styles reduced consistency of intervention. smith et al. (2013) population: health care workers (hcws): veterinary assistants, technicians, students, interns, residents and faculty at the intensive care unit (icu) of a veterinary teaching hospital at the university of georgia, college of veterinary medicine. sample size: uncontrolled due to staff movement, but interventions shown explicitly to 168 staff/students. no power calculations used to estimate sample size required. intervention details: observation time period determined with a randomisation procedure. 10–15 hand hygiene opportunities measured each period. over 12 weeks (-4 to -1 weeks for pre-intervention & 1 to 8 weeks for post-intervention) a single observer made randomised observations of hand hygiene opportunities using the world health organization’s guidelines and subsequent adherence (who, 2009). pre-intervention observations conducted in week -3 to -2 and post-intervention in week 6 to 7. intervention: educational video on correct technique for hand hygiene presented three times during week 1 to 24/65 (37%) of residents, faculty and interns and to 100/103 (97%) of incoming senior veterinary students who attended the presentation. the number of current senior veterinary students and technicians were not recorded. there is no explanation of how these individuals were chosen to participate. 25 posters showcasing an adapted who educational campaign were placed in different hospital locations and rotated every 3 weeks. study design: prospective observational study outcome studied: hand hygiene adherence pre and post educational implementation. data collection was objective whilst following who guidelines when deciding on appropriate opportunities/adherence. statistical analysis was performed using a fisher exact test to compare the pre and post intervention hand hygiene adherence demonstrated by the participants. main findings (relevant to pico question): pre-intervention: 222 observed hand hygiene opportunities, 61 were appropriate (27%). post-intervention: 249 observed hand hygiene opportunities, 73 were appropriate (29%). no significant difference observed post intervention, p = 0.76 (p<0.05). no confidence intervals or effect size listed. limitations: the population was uncontrolled due to regular rotation of staff members therefore individual improvement was unable to be assessed. population who participated in educational intervention were not necessarily observed in any of the data collection periods the hand-rub station by the entrance of icu was not observed: may have missed hh attempts related to observed opportunities hawthorne effect (eckmanns et al., 2006): participants may have changed their behaviour whilst being observed. post-intervention observations were not conducted until 6 weeks post-intervention. the authors have suggested there was a potential for a significant effect to be missed in the undocumented period. however, education should induce a long-lasting effect, so this may not be considered relevant. 84% of participants who received the intervention already had extra hand hygiene training so this educational campaign may not have been as impactful. shea & shaw (2012) population: hcws; faculty, interns, residents, students, technicians in teaching hospital at the cummings school of veterinary medicine, tufts university individuals of population were not controlled between preand post-intervention results. sample size: baseline n = 568 hand hygiene opportunities, post-intervention n = 103 hand hygiene opportunities intervention events: presentation n = 48 individuals; online module n = 103 individuals intervention details: anonymous direct observation; assessed number of hand hygiene opportunities and adequacy of hygiene for baseline and post-intervention data. observed by various hcws. hand hygiene opportunities were defined as before and after handling an animal. appropriate hand hygiene technique considered as either: antibacterial foam soap and water wearing gloves and removing immediately after handling. baseline data collected over two weeks (568 hand hygiene opportunities). authors reported baseline compliance rate to population throughout campaign. campaign implemented over 4 weeks: posters signs presentation (voluntary and available to 48 individuals) antibacterial foam slogans intern/resident discussion at induction (mandatory) online module (voluntary and available to 103 individuals). post-intervention data sampled 2 months after campaign completion. baseline and post-intervention data collection was anonymous and mandatory. outcome studied: baseline and post-intervention percentage of adequate hand hygiene opportunities were compared. data collected by multiple individuals through manual recording; observer bias meant that data collection was subjective. online module participation and presentation attendance were recorded. statistical analysis using chi-squared test. main findings (relevant to pico question): there was a significant positive effect post educational intervention: the population was 4.2 times (calculated using logistics regression) as likely to use soap with water or antibacterial foam post-intervention (p = 0.005) 6% hand hygiene opportunities appropriate at baseline compared to 41.7% hand hygiene opportunities appropriate post-intervention (p = 0.001). 20/48 (41.7%) of eligible population attended presentation. 25/103 (24.3%) of eligible population completed module. confidence interval and effect size not included. limitations: there was an uncontrolled sample size due to rotation of staff members around the hospital. therefore, individual improvement was unable to be assessed. post-intervention hand hygiene opportunities were less than 1/3 of baseline; observer bias holds greater implication on the results, thereby potentially distorting the data which decreases the reliability of the study. subjective assessment between multiple observers. the observers were aware of the campaign which led to observer bias as they may have looked for improvements in hhc post-intervention. no standard of hand hygiene was referenced in the study design therefore it is impossible to assess whether the criteria for hhc in the study would meet gold-standard practice. different types of educational intervention were applied at once; unable to assess the effect of each intervention independently. post-intervention data collected 2 months post-campaign: the change in compliance immediately compared to long-term is not reviewable. appraisal, application and reflection helder et al. (2010) listed hand hygiene compliance (hhc) as a protective measure against nosocomial infections in human medicine and concludes that educational implementation has a statistically significant positive effect on hhc. despite the stressed importance of hhc within human medicine (randle et al., 2006), extensive database searches generated only three articles which answered the pico; this displays a lack of veterinary evidence. the study conducted by anderson et al. (2014) showcased the highest transferability to general practice as the population consisted of first opinion clinics. nevertheless, the authors used “known contacts” (anderson et al., 2014) for recruitment. it was noted that the population who volunteered may have had a prior interest in hand hygiene, which could have exposed the results to inherent bias; this may have limited the true representation of the veterinary community. the world health organization (who) deemed direct observation the most appropriate data collection method for assessment of hhc (who, 2019). anderson et al. (2014) utilised video cameras to facilitate direct observation of participants to limit observation error. pre-defined guidelines based on ‘my 5 moments for hand hygiene’ (who, 2009) allowed objective quantification of hand hygiene opportunities. to gain informed consent the participants were briefed on the video camera purpose, therefore the hawthorne effect may have elevated the compliance with hand hygiene protocols (eckmanns et al., 2006).  in a study that assessed hhc observation methodology, (scherer et al. 2018) it was found that direct observation is subject to bias which can falsely increase the hhc rates observed when compared to a novel technique such as covert observations in 15 minute intervals, (chang et al., 2016; morgan et al., 2013; and yin et al., 2014). it is plausible to suggest that any improvement in hhc originally associated with the hawthorne effect, (eckmanns et al., 2006) may have been subject to habit formation due to progressive repetition (kurz et al., 2015). overall, anderson et al. (2014) detected no significant post-intervention change. the article detailed extensive transparent statistical analysis such as logistic regression, odds ratio and confidence intervals, which were all appropriate assessments of the data provided and subsequently, increased reliability of results. the two remaining studies by shea & shaw (2012) and smith et al. (2013) utilised similar methodology; both assessed the impact of a multimodal educational campaign on hhc and did not collect data immediately post-intervention. shea & shaw (2012) waited 2 months and smith et al. (2013) waited 6 weeks. both studies were set in teaching hospitals where regular staff rotation limited the ability to control the population; preand post-observations were not conducted on the same individuals so reproducibility of the results is limited. shea & shaw (2012) found a statistically significant positive effect of the educational campaign on hhc. despite the similarity in study design, smith et al. (2013) did not discover a statistically significant effect; the absence of data collection immediately post-intervention was instead discussed as a limitation. human medicine studies such as dubbert et al. (1990) and phan et al. (2018), have demonstrated the importance of obtaining immediate post-intervention data as well as delayed, to assess the effect of time on the impact of the educational interventions. the lack of justification of both methodologies may have compromised the result integrity. however, the statistical analysis applied, conducted with a chi-squared test for shea & shaw (2012) and a fishers’ exact test for smith et al. (2013), was an appropriate assessment of the data. excluding shea & shaw (2012), the two other studies used who (2009) guidelines of hand hygiene as an established measurement of compliance. shea & shaw (2012) did not report which hand hygiene guidelines were used as the basis of study design, therefore comparison with the other articles is difficult. human evidence, such as the who (2009) hand hygiene guidelines, is heavily relied upon to form veterinary hand hygiene protocols due to lack of veterinary evidence. comparison was also difficult due to the differences in educational interventions between all three studies; it was not clear which aspect of the intervention had an effect on hhc. further research could be conducted to compare individual educational approaches to find the most efficacious intervention.  the general techniques and opportunities for hand hygiene have been stated to be transferable between human and veterinary medicine, (mann, 2017) using the one health principle (committee on the national needs for research in veterinary science et al., 2005). however, there is a current disparity between the human and veterinary evidence with regards to the effect of education on hhc (helder et al., 2010). in addition, there is a lack of research which compares the motivational factors of hhc for human and veterinary care providers; therefore, it is difficult to determine whether the one health concept should be applied to veterinary practice in the field of hand hygiene. to validate the conclusions drawn by shea & shaw (2012), further research is needed with application of a standardised, clinically relevant assessment of hand hygiene in veterinary medicine. the veterinary evidence reviewed does not provide strong justification for the use of education in the improvement of hhc in small animal practice. this contrasts with extensive human evidence which supports the use of educational interventions (helder et al., 2010).  however, a limited veterinary knowledge base in the field of hand hygiene, combined with the flawed methodologies of the appraised literature, suggests that this finding is not representative of the effect education could have on hhc. until there is definitive assessment on the application of human hand hygiene research to veterinary medicine, it is recommended to utilise the results of this knowledge summary alongside the human evidence-base in order to improve hhc. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform – 1973–15/10/19 web of science – 1900–15/10/19 cinahl – 1981–15/10/19 pubmed – 1948–15/10/19 medline on ovid platform – 1946–15/10/19 search strategy: cab abstracts: vet* or rvn or svn or “small animal” or “companion animal” or “domestic animal” “hand washing” or "hand sterilising" or "hand hygiene" or " handwash" or “world health organisation” or sterillium or "hand cleaning" or chlor* or hibi* edu* or teach* or intervention or resource or poster compliance or effectiveness or efficacy or "standard operating procedure" or sop or "standard operating protocol” 1 and 2 and 3 and 4   web of science: (vet* or rvn or svn or “small animal” or “companion animal” or “domestic animal”) and (“hand washing” or "hand sterilising" or "hand hygiene" or " handwash" or “world health organisation” or sterillium or "hand cleaning" or chlor* or hibi*) and (edu* or teach* or intervention or resource or poster) and (compliance or effectiveness or efficacy or "standard operating procedure" or sop or "standard operating protocol”)   cinahl: s1: vet* or rvn or svn or “small animal” or “companion animal” or “domestic animal” s2: “hand washing” or “hand sterilising” or “hand hygiene” or “handwash” or “world health organisation” or sterillium or “hand cleaning” or “ chlor* or hibi* s3: edu* or teach* or intervention or resource or poster s4: compliance or effectiveness or efficacy or “standard operating procedure” or sop or “standard operating protocol” s5: s1 and s2 and s3 and s4   pubmed: (vet* or rvn or svn or “small animal” or “companion animal” or “domestic animal”) and (“hand washing” or "hand sterilising" or "hand hygiene" or " handwash" or “world health organisation” or sterillium or "hand cleaning" or chlor* or hibi*) and (edu* or teach* or intervention or resource or poster) and (compliance or effectiveness or efficacy or "standard operating procedure" or sop or "standard operating protocol)   medline: (vet* or rvn or svn or small animal or companion animal or domestic animal) and (edu* or teach* or intervention or resource or poster) and (hand washing or hand hygiene or handwash or world health organisation or sterilium or hand cleaning or chlor* or hibi*) and (compliance or effectiveness or efficacy or standard operating procedure or sop or standard operating protocol) {including related terms} dates searches performed: 15/10/2019 exclusion / inclusion criteria exclusion: does not answer pico, not an experiment, duplicate inclusion: answers pico, small animal medicine based, english language search outcome database number of results excluded – [does not answer pico] excluded – [not an experiment] excluded – [duplicate] total relevant papers cab abstracts 27 23 1 0 3 web of science 24 20 1 3 0 cinahl 19 19 0 0 0 pubmed 92 89 0 3 0 medline 26 22 1 3 0 total relevant papers 3 conflict of interest the authors declare no conflicts of interest. references anderson, m., sargeant, j. and weese, j. (2014). video observation of hand hygiene practices during routine companion animal appointments and the effect of a poster intervention on hand hygiene compliance. bmc veterinary research, 10(1), pp.106. doi: https://doi.org/10.1186/1746-6148-10-106 chang, n., reisinger, h., jesson, a., schweizer, m., morgan, d., forrest, g. and perencevich, e. (2016). feasibility of monitoring compliance to the my 5 moments and entry/exit hand hygiene methods in us hospitals. american journal of infection control, 44(8), pp.938–940. doi: https://doi.org/10.1016/j.ajic.2016.02.007 committee on the national needs for research in veterinary science, board on agriculture and natural resources, division on earth and life studies, and national research council (2005). the role of veterinary research in human society. critical needs for research in veterinary science. national academic press. washington, d.c. pp.13–20. doi: https://doi.org/10.17226/11366 dubbert, p., dolce, j., richter, w., miller, m. and chapman, s. (1990). increasing icu staff handwashing: effects of education and group feedback. infection control & hospital epidemiology, 11(4), pp.191–193. doi: https://doi.org/10.1086/646148 eckmanns, t., bessert, j., behnke, m., gastmeier, p. and rüden, h., (2006). compliance with antiseptic hand rub use in intensive care units the hawthorne effect. infection control & hospital epidemiology, 27(9), pp.931–934. doi: https://doi.org/10.1086/507294 helder, o., brug, j., looman, c., van goudoever, j. and kornelisse, r. (2010). the impact of an education program on hand hygiene compliance and nosocomial infection incidence in an urban neonatal intensive care unit: an intervention study with before and after comparison. international journal of nursing studies, 47(10), pp.1245–1252. doi: https://doi.org/10.1016/j.ijnurstu.2010.03.005 kurz, t., gardner, b., verplanken, b. and abraham, c. (2014). habitual behaviors or patterns of practice? explaining and changing repetitive climate-relevant actions. wiley interdisciplinary reviews: climate change, 6(1), pp.113–128. doi: https://doi.org/10.1002/wcc.327 mann, a. (2017). the importance of hand hygiene. veterinary nursing journal, 32(3), pp.82–85. doi: https://doi.org/10.1080/17415349.2016.1269624 morgan, d., pineles, l., shardell, m., graham, m., mohammadi, s., forrest, g., reisinger, h., schweizer, m. and perencevich, e. (2013). the effect of contact precautions on healthcare worker activity in acute care hospitals. infection control & hospital epidemiology, 34(1), pp.69–73. doi: https://doi.org/10.1086/668775 phan, h., tran, h., tran, h., dinh, a., ngo, h., theorell-haglow, j. and gordon, c. (2018). an educational intervention to improve hand hygiene compliance in vietnam. bmc infectious diseases, 18(1). doi: https://doi.org/10.1186/s12879-018-3029-5 randle, j., clarke, m. and storr, j. (2006). hand hygiene compliance in healthcare workers. journal of hospital infection, 64(3), pp.205–209. doi: https://doi.org/10.1016/j.jhin.2006.06.008 scherer, a., reisinger, h., goto, m., goedken, c., clore, g., marra, a., chasco, e., evans, c., rubin, m. and perencevich, e. (2018). testing a novel audit and feedback method for hand hygiene compliance: a multicenter quality improvement study. infection control & hospital epidemiology, 40(1), pp.89–94. doi: https://doi.org/10.1017/ice.2018.277 shea, a. and shaw, s. (2012). evaluation of an educational campaign to increase hand hygiene at a small animal veterinary teaching hospital. journal of the american veterinary medical association, 240(1), pp.61–64. doi: https://doi.org/10.2460/javma.240.1.61 smith, j., packman, z. and hofmeister, e. (2013). multimodal evaluation of the effectiveness of a hand hygiene educational campaign at a small animal veterinary teaching hospital. journal of the american veterinary medical association, 243(7), pp.1042–1048. doi: https://doi.org/10.2460/javma.243.7.1042 world health organization (2009). my 5 moments for hand hygiene. world health organization (2019). who | hand hygiene monitoring and feedback. yin, j., reisinger, h., weg, m., schweizer, m., jesson, a., morgan, d., forrest, g., graham, m., pineles, l. and perencevich, e. (2014). establishing evidence-based criteria for directly observed hand hygiene compliance monitoring programs: a prospective, multicenter cohort study. infection control & hospital epidemiology, 35(9), pp.1163–1168. doi: https://doi.org/10.1086/677629 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. the incidence of uterine pathology in ovariectomised bitches a knowledge summary by maria norell candetoft dvm 1* 1djursjukhuset anicura albano, rinkebyvägen 21a, 182 36 danderyd, sweden *corresponding author (maria.norell.candetoft@anicura.se) vol 5, issue 3 (2020) published: 18 sep 2020 reviewed by: soon hon cheong (dvm phd) and sebastian patrick arlt (dipl ecar) next review date: 24 jan 2020 doi: 10.18849/ve.v5i3.331 pico question what is the incidence of postoperative uterine pathology in ovariectomised bitches compared to ovariohysterectomised bitches?   clinical bottom line category of research question incidence the number and type of study designs reviewed three retrospective case series strength of evidence weak outcomes reported none of the reviewed case series found any uterine pathology for ovariectomised bitches in the long-term follow-up of several years, although none of the studies performed a proper gynaecological examination to confirm a lack of pathology conclusion with the limited evidence available, it appears that leaving the uterus when gonadectomising bitches does not seem to have a high risk for developing pathology as long as the ovaries are completely removed.   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision-making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care clinical scenario you work at a small animal clinic and an owner comes to you with her intact female dog to discuss gonadectomy. she has heard that it is better to remove the uterus together with the ovaries because of the risk for the development of pyometra than to leave the uterus in the bitch. she wants to know your opinion on this subject. the evidence three papers were identified which addresses the pico question and meet the inclusion and exclusion criteria applied. all three studies identified were retrospective case series. the number of cases included in the studies was moderately high: 278 (corriveau et al., 2017), 264 (okkens et al., 1997) and 72 (janssens & janssens, 1991). the studies describe shortand long-term outcomes after different surgical sterilisation methods in bitches: laparoscopic ovariectomy (lapove) and laparoscopic ovariohysterectomy (lapovh) (corriveau et al, 2017), ovariectomy and ovariohysterectomy via laparotomy and ovariectomy (okkens et al, 1997) and bilateral flank ovariectomy (janssons et al, 1991). all of the studies also include an owner questionnaire to identify long-term complications. the subjective nature of owner assessment may introduce bias.   corriveau et al. (2017) compared the outcome between laparoscopic ovariectomy with ovariohysterectomy in 278 cases, the medical records were examined and responses to a questionnaire were developed and provided. none of the dogs in the two groups that were available during a 10 year follow-up (207 out of 278) developed clinical signs of uterine pathology. okkens et al. (1997) compared the outcome of 264 bitches that had been randomly selected for either ovariectomy or ovariohysterectomy. a questionnaire concentrated on the occurrence of problems related to abnormalities of the urogenital tract (i.e. vaginal discharge, attracting male dogs, and urinary incontinence) was sent to the owners 8 to 11 years after surgery. complete data from 69 bitches in the ovariectomy group and for 66 bitches in the ovariohysterectomy group (135 out of 264) were available and analysed. no symptoms from the abdominal cavity as a consequence of the surgery were observed by any of the owners. vaginal discharge was reported in two bitches in each group, the discharge was not severe and not accompanied by any apparent illness. ovariectomy: discharge started 6 and 10 years after surgery, the discharge was colourless and was noticed in regular, but not cyclic, time intervals. ovariohysterectomy: discharge started 3 months and 10 years after surgery, the discharge was whiteish and occurred regularly but not cyclic. only one of these four bitches was presented to a veterinarian because of this problem, the article does not say what kind of diagnostics were used to examine the dog and no conclusion of the cause of the discharge is mentioned. none of the bitches were sexually attractive to male dogs after the sterilisation procedure. janssons & janssons (1991) described the outcome in 72 bitches that underwent bilateral flank ovariectomy, the owners received a questionnaire between 4 and 9 years after the operation and none of the bitches had developed pyometra.   article   ovariectomy   (number) ovariohysterectomy (number) follow-up time (years) uterine pathology (%)    corriveau et al. (2017)   147 131 14 d – 10 y 0    okkens et al.  (1997)   126 138 8–11 0    janssons & janssons (1991)   72 0 4–9 0   even though the evidence presented in the three articles is far from the ideal grade i (meta-analyses of randomised, controlled trials or evidence obtained at least from one properly randomised, controlled trial), the high number of cases all presenting the same result, no signs of uterine pathology, is suggestive that leaving the uterus during gonadectomy does not appear to dramatically increase the occurrence of pyometra and may be considered reasonably safe. to raise the quality of the evidence, these bitches should have undergone a proper gynaecological examination. summary of the evidence corriveau et al. (2017) population: female neutered dogs, located in the usa, from 125 breeds. most common breeds included great dane (11%), labrador retriever (10%) and golden retriever (6%). dogs were required to have undergone a lapovh or a lapove.  cases were excluded if records were incomplete, sterilisation was performed because of a neoplastic process, or the dog was found to have previously been sterilised. sample size: 278 dogs: lapovh n= 131 lapove n=147 intervention details: the medical record database of the ryan veterinary hospital of the university of pennsylvania was reviewed to identify eligible cases. the medical records from shelter-owned and client-owned female dogs undergoing lapovh or lapove during a 14 days to 10-year period from october 2003 through october 2013 were included. data collected from the medical record  consisted of breed, age, body weight, body condition score, history of urinary tract abnormalities, preoperative systemic disease, number of laparoscopic ports used, surgeon experience, total duration of anaesthesia, lapove or lapovh procedure time, additional procedures performed, intraoperative surgical complications, immediate postoperative complications, duration of hospitalisation, and short-term postoperative incisional complications. long-term follow-up (>14 days to 10 years after surgery) to assess postoperative complications and overall owner satisfaction was conducted by means of a questionnaire administered by telephone or email. questions were phrased to allow for initial ‘yes’ or ‘no’ responses by the owner regarding postoperative development of urinary incontinence, signs of oestrus, or pyometra as diagnosed by a veterinarian. if a complication was noted, additional information was requested, including time of onset of clinical signs or diagnosis, any diagnostic testing performed and any treatment performed. study design: retrospective case series outcome studied: the shortand long-term follow up information regarding complications after lapovh vs lapove main findings (relevant to pico question): short-term follow-up information (≤ 14 days after surgery) was available for 91/131 (69.4%) in the lapovh group and 133/147 (90.5%) in the lapove group. in total 54 dogs were lost to short-term follow-up. short-term postoperative incisional complications including erythema, seroma, or infection were reported in 15/224 dogs (6.7% of dogs that were available for follow-up) and were not significantly associated with the procedure. for every additional 30 minutes of anaesthetic time, the odds of developing an incisional complication increased by 24%. dogs that developed an immediate postoperative complication were 6.67 times as likely to develop an incisional complication. in summary results in the present 10-year (2003 through 2013) retrospective study suggests that shortand long-term outcomes were similar for the dogs undergoing sterilisation by means of lapovh or lapove. long-term follow-up information was available for 82/131 patients (62.6%) in the lapovh group and in 125/147 patients (85%) in the lapove group. no dogs were reported to have exhibited signs of oestrus, pyometra or a persistent ovarian remnant following laparoscopic sterilisation. urinary incontinence occurred in 19/201 dogs (9.2%) and was associated with the lapovh group on unadjusted analysis. however, on multivariable analysis, procedure was not independently associated with urinary incontinence following surgery, but was a confounding factor in the association between preoperative urinary tract abnormalities and postoperative incontinence. after adjusting for body weight, duration of follow-up, and procedure (lapovh vs lapove), dogs with preoperative urinary tract abnormalities, including incontinence, urinary tract infection, or calculi, were 3.27 times as likely to have postoperative urinary incontinence as were dogs without a history of preoperative urinary tract abnormalities. of the 182 dogs with no preoperative urinary tract abnormalities, 13 (7.1%) were reported to have postoperative urinary incontinence. overall, owners of 205/207 dogs (99%) for which long-term follow-up information was available, reported that they were satisfied with the surgery. limitations: retrospective case series provide low-level evidence. no other diagnostic tests were used to confirm that the remaining uterus was healthy; no blood samples were taken, no vaginal cytology was done and no ultrasound of the uterus was performed. the study did not include laparotomy surgery. if removing only the ovaries in open surgery affects the remaining uterus it was not investigated. the article does not say how much time may have passed since surgery and the performance of the questionnaire in each individual case. in the lapove group approximately 37% of dogs were lost to follow-up, in the lapovh group 15% of dogs were lost to follow-up. since the fate of the dogs lost at follow-up can´t be assessed it can´t be estimated if there are more complications with one method or the other. okkens et al. (1997) population: female neutered dogs, located in the netherlands. breeds represented with more than six bitches were german shepherds (11), bouviers des flandres (11) and dobermanns (8). the age of the bitches at the time of surgery ranged from 0.8–9.9 years (median 1.5 years) in the ovariectomy group and from 1.0–12.0 years (median 2.5 years) in the ovariohysterectomy group. all bitches had experienced at least one oestrus before neutering. the body mass at the time of the surgery ranged from 1.6 to 37.5 kg (median 22.0 kg) in the ovariectomy group and from 5.0 to 37.5 kg (median 20.5 kg) in the ovariohysterectomy group. cases were excluded if records were incomplete, sterilisation was performed because of a neoplastic process or the dog was found to have previously been sterilised. sample size: 264 neutered dogs: 126 ovariectomised 138 ovariohysterectomised intervention details: a questionnaire was sent to 264 owners of bitches as follow-up to a routine neutering procedure performed 8 to 11 years earlier. the bitches were randomly selected for either ovariectomy or ovariohysterectomy. both the ovariectomy group and the ovariohysterectomy group were neutered through a caudal midline incision. complete data analysis became available for 69 bitches in the ovariectomy group (54.7%) and for 66 bitches in the ovariohysterectomy group (47.8%). the questionnaires concentrated on the occurrence of problems that could possibly be related to abnormalities of abdominal organs, such as abdominal pain, and particularly to abnormalities of the urogenital tract, i.e. vaginal discharge, attraction of male dogs and urinary incontinence. if an owner responded positively to one or more of the questions, a detailed telephone interview concerning the signs of the problem, duration and timing of the problem, treatments, etc., was carried out. study design: retrospective randomised case series outcome studied: comparison between differences in short-term and long-term complications after ovariohysterectomy vs ovariectomy main findings (relevant to pico question): none of the bitches were sexually attractive to male dogs after the neutering procedure. no abdominal problems as a consequence of the surgery were observed by any of the owners. vaginal discharge was reported in two bitches in each group, the discharge was not severe and not accompanied by any apparent illness. ovariectomy: discharge started 6 and 10 years after surgery, the discharge was colourless and occurred regularly but not cyclic. ovariohysterectomy: discharge started 3 months and ten years after surgery, the discharge was whitish and was noticed in regular but not cyclic time intervals. there were no significant difference between the ovariectomy and ovariohysterectomy group in the incidence of urogenital problems listed during the follow-up period of 8 to 11 years. ovariectomy does not increase the risk of cystic endometrial hyperplasia (ceh) – endometritis or other complications compared with ovariohysterectomy. limitations: it was a retrospective study, which is lower on the evidence hierarchy compared to for example a randomised multi-centre prospective study. no other diagnostic tests were used to confirm that the remaining uterus was healthy; no blood samples were taken, no vaginal cytology done and no ultrasound or other diagnostic methods of the uterus was performed. the article does not say how much time may have passed since surgery and the performance of the questionnaire in each individual case. in the ovariectomy group approximately 45% of dogs were lost to follow-up, in the ovariohysterectomy group about 42% of dogs were lost to follow-up. whether the dogs left for follow-up developed uterine pathology or remained healthy is not clear and must be taken into account. janssens & janssens (1991) population: ovariectomised female dogs from 27 different breeds. the weight of the bitches at the time of surgery ranged from 1.3 and 55 kg (mean 15.3 kg) and the age varied between 0.5–7.0 years (mean 2.2 years). sample size: 72 dogs intervention details: the dogs underwent bilateral surgical flank approach and the ovaries were removed. the surgery was performed between 1 and 4 months after oestrus. if uterine abnormalities were observed the uterus was also removed. a questionnaire was handed out to 72 owners between 4 and 9 years after the operation. the questionnaires concentrated on the occurrence of long-term problems: weight gain, hair-shedding, coat changes, character changes, urinary incontinence and the development of pyometra. study design: non-comparative retrospective case series outcome studied: determination of short-term and long-term complications after ovariectomy main findings (relevant to pico question): in one dog an enlarged uterus was removed. in one obese dog the ovarian bursa was not found on the left side. therefore, a ventral midline incision was used to approach this ovary. short-term complications: blood-loss from the surgical wound 4/72 (6%) seroma formation 16/72 (22%) wound infection 2/72 (2.8%) herniation (0%) long-term complications: development of pyometra (0%) weight gain 43/72 (60%) hair-shedding 19/72 (26%) coat changes 5/72 (6.9%) character changes – less active 21/72 (29%), aggressive towards other dogs 16/72 (22%) urinary incontinence 13/72 (18%) limitations: no other diagnostic tests were used to confirm that the remaining uterus was healthy; no blood samples were taken, no vaginal cytology done and no ultrasound or other diagnostic methods of the uterus were performed. there were no defined exclusion or inclusion criteria. the article does not say how the data from the short-term complications were collected, did they see the animals at the clinic or did they ask the owners? the article does not say how much time may have passed since surgery and the performance of the questionnaire in each individual case. appraisal, application and reflection only three studies were identified that addressed the pico question and these studies were retrospective case series. thus, the evidence base for answering the question is limited, but at least all three of the studies did not report a case where uterine pathology developed in an ovariectomised bitch. van goethem et al. (2006) reviewed the outcome for ovariectomy and ovariohysterectomy, and they found that there was no difference in outcome when they analysed the present literature comparing the two methods. ovariectomy did not lead to any pathologic changes in the remaining uterus. bitches undergoing ovariectomy did not show symptoms of pyometra or endometritis years after the surgery. in 1958, dow reported the ability to experimentally induce cystic endometrial hyperplasia (ceh) or ceh-endometritis by administration of progesterone, even in ovariectomised bitches. withdrawal of the progesterone treatment causes regression of the experimentally produced disease. similarly, ovariectomy leads to regression of the natural disease (dow, 1958), thus exposure to progestogen appears to be necessary for the development of ceh-endometritis and that is the main proposed answer to why the uterus seems to remain healthy after ovariectomy (okkens et al. 1997). stump pyometra have been reported in bitches that have had an improperly performed ovariohysterectomy in association with ovarian remnant syndrome, breaks in aseptic technique, or exogenous progesterone administration (de tora & mccarthy, 2011; van goethem et al., 2006; janssens & janssens, 1991; and okkens et al., 1997). uterine neoplasia can develop after ovariectomy; however, uterine tumors are reportedly rare (0.03%) and are benign in 85% to 90% of the cases (brodey, 1967). therefore, the overall risk has to be balanced against the disadvantages of ovariohysterectomy compared with ovariectomy in terms of surgical time, additional trauma, and potential complications. it is important to note that none of the articles reviewed performed any diagnostic tests as part of the follow-up, and all three articles relied solely on owner responses to the questionnaires for data on uterine pathology or ovarian remnants. also, in the study by corriveau et al. (2017) 15% of the patients in the group that underwent ovariectomy were lost to follow-up and in the study by okkens et al. (1997) 45% of the ovariectomised patients were lost to follow-up and the status of the remaining uterus in those patients is unknown. to bring more evidence to properly answer the pico question, a randomised multi-centre prospective study should be done with active follow-up including diagnostic workup (ultrasound, vaginal cytology, luteinizing hormone (lh) test, anti-muellerian-hormone tests etc.) to confirm the lack of uterine pathology or ovarian remnant occurring for a period of at least 5 to 10 years after the surgery. methodology section search strategy databases searched and dates covered: cab abstracts on the ovid interface 1973–2020 week 03 pubmed accessed via the ncbi website 1910–jan 2020 search strategy: cab abstracts: (dog or dogs or canine or canines or canis or bitch or bitches) or exp dogs/ or exp bitches/ or exp canis/ (spey* or spay* or neuter* or ovariectom* or ovariohysterectom* or ovario-hysterectom* or hysterectom* or sterilis* or steriliz* or desex* or de-sex* or gonadect*) or exp ovariectomy/ or exp sterilization/ or exp hysterectomy/ or exp gonadectomy/ (pyometra or hydrometra or mucometra or uterine neoplasia or endometrial hyperplasia) ((uterine or uterus) and (disease* or pathology)).mp. or exp uterine diseases/ 1 and 2 and (3 or 4) pubmed: (dog or canine or bitch or canis) (spey or spay or neuter or ovariectomy or ovariohysterectomy or ovario-hysterectomy or hysterectomy or sterilise or sterilize or desex or de-sex or gonadectomy) (pyometra or hydrometra or mucometra or uterine neoplasia or endometrial hyperplasia) (uterine or uterus) and (disease or pathology) 1 and 2 and (3 or 4) dates searches performed: 24 jan 2020 exclusion / inclusion criteria exclusion: non-english language wrong species articles not about uterine pathology after neutering conference proceedings and commentaries inclusion: only articles about uterine pathology after neutering full text articles available in english dogs only search outcome database number of results excluded – not relevant to the pico question excluded – not in english excluded – review papers, proceedings, conference papers or book chapters excluded – wrong species total relevant papers cab abstracts 578 424 94 32 25 3 pubmed 317 251 22 8 34 2 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflicts of interest. references corriveau, k. m., giuffrida, m. a., mayhew, p. d. & runge, j. j. (2017). outcome of laparoscopic ovariectomy and laparoscopic-assisted ovariohysterectomy in dogs: 278 cases (2003–2013). journal of the american veterinary medical association, 251(4):443–450. doi: https://doi.org/10.2460/javma.251.4.443 brodey, r.s. (1967). neoplasms of the canine uterus, vagina, and vulva: a clinicopathologic survey of 90 cases. journal of the american veterinary medical association, 151(10):1294–307. de tora, m. & mccarthy, r.j. (2011). ovariohysterectomy versus ovariectomy for elective sterilization of female dogs and cats: is the removal of the uterus necessary? journal of the american veterinary medical association, 239(11):1409–12. doi: https://doi.org/10.2460/javma.239.11.1409 dow, c. (1959). the cystic hyperplasia-pyometra complex in the bitch. journal of comparative pathology and therapeutics,, 69:237–250. doi: https://doi.org/10.1016/s0368-1742(59)80023-0 janssens, l. a. a. & janssens, g. h. r. r. (1991). bilateral flank ovariectomy in the dog surgical technique and sequelae in 72 animals. journal of small animal practice, 32(5):249–252. doi: https://doi.org/10.1111/j.1748-5827.1991.tb00557.x okkens, a.c., kooistra, h.s. & nickel, r.f. (1997). comparison of long-term effects of ovariectomy versus ovariohysterectomy in bitches. journal of reproduction and fertility supplement, 51:227–31. van goethem, b., schaefers-okkens, a. & kirpensteijn, j. (2006). making a rational choice between ovariectomy and ovariohysterectomy in the dog: a discussion of the benefits of either technique. veterinary surgery, 35(2):136–143. doi: https://doi.org/10.1111/j.1532-950x.2006.00124.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. evaluating the reliability of computed tomography for the diagnosis of intervertebral disc extrusion in dogs a knowledge summary by chloe smith bvsc (dist) pgdip vcp mrcvs 1* 1langford veterinary services, langford house, langford, bs40 5du, uk *corresponding author (cs13407@bristol.ac.uk) vol 6, issue 4 (2021) published: 01 dec 2021 reviewed by: elizabeth baines (ma vetmb dvr dipecvdi fhea mrcvs) and tom shaw (bvetmed ma mrcvs dipecvn) next review date: 08 dec 2022 doi: 10.18849/ve.v6i4.384 pico question in dogs with an acute thoracolumbar myelopathy, is non-contrast computed tomography (ct) a reliable method for the diagnosis of intervertebral disc extrusion, compared to magnetic resonance imaging (mri)?   clinical bottom line category of research question diagnosis the number and type of study designs reviewed four papers were critically reviewed. two were retrospective, cross-sectional studies, and two were prospective, observational cohort studies strength of evidence moderate outcomes reported the current literature suggests that ct is often sufficient for the diagnosis of thoracolumbar intervertebral disc extrusion, with mri superior to ct for lesion characterisation. non-contrast ct is likely sufficient for the diagnosis and surgical planning for intervertebral disc disease in dachshunds. however, mri is recommended for diagnosis and surgical planning of thoracolumbar intervertebral disc disease in non-dachshund breeds conclusion computed tomography is often sufficient for the diagnosis of thoracolumbar intervertebral disc extrusion. however, mri is superior to ct for lesion characterisation and it is therefore recommended to use mri for cases requiring surgical planning. computed tomography is likely sufficient for the diagnosis and surgical planning of intervertebral disc disease in dachshunds regard for the reason of diagnostics performed (e.g. surgical planning) and the likelihood of other differential diagnoses (e.g. spinal neoplasms) should be taken before deciding to use one imaging modality over the other. consideration into the risks associated with anaesthetising an animal with a spinal cord lesion, the ability of the practitioner to accurately localise the myelopathy and interpret the results, should be taken before pursuing diagnostics in these cases   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are presented with a dachshund, with acute onset paraplegia, that you suspect has an intervertebral disc extrusion between the t3 and l3 spinal cord segments. you are confident performing a hemilaminectomy procedure and have access to both computed tomography (ct) and magnetic resonance imaging (mri). you therefore want to know if ct, in comparison to mri, is a reliable modality for the diagnosis and surgical planning of thoracolumbar disc extrusions in dogs. the evidence of the four papers reviewed, two were prospective and two were retrospective studies in nature. the strength of evidence for each paper is considered moderate, with the absence of a systematic review or meta-analysis for this topic. paper one (cooper et al., 2014) is the only study to directly compare the sensitivity of mri versus ct in the diagnosis of thoracolumbar intervertebral disc disease in dogs and this evidence was therefore considered stronger when reaching a clinical bottom line. however, the other three papers all provide insight into the use of both imaging modalities in the diagnosis of thoracolumbar myelopathies and provide evidence to concur with the conclusions drawn by cooper et al. (2014). summary of the evidence cooper et al. (2014) population: dogs with neurological signs localised to t3-s1. sample size: 44 dogs (35 chondrodystrophic, nine other breeds). intervention details: all dogs had both a non-contrast ct and an mri. study design: observational cohort study. outcome studied: sensitivity of non-contrast ct versus mri for detecting intervertebral disc herniation. accuracy of non-contrast ct versus mri for lesion localisation and lateralisation. main findings (relevant to pico question): mri was deemed to have a sensitivity of 98.5% (95% confidence interval (ci), 1–99.7%) for detecting intervertebral disc herniation, compared to a sensitivity of 88.6% (95% ci, 79.5–94.2%) with ct examination. mri was more accurate (93.2%; 95% ci, 85.6–1%) when compared with ct (84.1%; 95% ci, 74.4–90.7%, for locating intervertebral disc herniation. mri was also more accurate in differentiating disc protrusion versus extrusion (mri: 94.4% (95% ci, 88.4–97.5%), ct: 85.7% (95% ci, 75.3–92.4%)), and lesion lateralisation (specifically lateralisation lesion in non-chondrodystrophic dogs – mri: 95.0%, (95% ci,73.1–99.7%), ct: 69.6%, (95% ci, 39.3–89.8%). limitations: all measurements have not been adjusted for prevalence and therefore specificity could not be evaluated. surgery was used as the confirmatory technique for the characterisation of the intervertebral disc herniation, risking bias and restricting the areas that can be investigated to confirm disc herniation. no evaluation of ct positive, mri negative disc herniations and therefore an inability to fully compare mri to ct for lesion characterisation. tamura et al. (2015) population: dogs with thoracolumbar intradural disc herniation, confirmed at surgery. sample size: eight dogs. intervention details: three dogs had a ct myelogram and five dogs had an mri. study design: retrospective cross-sectional study. outcome studied: presence of intradural herniation as confirmed at surgery. main findings (relevant to pico question): mri misdiagnosed all cases in the study, failing to identify any intradural herniation and instead characterising the cases as standard intervertebral disc herniation. the ‘golf tee sign’ and subarachnoid filling deficits were observed in 3/8 cases using ct myelography, suggesting that ct myelography may be more sensitive for detecting intradural disc herniations. limitations: mri and ct examinations were not performed in the same animal and so could not be directly compared. the mri used was a low-field scanner and therefore findings may differ if a high-field scanner were used. 5/8 cases evaluated were of the same breed and therefore the results may not be representative of every breed. both mri and ct studies were not standardised, with different techniques and machines used (for example, not all studies included both t1-weighted and t2-weighted scans). small case numbers. descriptive analysis only performed. emery et al. (2018) population: dogs with thoracolumbar myelopathies. sample size: 555 dogs: 450 chondrodystrophic; 105 non-chondrodystrophic 335 dachshunds; 220 other breeds intervention details: all dogs underwent ct imaging. study design: retrospective cross-sectional study. outcome studied: the need for additional imaging (beyond thoracolumbar ct) for the diagnosis of a thoracolumbar myelopathy in dogs. breed, age, sex, chronicity, site of lesion, time of study and contrast administration. main findings (relevant to pico question): dachshunds were the least likely breed to need additional imaging (on top of non-contrast ct imaging) with only 12/335 (3.6%) of dachshunds requiring further imaging compared to 30/220 (13.6%) of other dog breeds. no statistically significant difference was noted in the need for further imaging when comparing chondrodystrophic to non-chondrodystrophic breeds. the presence of a normal ct, or multiple intervertebral disc herniations identified on non-contrast ct (and therefore the difficulty distinguishing acute from chronic lesions) were both cited as common reasons for requiring additional imaging techniques. 42/555 (7.6%) of dogs presenting with a thoracolumbar myelopathy required further advanced imaging beyond a plain ct scan. ct scans performed with positive contrast media intravenously did not alter the need for additional imaging, compared to those where an intravenous contrast agent was not used. limitations: the accuracy of lesion localisation and lateralisation was not assessed in this study and therefore cannot be evaluated. retrospective study and therefore no standardisation of protocols used. referral population with patient pre-selection of imaging modality based on signalment and history. therefore, not a true representation of the general case population. noyes et al. (2017) population: chondrodystrophic dogs with thoracolumbar intervertebral disc extrusion. sample size: 40 dogs. intervention details: all dogs underwent ct and mri. study design: prospective observational study. outcome studied: influence of pre-operative planning considerations for hemilaminectomies based on ct versus mri. factors studied include; location, lateralisation and extent. main findings (relevant to pico question): large range in inter-observer agreement for both imaging modalities (43.5–6%) when assessing the site, side and size of laminectomy approach. all observers planned a larger laminectomy defect based on mri compared to ct imaging. all lesions were identified in cases when using mri, however lesions were not identified in four of these cases when assessing ct images alone. limitations: confirmation of imaging findings was not evaluated (e.g. surgical visualisation of disc herniation). no statistics therefore performed to directly compare the reliability of ct and mri in detecting lesion localisation. appraisal, application and reflection the literature search performed found four papers which addressed, or partially addressed the pico. mri was found to have an increased sensitivity for the detection of intervertebral disc disease in dogs, compared to non-contrast ct (cooper et al., 2014; and noyes et al., 2017). however low-field mri misdiagnosed all cases of thoracolumbar intradural disc herniation when compared with ct myelography in dogs (tamura et al., 2015). non-contrast ct appears to be a sufficient imaging modality for intervertebral disc disease and surgical planning in the majority of dachshunds (96.4%; 323/335) (emery et al., 2018). regard for the reason for diagnostics performed (e.g. surgical planning) and the likelihood of other differential diagnoses (e.g. spinal neoplasms) should be taken before deciding to use one imaging modality over the other. cost, procedure time, and need for a general anaesthetic are also factors that should be considered when assessing between mri and ct examinations. methodology section search strategy databases searched and dates covered: cab abstracts (on ovid sp): 1973–december 2020 medline (on ovid sp): 1946–december 2020 web of science: 1900–2020 search strategy: cab abstracts and medline: dog* or bitch* or canin* or canid* or dogs/ intervertebral disc* or ivd or ivdd or disc* or disk* or hansen or intervertebral disc disease/ thoracolumbar or t3l3 or t3-l3 or thoraco* ct or computed tomography mri or magnetic resonance 1 and 2 and 3 and 4 and 5   web of science: cited reference search using noyes et al. (2017) dates searches performed: 08 dec 2020 exclusion / inclusion criteria exclusion: lack of relevance to the pico question lack of online full text availability full text not available in the english language single case reports clinical research presentations inclusion: articles published between 1973–2020 assessing dogs presenting with clinical signs attributable to intervertebral disc disease, in which ct and mri modalities are compared search outcome database number of results excluded – not relevant to the pico excluded – not available for review/not available for review in the english language total relevant papers cab abstracts 26 22 0 4 medline 18 14 0 4 web of science 30 25 4 1 total relevant papers when duplicates removed 4 conflict of interest the author declares no conflicts of interest. references cooper, j.j., young, b.d., griffin iv, j.f., fosgate, g.t. & levine, j.m. (2014). comparison between noncontrast computed tomography and magnetic resonance imaging for detection and characterization of thoracolumbar myelopathy caused by intervertebral disk herniation in dogs. veterinary radiology & ultrasound. 55(2), 182–189. doi: http://dx.doi.org/ 10.1111/vru.12114 emery, l., hecht, s. & sun, x. (2018). investigation of parameters predicting the need for diagnostic imaging beyond computed tomography in the evaluation of dogs with thoracolumbar myelopathy: retrospective evaluation of 555 dogs. veterinary radiology & ultrasound. 59(2), 147–154. doi: https://doi.org/10.1111/vru.12576 noyes, j. a., thomovsky, s.a., chen, a.v., owen, t.j., fransson, b.a., carbonneau, k.j. & matthew, s.m. (2017). magnetic resonance imaging versus computed tomography to plan hemilaminectomies in chondrodystrophic dogs with intervertebral disc extrusion. veterinary surgery. 46(7), 1025–1031. doi: https://doi.org/10.1111/vsu.12700 tamura, s., doi, s., tamura, y., takahashi, k., enomoto, h., ozawa, t. & uchida, k. (2015). thoracolumbar intradural disc herniation in eight dogs: clinical, low-field magnetic resonance imaging, and computed tomographic myelography findings. veterinary radiology & ultrasound. 56(2), 160–167. doi: https://doi.org/10.1111/vru.12213 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. comparative gene approach to the investigation of snps within the tenascin-c gene in achilles tendon injury in the canine patient nina r. kieves dvm, dacvs-sa, dacvsmr, ccrt1* alycen p. lundberg dvm2 vicki l. wilke dvm, phd, dacvs3 1department of veterinary clinical sciences, the ohio state university, 601 vernon l tharp st, columbus, oh 43210 2university of illinois, veterinary clinical medicine, 1008 w hazelwood dr, urbana, il 61802 3glenwood city veterinary clinic, 308 syme ave, glenwood city, wi 54013 *corresponding author (nkieves@gmail.com) vol 1, issue 3 (2016) published: 04 august 2016 reviewed by: matthew stewart (mvet, phd) doi: 10.18849/ve.v1i3.36 section index:    abstract | introduction | methods | results | discussion | footnotes | conflict of interest | references | supplementary files abstract objective: to evaluate for single nucleotide polymorphisms (snps) within the tenascin-c (tnc) gene in a population of dogs with atraumatic achilles tendon rupture. background: in humans, achilles tendinopathy has been extensively studied for numerous polymorphisms within several genes and has been associated with polymorphisms in collagen (col5a1) and the tnc genes. evidentiary value: this study serves as a starting point for evaluating a genetic component of achilles tendinopathy in the dog. methods: whole blood from twenty dogs with atraumatic achilles tendon rupture and 14 matched control samples were used. dna was extracted from whole blood run with primers designed around two snps previously identified to be related to achilles tendinopathy in humans. one snp was located in exon 29, and one exon 17 of the canine tnc gene. polymerase chain reaction (pcr) was run on the samples and they were sequenced. sequences of the affected canine population were compared to the control sample sequences. results: there were no significant differences in genotype or allele frequency of the snps rs13321 and rs2104772 between any of the affected and control subjects with a p-value of 1.0. conclusion: this study evaluated a population of canines with atraumatic achilles tendon rupture for snps in the tnc gene. we found no difference in gene sequence for the study population compared to age, sex, and breed matched controls. application: though the data from this study did not show a correlation between the specific polymorphisms investigated, it is possible that other snps within the tnc gene or other genes involved in tendon composition and repair such as collagen may be associated with atraumatic achilles tendon injury in the dog. introduction the common calcanean tendon, or achilles tendon, is comprised of three main components; the paired tendon of the gastrocnemius muscles; the combined tendon of the gracilis, semitendinosus, and biceps femoris muscles; and the tendon of the superficial digital flexor muscle. tendons are exposed to high mechanical stresses, and disruption can be partial or complete. in the canine patient, disruption can be secondary to a traumatic rupture, often involving direct laceration of the tendon, or can be atraumatic or spontaneous with no distinct injury or event noted1,2. intrinsic and extrinsic factors can affect an individual’s risk for developing a tendinopathy. extrinsic factors shown to be associated with achilles tendon rupture in humans include type of training program, poor technique, type of footwear, previous injuries sustained, and environmental factors3. intrinsic risk factors for developing tendinopathy, including genetic variations in chromosome 9, are well documented in humans4-6 . in humans, achilles tendinopathy has been extensively studied for numerous polymorphisms within several genes and has been found to be associated with polymorphisms in collagen (col5a1) and the tenascin genes4,7-16. tenascin encodes the extracellular matrix tenascin-c glycoprotein, which is expressed during wound healing and remodeling of adult tissues, especially those exposed to high tensile and compressive stress. a 2012 study by saunders et al., evaluated a number of snps within the human tnc gene of patients affected with achilles tendon injury7. they found that several snps were significantly associated with an increased risk of acute achilles tendon injury in a south african and australian study population when compared to asymptomatic controls7. in the canine, traumatic lacerations of the achilles tendon are often primarily repaired, followed by a period of immobilization of the hock joint. atraumatic injuries, however, are often insidious, and can be frustrating to treat successfully often causing decreased function to the patient in the long-term. if there is a genetic mutation predisposing dogs to atraumatic achilles tendon injuries, this could help target therapies to treat these patients more successfully, and possibly allow screening for at risk patients. to the author’s knowledge, no investigation has been made into a genetic etiopathogenesis of atraumatic achilles tendon injury in the canine. therefore, the objective of our study was to evaluate the canine tnc gene for snps rs13321 and rs2104772 previously identified to be expressed in human populations undergoing atraumatic achilles tendon injury. we hypothesised that there would be expression of a similar snp in the canine genome in dogs with atraumatic achilles tendon injury in comparison to an age, sex, and breed matched control group. methods sample collection   electronic medical records at the university of minnesota veterinary medical center were retrospectively reviewed for achilles tendon injuries between 2005-2010. dogs with traumatic rupture were excluded. dogs were included if they had been diagnosed with an atraumatic achilles tendon injury, and were alive and available to return to the hospital, where whole blood samples were obtained, with owner consent. age, breed, and gender matched control samples were obtained from a dna storage bank maintained at the university of minnesota surgical research laboratory. dna isolation dna was extracted from approximately 10 mls of whole blood using the qiaamp dna blood midi/maxi kita. protocol, as determined from the january 2005 handbook22, is to lyse the red blood cells, bind the dna to a spin column, wash with multiple buffers, and then elute the dna into nuclease-free water and store at -20°c. concentration and purity of the dna were assessed with a spectrophotometerb. primer sequence primers were designed using primer 3 plusc. primers were designed around two snps identified and investigated by saunders et al. in 20127. the blast algorithm was used to compare the human tnc snps rs13321 and rs2104772 sequence determined by national center for biotechnology information snp databased to the canine genome; the blast algorithm revealed the synonymous sequences. the synonymous canine coding region surrounding snp rs13321 was located in exon 29 of the canine tnc gene and the synonymous canine coding region of snp rs2104772 was located in exon 17 of the canine tnc genome. the sequences of the exons were inputed into primer 3 for primer design; the forward and reverse primers were then forced to include the known snps (table 2). pcr and gel electrophoresis for this reaction, a 10 ml pcr volume was prepared that contained approximately 12.5 ng of genomic canine dna, 2.5 pmol of each primer, 0.20 mm dntp, 2.0 ml of 5x gotaq reaction buffer, 1 mm mgcl2, 0.05 u gotaq hot start polymerase and distilled, nuclease-free water to bring the total volume to 10 ml. a 269 bp the product was amplified using a thermocyclere. the thermal cycling protocol was set to an initial denaturing for 3 minutes at 94°c, 35 cycles at 94°c for 30 seconds denaturing, 61.1°c for 45 seconds annealing, and 72°c for 45 seconds of extension, with a final extension of 10 minutes at 72°c. pcr products were stored at 4°c for less than 24 hours until gel electrophoresis was run. two ml of each pcr product was run on a 2% agarose gelf for 1 hour at 109v. a 100 bp dna ladderg with size markers was used to confirm correct product size (figure 1). product sequencing once correct products were confirmed, the pcr products were cleaned with exosap-ith. exosap-it reagent (3.2 ml) was added to each pcr product and then placed in the thermal cycler for a program of 15 minutes at 80°c and then 15 minutes at 37°c. in preparation for sequencing, 2 ml of each pcr product was prepared with 9 ml of nuclease-free water and 25 pmol of primer (forward in one preparation, reverse in the other). samples were sent to biomedical genomics center (bmgc)i to be sequenced using sanger sequencing. results were analysed with sequencher softwarej. statistics a fisher’s exact statistical test was performed utilising commercially available softwarek to compare the cases and controls. a p-value of <0.05 was considered statistically significant. results twenty dogs met the inclusion criteria for the study. the mean age was 7.1 years ± 2.4 (range 2-10 years), and mean weight was 33.1kg ± 7.1 (range 22.7-46.8kg). breeds affected included labrador retrievers (14), german shorthair pointers (4), and one each of golden retriever and munsterlander. there were 6 males (5 neutered, 1 intact) and 14 females (13 spayed, 1 intact) represented (see table 1). age, sex, and breed matched control samples were available from a dna databank for 14 of the 20 affected dogs. dogs 8, 13, and 17-20 listed did not have a matched control (table 1). the sequences were analysed for the known human snps, as well as for any deletions or insertions of these alleles. there were no significant differences in genotype or allele frequency of the snps rs13321 and rs2104772 between any of the affected and control subjects with a p-value of 1.0 indicating there was no statistically significant difference between either snps in the affected population of dogs and the control samples. discussion this study evaluated a population of canines with atraumatic achilles tendon rupture for snps in the tnc gene. we found no difference in gene sequence for the study population compared to age, sex, and breed matched controls. though the same snp found in human populations with chronic achilles tendon rupture was not associated with achilles tendon rupture in this canine population, further evaluation is still warranted. tendinopathies are likely polygenic, involving complex interactions between multiple genes. tenascin is present in numerous tissues both abnormal and normal. in normal human tendons, it is expressed in the extracellular matrix near collagen fibers17. studies evaluating the difference in composition of tnc within tendons show increased expression in areas of increased mechanical stress, indicating its role in maintaining fibrocartilaginous regions by decreasing cell-matrix adhesion18. tnc expression is also increased in acute tendon injury in association with disorganised regions of tendon matrix17. a 6-fold increase in achilles tendon injury is seen in humans with genetic variation found at the tenascin c gene locus15. the authors of this study speculate that altered synthesis of tnc may lead to apoptosis of tendon cells, predisposing such individuals to injury15. further study is required to determine a cause and effect relationship. in addition to further evaluating the role tnc may play in achilles tendinopathy, collagen genes could be explored as they have been implicated in human achilles tendinopathy15. the col5a1 gene encodes for a structural component of type v collagen that forms heterotypic fibers with type i collagen in tendons, and possibly plays an important role in regulating fibrillogenesis and, therefore, tendon strength. this alteration in structure is thought to be affected by four col5a1 polymorphisms via post-transcription regulation in humans19. individuals with the a2 allele for the col5a1 gene are less likely to develop achilles tendinopathy15. sequence variants have also been found in collagen genes in association with anterior cruciate ligament ruptures20,21. limitations of this study include a small sample size of affected subjects and only testing for two polymorphisms. acute achilles tendon injury is complex and interactions between numerous proteins encoded by different genes and interaction between these genetic components and environmental factors likely exist. though the data from this study did not show a correlation between the specific polymorphisms investigated, it is possible that other snps within the tnc gene or other structural genes may be associated with achilles tendon injury. if an underlying cause for the alteration of achilles tendon composition can be found, it is possible that targeted therapy may increase the success of treatment of atraumatic achilles tendon rupture in the canine patient. further investigation into additional genetic mutations within the tnc and col genes is warranted. footnotes qiagen inc., valencia, ca, usa nanodrop 1000 spectrophotometer, wilmington, de, usa primer3plus; www.bioinformatics.nl/primer3plus/ national center for biotechnology information, bethesda, md, usa dna engine thermal cycler version 4.0 bio-rad laboratories, hercules, ca, usa seakem le agarose, cambrex bioscience, rockland, me, usa new england biolabs, inc. ipswich, ma, usa usb, cleveland, oh usa university of minnesota, saint paul, mn, usa gene codes corporation, ann arbor, mi, usa microsoft, 2007. microsoft excel. alycen lundberg, redmond, washington, usa conflict of interest the authors declare no conflicts of interest. references charmichael, s. and marshall, w. (2012) tarsus and metatarsus. in: tobias km, johnston sa. veterinary surgery: small animal, st. louis mo: elsevier, pp. 1014-1028. meustage, f.j. (1993) the classification of canine achilles’ tendon lesions. veterinary and comparative orthopaedics and traumatology, (1), pp. 57-59. mahieu, n.n. et al. (2006) intrinsic risk factors for the development of achilles tendon overuse injury: a prospective study. american journal of sports medicine, 34 (2), pp. 226-35. http://dx.doi.org/10.1177/0363546505279918 september, a.v. schwellnus, m.p. and collins, m. (2007) tendon and ligament injuries: the genetic component. british journal of sports medicine, 41 (4), pp. 241-246. http://dx.doi.org/10.1136/bjsm.2006.033035 kannus, p. and natri, a. (1997) etiology and pathophysiology of tendon ruptures in sports. scandinavian journal of medicine & science in sports, 7 (2), pp. 107-12. http://dx.doi.org/10.1111/j.1600-0838.1997.tb00126.x maffulli, n. and kader, d. (2002) tendinopathy of tendo achillis. the journal of bone and joint surgery, 84 (1) pp. 1-8. http://dx.doi.org/10.1302/0301-620x.84b1.12792 saunders, c.j. et al. (2013) investigation of variants within the col27a1 and tnc genes and achilles tendinopathy in two populations. journal of orthopaedic research, 31(4), pp. 632-637. hay m, et al. (2013) association of type xi collagen genes with chronic achilles tendinopathy in independent populations form south africa and australia. british journal of sports medicine, 47 (9), pp. 569-74. posthumus, m. et al. (2009) investigation of the sp1-binding site polymorphism within the col1a1 gene in participants with achilles tendon injuries and controls. journal of science and medicine in sport, 12 (1) pp. 184-189. http://dx.doi.org/10.1016/j.jsams.2007.12.006 raleigh, s.m. et al. (2009) variants within the mmp3 gene are associated with achilles tendinopathy: possible interaction with the col5a1 gene. british journal of sports medicine, 43 (7), pp. 514-520. http://dx.doi.org/10.1136/bjsm.2008.053892 september av, et al. (2009) variants within the col5a1 gene are associated with achilles tendinopathy in two populations. british journal of sports medicine, 43 (5), pp. 357-365. http://dx.doi.org/10.1136/bjsm.2008.048793 september, a.v. et al. (2008) the col12a1 and col14a1 genes and achilles tendon injuries. international journal of sports medicine, 29 (3), pp. 257-263. http://dx.doi.org/10.1055/s-2007-965127 magra, m. and maffulli, m. (2007) genetics: does it play a role in tendinopathy? clinical journal of sport medicine, 17 (4), pp. 231-33. http://dx.doi.org/10.1097/jsm.0b013e3180425879 abrahams, y. et al. (2013) polymorphisms within the col5a1 3'-utr that alters mrna structure and the mir608 gene are associated with achilles tendinopathy. annals of human genetics, 77 (3), pp. 204-214. mokone, g.g. et al. (2006) the col5a1 gene and achilles tendon pathology. scandinavian journal of medicine and science in sports, 16 (1), pp. 19-26. http://dx.doi.org/10.1111/j.1600-0838.2005.00439.x mokone, g.g. et al. (2005) the guanine-thymine dinucleotide repeat polymorphism within the tenascin-c gene is associated with achilles tendon injury. american journal of sports medicine, 33 (7), pp. 1016-1021. http://dx.doi.org/10.1177/0363546504271986 riley, g.p. et al. (1996) tenascin-c and human tendon degeneration. the american journal of pathology, 149 (3), pp. 933-43. mehr, d. et al. (2000) tenascin-c in tendon regions subjected to compression. journal of orthopaedic research, 18 (4), pp. 537-45. http://dx.doi.org/10.1002/jor.1100180405 ribbans, w.j. and collins, m. (2013) pathology of the tendo achillis: do our genes contribute? the bone & joint journal, 95-b (3), pp. 305–13. http://dx.doi.org/10.1302/0301-620x.95b3.30066 postumus m, et al. (2010) the association between the col12a1 gene and anterior cruciate ligament ruptures. british journal of sports medicine, 44 (16), pp. 1160-5. http://dx.doi.org/10.1136/bjsm.2009.060756 postumus, m. et al. (2009) genetic risk factors for anterior cruciate ligament ruptures: col1a1 gene variant. british journal of sports medicine, 43 (5), pp. 352-6. http://dx.doi.org/10.1136/bjsm.2008.056150 qiaamp® (2005) dna blood midi/maxi handbook. [online] available from: https://www.qiagen.com/gb/resources/resourcedetail?id=bf32146a-77fd-40c2-8743-c28974f7935b&lang=en [accessed february 2010] supplementary files, images & tables figure 1: electrophoresis gel showing 100bp dna ladder (l), positive control (+) lane, empty negative control lane (–), and samples 1-16 as indicated in the corresponding lanes. table 1: affected dogs: fi = female intact fs = female spayed gsp = german shorthair pointer mn = male neutered mi = male intact table 2: primer sequences. all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. is removal of proximo-plantar osteochondral fragments necessary in young thoroughbreds? a knowledge summary by julia dubuc dmv, dés, dacvs-la, m.sc, mrcvs 1* christopher akkari bvmedsci (hons), bvm bvs (hons), mrcvs2 1university of nottingham, sutton bonnington campus, sutton bonnington, leicestershire, le12 5rd 2ringneill equine clinic, 53 ringneill road, comber, newtownards, bt23 6ef *corresponding author (julia.dubuc@nottingham.ac.uk) vol 4, issue 4 (2019) published: 03 oct 2019 reviewed by: peter clegg (ma, vetmb, phd, certes, dipevcs, mrcvs) and christopher bruce riley (bsc, bvsc(hons), msc, phd, dipl acvs, pgcinnovmgt, manzcvs) next review date: 03 jun 2020 doi: 10.18849/ve.v4i4.186 pico question in young thoroughbreds with osteochondral fragments of the proximo-plantar aspect of the proximal phalanx, does pre-emptive surgical removal of the fragments compared to conservative (non-surgical) management reduce the incidence of subsequent lameness? clinical bottom line there is currently insufficient data to determine the impact, on subsequent lameness, of conservative versus surgical management of proximo-plantar osteochondral fragments in young thoroughbreds. indeed, only three relevant studies were found, which include one retrospective study and two smaller case series. since there are no substantive studies that have specifically focused on the treatment of plantar osteochondral fragmentation in thoroughbred racehorses, the strength of evidence currently available is low. clinical scenario you are required to perform prepurchase radiographs (including both stifles, tarsi and carpi as well as all four fetlocks) on a young racing thoroughbred. all joints radiographed are unremarkable aside from the left metatarsophalangeal joint, which presents a proximo-plantar osteochondral fragment (plof) of the medial aspect of the proximal phalanx. while the horse’s training is well under way, it has not raced yet. no lameness has been reported by the trainer and there is no obvious joint effusion on physical examination. however, the response to full hindlimb flexion is positive. the trainer asks if surgical removal is advised at this stage. the evidence based on the literature currently available, there is no definitive evidence that preventative surgical removal of plof from the proximal phalanx in young thoroughbreds decrease the incidence of subsequent lameness. on the other hand, a more substantial amount of publications are focused on other breeds, namely standardbred racehorses and warmbloods. the literature comprises mostly small case series and retrospective studies and the evidence, as is pertains to young thoroughbreds, is therefore of low quality. summary of the evidence barclay et al. (1987) population: horses review of medical records of horses presented for lameness caused by plof of the proximal phalanx only two horses presented with a moderate hindlimb lameness on physical examination the other 17 cases presented no lameness regional or intra-articular anaesthesia of the metatarsophalangeal joint did eliminate the existing lameness (number unknown) none of the horses were positive to fetlock flexion, but all were positive to hock flexion sample size: n=19 horses intervention details: all horses were divided into two groups: surgical removal (arthrotomy) in 10 horses conservative treatment in nine horses intra-articular polysulphated glycosaminoglycans (psgags) in five horses (up to 5 times, weekly intervals, no specific dosage given) intra-articular corticosteroids in two horses (up to 2 years, every 2 months or so, no specific dosage given) no treatment for two horses (classified as conservative management by barclay et al.) follow-up information was acquired by examination or telephone conversation with the owner or the trainer study design: retrospective case series outcome studied: return to previous level of training or performance or pre-lameness level (unclear) main findings (relevant to pico question): of the 10 horses in the surgical group, all returned to training or to performing at previous or above presurgical level of the nine horses treated conservatively, 8 (89%) were unable to perform at pre-lameness levels: the five horses treated with intra-articular psgags had some temporary relief of clinical signs one horse received psgags 3 times, at weekly interval, swam instead of training and returned at higher racing level the two horses treated with intra-articular corticosteroids showed relief from lameness for 2 months one of the two horses not treated was retired immediately and the other one was sold as failing to train as required speed limitations: small number of cases outcome is unclear (what defines pre-lameness level is not specified) and earnings could have been used to standardise very little detail regarding the population (breed, sex, age, etc.) and their intended purpose, including if raced prior to entering the study unknown number of metatarsophalangeal joint blocked for diagnosis no information on fragment location within the joint or the type of fragmentation (i: articular vs ii: nonarticular) nor concurrent intra-articular lesion found in surgery no details regarding the type and amount of corticosteroid nor amount of psgags used no detailed information regarding follow-up (including length of follow-up, if further joint medication was required, if any lameness recurred, etc.) no control (fragment free) group whitton et al. (1994) population: racehorses (three thoroughbreds and 23 standardbreds) 18 males and eight females mean age 3.9 years old (±6 yr) the case records of horses with a diagnosis of plantar/palmar osteochondral fragments of plantar/palmar p1 were reviewed: 19/26 (73%) horses presented a lameness (american association of equine practitioners, aaep grade 1 to 3/5) on physical examination 2/26 (7.7%) horses had palmar osteochondral fragmentation 24/26 (92%) horses had plantar osteochondral fragmentation 26/29 joints were positive to fetlock flexion sample size: 26 horses (29 joints) intervention details: horses were divided into two groups: surgical removal (arthroscopy (23 joints in 21 horses and 1 arthrotomy in one horse) conservative treatment (non-defined by authors) in four horses: one had intra-articular injection of 120 mg methylprednisolone acetate (mpa) follow-up information was acquired by examination or telephone conversation with the owner or the trainer study design: retrospective case series outcome studied: return to previous performance level or to racing (unclear) main findings (relevant to pico question): fragments identified in 27 hindlimbs and two forelimbs (overall, including surgical and conservative treatments) of the 21 horses in the surgical group, 16 (76%) returned to racing 8/21 (38%) horses had degenerative changes in the joint on arthroscopy 3/21 (14%) horses re-presented for re-fragmentation after the first surgery two of these improved again after the second surgery when performance before and after surgery was compared, 12 (21%) showed improved performance, three (14%) did not improve and one retired due to chronic suspensory desmitis of the four horses in the conservative group, one returned to previous level at 6 weeks after an intra-articular injection of 120 mg mpa one returned to lower level and two were still resting resting horses were not in work due to other musculoskeletal issues (suspensory desmitis and acute tendonitis of the superficial digital flexor tendon (sdft)) limitations: only three thoroughbreds included outcome is unclear and earnings could have been used to standardise unknown number of metatarsophalangeal joint blocked for diagnosis no information on fragment location within the joint or the type of fragmentation (i vs ii) no detailed information regarding follow-up (including length of follow-up, if further joint medication was required, if any lameness recurred, etc.) no control (fragment free) group some horses appear unaccounted for in the result section and it is unclear how many were lost to follow-up fortier (1995) population: thoroughbreds (three), standardbred racehorses (109), quarter horses (two), warmbloods (two), arabian (one), american saddle horse (one) 47 females, 27 colts, 45 geldings majority (93%) < 3 years old medical records of horses that had a diagnosis of palmar/plantar osteochondral fragments arthroscopically removed were included 82 horses had a lameness examination performed: lameness reported to be mild by clinician 17/82 horses (21%) had slight to moderate positive hock flexion sample size: n=119 horses intervention details: all fragments included were type i (axial) all horses included had surgical removal of the fragments in arthroscopy follow-up information was acquired by examination or telephone conversation with the owner or the trainer and confirmed via race records study design: retrospective study outcome studied: for racehorses, successful if mean postoperative earnings/race were equal or above the pre-operative earnings/race for the non-racehorses, successful if return to pre-operative performance level main findings (relevant to pico question): full-thickness cartilage defects identified by arthroscopy in 9/155 (6%) metatarsophalangeal joints and in none of the forelimbs 22/109 (20%) standardbred did not have a career start at the time of follow-up: 6/22 (27%) were in training and sound 87/109 (80%) standardbred racehorses that previously raced returned to racing: 55/87 (63%) were back at or above preoperative level 32/87 were unsuccessful: 10/32 unsuccessful horses (31%) had articular cartilage loss or synovial proliferation all non-racehorses returned to their preoperative level significant association (p<0.0001) between unsuccessful horses and articular cartilage loss or synovial proliferation limitations: only three thoroughbred included and does not specify if these were racehorses no information on preoperative earnings/race and no comparison with postoperative earnings/race. earnings after surgery are reported only as a single finding no detailed information regarding follow-up (including length of follow-up, if further joint medication was required, if any lameness recurred, etc.) all horses were not accounted for in the methods and results section no conservative management or control groups appraisal, application and reflection there are very few studies evaluating the impact of proximo-plantar osteochondral fragmentation (plof) in young thoroughbreds. by contrast, a larger number of publications on plof of the proximal phalanx (p1) focused on standardbred racehorses and warmbloods is available. based on the three studies mentioned above and taking into consideration that the breed of the horses included in the paper from barclay et al. (1987) is not specified, a grand total of six thoroughbreds were included and it remains unclear if all six were destined for racing. the reported prevalence of plof of p1 in racing thoroughbreds is 5.9%, with 4.1% type i and 1.8% type ii fragments (kane et al., 2003). both dorsal and plantar fragmentation were found to be twice as common in the hind fetlocks compared to forelimbs. the same authors (kane et al., 2003), in their retrospective radiographic survey of yearling thoroughbred sales, also reported twice as many type i fragmentation compared to type ii and that these tended to be unilateral. it is thought that plof of p1 would cause lameness at high speed, or mostly during performance (fortier et al., 1995; houttu, 1991; whitton et al., 1994). as previously stated, this has been investigated mostly in another type of racehorse, the standardbred trotters. carmalt et al. (2015) reported that standardbred racehorses which had osteochondral fragmentation of the proximo-palmar/plantar aspect of the proximal phalanx did not slow down prior to surgery, or speed up after. in a case-control study from the same group (carmalt et al., 2014), 174 standardbred racehorses with plof were compared with ones radiographically normal (613 horses). no difference in race speed was found between the two groups before surgical removal. moreover, the horses did not slow down prior to, nor sped up after surgery. the authors concluded that surgical removal of proximal palmar or plantar fragmentation was not recommended. houttu (1991), in an older study including mainly standardbred trotters undergoing fragment removal, reported that 23/45 (51%) of the horses successfully returned to training speed in 3 months and this increased to 41/45 (91%) at 6 months postsurgery. while this information is very valuable and relates to racehorses working at high speed, extrapolation of these findings to young thoroughbreds is questionable. despite the evidence stated above appearing quite dated, these are the only three studies containing a variable number of thoroughbreds to provide any follow-up information. there is no mention of a mean time to follow-up making it difficult to draw any conclusions regarding the soundness of these horses in the long-term. although whitton et al. (1994) reported three horses presenting refragmentation in previously operated joints, there is generally very few details regarding recurrence of the lameness and how this was subsequently addressed. houttu (1991) reported that 3/45 (6%) of the horses which underwent surgical removal of the fragmentation were lame 3 months after surgery when the trainer attempted working at high speed and that 2/45 (4%) stayed lame due to a lesion located in the joint. however, these lesions are not described in the publication. fortier et al. (1995) found significant association between unsuccessful racehorses and the presence of cartilage loss or synovial proliferation. while related articular cartilage or any other intra-articular pathology could influence potential future lamenesses, the data currently available in the literature is presented in ways not amenable to comparison between the different studies: 9/155 metatarsophalangeal joints had full thickness articular cartilage defect (fortier et al., 1995) whereas 8/21 horses (38%) had intra-articular degenerative changes in arthroscopy (whitton et al., 1994). a clear, exhaustive description of concurrent intra-articular pathology and long-term follow-up of these specific cases is needed to determine the impact of surgical or conservative management of plof of p1 on subsequent lameness. the authors failed to find studies including a separate group composed of fragment free thoroughbred horses, to act as control group as well as a conservative and surgical group. while the papers from barclay et al. (1987) and whitton et al. (1994) compare surgical and conservative management of these fragments, higher quality evidence, in the form of a prospective study with an extensive long-term follow-up and more detailed description of intra-articular findings, is required to determine if pre-emptive surgical removal of plof of the proximal phalanx is warranted and reduces the risk of lameness. as previously mentioned, supplemental literature concerning proximal phalanx osteochondral fragmentation is available namely in warmbloods (declercq et al., 2011; declercq et al., 2009; declercq et al., 2008) and also concerning dorsal osteochondral fragmentation of the proximal phalanx in thoroughbreds (walsh et al., 2018). methodology section search strategy databases searched and dates covered: cab abstracts 1973 to week 18 2018 pubmed ncbi 1900 to week 23 2018 search terms: cab abstracts (equine* or horse* or equus or equid* or mare or mares or broodmare* or 'brood mare*' or pony or ponies or filly or fillies or colt or colts or stallion* or thoroughbred* or standardbred* or racehorse* or 'race horse*').mp. or exp horses/ or exp equus/ or exp equidae/ or exp mares/ or exp colts/ or exp foals/ or exp stallions/ or exp thoroughbred/ or exp racehorses/ ((osteochond* and (fragment* or chip or chips or dissecans)) or ocf or ocd).mp. (((proximal or proximo) and plantar) or (proximal and phalanx) or p1 or proximoplantar*).mp. (arthroscop* or surger* or surgical* or operat* or excision* or excise* or dissect*).mp. or exp surgery/ or exp surgical operations/ 1 and 2 and 3 and 4   pubmed (equine* or horse* or equus or equid* or mare or mares or broodmare* or 'brood mare*' or pony or ponies or filly or fillies or colt or colts or stallion* or thoroughbred* or standardbred* or racehorse* or 'race horse*') ((osteochond* and (fragment* or chip or chips  or dissecans)) or ocf or ocd) (((proximal or proximo) and plantar) or (proximal and phalanx) or p1 or proximoplantar*) (arthroscop* or surger* or surgical* or operat* or excision* or excise* or dissect*) 1 and 2 and 3 and 4 dates searches performed: 14/5/2018 and 3/6/2018 exclusion / inclusion criteria exclusion: articles not relevant to pico question dorsoproximal fragments other joints than fetlock other breeds than thoroughbred only conference papers/proceedings not published non-english language publications inclusion: relevant to pico question thoroughbred or thoroughbred racehorse conservative and surgical treatment, proximo-plantar fragments of p1 search outcome database number of results excluded – not relevant to pico excluded – duplicates excluded – conference papers not published excluded – other languages total relevant papers cab abstracts 25 18 0 1 3 3 pubmed 45 38 7 0 0 0 total relevant papers when duplicates removed 3 conflict of interest the authors declare no conflicts of interest. references barclay, w., foerner, j. and phillips, t. 1987. lameness attributable to osteochondral fragmentation of the plantar aspect of the proximal phalanx in horses: 19 cases (1981–1985). journal of the american veterinary medical association 191, 855–857. carmalt, j.l., borg, h., näslund, h. and waldner, c. 2014. racing performance of swedish standardbred trotting horses with proximal palmar/plantar first phalangeal (birkeland) fragments compared to fragment free controls. the veterinary journal 202, 43–47. doi: https://doi.org/10.1016/j.tvjl.2014.07.017 carmalt, j., borg, h., näslund, h. and waldner, c. 2015. racing performance in standardbred trotting horses with proximal palmar/plantar first phalangeal fragments relative to the timing of surgery. equine veterinary journal 47, 433–437. doi: https://doi.org/10.1111/evj.12317 declercq, j., martens, a., bogaert, l.., boussauw, b., forsyth, r. and boening, k.j. 2008. osteochondral fragmentation in the synovial pad of the fetlock in warmblood horses. veterinary surgery 37, 613–618. doi: https://doi.org/10.1111/j.1532-950x.2008.00426.x declercq, j., martens, a., maes, d., boussauw, b., forsyth, r. and boening, k.j., 2009. dorsoproximal proximal phalanx osteochondralfragmentation in 117 warmblood horses. veterinary and comparative orthopaedics and traumatology 22, 1–6. doi: https://doi.org/10.3415/vcot-08-02-0016  declercq, j., hauspie, s., saunders, j. and martens, a. 2011. osteochondral fragments in the metacarpoand metatarsophalangeal joint and their clinical importance. (osteochondrale fragmenten in het kogelgewricht en hun klinisch belang) vlaams diergeneeskundig tijdschrift, 80, 271–280. fortier, l., foerner, j. and nixon, a. 1995. arthroscopic removal of axial osteochondral fragments of the plantar/palmar proximal aspect of the proximal phalanx in horses: 119 cases (1988–1992). journal of the american veterinary medical association 206, 71–74. doi: https://doi.org/10.1111/j.1532-950x.2004.04061.x houttu, j. 1991. arthroscopic removal of osteochondral fragments of the palmar/plantar aspect of the metacarpo/metatarsophalangeal joints. equine veterinary journal 23, 163–165. doi: https://doi.org/10.1111/j.2042-3306.1991.tb02747.x  kane, a.j., park, r.d., mcilwraith, c.w., rantanen, l.w., morehead, j.p. and bramlage, l. r. 2003. radiographic changes in thoroughbreds yearlings. part i: prevalence at the time of yearling sales. equine veterinary journal 35, 354–365. doi: https://doi.org/10.2746/042516403776014280  walsh, r., smith, m.r.w. and wright, i.m. 2018. frequency distribution of osteochondral fragmentation of the dorsoproximal articular surface of the proximal phalanx in racing thoroughbreds in the uk. equine veterinary journal 50, 624–628. doi: https://doi.org/10.1111/evj.12795  whitton, r. and kannegieter, n. 1994. osteochondral fragmentation of the plantar/palmar proximal aspect of the proximal phalanx in racing horses. australian veterinary journal 71, 318–321. doi: https://doi.org/10.1111/j.1751-0813.1994.tb00906.x acknowledgement rcvs knowledge was supported in producing this knowledge summary by an educational grant from petplan charitable trust. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. how and why you should segment veterinary markets joseph hill bsc (hons), bvsc, mba, mrcvs1* 1vet partners, leeman house, station business park, holgate park drive, york, yo26 4gb *corresponding author (joe.hill@me.com) vol 5, issue 2 (2020) published: 28 apr 2020 reviewed by: peter cockcroft (ma, vetmb, msc, dchp, dvm&s, dipecbhm, mba, mrcvs), elizabeth mcinnes (bvsc, frcpath, phd, mba, mrcvs) and martin hawes (bpharm, bvetmed, mba, mrpharms, mrcvs, mcmi, fvpa) doi: 10.18849/ve.v5i2.289 section index:    abstract | introduction | main content | conclusion | conflict of interest | references abstract veterinary markets are traditionally split into three main species related categories. for a business to compete effectively, a greater understanding of the relevant markets and client expectations are required. segmenting markets into defined sections allows a business to gain a comprehensive insight into where it currently operates and where it needs to position itself in the future. introduction as with other professional firms, veterinary practices sell their technical knowledge and capabilities in the context of a competitive business environment known as a market. in itself the veterinary market is broad, covering an array of clinical and non-clinical products and services which are concerned with both animal and human health. with so many potential revenue streams it is important that businesses develop a method which enables them to assess where they currently sit, how their revenue is generated and where they intend to position themselves going forward. this article explores how market segmentation allows veterinary practices to gain these key insights into the commercial world in which they operate. main content segmentation few, if any, companies can be ‘all things to all people’ (mcdonald et al., 2003). therefore, a key decision facing veterinary practices is to understand how the various components of its business (both services and products) impact both turnover and profit. the characteristics of these elements will not be identical. for example, some elements will grow whilst others contract, some will be highly competitive whilst other less competitive areas will require specific equipment and skill in order to be effectively delivered. once these factors are understood it enables services and products with similar characteristics to be grouped into different markets. as markets are inherently complex they can be defined and segmented in various ways (walker et al., 2011). the uk veterinary industry is historically separated into three primary market segments which correspond to traditional undergraduate teaching: small animal sector – covers the treatment of a wide range of animals; most commonly cats and dogs. other species included in this sector are rabbits, rodents, birds, small reptiles and amphibians. farm animal sector – predominately involved in the treatment of cattle and sheep. equine sector – concerned with the treatment or horses and other equids. outside of these sectors, there are many other smaller segments including veterinary pathology, zoo medicine and pharmacology. regardless of the industry, there are common approaches to market segmentation. the process is not one of absolute precision, its aim is to create relatively homogeneous segments (walker et al., 2011) which will allow businesses to gain a clearer insight into customer wants and needs. below are two examples set within the uk small animal sector. customer segmentation splitting a potential market (i.e. all the potential customers who may use a business) into demographic groups is a common approach. in this way, a population is segmented depending on one or a combination of their age, sex, occupation, education, ethnicity and income. often a combination of demographic features, plus associated behaviours, is used to form ‘segments’ (see figure 1) which represent different customer lifestyles (walker et al., 2011).   type of client pet households group type % population suburban lifestyle 8,932 high levels of disposable income 10 37 city commuters 6,981 8 working parents with children 14,321 15 professional workers 4,534 5 new home owners 28,453 restricted disposable income 31 31 industrial workers 13,578 low disposable income 15 32 ex-council home owners 12,561 14 mixed low income housing 3,574 4 total 92,934   100 100 figure 1. a theoretical small animal sector segmentation of a uk town based on ‘lifestyle’ groups   this approach can help businesses gain a visualisation of who their customers are and what their requirements might be (e.g. opening hours, product/service range and price sensitivity). this combination of requirements is known as a ‘marketing mix’ and once understood, it can be tailored to meet a particular market segment and encourage them to use one business over another (lee, 2006). lifestyle segmentation generates an understanding of an actual or potential client base. however, levels of disposable income, age and education are not necessarily a reliable indication of the value owners place on veterinary services or their willingness to spend money on their pet (lee, 2006). instead, the ‘ever-present influence of emotions’ (gabay et al., 2014), the owner-pet bond and the client-veterinarian relationship all have a significant part to play on a customers decisions (lue et al., 2008). choice criteria within any given sector, veterinary practices tend to offer the same range of products and services (lee, 2006). this lack of diversity stems from two main factors. firstly, there is a narrow selection criteria applied when choosing university entrants (dimaggio & powell, 1983) resulting in a small subsection of the potential population entering the profession. the second component is the inherent tendency of industries to adopt similar behaviours, rituals and ways of working (eisenhardt, 1988). the combination of these two factors limits the opportunity for new business approaches, however, it also creates a stable environment enabling practices to interact effectively and people to switch employment with minimum disruption (meyer, & rowan 1977; and zucker, 1987). within such stable environments, change is rarely driven internally (greenwood & suddaby, 2006) and thus tends to occur through external jolts (meyer, 1982). inevitably, these jolts create a degree of turmoil and uncertainty as they challenge the accepted organisational structure and processes (clemens & cook, 1999) and tend to take the form of ‘social upheaval, technological disruptions, competitive discontinuities or regulator change’ (greenwood & suddaby, 2006). excluding elements which have impacted all aspects of uk society (e.g. social media), there has been little change in the uk veterinary sector over the last 20 years. the two notable exceptions are: change in ownership structure: in november 1997 the royal college of veterinary surgeons (rcvs) modified its stance on veterinary practice ownership (gripper, 1998) with a formal modification of its guide to professional conduct occurring in 2000 (rcvs, 2000). these changes meant that the ability to own and run veterinary practices was no longer restricted to veterinary surgeons enabling companies to undertake these roles (gripper, 1998 and rcvs, 2000). change in medicines regulation: in 2001 the competition commission (cc) was asked to investigate the supply of veterinary prescription medicines in the uk. the resulting report determined that multiple monopolies existed within the industry and presented nine recommendations to parliament (the national archives, 2012). the impact of these regulatory changes on the uk veterinary market has been varied. the change in ownership legislation has influenced business structures, pricing and marketing approaches but has not fundamentally altered the goods and services that are offered by veterinary practices. in contrast, the legislative changes instigated by the cc findings significantly altered the veterinary pharmaceutical industry. the declassification of some medicines, in combination with ensuring pharmacies are able to obtain veterinary medicines under the same buying conditions as veterinary practices (the national archives, 2012) has opened up this market to wholesalers, pet shops and online pharmacies. the inherent difficulty in setting up unique products, services and strategies in the veterinary sector alongside the scarcity of genuine industry disruption has lead to the development of a different approach to segmentation. the method involves understanding a customer’s ‘choice criteria’ (walker et al., 2011) when they select where to purchase their services or products. small animal sector market segments before applying customer choice criteria to the small animal sector market segments it is important to review the characteristics of the products and services currently delivered in the uk. the market can be split into three distinct sectors which can then be further subdivided to form six market segments (see figure 2) which are discussed below.   sector and segment description over the counter products (otc) comprises veterinary related products associated with aspects of animal health and nutrition plus a range of auxiliary items prescription only medicines (pom) acute prescription only medicines for the treatment of short-term, acute conditions chronic prescription only medicines for the treatment of long-term, previously diagnosed conditions level of veterinary clinical complexity routine low skill clinical work, including vaccinations, neutering and simple wound repairs mid-range mid-level diagnostic, medical and surgical work complex complex diagnostic, medical and surgical work including referral procedures and overnight hospitalisation figure 2. small animal sector market segments   over the counter products (otc) this segment comprises veterinary-related products associated with various aspects of animal health and nutrition plus a range of auxiliary items. the products sold will vary from business to business and includes the sale of unregulated medicines and those sold under an avm-gsl (authorised veterinary medicine – general sales list) and a nfa-vps (non-food animal medicine – veterinarian, pharmacist, suitably qualified person) licence (noah, 2019). these products range from pet foods and accessories (e.g. collars, leads and baskets) to prescription food and pharmaceuticals, such as nutraceuticals and some worming and anti-parasite products. this segment differs from the others as competition is not limited to the veterinary sector but includes non-veterinary businesses such as pet shops, supermarkets and online suppliers. prescription only medicines (pom) the pom segment is comprised of pharmaceutical products falling under two licences, namely pom-vps (prescription only medicine – veterinarian, pharmacist, suitably qualified person) and pom-v (prescription only medicine – veterinarian). pom-v products must be prescribed by a veterinary surgeon and can only be supplied to clients after a clinical assessment of their animal(s) has been completed (noah, 2019). the associated pom sales account for over 75% of the uk regulated veterinary drug market (noah, 2019) and the sale of these products is a major source of income for veterinary practices across all sectors. there are two distinct segments within this sector: chronic/long-term medication relates to poms which are prescribed for chronic or long-term conditions (a disease with a time course of 3 months or longer (polzin, 2011)). once diagnosed, lifelong treatment is often required. these conditions are mainly medical in origin (e.g. hyperthyroidism or diabetes) and also include the medication for chronic pain and arthritis. acute/short-term medication are poms that are prescribed to treat acute disease – one which appears suddenly and is either fatal or resolves quickly (boden, 2005). medication is given for either a short period of time or on an infrequent basis. examples include medication for infections, injuries and surgical cases. clinical complexity the range of clinical services that can be offered by a practice is defined by multiple factors, notably the equipment available, the clinical capability of staff and the opening hours of a clinic. separating out this market segment is subjective as there are some procedures which cross the boundaries of two categories (e.g. fracture diagnosis and subsequent treatment). however, as with other segmentation methods, the purpose of this task is not one of absolute precision but to gain an understanding of how different elements of clinical work are associated with varying client expectations and require differing equipment and skills to perform. in addition, it is essential that business owners understand which market segment(s) account for the majority of their revenue and profit. this will enable them to better understand customer requirements and adjust their business to meet them, where required. three segments in this sector are recognised and are described below. routine clinical work requires limited clinical experience, expertise and equipment. the work can be performed during a ‘normal’ working day by almost all clinicians in the veterinary sector. the segment primarily comprises of two types of work: low value, high volume – repetitive procedures involving the same client (repeat work) such as vaccinations. low value, high volume – non-repeat procedures such as neutering, basis wound repair, simple gastrointestinal disorders and other primary consultations.    this sector has traditionally been seen as the most significant revenue generator for most first opinion practices and is often deemed to be highly competitive and thus price sensitive. mid-range clinical procedures require a greater degree of individual experience and expertise and rely on a practice having a greater range of equipment and associated capital investment. the segment is composed of higher value work than the ‘routine’ segment and are inherently lower in volume often requiring more time to complete. there is a mixture of procedures within this sector, some are non (or infrequent) repeat work (e.g. mass removals, dental procedures, lameness diagnosis and imaging) while others fall into the high repeat sector (e.g. treatment of diabetic and hyperthyroid patients). complex clinical work requires a substantially experienced clinical team with high levels of clinical knowledge. this intricate level of work relies on ever more specialised and expensive equipment for diagnosis, treatment and aftercare including 24-hour hospital facilities. the work within this sector is almost exclusively categorised as high value, low volume, non-repeat services (e.g. spinal surgery, diabetic ketoacidosis treatment, mri (magnetic resonance imaging) and ct (computed tomography) scans). the first part of the analytical process of a business is to assess the financial contribution of each market segment. invariably this approach will provide a comprehensive understanding of the non-clinical elements but, depending on the practice management system (pms), will not enable a true assessment of the clinical components. most pms systems will be able to generate numerical and financial details of clinical services (e.g. number of consultations and associated revenue) but these need to be analysed and separated into the three relevant segments (see figure 3).   business type of clinical work consultations procedures (operations and diagnostic work) hospitalised cases routine mid complex routine mid complex routine mid complex a number 279 20 2 14 1 0 0 1 0 % 92.7 6.6 0.7 93.3 6.7 0.0 0.0 100.0 0.0 b number 1004 191 7 56 23 1 0 2 0 % 83.5 15.9 0.6 70.0 28.7 1.3 0.0 100.0 0.0 c number 877 266 14 49 108 3 32 143 13 % 75.8 23.0 1.2 30.6 67.5 1.9 17.0 76.1 6.9 figure 3. segmentation of clinical work undertaken at three east midlands small animal clinics   the analysis in figure 3 is representative of the uk sector and shows a marked difference between the three businesses in terms of both the types of work performed and the relative complexity within each sector. business c operates 24 hours a day which enables it to undertake work that the other two businesses cannot offer (e.g. hospitalisation of complex cases). with fewer competitors, these revenue streams are inherently less price sensitive but require more staff with greater clinical capability and a larger range of medical equipment in order to perform them effectively. however, these resources also allow business c to perform more complex procedural work (whether during the day or at night) which is reflected in the analysis. both business a and b are open 6 days a week and outsource their out-of-hour (ooh) work and the majority of their complex work to other clinics such as business c. consequently, they perform little complex work in any sector (see figure 3). despite these similarities, there are distinct differences between the two businesses with b performing a much more significant percentage of mid-range work. both practices undertake work in the same market segments, but they are positioned differently within these sectors and therefore should not be considered as similar businesses. the current uk veterinary market is a competitive environment with most practices offering a similar choice of products and services. with multiple options, it is important to understand which ‘choice criteria’ clients use when selecting one practice over another. there is little research into these decision factors. a lack of meaningful data means that in order to understand these decisions, clinicians have to apply their own set of criteria based on market research, personal opinion or the thoughts of others. the price of veterinary services may be deemed to be a significant choice criteria for clients however, there is little evidence to support this. research conducted by kpmg (klynveld peat marwick and goerdeler) concluded that price was the ninth most important factor (see figure 4) with both location and range of services scoring more highly (brown & silverman, 1999). the relatively low significance that owners place on price is a continuous finding (lee, 2006; lue et al., 2008;  moser & johns; 2012; and gabay et al., 2014)  and would indicate that not only do veterinary surgeons undervalue their skills but the veterinary market is less price sensitive than often perceived (lee, 2006).   figure 4. client selection factors when choosing a veterinarian (brown & silverman, 1999)   in addition to price, location and product range, service industries have a common set of choice criteria that can be applied to them (hill & hill, 2018): delivery speed denotes the time taken for customers to receive the service or product they have purchased. in a veterinary context this includes the time taken to obtain an appointment when one is required. quality conformance relates to the provision of a service or product to the stated specification. this can be set by the business directly (e.g. the way a product looks or feels) or can be formed through a customer’s previous purchase of goods or services (e.g. the clinical examination relating to a vaccination). customer relationships are a key component in any service industry and are the single biggest decision factors for clients (see figure 4). delivery reliability refers to whether a product or service is delivered on time (either promised by the business or expected by the customer). these choice criteria apply across all veterinary market segments, but will be of varying importance, for clients, across each sector. for example, the financial value placed on different services will vary (e.g. a vaccination compared to an emergency appointment) as will a customer’s expectations of what that service entails. this variation has to be assessed and understood in order for a practice to gain a full understanding of the strategy required to be successful. figure 5 (below) shows how the importance of one ‘choice criteria’ price may vary across the small animal segments.   sector and segment price over the counter products (otc) otc products are sold by multiple businesses through different channels. price in this sector is likely to be a major factor for most clients. prescription only medicines (pom) acute the provision of short-term medications is the direct result of clinical advice. there is little opportunity or desire for clients to source alternative sources as the treatment of their animal is paramount. these factors mean that price is unlikely to be of primary importance. chronic although initially provided as a direct result of clinical advice, the nature of these products is that they are given time and time again over a long period. the predictability of their requirement and the development of online retailers has resulted in this segment becoming increasingly price sensitive. level of veterinary clinical complexity routine this segment has become the most price sensitive segment of all the clinical work. many practices have adopted a low margin approach to this high volume work and have this strategy at the forefront of their business. mid-range the importance of price in this segment begins to reduce dramatically. the increased complexity of cases makes it difficult for clients to directly price compare between businesses. other factors, especially customer relationships, become increasingly important. high-end price ceases to be a primary decision factor in this segment. operating these services is expensive due to the required level of facilities and staff. consequently the price of these services is also high and will be prohibitive for some clients. customer relationships are paramount in this segment. figure 5. the varying importance of price in small animal market segments   the identification of how each market segment impacts practice revenue and the associated importance of the relevant choice criteria forms a fundamental understanding of a business. once this base is established a business can then decide how it should progress given both its internal capabilities and the external competition it faces. choosing the markets in which to compete is a business based decision that sits at the heart of both current and future strategy development. it is not a singular process as it influences and is influenced by all relevant functions that comprise a veterinary practice (see figure 6). figure 6. core functions of a business   once understood, a practice can fully review the factors that have created success, those that need to improve and identify the capabilities necessary to compete more effectively in the future. these insights will then directly impact the recruitment and retention of staff (hill & moffett, 2017) as well as the processes, equipment and procedures that need to be used and developed. to succeed a practice needs to be able to utilise its finite resources in order to maximise its current market position and develop a sustainable future.   conclusion the ability to analyse the market in which a business sits, remains one of the key elements for success. the veterinary sector is no exception where traditionally the markets have been simply assessed in terms of the species of animal being treated. breaking these markets down into smaller segments allows a greater understanding of what products and services are provided by a business, how important these segments are to revenue generation, which clients (or potential clients) may use them and what factors influence their choice. this greater depth of analysis enables different businesses to create a clear and consistent approach to the way they work, guiding decisions such as pricing and employment. as a business evolves, 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(1987). institutional theories of organization. annual review of sociology, 13, 443–464. doi: http://dx.doi.org/10.1146/annurev.so.13.080187.002303 intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in greyhounds with paw pad corns, is surgical excision more effective at resolving lameness than extirpation? a knowledge summary by dan kenny bvsc mrcvs1* 1paragon veterinary referrals, red hall crescent, wakefield, west yorkshire, wf1 2df *corresponding author (dan-kenny@hotmail.co.uk) vol 5, issue 3 (2020) published: 03 sep 2020 reviewed by: robert pettitt (bvsc pgcertlthe dsas (orth) sfhea frcvs) and stephen jones (mvb ms dacvs) next review date: 22 nov 2021 doi: 10.18849/ve.v5i3.316 pico question in greyhounds (and sighthounds) with recurring pedal corns, is surgical excision in comparison to corn extirpation more effective at resolving lameness?   clinical bottom line category of research question treatment the number and type of study designs reviewed three case series were included, all three were retrospective, one included a prospective component. there was one opinion-based narrative review and one opinion-based article. strength of evidence weak outcomes reported extirpation allows only a short palliation of lameness and repeated treatment is required at variable intervals. surgical excision may provide good rates of short-term resolution however, in the long-term recurrence rates are still moderate. it should also be born in mind that further corns may develop in different digits. conclusion in greyhounds (and sighthounds) with recurring pedal corns, surgical excision of the corn is more likely to provide long-term resolution of lameness in comparison to extirpation. however, the current level of evidence on this topic is weak.   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision-making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a 9-year-old ex-racing greyhound presents with a 3 week history of right thoracic limb lameness which worsens when walking on hard surfaces. the dog has a firm well circumscribed, circular lesion on the pad surface of digit three of the right thoracic limb which is painful on palpation. you suspect that the lesion is a corn however you have never treated one before. you can recall that a previous colleague used to manage them by hulling them out with a dental elevator, your current colleagues suggest surgical excision of the lesion. as you have never treated this condition before you decide to look for higher level evidence. the evidence there is limited evidence to suggest that one technique is superior to the other with regards to outcome as none of the cited studies directly compare these techniques. all cited studies are either opinion pieces or case series with no statistical analysis performed and are therefore low on the hierarchy of evidence. summary of the evidence görtz et al. (2003) population: dogs with focal circular hyperkeratosis (paw pad corns). case 1: 6-year-old whippet with bilateral lesions on digit four of the thoracic limbs. case 2: 6-year-old whippet with lesions on digit three and four right thoracic limb. case 3: 5-year-old greyhound with lesions on digital pads three and four of the right thoracic limb. sample size: 3 dogs intervention details: case 1: deep surgical excision of the lesions with 8 mm punch biopsy and wounds dressed and treated with paw wax. case 2: deep surgical excision and paw wax bandage. case 3: superficial excision performed. study design: retrospective case series outcome studied: resolution of lesion and lameness, recurrence of lesion and lameness. main findings (relevant to pico question): deep surgical excision provided shortto long-term resolution of the lesions based on follow-up at 4 months and 5 years. case 1: no recurrence 4 months post-surgery. case 2: the dog was euthanised for unrelated reasons 5 years later with no recurrence of the lesion. superficial excision provided very short-term resolution (1 week to 5 months); repeated excision was required to manage recurrence. case 3: 18 day post-surgery another lesion believed to be a corn developed on the left thoracic limb. repeated superficial excision was performed, initially weekly then at 5 monthly intervals. in the meantime, the dog was symptom free. follow-up: 4 months – 5 years limitations: case series and therefore low on hierarchy of evidence. retrospective series. low number of cases. limited follow-up length in one case (4 months), recurrence may have occurred after this point. case history details regarding treatment are very brief in some cases. only two cases had a histopathological diagnosis suggestive of the lesion being a corn (case 1 and case 3). case 2 did not have histopathological analysis performed. although the lesion had the gross appearance of a corn, without histopathology it is possible that this case was misdiagnosed. no details of superficial excision technique were available. macherey & feeman (2006) population: dogs with paw pad corns sample size: not applicable intervention details: extirpation of corn using dental root elevator study design: narrative review article with opinion-based outline of corn extirpation technique outcome studied: resolution of lesion and lameness, recurrence of lesion and lameness main findings (relevant to pico question): extirpation (or ‘hulling’) of corns can improve lameness. extirpation can be relatively simple and is frequently performed without requirement for sedation. recurrence can occur in as little as 3 weeks. limitations: this is an opinion-based article which is at the bottom of the hierarchy of evidence. there is no scientific data to support conclusions for this technique. balara et al. (2009a) population: dogs with paw pad corns (single and multiple) sample size: 24 dogs (18 greyhounds) intervention details: surgical excision or debridement, topical application of tea tree oil or other ointments, application of duct tape and use of padded boots. histologic analysis and immunohistochemical staining and polymerase chain reaction (pcr) for papilloma virus. of the 11 biopsy specimens available, six were from greyhounds and five were from non-greyhound dogs. none of the greyhounds were positive for papilloma virus on immunohistochemical staining, whereas 3/5 non-greyhound dogs tested positive for papilloma virus. for these three lesions results of pcr were suggestive of a previously undiagnosed strain of papilloma virus, two lesions had histological evidence of viral inclusion bodies. study design: retrospective case series outcome studied: histologic and immunohistochemical staining and pcr for papilloma virus. recurrence of lesion. main findings (relevant to pico question): owners of 17/24 (71%) dogs including 11/18 (61%) greyhounds were contacted by telephone to obtain follow-up information. one greyhound was euthanised for unrelated reasons 6 months post-surgical excision with no recurrence at this time. the remaining 10/18 (55%) had recurrence of the original lesions or developed new lesions either on the same digit or on a different digit or paw. all 10 owners reported some degree of distress related to the dogs’ level of discomfort. two owners had considered euthanasia because of concerns over their dogs’ welfare. the remaining 6/24 (22%) dogs with available follow-up were all non-greyhounds with a single lesion in which surgical excision was reportedly curative. this may suggest differing aetiology between greyhounds and other breeds. limitations: main objective of study was to determine clinical, histologic and immunohistochemical findings with wart-like lesions involving the paw pads and was not an assessment of treatment success. outcome was not recorded or matched to treatment type, so it is unknown how many of these patients were surgically managed and how well they did. lack of objective follow-up data. outcome was based on owner perception via telephone conversation. follow-up time was not defined. the study was retrospective and therefore subject to confounding variables. the study was a case series which is low on the hierarchy of evidence. the sample size was small. balara et al. (2009b) population: dogs with paw pad corns sample size: not applicable intervention details: surgical excision of single lesions with a 2 week follow-up of splint or soft padded bandaging. study design: opinion piece – letter to author, author response. outcome studied: not applicable main findings (relevant to pico question): author acknowledges that extirpation of corns can be associated with temporary reduction in pain and lameness. however, given the suspected mechanical aetiology, recurrence is inevitable. author recommends surgical excision of single lesions, followed by 2 weeks of splinting or soft bandaging of the limb. surgical excision is not recommended in dogs with multiple lesions. limitations: this is an opinion-based article and therefore at the bottom of the hierarchy of evidence. there is no scientific evidence put forward to support these recommendations. guilliard et al. (2010) population: dogs with paw pad corns (single or multiple) sample size: 30 dogs (13 retrospective and 17 prospective cases). seven dogs had multiple corns making a total of 40 corns. intervention details: primary treatment: surgical excision (27 dogs, 34 corns): an elliptical incision was made through the dermis around the corn, the corn was then dissected from underlying connective tissues. the pad was sutured using simple interrupted sutures placed away from the margins of the incisions. the foot was then bandaged. this was changed at weekly intervals for 3 weeks when sutures were removed. distal digital ostectomy (three dogs, three corns): involving removal of the distal condyles of the second phalanx with any remaining bone and nail of the third phalanx. the pad was sutured on its dorsal aspect over the stump of the second phalanx. a full thickness oval skin incision was made just caudal to the palmar/plantar aspect of the pad and closed in order to prevent the pad from rotating dorsally. corn excision was performed if the corn would still be left on the weight-bearing part of the pad after reconstruction. no treatment (two dogs, three corns): these lesions did not elicit pain on digital pressure and were considered asymptomatic. follow-up: 1 year – 5 years study design: case series (4 year retrospective and 2 year prospective components) outcome studied: resolution of lameness and recurrence of lameness and lesion. main findings (relevant to pico question): dogs undergoing surgical excision (27 dogs, 34 corns): 1/27 (3.7%) dogs lameness remained unchanged, 2/27 (7.4%) had reduced lameness and 11/27 (40.7%) had recurrence of lameness. 3/27 (11%) dogs (four corns) had the surgical procedure repeated due to recurrence. the resolution rate following subsequent surgery is unknown. reported short-term outcome (up to 1 year): 20/27 (74%) of dogs had resolution of lameness. reported long-term outcome (up to 5 years): 14/27 (52%) dogs had a recurrence of lameness due to corn regrowth. dogs undergoing distal digital ostectomy (three dogs, three corns): no recurrence of lameness, in two cases the corn was not removed, and it resolved on its own accord. limitations: case series so descriptive study type. retrospective component which is lower on hierarchy of evidence. low number of dogs in distal digital ostectomy group. no statistical analysis so no comparison between treatment methods could be made. complete individual patient follow-up unknown. the number of corns per dog in the results is unclear at times which renders the results and outcomes difficult to interpret in places. true recurrence rate following surgical excision is likely higher as the minimum follow-up was 1 year and a recurrence was only noted if the dog became lame. concomitant injuries were present in some cases (such as carpal hyperextension, p2/3 luxation or ankylosis and deep digital flexor tendon (ddft)/superficial digital flexor tendon (sdft) injury) which may affect outcome measures. one dog was found to have a plant based foreign body at histopathology and one dog was found to have a radiopaque foreign body (grit) at radiography which was surgically removed. these differing aetiologies may affect treatment outcome. subjective measurement of lameness. some follow-up was by telephone which relies on owner assessment of lameness. histological confirmation of disease was only made in 15 cases (three cases seen subsequent to closure of the study). otherwise diagnosis was based on appearance only. appraisal, application and reflection numerous treatments have been described for digital pad corns in sighthounds but currently none of these appear to result in a predictable and satisfactory long-term resolution of lameness. two of the most commonly used treatment methods in veterinary practice are extirpation (‘hulling’) or deep surgical excision of the lesions. extirpation involves removing the hard, central core of the corn. an instrument such as a dental elevator is used to work around the junction of the hard centre of the corn and the soft tissue of the pad. a twisting or rocking motion is used to separate the lateral edges of the corn from the pad. once the sides are free, the base of the corn is released by angling the instrument parallel to the footpad surface at the base of the corn, scissors may be required to remove any remaining attachment. there should be no pain or bleeding. surgical excision of a whole corn involves making an incision through the dermis around the periphery of the corn. this can be performed with a scalpel blade or punch biopsy instrument. the underlying soft tissues are then dissected away, and the corn removed. the pad is sutured, and the foot can be placed in a protective dressing. there are no studies directly comparing these two techniques so papers assessing individual techniques were reviewed. the only article to discuss extirpation or hulling of corns in relative detail, described the use of a dental elevator to remove corns in conscious dogs. although the author reports that lameness initially improves, recurrence was reported to occur in as little as 3 weeks post-procedure (macherey & freeman, 2006). unfortunately, this article was a narrative review and stated outcomes were not supported with scientific evidence. case 3 in the case series by görtz et al. (2003) underwent superficial excision of corns which may also refer to a procedure similar to the extirpation described by macherey & freeman (2006). the details of the procedure, however, were not available making this conclusion impossible to draw. surgical excision was the treatment modality used in two papers for which the outcomes were recorded görtz et al., 2003; and guilliard et al., 2010). no recurrence was reported at 4 months and 5 years post-surgical excision of corns in two whippets (görtz et al., 2003). guilliard et al. (2010) reported a 1 year success rate of 74% in surgically excised corns but in the long-term, up to 5 years, 52% had regrowth of the lesions. out of 27 dogs which had initial surgical excision one dog remained lame, two dogs had improved lameness and 11 dogs had recurrence of lameness. three dogs had the procedure repeated once and one dog had the procedure repeated four times at a mean period of 20 months between surgeries. balara et al. (2009a) reported that 10/18 (55%) greyhounds with corns treated in the study had recurrence of the original lesion or developed novel lesions. unfortunately, the treatment modality was not linked to recurrence as an outcome measure and therefore it is impossible to ascertain what rate of recurrence was present amongst dogs treated by debridement or by deep surgical excision. however, in an opinion-based article the authors of this study recommend that single corns are treated by surgical excision with postoperative splinting or bandaging, they also acknowledge that although extirpation can be associated with reduction or resolution of lameness, recurrence is inevitable (balara et al., 2009b). retrospective case series, case reports and opinion articles are very low on the hierarchy of evidence therefore drawing accurate conclusions regarding the superiority of either technique is challenging. the highest level of evidence regarding extirpation is based on opinion and regarding surgical excision, although the evidence is of a higher level, it is scarce and generally retrospective. it is clear that there is requirement for higher level evidence and studies involving larger number of dogs to accurately assess the two treatment modalities. until this evidence is available veterinary surgeons should consider that the current literature, although low quality suggests that extirpation appears to be a palliative treatment with recurrence invariably occurring following the procedure. deep excision of the lesion may lead to a potential resolution however there is a moderate rate of long-term recurrence alongside the occurrence of novel lesions.   the aetiology of paw pad corns is currently poorly understood. suggested causes include; chronic mechanical trauma or pressure, foreign bodies, scar tissue, deficiencies in the fatty layer in the pad and papillomavirus (guilliard et al., 2010). in one study, canine papillomavirus was isolated from corn lesions in two greyhounds (anis et al., 2016). however, balara et al. (2009a) found no evidence of papillomavirus on immunohistochemistry staining in six greyhounds, but 3/5 dogs which were not greyhounds were positive for papillomavirus. given the paucity of reports assessing the involvement of papillomavirus in this condition, it is currently difficult to ascertain its significance. a greater understanding of the aetiology of the condition in greyhounds may lead to the development of new treatment modalities and therefore better management of the condition. with such high recurrence rates and poor curative treatment options this condition is problematic for the veterinary surgeon. methodology section search strategy databases searched and dates covered: cab abstracts on ovid interface [1973–2019 week 45] pubmed accessed via the ncbi website – veterinary science filter [1910–current] search strategy: cab abstracts: 1     (sighthound* or lurcher* or greyhound* or whippet* or dog or dogs or canine* or canis).mp. or exp dogs/ or exp canis/ or exp greyhound/ or exp racing animals/ 2     (corn or corns or hyperkerat* or keratoma* or keratinis* or keratiniz* or keratos* or "hard pad disease*").mp. or exp hyperkeratosis/ or exp keratosis/ or exp hyperkeratotic scabies/ or exp keratinization/ 3     (pedal* or foot or feet or paw* or digit* or heel* or sole* or footpad* or pad*).mp. or exp feet/ or exp digits/ or exp footpads/ or exp soles/ 4     1 and 2 and 3   pubmed: #1     (sighthound* or lurcher* or greyhound* or whippet* or dog or dogs or canine* or canis) #2     (corn or corns or hyperkerat* or keratoma* or keratinis* or keratiniz* or keratos* or "hard pad disease*") #3     (pedal* or foot or feet or paw* or digit* or heel* or sole* or footpad* or pad*) #4     #1 and #2 and #3 dates searches performed: 22 nov 2019 exclusion / inclusion criteria exclusion: not relevant to pico wrong species wrong breed textbook chapters review article with no detail of technique outcome inclusion: greyhounds or sighthounds with pedal corns or keratomas surgical excision of lesion performed extirpation of lesion performed outcome and recurrence of lesion reported search outcome database number of results excluded – not relevant to pico question excluded – wrong species excluded – wrong breed excluded – textbook chapter excluded – review article total relevant papers cab abstracts 186 177 1 1 2 1 4 pubmed 87 84 0 0 0 0 3 total relevant papers when duplicates removed 5 conflict of interest the author declares no conflicts of interest. references anis, e.a., frank, l.a., francisco r. & kania, s.a. (2016). ‘identification of canine papillomavirus by pcr in greyhound dogs’. peerj 4:e2744. doi: https://doi.org/10.7717/peerj.2744 balara, j.m., mccarthy, r.j., kiupel, m., buote, m.a., wise, a.g. & maes, r.k. (2009a). ‘clinical, histologic, and immunohistochemical characterization of wart-like lesions on the paw pads of dogs: 24 cases (2000–2007).’ journal of the american veterinary medical association 234(12), p. 1555–1558. doi: https://doi.org/10.2460/javma.234.12.1555 balara, j.m., mccarthy, r.j. & buote, m.a. (2009b). ‘comments on study of paw pad lesions in dogs.’ journal of the american veterinary medical association 235(6), p. 657–659. doi: https://doi.org/10.2460/javma.235.6.620 görtz, k., rooster, h., chiers, k., kramer, m. & declerq, j. (2003). ‘digital hyperkeratosis as a cause of severe lameness in two whippets and a greyhound.’ kleintierpraxis 48 p. 435–439. guilliard, m.j., segboer, i. & shearer, d.h. (2010). ‘corns in dogs; signalment, possible aetiology and response to surgical treatment. .’ journal of small animal practice 51(3), p. 162–168. doi: https://doi.org/10.1111/j.1748-5827.2010.00892.x macherey, c.l. & feeman, w.e. (2006). ‘using a dental root elevator to remove footpad corns in dogs: two practitioners’ experience.’ veterinary medicine 101 p. 778–781. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. does heat stress affect immune function in dairy cows? a knowledge summary by michael steele bsc(hons), bvsc, mrcvs1* 1dairy consultant, 10 granborough road, winslow, buckinghamshire, mk18 3bp *corresponding author (steelemi@elanco.com) vol 1, issue 3 (2016) published: 14 sep 2016 reviewed by: james breen (bvsc phd dchp mrcvs) next review date: 20 jan 2018 doi: 10.18849/ve.v1i3.39 clinical bottom line heat stress appears to generally suppress innate immune function in both dry and lactating dairy cows. immune effects that are decreased include cytokine production, proliferation of immune cells, migration of lymphocytes to the udder and cell viability. this may lead to an increase in the risk of clinical diseases such as mastitis and metritis. question in dairy cows experiencing heat stress (in most papers defined as a temperature/humidity index of >65 at the lowest threshold (bernabucci, 2014), vs. cows in environmentally cooled conditions, is innate immune functionality affected? clinical scenario a previously published review revealed that cows experiencing high temperature humidity indices reduce milk yields beyond that expected of the reduction in dry matter intake (baumgard, 2013) and therefore do not appear to experience ketosis. it is clear however, that cows experience some discomfort. the innate immune system is the first line of defense against invading pathogens, and any factor which suppresses the efficiency of this protection increases the risk of diseases (kehrli, 1989). acronyms: imi=intramammary infections; dim=days in milk; resp=respiration; tlr=toll-like receptor; il=interleukin; tnf=tumour necrosis factor; temp=temperature; hstf=heat shock transcription factor; hsp=heat shock protein; bst=bovine somatotropin; thi=temperature humidity index; brs=brown swiss; hol=holstein; pmn=polymorphonuclear leukocytes; th1=t-helper 1 response; ig=immunoglobulin thompson (2014) population: multiparous dairy cows in the dry period sample size: 15 cooled dry cows and 15 heat stressed cows. 5 from each group were induced streptococcus uberis imi at 5dim intervention details: thi in non-cooled conditions was 77.9-78.3. cooling involved fans, water sprinklers and shade in this group study design: cohort study outcome studied: rectal temperature, respiratory rate, milk yield and composition, blood parameters: immune response genes (tlr2, il1-β, il6, il8, il10, and tnfα) main findings (relevant to pico question): cooled dry cows had: lower temperature and respiratory rate, higher milk yield (no change in composition) by 3.8l/d higher neutrophil count after imi higher il10 higher tlr2 all other cytokines had no difference limitations: very low cow numbers measured over 0-36 hours post imi for cytokines and to 40 weeks into lactation for physiology all cows were cooled after calving insufficient power to conclude an effect on milk yield, however, any numerical effects seen are valid as the primiparous group were not included collier (2008) population: dairy cows experiencing heat stress >35°c sample size: na intervention details: na study design: review of cohort studies outcome studied: na main findings (relevant to pico question): gene expression changes to heat above 35°c include: activation of heat shock transcription factor 1 hstf1 increased expression of heat shock proteins (hsp) increased glucose and amino acid oxidation and reduced fatty acid metabolism endocrine system activation of the stress response immune system activation via extracellular secretion of hsp limitations: na kamwanja (1994) population: lymphocytes from 3 breeds of heifers sample size: 12 heifers of angus, brahman and senepol intervention details: killing lymphocytes after incubation at 45°c for 1 or 12 hours study design: cohort study on lymphocyte populations outcome studied: viability of lymphocytes and hsp production when killed after 45°c for 1 hour or 12 hours main findings (relevant to pico question): decrease in viability at 45°c in brahman and senepol limitations: in vitro work with little relevance to in vivo effects elvinger (1992) population: dairy cows during lactation sample size: 34 cows at parity 1-8 and dim 30-209 given either bst or placebo (16 in control, 18 in bst treated group). on day 10 after initialising placebo or bst cows were placed in cross over heat stress and normalised environments) intervention details: heat stress (35-44°c) or normalised (26-33°c) study design: cohort study (cross-over) outcome studied: temperature, respiratory, cortisol, milk yield, lymphocyte numbers (cd4+ and 8+) main findings (relevant to pico question): heat stress increased rectal temperatures, respiration rates, and plasma cortisol concentrations and decreased milk yield no discernible effects on immune function due to bst heat stress reduced lymphocyte migration to udder limitations: very low cow numbers cows ranged from lactation 1-8 with no specification as to numbers in each lactation. this may affect yield results (lactation 1 cows give less milk than lactation >1). elvinger (1991) population: heat stressed lactating dairy cows sample size: na intervention details: incubated lymphocytes in high or low temperatures to see viability study design: case study outcome studied: viability of leukocytes incubated at 38°c and 42°c main findings (relevant to pico question): during spring thi was 72 and in the summer it was 79. in summer: dna synthesis was lower immunolglobulin m secretion was higher plasma cortisol was higher (2ng vs >4ng/ml before calving, not after) limitations: the cows weren’t grouped variation in feed possible and other management factors (stocking etc.) lacetera (2006) population: comparing leukocytes from brs and hol lactating dairy cows sample size: 5 brs and 5 hol cows intervention details: incubation of pmns at 39°c and 43°c study design: cohort study outcome studied: pmn: proliferation hsp72 synthesis main findings (relevant to pico question): pmns from brs breed appeared to have a lower tolerance to heat. brs is supposed to be a more heat tolerant breed. heightened temperature lowered ros activity higher hsp72 synthesis in brs but not hol hol appeared to have a more tolerant effect to higher temperatures than brs limitations: low numbers of cows, however the study is comparing cells rather than cows hsp72 synthesis may not be conclusive as it is unclear whether or not pre-or post-transcription levels on mrna are determined. lacetera (2005) population: transition hol dairy cows (dry and in early lactation) sample size: 34 cows. 28 calving in spring and 12 in summer. during spring thi averaged 72 and in the summer it averaged 79. intervention details: comparing cows calving in spring and summer study design: cohort study outcome studied: blood (leukocytes) taken weekly, from -4wk to +4wk around calving main findings (relevant to pico question): in summer: dna synthesis was lower igm secretion was higher plasma cortisol was higher (2ng vs >4ng/ml before calving, not after) limitations: very low cow numbers many more cows in winter group vs summer group variation in feed possible and other management factors (stocking etc.) from spring to summer. this may have affected physiological factors do amaral (2010 and 2011) population: comparing lymphocyte function in heat stressed and cooled multiparous lactating cows sample size: 21 heat stressed and 16 cooled lactating cows (from 42 days pre calving) intervention details: cooling system had fans and sprinklers active at greater than 21°c study design: cohort study outcome studied: mrna expression of prolactin receptor prl-r, suppressor of cytokine activity proteins socs-1, socs-2, socs-3, cytokine-inducible sh2-containing protein, and heat shock protein 70 typed at kilodalton a5 (or hspa5) main findings (relevant to pico question): heat stress: had greater prolactin (prl) in plasma had lower lymphocyte proliferation had lower socs (suppressors of cytokine function) levels had lower tnfα expression had lower prl receptor expression limitations: low cow numbers did not concentrate on many innate, th1 parameters did not mention the difference in temperature of cooled vs heat stressed groups lacetera (2002) population: transition dairy cows in spring and summer sample size: 20 spring calving cows and 9 summer calving cows intervention details: spring thi 58 summer thi 72 study design: cohort study outcome studied: rectal temperature respiratory rate proliferation of pmns colostrum ig levels main findings (relevant to pico question): summer vs spring: increased rectal temperature increased respiratory rate no effect on proliferation or colostrum ig levels limitations: may be different management systems at different times, small cow numbers and very moderate thi for heat appraisal, application and reflection there are relatively few papers directly addressing the effects of heat stress on immune function specifically, especially those concentrating on non-specific, innate effects that may be significant to the development of subsequent diseases. however, there are some agreements between the above papers that physiological effects are apparent as well as immune suppressive effects in temperature and humidity levels over thi levels at greater than or equal to 72. most papers compare cooled cows to heat stressed cows and either focus on outcomes in vivo or from leukocytes taken from the cows and subsequent functions in vitro. cows or leukocytes in cooled conditions appear to have: lower rectal temperatures lower respiratory rates lower cortisol levels in plasma higher milk yield (3.8l/d) higher il10,2, neutrophil count, lower tnf α, lower suppressors of cytokine function higher viability of leukocytes no effect on ig levels in colostrum better migration of lymphocytes to udder higher prolactin receptor expression lower prolactin production higher heat shock transcription factor hstf1 and heat shock protein hsp72 expression (but(b. u. lacetera n. 2006) states that the function of the latter molecule remains unknown) but post-transcriptive effects are not determined. methodology section search strategy databases searched and dates covered: used 3 databases: pubmed, cab abstracts (1973-2015) accessed on the ovid platform) and google scholar. pubmed did not achieve many hits (5) so i tried google scholar. pubmed also had too many results to process when using immun*, so i had to restrict to (immune or immunity). hit 16,400 results. filtered to 2000-2016, after the first 4 pages, virtually none were relevant to the pico. search terms: ((((cow$ and cattle and bovi*))) and heat stress) and ((immune or immunity)) – pubmed does heat stress affect dairy cow immun* google scholar (cow$ and cattle and bovi* and heat stress and (immune or immunity)).mp   cab abstracts dates searches performed: 18th march, 2016 exclusion / inclusion criteria exclusion: na inclusion: relevance to pico, sufficient evidence level, answers the clinical question search outcome database number of results excluded – relevance to pico total relevant papers ncbi pubmed 17 12 5 google scholar 16,400 16,394 6 cab abstracts 53 47 6 total relevant papers when duplicates removed 9 conflict of interest the author declares no conflict of interest references baumgard, l.h, and rhoads, r.p. (2013) effects of heat stress on postabsorptive metabolism and energetics. annual reviews in animal biosciences, 1 (1), pp. 311-337. http://dx.doi.org/10.1146/annurev-animal-031412-103644 bernabucci, u. et al. (2014) the effects of heat stress in italian holstein dairy cattle. journal of dairy science, 97 (1), pp. 471-486. http://dx.doi.org/10.3168/jds.2013-6611 collier, r.j. et al. (2008) invited review: genes involved in the bovine heat stress response. journal of dairy science, 91 (2), pp. 445-454. http://dx.doi.org/10.3168/jds.2007-0540 do amaral, b.c. et al. (2010) heat stress abatement during the dry period influences prolactin signaling in lymphocytes. domestic animal endocrinology, 38 (1), pp. 38-45. http://dx.doi.org/10.1016/j.domaniend.2009.07.005 do amaral b.c. et al. (2011) heat stress abatement during the dry period influences metabolic gene expression and improves immune status in the transition period of dairy cows. journal of dairy science, 94 (1), pp. 86-96. http://dx.doi.org/10.3168/jds.2009-3004 elvinger, f. hansen, p.j. and natzke, r.p. (1991) modulation of function of bovine polymorphonuclear leukocytes and lymphocytes by high temperature in vitro and in vivo. american journal of veterinary research, 52 (10), pp. 1692-1798. elvinger, f. natzke, r.p, and hansen, p.j. (1992) interactions of heat stress and bovine somatotropin affecting physiology and immunology of lactating cows. journal of dairy science, 75 (2), pp. 449-462. http://dx.doi.org/10.3168/jds.s0022-0302(92)77781-9 kamwanja, l.a. et al. (1994) responses of bovine lymphocytes to heat shock as modified by breed and antioxidant status. journal of animal science, 72 (2) pp. 438-444. kehrli, m.e. nonnecke, b.j. and roth, j.a. (1989) alterations in bovine neutrophil function during the periparturient period. american journal of veterinary research, 50 (2) , pp. 207-214. lacetera, n. et al. (2002) moderate summer heat stress does not modify immunological parameters of holstein dairy cows. international journal of biometeorology 46, no. 1 (2002): 33-37. http://dx.doi.org/10.1007/s00484-001-0115-x lacetera, n. et al. (2006) heat stress elicits different responses in peripheral blood mononuclear cells from brown swiss and holstein cows. journal of dairy science, 89 (12), pp. 4606-4612. http://dx.doi.org/10.3168/jds.s0022-0302(06)72510-3 lacetera, n. et al. (2005) lymphocyte functions in dairy cows in hot environment. international journal of biometeorology, 50 (2), pp. 105-110. http://dx.doi.org/10.1007/s00484-005-0273-3 thompson, i.m. (2014) effect of cooling during the dry period on immune response after streptococcus uberis intramammary infection challenge of dairy cows. journal of dairy science, 97 (12), pp. 7426-7436. http://dx.doi.org/10.3168/jds.2013-7621 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. in horses undergoing volatile anaesthesia, does intraoperative alpha-2-agonist infusion improve recovery? a knowledge summary by alison bennell bvms certavp(em) certavp(va) msc fhea mrcvs 1* 1institute of veterinary science, university of liverpool, chester high road, neston, ch64 7te *corresponding author (alison.bennell@liverpool.ac.uk) there is an erratum to this paper published in veterinary evidence vol 7, issue 2 (2022): https://doi.org/10.18849/ve.v7i2.588 vol 6, issue 1 (2021) published: 17 feb 2021 reviewed by: jackie brearley (ma vetmb phd mrcvs dva dipecvaa), john hird (ma bvsc (hons) dva dipecvaa mrca mrcvs) and kate loomes (bvsc(hons) msc certavp(ep) certavp(va) dip. ecvaa mrcvs) next review date: 30 jan 2022 doi: 10.18849/ve.v6i1.341 pico question in horses undergoing volatile anaesthesia with isoflurane or sevoflurane, does administration of an alpha-2 agonist as a cri compared to anaesthetic maintenance with volatile alone improve recovery quality?   clinical bottom line category of research question treatment the number and type of study designs reviewed eight papers were critically appraised. all prospective, randomised clinical trials. 7/8 papers were blinded and 4/8 were crossover design strength of evidence moderate outcomes reported one paper investigating detomidine and one on romifidine showed no improvement in recovery quality. 3/3 medetomidine papers and 2/3 dexmedetomidine papers showed a significant improvement in recovery quality in the alpha-2 agonist cri group conclusion in a healthy horse undergoing general anaesthesia with isoflurane or sevoflurane maintenance, an intra-operative constant rate of infusion (cri) of medetomidine and dexmedetomidine can lead to better recovery quality when compared to horses who are maintained on isoflurane or sevoflurane alone   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a 4-year-old warmblood has presented for a bilateral stifle arthroscopy under general anaesthesia. after discussing the risks of general anaesthesia with the owner, they ask if there are any ways of making recovery safer. you decide to look up the evidence of giving an alpha-2 adrenoceptor agonist as a constant rate of infusion (cri) intraoperatively and the effects on recovery from general anaesthesia. the evidence although little evidence is available, there is high quality evidence in the form of prospective, randomised blinded studies to support the use of a cri of an alpha-2 adrenoreceptor agonist intraoperatively to improve the quality of recovery in healthy horses undergoing volatile agent anaesthesia with isoflurane or sevoflurane. crossover studies are less applicable to studies investigating anaesthetic recovery quality as recovery behaviour is learned and recoveries will improve with multiple general anaesthetics (platt et al., 2017; and valverde et al., 2013). dexmedetomidine and medetomidine are the most investigated drugs in this class used in a partial intravenous anaesthesia (piva) protocol and the evidence shows that recovery quality is improved with the use of these drugs as a cri when compared to volatile use alone. no adverse effects of using these drugs were observed in any of the studies and cardiorespiratory stability was maintained, which makes them valid choices to improve recovery. summary of the evidence creighton et al. (2012) population: healthy adult standardbred research horses: age 3–7 years weight 400–560 kgs 150 minutes anaesthesia time sample size: 10 horses intervention details: standard anaesthetic protocol (isoflurane maintenance) and either: group 1 (n = 10) – premedication of 7mcg/kg medetomidine iv. cri of medetomidine at 5mcg/kg/hr group 2 (n = 10) – premedication with xylazine 0.7 mg/kg iv. no cri and 0.2 mg/kg xylazine iv at end of anaesthesia unassisted recovery from general anaesthesia crossover study and 10 day washout period study design: prospective, blinded, randomised crossover study outcome studied: subjective recovery score on 1–10 visual analogue scale (vas) and 11–100 behavioural recovery score (brs) and objective mean attempt interval (mai) recovery scores by two blinded anaesthetists objective recovery time variables recorded for time until extubation, time until first movement, time until sternal recumbency and time until standing main findings (relevant to pico question): time until extubation, first movement, time until standing and number of attempts to stand were not statistically different between the two groups time to sternal recumbency was significantly longer in group 1 (p = 0.019) mai (p = 0.025) and vas (p = 0.047) significantly better with group 1 brs was better with group 1, but no statistical difference limitations: small sample number only two blinded observers crossover design may influence results as horses have been shown to have improved recoveries after multiple anaesthetics no surgery was performed, so it is difficult to extrapolate to clinical practice devisscher et al. (2010) population: horses undergoing routine arthroscopy: american society of anesthesiologists (asa) category i or ii age 3–6 years weight 339–627 kgs 116 ± 33 minutes anaesthesia time sample size: 30 horses intervention details: standard anaesthetic protocol (isoflurane maintenance) with premedication of romifidine at 80 mcg/kg iv then divided into two groups: group 1 (n = 15) – romifidine cri at 40 mcg/kg/hr group 2 (n = 15) – saline placebo cri all horses given 20 mcg/kg romifidine iv for recovery (before transport to recovery box) unassisted recovery from general anaesthesia study design: randomised, blinded, prospective clinical trial outcome studied: subjective assessment of recovery quality score (1–5) using a previously described scoring system (gozalo-marcilla et al., 2010) objective measurement of time until extubation, time to sternal recumbency and time until standing were recorded paper does not specify who scored recovery main findings (relevant to pico question): quality of recovery did not significantly differ between groups (p = 0.109) more horses in group 1 stood at the first attempt (it is unclear how many horses this applied to) recovery times did not differ between the two groups limitations: subjective recovery quality scores the method of blinding and scored recoveries was not explained clearly all horses were sedated for recovery, which may have influenced recovery quality significantly gozalo-marcilla et al. (2013) population: healthy research ponies: age 12.7 ±8 years weight 294 ± 51 kgs 146–362 minutes anaesthesia time sample size: six ponies intervention details: standard anaesthetic protocol (sevoflurane induction and maintenance) then ponies divided into two groups: group 1 (n = 6) – dexmedetomidine bolus at 3.5 mcg/kg iv then cri at 1.75 mcg/kg/hour group 2 (n = 6) – sevoflurane only with saline placebo (volume equivalent to other group) all ponies given 0.875 mcg/kg medetomidine iv for recovery and assisted with manual tail support crossover study and 3 week washout period study design: blinded, prospective, randomised, crossover experimental study outcome studied: subjective assessment of recovery quality score (1–5) using a previously described scoring system (gozalo-marcilla et al., 2010) scored by one blinded anaesthetist objective time variables recorded: time to extubation, time until sternal recumbency and time until standing main findings (relevant to pico question): there was no difference in recovery scores between the two groups objective time variables were not different between the two groups limitations: small sample number only one blinded observer crossover design, and ponies were used for previous studies where they were anaesthetised, which may influence results as horses have been shown to have improved recoveries after multiple anaesthetics small horses may not be representative of horse population no surgery was performed, so it is difficult to extrapolate to clinical practice ponies were manually assisted in recovery, which may not be applicable to many clinical situations marcilla et al. (2012) population: client-owned horses: asa i or ii age 7 months–16 years weight 491 ± 102 kgs undergoing elective orthopaedic or soft tissue surgery >60 minutes duration sample size: 40 horses intervention details: standard anaesthetic protocol (isoflurane maintenance) with premedication of dexmedetomidine at 3.5 mcg/kg iv then horses divided into two groups: group 1 (n = 20) – cri dexmedetomidine 1.75 mcg/kg/hr group 2 (n = 20) – saline cri (equivalent volume to other group) all sedated with 0.875 mcg/kg dexmedetomidine for recovery. unassisted recoveries performed study design: prospective, randomised, blinded clinical study outcome studied: subjective assessment of recovery quality score (1–5) using a previously described scoring system (gozalo-marcilla et al., 2010) by one blinded observer objective measurement of time until extubation, time to sternal recumbency, time until standing were recorded main findings (relevant to pico question): recovery scores better in group 1 (p = 0.03) compared with group 2 group 1 took fewer attempts to stand (p = 0.04) first attempts to stand were significantly longer in group 1 (p = 0.04) compared to group 2 limitations: subjective recovery score recoveries scored by one blinded observer all horses were sedated for recovery, which may have influenced recovery quality significantly different premedicant doses were used in different horses due to the varying temperament of horses risberg et al. (2016) population: standardbreds research horses: age 10 ±3 years weight 478 ± 58 kgs 163–401 minutes anaesthesia time sample size: eight horses intervention details: standard anaesthetic protocol (isoflurane maintenance) with a premedication of 8 mcg/kg dexmedetomidine then divided into two groups: group 1 (n = 8) – 1.75 mcg/kg/hr dexmedetomidine cri group 2 (n = 8) – saline cri (equivalent volume to other group) crossover study and minimum washout period of 10 days study design: sequential, blinded, randomised, balanced, crossover study outcome studied: subjective recovery score on 1–100 vas by one blinded anaesthetist objective recovery time variables recorded were time to sternal recumbency, number of attempts to stand and total time until standing main findings (relevant to pico question): recovery times did not significantly differ between groups recovery scores were better with dexmedetomidine than saline (p = 0.023) all horses in group 1 stood on the first attempt, horses in group 2 made a median of three attempts to stand limitations: small sample size subjective recovery quality score only one observer scored recoveries no surgery was performed, so it is difficult to extrapolate to clinical practice crossover design may influence results as horses have been shown to have improved recoveries after multiple anaesthetics schauvliege et al. (2011) population: healthy client-owned horses undergoing elective soft tissue and orthopaedic surgery: asa i or ii age 1.5–9 years weight 325–672 kgs 45–90 minutes anaesthesia time sample size: 20 horses intervention details: standard anaesthetic protocol (isoflurane maintenance) with premedication of detomidine at 10 mcg/kg then divided into two groups: group 1 (n = 10) – cri of detomidine at 5 mcg/kg/hr group 2 (n = 10) – saline cri (equivalent volume to other group) all sedated with 0.25 mcg/kg detomidine iv for recovery unassisted recoveries performed study design: prospective, randomised, blinded clinical trial outcome studied: subjective assessment of recovery using a 1–6 point recovery scoring system by the blinded anaesthetist who performed the general anaesthetic objective time variables of time to extubation, time to sternal recumbency, time until standing were recorded main findings (relevant to pico question): recovery scores were not statistically different between the two groups objective time variables were not statistically different between the two groups limitations: non-validated subjective recovery score only one, unblinded observer which can introduce significant bias small sample number all horses were sedated for recovery, which may have influenced recovery quality significantly simeonova et al. (2017) population: healthy research horses: age 4–20 years weight 272 ± 27 kgs 3 hours anaesthesia time sample size: six horses intervention details: standard anaesthetic protocol (sevoflurane maintenance) with premedication of 0.8 mg/kg xylazine then divided into two groups: group 1 (n = 6) – 1.75 mcg/kg/hr medetomidine cri group 2 (n = 6) – saline cri (equivalent volume to other group) unassisted recovery from general anaesthesia crossover study with 2 week washout period study design: prospective, randomised, crossover study outcome studied: subjective assessment of recovery quality score (1–5) using a previously described scoring system (gozalo-marcilla et al., 2010) objective timings from end of anaesthesia until sternal recumbency and standing main findings (relevant to pico question): timings to extubation, sternal recumbency and standing were similar between the groups group 1 had better recoveries than group 2 (p<0.05) limitations: small sample number not blinded crossover design may influence results as horses have been shown to have improved recoveries after multiple anaesthetics small horses may not be representative of horse population unsure who scored recoveries no surgery was performed, so it is difficult to extrapolate to clinical practice tokushige et al. (2015) population: thoroughbred racehorses undergoing arthroscopy: age 3.7 ± 1 years weight 456 ± 34 kgs sample size: 50 horses intervention details: standard anaesthetic protocol (sevoflurane maintenance) with premedication of 5 mcg/kg medetomidine then horses divided into two groups: group 1 (n = 25) – medetomidine cri at 3 mcg/kg/hr and no sedation for recovery group 2 (n = 25) – sevoflurane maintenance only, 1 mcg/kg medetomidine for recovery unassisted recoveries from anaesthesia study design: blinded, prospective, randomised clinical study outcome studied: subjective assessment of recovery quality score (1–5) using a previously described scoring system (gozalo-marcilla et al., 2010) by two blinded observers objective time variables recorded: time to extubation, first movement, time until sternal recumbency, time until first attempt to stand, number of attempts to stand and time until standing main findings (relevant to pico question): number of attempts to stand was fewer in group 1 (p=0.003) recovery score was significantly better in group 1 (p=0.014) objective time variables were not different between the two groups limitations: subjective recovery quality scoring system the sevoflurane only group received additional sedation for recovery which may have influenced outcome medetomidine can provide analgesia, which may influence recovery from anaesthesia only two blinded observers appraisal, application and reflection equine anaesthesia is high risk, with a mortality rate of approximately 0.12–1% in healthy horses undergoing elective surgery (bidwell et al., 2007; and johnston et al., 2002). recovery is one of the highest risk periods as catastrophic injury can occur, such as limb fractures or subluxations, accounting for 71.4% of fatal recovery complications (dugdale et al., 2016). a good quality of recovery plays a major part in the outcome of anaesthesia and surgery, and although many variables such as age, duration of anaesthesia, bodyweight, time of surgery and asa physical status may influence recovery (dugdale et al., 2016), any anaesthetic protocol which is proven to improve recovery quality should be considered. the aim of partial intravenous anaesthesia (piva) is to reap the multiple benefits of the minimum alveolar concentration (mac)-sparing effects (ringer et al., 2007), due to additional analgesia so a less volatile agent is required to maintain a suitable plane of anaesthesia. benefits of piva include reduced cardiovascular depression, as lower doses of commonly used inhalational agents are required, and it may also provide a positive influence on recoveries, leading to a smoother and more controlled recovery period. although many drugs, such as lidocaine, ketamine and opioids can also be used in piva protocols, alpha-2 agonists may provide additional benefits in terms of recovery quality due to their mental-calming effects. recovery quality encompasses several factors. these factors include successfully recovering and standing after anaesthesia without injury, how calm the horse is during recovery, how ataxic the horse is during and immediately after standing, the number of attempts to stand and the time taken until standing after the cessation of anaesthesia. a recovery of good quality will be uneventful and controlled, the horse stands successfully with no injury, return to consciousness is smooth (so no emergence delirium occurs), transitions from lateral recumbency to sternal recumbency to standing are smooth, horses stand after one or two attempts as they have adequate musculoskeletal strength and coordination and they remain standing with minimal or no ataxia being present. this then ranges through to poor recoveries where horses can thrash around, injury is sustained (which can range from a skin abrasion through to a fatal catastrophic injury), the horse falls after standing or is severely ataxic, there are multiple attempts to stand or the horse fails to stand after anaesthesia. the most commonly used recovery scoring system in the appraised papers is described by gozalo-marcilla et al. (2010), which is based on an original paper by young & taylor (1993). vettorato et al. (2010) validated four different recovery scoring systems and found them all to be adequately reliable. eight relevant papers were found which investigated the effects of cris of alpha-2 agonists on recovery in horses to answer the pico question. they are all prospective, randomised studies with varying degrees of blinding. most involve client-owned horses undergoing elective anaesthesia, but there is also evidence from research horses undergoing research anaesthesia, mainly for cardiorespiratory studies. there is little published evidence directly comparing recovery in horses undergoing volatile agent anaesthesia only and those receiving a cri of alpha-2 agonists, without sedation in recovery for either or both groups. papers have also been published comparing recovery after an alpha-2 agonist cri where additional cris, such as ketamine or lidocaine, have also been used in both study groups (kempchen et al., 2012; sacks et al., 2017; and valverde et al., 2010). in examining the evidence for the pico question, the assessment of the influence of the cris on recovery quality will likely be complicated by the administration of further sedation in recovery. performing studies without further sedation for recovery can be challenging as in many centres horses need to be transported to recovery boxes, so further sedation is given for safety reasons, to try to prevent a premature recovery. a bolus of sedation has been shown to improve recoveries (santos et al., 2003), however many patient factors, clinical factors and individual preference helps guide decision making as there is little evidence in this area. there are several limitations to the papers. sample sizes are small to moderate,. alpha-2 agonists are known to be mac-sparing (gozalo-marcilla et al., 2010 and tokushige et al., 2015), so horses undergoing infusions often have more stable planes of anaesthesia. this can lead to comparatively more frequent administration of rescue top-up doses of ketamine or thiopental in the control groups to maintain a suitable plane of anaesthesia (marcilla et al., 2012). these drugs are known to have a negative impact on recovery quality as they can cause ataxia, so this could lead to considerable bias for better recoveries in the cri group. another point to note when interpreting the evidence is that different piva protocols will provide variable levels of analgesia and as most of the study horses were undergoing elective surgery (devisscher et al. 2010; marcilla et al., 2012; schauvliege et al., 2011; and tokushige et al., 2015) and therefore surgical stimulation, the presence of pain may also have a negative influence on recovery quality in horses not receiving an alpha-2 agonist cri. the studies where anaesthesia was performed without surgery (creighton et al., 2012; gozalo-marcilla et al., 2013; risberg et al., 2016; and simeonova et al., 2017) may not be very applicable to clinical scenarios as surgical factors are important at influencing recovery from anaesthesia. assessing the quality of recovery in horses after general anaesthesia is challenging as scores are often descriptive or subjective as objective measurements are restricted to timing of variables, such as time until sternal recumbency is achieved or number of attempts taken to stand. however, some of these also have a degree of subjectivity such as what constitutes an attempt to stand. assessment of ataxia is used in many papers, but again is open to interpretation by the observer. all the papers used subjective or descriptive recovery quality scores, with a varying number of observers from one to two. blinding of the observers was also variable in the studies, which has the potential to introduce significant bias there is no objective way to appraise recovery, and good recovery scores do not always equate to a successful outcome as horses which have a calm and relaxed recovery with minimal attempts to stand can still suffer catastrophic injury; but it is currently regarded as the most appropriate way to quantify the quality of recoveries. the papers all stated that no horses suffered adverse consequences directly related to the recovery period. many alpha-2 agonists are used during anaesthetic protocols, although medetomidine and dexmedetomidine are the most commonly used for an infusion for piva according to studies. no alpha-2 adrenoceptor agonists are currently licensed in the uk for intravenous infusions and neither medetomidine or dexmedetomidine have a uk marketing authorisation for use in horses, therefore need to be used in accordance with the cascade. the application of the evidence obtained from the papers can easily be applied to clinical practice as the protocols are all easy achievable and are cost effective in real-life scenarios. after appraising the evidence available, a cri of an apha-2 agonist leads to equal (3/8 papers) or better (5/8 papers) recovery scores in healthy horses undergoing general anaesthesia, with isoflurane or sevoflurane, compared to those who have received volatile only anaesthesia maintenance. sacks et al. (2017) directly compared medetomidine and dexmedetomidine infusions and showed dexmedetomidine to be favourable in terms of anaesthetic recovery quality, with no negative effects of using this protocol noted. further evidence in this area would be beneficial, and by increasing recovery observer numbers, and the number of horses included in the study, the evidence would be of higher quality. the small number of studies performed have only included healthy horses undergoing anaesthesia, which may not represent many real-life scenarios of prolonged anaesthesia in sick patients prolonged administration of alpha-2 agonists may also affect muscle perfusion in horses, which can have significant effects on oxygen delivery and a successful recovery. none of the horses in the alpha-2 cri groups had evidence of equine post anaesthetic myopathy in any of the papers. in summary, there is limited high quality evidence to show that the following drugs as a cri will improve recovery quality when compared to volatile agent only anaesthetic maintenance and recommendations for using a cri to improve recovery quality would be: medetomidine at a bolus of 5–7 mcg/kg, followed by a cri of 1.75–5 mcg/kg/hour (creighton et al., 2012; simeonova et al., 2017; and tokushige et al., 2015), or dexmedetomidine as a bolus of 3–8 mcg/kg iv followed by a cri of 1.75 mcg/kg/hour (marcilla et al., 2012; and risberg et al., 2016) more evidence is needed to further investigate if there is a beneficial effect of further sedation on recovery after a cri of an alpha-2 agonist, compared to maintenance of anaesthesia on volatile agents alone in larger populations of horses undergoing surgery in real-life clinical scenarios. methodology section search strategy databases searched and dates covered: cab abstracts on ovid interface: 1973 to 30/1/2020 pubmed via the ncbi website: 1910 to 30/1/2020 search strategy: cab abstracts: (equine* or horse* or equus or equid* or mare or mares or pony or ponies).mp. or exp horses/ or exp equus/ or exp equidae/ or exp mares/ or exp foals/ (anaesthetic* or anesthetic* or anaesthesia* or anesthesia*).mp. or exp anaesthesia/ or exp anaesthetics/ (isoflurane* or sevoflurane*).mp. or exp isoflurane/ or exp sevoflurane/ ("alpha 2 agonist*" or "alpha 2 receptor agonist*" or "α2 adrenoceptor agonist*" or "alpha-2-agonist*" or "alpha-2-adrenoceptor agonist*" or medetomidine or dexmedetomidine or detomidine or romifidine or xylazine).mp. 1 and 2 and (3 or 4)   pubmed: equine or horse or equus or equid or mare or broodmare or pony anaesthetic or anesthetic or anaesthesia or anesthesia isoflurane or sevoflurane "alpha 2 agonist" or "alpha 2 receptor agonist" or "î±2 adrenoceptor agonist" or "alpha-2-agonist" or "alpha-2-adrenoceptor agonist" or medetomidine or dexmedetomidine or detomidine or romifidine or xylazine (#1 and #2 and (#3 or #4)) limit #5 to english language dates searches performed: 30 jan 2020 exclusion / inclusion criteria exclusion: studies unrelated to the pico question book chapters/reviews or other non-research articles publications not in english articles where full-text is not available inclusion: studies related to the pico question in english search outcome database number of results excluded – unrelated to pico question excluded – full article not available excluded – not original research article excluded – full text not in english total relevant papers cab abstracts 1539 951 87 239 256 6 pubmed 753 680 4 48 14 7 total relevant papers when duplicates removed 8 conflict of interest the author declares no conflicts of interest. references bidwell, l.a., bramlage, l.r. & rood, w.a. 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(2016). twenty years later: a single-centre, repeat retrospective analysis of equine perioperative mortality and investigation of recovery quality. veterinary anaesthesia and analgesia. 43(2), 171–178. doi: http://dx.doi.org/10.1111/vaa.12285 gozalo-marcilla, m., hopster, k., gasthuys, f., hatz, l., krajewski, a.e. & schauvliege, s. (2013). effects of a constant-rate infusion of dexemedtomidine on the minimal alveolar concentration of sevoflurane in ponies. equine veterinary journal. 45(2), 204–208. doi: https://doi.org/10.1111/j.2042-3306.2012.00613.x johnston, g.m., eastment, j.k., wood, j.l.n. & taylor, p.m. (2002). the confidential enquiry into perioperative equine fatalities (cepef): mortality results of phases 1 and 2. veterinary anaesthesia and analgesia. 29(4), 159–170. doi: http://dx.doi.org/10.1046/j.1467-2995.2002.00106.x kempchen, s., kuhn, m., spadavecchia, c. & levionnois, o.l. 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(2010). a comparison of four systems for scoring recovery quality after general anaesthesia in horses. equine veterinary journal. 42(5), 400–406. doi: https://doi.org/10.1111/j.2042-3306.2010.00093.x young, s.s. & taylor, p.m. (1993). factors influencing the outcome of equine anaesthesia: a review of 1,314 cases. equine veterinary journal. 25(2), 147–151. doi: https://doi.org/10.1111/j.2042-3306.1993.tb02926.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. developments in surgical fluid therapy rates in cats and dogs a knowledge summary by kristina naden bvn 1* 1unitec institute of technology, 139 carrington road, mount albert, auckland 1025, new zealand *corresponding author (knaden@unitec.ac.nz) vol 5, issue 3 (2020) published: 09 jul 2020 reviewed by: matt gurney (bvsc certva pgcertvbm dipecvaa mrcvs) and jodie hughes (bvsc certavp(va) dip.ecvaa mrcvs) next review date: 22 jul 2021 doi: 10.18849/ve.v5i3.299 pico question is there sufficient evidence to show surgical fluid therapy delivered at the recommended 3 ml/kg/hour for cats and 5 ml/kg/hour for dogs leads to a better outcome compared with widely accepted rates of 10 ml/kg/hour for both cats and dogs?   clinical bottom line category of research question treatment the number and type of study designs reviewed five studies were appraised. two of these were opinion pieces, with one non-comparative prospective study, one randomised controlled trial, and one case control study strength of evidence weak outcomes reported currently there is limited evidence to show that the surgical fluid therapy recommendations made by the 2013 journal of the american animal hospital association guidelines (davis et al., 2013) for cats and dogs lead to a better outcome than accepted fluid therapy rates used. fluid overload in humans can cause long-term adverse effects, however the same effects have yet to be shown specifically in veterinary patients conclusion no evidence was found that provides strong, conclusive evidence that the 2013 recommendations by the american animal hospital association and american association of feline practitioners leads to a better outcome for both cats and dogs. the resulting research outlined below identifies a need to conduct clinical studies on the effects of fluid therapy on cats and dogs, and identify clear monitoring protocols to minimise and ideally avoid, fluid overload. when adequate, valid clinical studies have been carried out, this will provide sufficient information for the development of evidence-based recommended rates of fluid therapy for veterinary medicine, in a range of contexts   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision-making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. the evidence the author of this knowledge summary was unable to find any specific evidence supporting the fluid rates recommended by davis et al. (2013). however, there was also no evidence found to support the widely accepted higher recommended rate of fluid (typically 10–20 ml/kg/hour) used for cats and dogs (davis et al., 2013; and hopper et al., 2018). there has, however, been some research around the effects of fluid therapy on the cardiovascular system. a small study carried out on dogs assessed the delivery of fluid therapy at 1 ml/kg/minute for 1 hour to healthy, normovolaemic dogs when various depths of anaesthesia were induced. dogs were maintained under light anaesthesia with an end tidal isoflurane (eti) of 1.3%, (1.0 minimum alveolar concentration (mac)) for at least 15 minutes, then anaesthesia was increased to 3% eti (2.3 mac) for at least 15 minutes to induce a hypotensive state from anaesthesia, when fluid therapy was begun. this deep state of anaesthesia was maintained for 45 minutes, until the last 15 minutes of fluid therapy when mac was reduced to 1.2 (eti of 1.6%). this intervention impacted cardiovascular function, primarily stroke volume variation (svv) (valverde et al., 2012). svv measures the change in volume of blood expelled from the left ventricle to the aorta, with each heartbeat, and was found to decrease by 67%, 60 minutes after the commencement of fluid therapy, with a concurrent reduction in isoflurane concentration. valverde et al. (2012) reports that svv is well-documented to be a sensitive measure of responsiveness to fluid therapy, namely by demonstrating improvements to venous return. valverde et al. (2012) also noted that high rates of isotonic fluid therapy did not affect arterial blood pressure in the short-term (arterial blood pressure was measured up to 60 minutes following administration of fluids). this result suggests that solely monitoring arterial blood pressure is not the most accurate measure of fluid balance – a conclusion also noted in more recent studies that report hypovolaemia-induced hypotension occurring only after 30–40% of estimated blood volume has been lost (drozdzynska et al., 2018; and hopper et al., 2018). valverde et al. (2012) also noted that cardiac output and stroke volume did not increase at high rates of fluid therapy (60 ml/kg/hour), when hypotension was due to deep anaesthesia. packed cell volume (pcv) did however decrease significantly, due to plasma dilution. a pcv decrease of 16% at 30 minutes and 24% at 60 minutes was noted, and attributed to blood volume expansion of 32%. this change in pcv due to plasma dilution by fluid therapy is an important one to note, when interpreting results on an intra-operative haematocrit of an animal receiving fluid therapy. a smaller pcv decrease would be expected with a lower rate of fluid therapy. urine output was not influenced until up to 60 minutes after fluid therapy was begun, however this is more likely due to the effects of a lighter anaesthetic plane also achieved at this point of the study (valverde et al., 2012). brodbelt et al. (2007) offered some evidence that fluid therapy in cats had increased mortality rates fourfold, compared to cats not receiving fluid therapy. while this was a large study, with results provided by over 100 veterinary clinics, specific details around the data received from clinics was not fully described in the report. a lack of information in the study about the selection criteria for clinics, the fluid rates given to cats in the study, and any correlation between postoperative mortality and pre-anaesthetic health assessments, may have confounded the data. it should also be remembered that cats are more susceptible to overhydration than dogs, due to the lower total blood volume of cats (approximately 170 ml for a 3 kg cat). many clinics did not measure central venous pressure, or use infusion pumps – with the latter being a factor in accuracy of fluid rate delivery (brodbelt, 2010). a number of human studies have identified increased mortality rates, and an increased incidence of acute kidney injury (aki) due to fluid overload (mcdermid et al., 2014; ostermann et al., 2015; and wang et al., 2015). however, there is limited information currently available about the relationship between fluid overload and aki in a veterinary context. much information for veterinary patients has been extrapolated from human data. research around the efficacy of fluid therapy in humans focuses on fluid therapy volumes, and often refers to goal directed therapy (gdt) or zero-balance fluid therapy (voldby & brandstrup, 2016). zero-balance fluid therapy in humans focuses on not adding more than 1 kg of body weight to a patient following surgery with concurrent fluid therapy (voldby & brandstrup, 2016). gdt uses parameters such as stroke volume and pulse pressure variation analysis to determine appropriate fluid rates, in order to maximise cardiac output and oxygen delivery (drozdzynska et al., 2018; licker et al., 2016; and voldby & brandstrup, 2016). in veterinary medicine, current practice typically does not include measuring any of these parameters following clinical examination, and of these parameters, weight is typically the only measurement taken (k. n. pers. obs.). the purpose of these two approaches to fluid therapy is to minimise tissue inflammation, wound dehiscence, and poor collagen regeneration, perioperative morbidity and mortality – all of which can be caused by excessive positive fluid balance (drozdzynska et al., 2018; licker et al., 2016; and voldby & brandstrup, 2016). the complications detailed above were considered in depth by kehlet (1997), who proposed a multimodal approach in human medicine to control general post-operative dysfunction – with avoidance of fluid overload specifically noted to minimise cardiopulmonary complications. this concept, coined enhanced recovery after surgery (eras), was revisited almost 20 years later, when collaboration was further emphasised between anaesthesiologists, surgeons, surgical nurses and post-surgical rehabilitation services such as physiotherapy, in order to minimise complications (kehlet, 2015). the approaches noted above to fluid therapy in humans should also be considered in two contexts – low-risk patients undergoing low-risk procedures, and high-risk patients undergoing higher risk procedures. in lower risk human patients, high-volume crystalloid fluids (20–30 ml/kg, or 2 litres over 30 minutes for an average adult) proved beneficial to recovery, while high-risk patients, undergoing major procedures benefitted from a lower fluid rate, that was undefined by the authors but assumed an intraoperative urine output of 0.5–1.0 ml/kg/hour (doherty & buggy, 2012). these approaches may be applicable to veterinary medicine. recommended fluid rates in human surgery range from not exceeding 6–8 ml/kg/hour for thoracic surgery (licker et al., 2016) to 15 ml/kg/hour for the first hour of general surgery and then decreasing as required (voldby & brandstrup, 2016). current trend in veterinary surgical practice is to provide a generic rate of fluid therapy for a range of surgical procedures (davis et al., 2013). this may vary in clinics where blood pressure, (in addition to other more standard parameters such as heart rate, and respiratory rate) is monitored intra-operatively, with fluid therapy levels adjusted in response to variance in this parameter (pers. obs.). this parameter may have limited uses as a measure of overhydration of animals, given fluid overload in humans is not measurable via blood pressure (voldby & brandstrup, 2016). kehlet’s (2015) principle of a multimodal approach to minimise postoperative complications in human medicine has been applied to veterinary medicine, with recommendation that the eras programme be used in animals (gurney, 2018). while gurney (2018) does not recommend specifics around fluid therapy, it is noted that overload of fluids be avoided, and the gdt approach be used in veterinary medicine, in order to avoid postoperative complications. this limited amount of evidence suggests further research is required to identify the impact of current recommendations for fluid therapy in cats and dogs. summary of the evidence davis et al. (2013) population: cats and dogs sample size: n/a – recommendation intervention details: n/a – recommendation study design: opinion article outcome studied: n/a – recommendation main findings (relevant to pico question): fluid therapy should be individualised for each patient fluid selection may need to be adjusted from one type of fluid to another during hospitalisation while blood pressure is often used to assess tissue perfusion, intraoperative hypotension may not always be related to dehydration. anaesthetic depth should be considered prior to administering or increasing fluid rates there is limited evidence-based research for fluid therapy rates in a veterinary context limitations: the recommendations in the report are based on a limited number of research articles, providing minimal evidence to support these new recommendations the recommendations used are based on human evidence of over-infusion of fluids, including damage to the kidneys and the endothelial glycocalyx. this may or may not hold true for cats and dogs this recommendation is not based on clinical studies for cats and dogs valverdeet al. (2012) population: normovolaemic adult dogs between the age of 1 and 4-years-old sample size: six mixed-breed dogs (three male, three female), with a mean weight of 22.1 kg (±2.8) intervention details: anaesthesia was induced and maintained using gaseous agents of isoflurane and oxygen, until a steady haemodynamic state was achieved at 1.3% end tidal isoflurane baseline cardiovascular parameters (including heart rate, arterial blood pressure, central venous pressure, stroke volume variation and cardiac output) were taken at this point, and again 10, 30 and 60 minutes following the commencement of fluid therapy diagnostic samples of urine and blood were collected to measure blood gases, electrolytes, pcv and plasma volume at 30 and 60 minutes after fluid therapy began a hypotensive state under deep anaesthesia (3% end tidal isoflurane) was induced and maintained for at least 15 minutes, with cardiovascular parameters taken again at this point isotonic fluids (plasma-lyte a solution) were administered at a rate of 1 ml/kg/minute for 1 hour end tidal isoflurane was gradually reduced 45 minutes after fluid therapy began, to 1.6% dogs were recovered from anaesthesia and administered intravenous meloxicam 0.1 mg/kg study design: non-comparative prospective study outcome studied: the effect of high-volume isotonic fluid therapy on normovolaemic dogs with isoflurane-induced hypotension main findings (relevant to pico question): intravenous fluid therapy at high volumes (15–80 ml/kg/hour) does not increase arterial blood pressure in anaesthetised normovolaemic patients, during normotensive and hypotensive states isotonic fluid therapy at 1 ml/kg/minute does not increase cardiac output or stroke volume, in dogs where hypotension is a result of a deep anaesethetic plane plasma volume increased by 41% at 30 minutes after fluid therapy began, and by 49% at 60 minutes limitations: no control group was used to assess the cumulative cardiodepressive effects of 3% end tidal isoflurane the sample size used in this study was small, with only six dogs the sample was a group of healthy, normovolaemic dogs, and application of any results is limited to this type of patient silverstein et al. (2014) population: healthy client-owned female dogs undergoing elective ovariohysterectomy sample size: 48 dogs intervention details: dogs were premedicated, anaesthesia was induced with propofol and diazepam, and maintained using isoflurane and oxygen baseline cardiovascular parameters were measured at intubation, including arterial blood pressure (using a doppler flow detector), heart rate, mucous membrane colour, capillary refill time, with tissue oxygen saturation data was collected using pulse oximetry the same cardiovascular parameters were measured 30 and 60 minutes following induction of anaesthesia a video microscope was used to assess microcirculation in the buccal mucosa dorsal to the maxillary canine of all dogs upon induction, then again 30 and 60 minutes following induction dogs were randomly assigned one of three fluid therapy treatments using lactated ringer’s solution – none, 10 ml/kg/hour, or 20 ml/kg/hour, with 16 dogs in each treatment group all dogs were recovered successfully from anaesthesia study design: randomised controlled trial outcome studied: the effects of intravenous fluid administration on microcirculatory blood flow to the oral mucosa in healthy anaesthetised dogs main findings (relevant to pico question): blood vessels < 20μm in diameter show no change in vessel density for any of the three treatment groups vessel diameter was found to be significantly different in vessels < 20μm, between the group receiving 20 ml/kg/hour and the group receiving 0 ml/kg/hour of fluid density of vessels ≥ 20μm (most likely venules and/or arterioles) was significantly more in dogs receiving 20 ml/kg/hour compared with dogs receiving 0 ml/kg/hour of fluid overall, no significant association was found between intravenous fluid administration and tissue perfusion limitations: the study reported primarily on one parameter only (tissue perfusion in the oral mucosa) and does not consider tissue perfusion of other organs the fluid balance of the sample was not reported, giving no suggestion if dogs were normovolaemic small sample size of 48 dogs (one dog excluded from the study due to excessive pigmentation of the oral mucosa interfering with the video microscope’s ability to collect data) brodbelt et al. (2007) population: cats admitted to 117 veterinary clinics in the united kingdom for procedures where sedation or anaesthesia was required sample size: 79,178 cats intervention details: no specific interventions. cats were already being sedated/anaesthetised and monitored to that veterinary clinic’s usual standards study design: case control study details of patient, procedure, and perioperative management for all cats in 117 participating clinics were recorded, however not included in the report. the study was carried out with a control group nested in the main cohort of cats the ‘study’ cohort consisted of all cases, with details of each case recorded for 48 hours post-anaesthesia or sedation. outcomes for the main study cohort were limited to alive, dead or euthanised. treatment types for the cohort were not included a nested ‘control’ cohort consisted of randomly selected cats that were alive more than 48 hours post-anaesthesia or sedation. it was not noted if these cats received fluid therapy or not. the ratio of study to control cases was 1:4. demographics and procedure data of the control cohort was compared to that of the study cohort outcome studied: the frequency of risk (including death) for sedated or anaesthetised cats in british veterinary clinics main findings (relevant to pico question): cats receiving fluid therapy experienced a mortality rate four times that of cats not receiving fluid therapy current usage of fluid therapy may have adverse effects on anaesthetised and/or sedated cats, and there is room for improvement in the monitoring and general management of fluid therapy in cats the potential for fluid overload in cats due to the lower fluid volume in cats – careful administration and monitoring is recommended limitations: this study focused on feline deaths in clinical practice, due to anaesthetic complications, with limited data provided on fluid therapy the study did not identify causality, and authors suggested a lack of monitoring could be related to the increased mortality rate for cats receiving fluid therapy the rate of fluid therapy (where given) was not stated, which could have assisted with understanding of the high mortality rate in cats receiving fluid therapy the study did not identify how veterinary clinics were selected, or what criteria were required for participation in the study minimum monitoring and treatment standards were not identified the study did not specify or categorise cats according to risk factor (for example, anaesthetic risk assessment [asa] risk levels), which may have had an impact on the outcome studied thomovsky et al. (2016) population: n/a – review sample size: n/a – review intervention details: n/a – review study design: opinion article outcome studied: defining “fluid overload” in small animals, and means of avoiding this in small animals main findings (relevant to pico question): heart rate and blood pressure do not change in dogs with fluid overload, demonstrating the limitations of these two parameters as measures of fluid overload fluid overload causes fluid to leave the vascular space and move into the interstitial space, damaging the endothelial glycocalyx in the process oedema in abdominal organs (due to fluid overload) may add pressure to abdominal blood vessels and the vena cava, impeding blood flow to other organs and restricting venous return to the heart fluid overload can be avoided using the rose principle (resuscitation, optimisation, stabilisation, evacuation) for phases of fluid delivery fluid therapy should be considered with the same principles as delivery of drugs or other medical interventions limitations: limited methods of identifying fluid overload are provided while a link between fluid overload, and increased mortality and acute kidney injury is noted, the article does not explore the physiological pathway of mortality due to fluid overload the article provides one example case of fluid overload (a 10-years-old female desexed domestic shorthaired cat) and one theoretical case (a 9-years-old entire male dog with parvovirus) showing a comparison of a traditional approach to fluid therapy vs the rose approach appraisal, application and reflection the concept of the need to replace lost body fluids, either via trauma, illness, or surgery, has existed for hundreds of years (driessen & brainard, 2006), and intravenous fluid therapy has been administered to humans since 1832 when salt water solutions were first used by robert lewins to treat cholera (stanzani & chan, 2010). in these early days of using fluid as a therapy to treat disease, lewins was already considering the decision over the volume of fluid that would be required. his objective was to replace the volume of serum lost, in order to return the patient to normovolaemia (myburgh & mythen, 2013). the first use of fluid therapy in animals is not well documented, however studies on the use of crystalloid fluids on veterinary patients were carried out in the 1960s (silverstein et al., 2014). fluid therapy plays a vital role in stabilising patients in shock, and improving cardiac output (marshall et al., 2016). there is currently a paucity of research that has been carried out in veterinary medicine in terms of the rate that this fluid therapy should be delivered. traditionally, a rate of 10 ml/kg/hour was delivered to anaesthetised veterinary patients (davis et al., 2013; and hopper et al., 2018) – how this rate was calculated is unclear, although may be based around human recommendations of 6–8 ml/kg/hour for patients undergoing thoracic or abdominal surgery (borland & bennett, 2018; and licker et al., 2016), and 15 ml/kg/hour for patients undergoing other procedures (voldby & brandstrup, 2016). the most recent literature (davis et al., 2013), recommends lower rates of fluid therapy, with a rule of thumb guide given as 3 ml/kg/hour for cats, and 5 ml/kg/hour for dogs. davis et al. (2013) also recommended the following: provide maintenance rate plus necessary replacement at less than 10 ml/kg/hour; adjust fluid rates based on patient assessment and monitoring; patients with cardiovascular disease and renal disease should be administered a lower rate of fluid; and rates should be decreased if anaesthesia is more than one hour, with suggested reduction to be 25% per hour until fluid is being delivered at maintenance rate (assuming a stable patient). these recommendations appear to be based on human research identifying excessive fluid therapy causing a range of postoperative complications mentioned earlier in this knowledge summary. while many clinics are adopting this lower rate of fluid therapy, a recent survey of 113 new zealand veterinary clinics found that more than half the respondents currently administer fluids at a rate of 10 ml/kg/hour during surgery (sano et al., 2018). members of the veterinary information network (vin) stated that determining fluid rates for animals remained the most challenging aspect of fluid therapy (hopper et al., 2018). to determine optimal assessment methods of fluid therapy, it should be remembered that two of the key goals of this therapy are to improve cardiac output and improve oxygen delivery (licker et al., 2016; and marshall et al., 2016). several articles suggest monitoring of central venous pressure (cvp) (lunn, 2011; marshall et al., 2016; and siemionow et al., 2012) as a good starting point to ascertain the risk of fluid overload, with marshall et al. (2016) also suggesting some less invasive methods, however there is emerging strong evidence that blood pressure is an inaccurate measure of fluid overload, and cvp is no longer considered an adequate method of measuring fluid responsiveness in an animal (borland & bennett, 2018; drozdzynska et al., 2018; fantoni et al., 2017; and o’dwyer, 2011). pulse pressure variation (ppv) is reported to be the most sensitive measure of fluid responsiveness, with changes in ppv occurring earlier than arterial blood pressure, heart rate or cvp (celeita-rodríguez et al., 2019; drozdzynska et al., 2018; fantoni & shih, 2017). ppv is expressed as a percentage, and measures the difference in maximum and minimum pulse pressure in one respiratory cycle, which is then divided by the mean of these two values (drozdzynska et al., 2018). ppv is measured non-invasively in humans, with a finger cuff that transmits data to a multi-parameter monitor, and some recent studies have compared the use and accuracy of ppv measurement in anaesthetised dogs. in a study comparing the use of cvp and map with ppv, the latter was found to predict fluid responsiveness to volume expansion, when cvp and map did not (fantoni et al., 2017). this study used “non-invasive methods” (a multi-parameter monitor) to calculate ppv on mechanically ventilated, hypotensive (map <60 mmhg), anaesthetised dogs administered a fluid challenge of 15 ml/kg over 15 minutes. gonçalves et al. (2020) also compared the accuracy of invasive arterial blood pressure monitoring with the use of ppv and found the latter method predicted fluid responsiveness in hypotensive anaesthetised, mechanically ventilated dogs (map <65 mmhg), administered a fluid challenge of 5 ml/kg over 15 minutes, reliably as invasive methods. while this study stated ppv was assessed in a non-invasive manner, the placement of an arterial catheter was still required for calculation of ppv via the multi-parameter monitor. an additional method of assessing fluid responsiveness and guiding gdt is pleth variability index (pvi), a method that uses a pulse oximeter (equipment that is commonplace in veterinary clinics) to measure changes in the perfusion index, over one respiratory cycle (den boogert et al., 2018). this method would be considered completely non-invasive, with no arterial catheterisation required. human studies have found pvi and ppv both optimised fluid preload outcome in patients undergoing lowto moderate-risk abdominal surgery (coeckelenbergh et al., 2019). pvi has been shown to be less consistent in detecting fluid responsiveness in patients undergoing renal transplant (coeckelenbergh et al., 2019), and is not suitable in critically ill or haemodynamically unstable adults (den boogert et al., 2018). the choice to administer fluids in non-anaesthetised patients is usually based on signs of dehydration in cats and dogs: skin tenting, dry mucous membranes, oliguria, systolic hypotension. many anaesthetised patients are administered fluids during surgery based on anaesthesia-induced hypotension, or blood loss. however, the question remains, what is an appropriate fluid rate, based on the physiological changes caused by anaesthesia and surgery? what is clear is that monitoring of fluid therapy is vital – the use of fluid therapy should be likened to using substances such as antibiotics, opioid analgesics, or non-steroidal anti-inflammatory drugs on cats and dogs, and should be administered in such a way. anaesthetised patients are monitored constantly to assess basic cardiovascular, neurological and respiratory functions. monitoring currently often only focuses on the anaesthetic depth of the patient, and this may be a very blinkered approach to our care of anaesthetised patients. this approach to monitoring omits the renal system entirely, and monitoring of the pulmonary system is often limited to respiratory rate and depth and end tidal carbon dioxide, with little consideration often given to actual blood loss volumes. weighing saturated swabs, sponges and any blood removed via suction should also be considered as an additional assessment tool of blood loss. it should be remembered that many of the fluid products commonly used during anaesthesia, do not replace the blood components lost as part of a surgical procedure. blood products such as plasma, whole blood or packed red blood cells may be more appropriate to use in some situations. due to the limited amount of evidence in veterinary medicine, some research included in this knowledge summary is from human medicine. while this is valid in a human medical context, it should be remembered that there are still physiological differences between animals and humans, which may impact the transferability of results (valverde et al., 2012; and yozova et al., 2017). it was challenging to find a range of comprehensive clinical studies that looked at the effect of fluid rates and hence fluid overload in a veterinary context, suggesting there is still a great need to carry out clinical research in this area of veterinary medicine. in the interim, robust pre-anaesthetic assessment of hydration status, type of surgical procedure (and therefore likely risk of blood and/or fluid loss), and pre-existing medical conditions of the patient should all be considered and should be used to determine the need for fluid therapy. this, combined with intra-operative monitoring of patients on fluid therapy (non-invasive and invasive where equipment and expertise exists to carry this out) are currently the only available techniques in minimising potential physiological trauma to patients caused by excessive fluid therapy. in terms of specific rates for fluid therapy in veterinary patients, it is difficult at this stage to definitively state a generic rate for a species, without considering comorbidities, procedures and existing hydration status. in the healthy cat or dog, 3 ml/kg and 5 ml/kg, respectively, may suffice as a starting point for fluid therapy. veterinarians and veterinary nurses should consider a collaborative approach to fluid rates, based on an animal’s pre-, post and intra-operative hydration status, and underlying health conditions, and adjust rates accordingly. investigation into the use of non-invasive methods of assessing fluid responsiveness, such as pvi, would be recommended for those practitioners providing fluid therapy on a regular basis. methodology section search strategy databases searched and dates covered: cab abstracts 1973–2019, week 28 pubmed central 1950–2019 search strategy: cab abstracts (using ovid): (dog or dogs or canine or canines or cat or cats or feline or felines or 'small animal' or 'companion animal').mp. or exp dogs/ or exp cats/ fluid therapy.mp. or exp fluid therapy/ (surg* or intraoper* or perioper*).mp. (rate or overload).mp. 1 and 2 and (3 or 4)   pubmed (via ncbi website): dog or dogs or canine or canines fluid therapy surgery or surgical or interoperative or perioperative rate or overload 1 and 2 and (3 or 4) dates searches performed: 22 jul 2019 exclusion / inclusion criteria exclusion: non-english language journals, articles pre-2009, journals related to human medicine inclusion: veterinary journals, peer-reviewed journals search outcome database number of results excluded – non-peer reviewed journals excluded – non-english language excluded – pre-2009 excluded – not from small animal veterinary specific excluded – not relevant to pico question total relevant papers cab abstracts 557 145 58 194 0 156 4 pubmed 508 5 15 266 2 217 3 total relevant papers when duplicates removed 5 conflict of interest the author declares no conflicts of interest. references borland, k. & bennett, r. c. 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(2018). evaluation of the dynamic predictors of fluid responsiveness in dogs receiving goal-directed fluid therapy. veterinary anaesthesia and analgesia, 45(1), 22–30. doi: https://doi.org/10.1016/j.vaa.2017.06.001 fantoni, d. & shih, a. c. (2017). perioperative fluid therapy. the veterinary clinics of north america. small animal practice, 47(2), 423–434. doi: https://doi.org/10.1016/j.cvsm.2016.11.004 fantoni, d. t., ida, k. k., gimenes, a. m., mantovani, m. m., castro, j. r., patricio, g. c. f., ambrósio, a. m. & otsuki, d. a. (2017). pulse pressure variation as a guide for volume expansion in dogs undergoing orthopedic surgery. veterinary anaesthesia and analgesia, 44(4), 710–718. doi: https://doi.org/http://dx.doi.org/10.1016/j.vaa.2016.11.011 gonçalves, l. a., otsuki, d. a., pereira, m. a., nagashima, j. k., ambrósio, a. m. & fantoni, d. t. (2020). comparison of pulse pressure variation versus echocardiography-derived stroke volume variation for prediction of fluid responsiveness in mechanically ventilated anesthetized dogs. veterinary anaesthesia and analgesia, 47(1), 28–37. doi: https://doi.org/10.1016/j.vaa.2019.08.047 gurney, m. (2018). a procedure-specific approach to recovery after surgery. hopper, k., garcia rojas, a. & barter, l. (2018). an online survey of small animal veterinarians regarding current fluid therapy practices in dogs and cats. journal of the american veterinary medical association, 252(5), 553–559. doi: https://doi.org/10.2460/javma.252.5.553 kehlet, h. (1997). multimodal approach to control postoperative pathophysiology and rehabilitation. british journal of anaesthesia, 78(5), 606–617. doi: https://doi.org/10.1093/bja/78.5.606 kehlet, h. (2015). enhanced recovery after surgery (eras): good for now, but what about the future? canadian journal of anesthesia, 62(2), 99–104. doi: https://doi.org/10.1007/s12630-014-0261-3 licker, m., triponez, f., ellenberger, c. & karenovics, w. (2016). fluid therapy in thoracic surgery: a zero-balance target is always best! turk anesteziyoloji ve reanimasyon dernegi dergisi, 44(5), 227–229. doi: https://doi.org/10.5152/tjar.2016.006 lunn, k. f. (2011). the kidney in critically ill small animals. veterinary clinics of north america small animal practice, 41(4), 727–744. doi: https://doi.org/10.1016/j.cvsm.2011.03.020 marshall, k., thomovsky, e., johnson, p. & brooks, a. (2016). a review of available techniques for cardiac output monitoring. topics in companion animal medicine, 31(3), 100–108. doi: https://doi.org/10.1053/j.tcam.2016.08.006 mcdermid, r. c., raghunathan, k., romanovsky, a., shaw, a. d. & bagshaw, s. m. (2014). controversies in fluid therapy: type, dose and toxicity. world journal of critical care medicine, 3(1), 24. doi: https://doi.org/10.5492/wjccm.v3.i1.24 myburgh, j. a. & mythen, m. g. (2013). resuscitation fluids. new england journal of medicine, 369(13), 1243–1251. doi: https://doi.org/10.1056/nejmra1208627 o’dwyer, l. (2011). how to perform central venous pressure measurement. the veterinary nurse, 2(10), 600–603. ostermann, m., straaten, h. m. o. & forni, l. g. (2015). fluid overload and acute kidney injury: cause or consequence? critical care (london, england), 19, 443. doi: https://doi.org/10.1186/s13054-015-1163-7 sano, h., barker, k., odom, t., lewis, k., giordano, p., walsh, v. & chambers, j. p. (2018). a survey of dog and cat anaesthesia in a sample of veterinary practices in new zealand. new zealand veterinary journal. doi: https://doi.org/10.1080/00480169.2017.1413959 siemionow, k., cywinski, j., kusza, k. & lieberman, i. (2012). intraoperative fluid therapy and pulmonary complications. orthopedics, 35(2), 184–191. doi: https://doi.org/10.3928/01477447-20120123-06 silverstein, d. c., cozzi, e. m., hopkins, a. s. & keefe, t. j. (2014). microcirculatory effects of intravenous fluid administration in anesthetized dogs undergoing elective ovariohysterectomy. american journal of veterinary research, 75(9), 809–817. doi: https://doi.org/10.2460/ajvr.75.9.809 stanzani, g. & chan, d. l. (2010). controversies in fluid therapy. european journal of companion animal practice, 24(2), 14–23. thomovsky, e., brooks, a. & johnson, p. (2016). fluid overload in small animal patients. topics in companion animal medicine, 31(3), 94–99. doi: https://doi.org/10.1053/j.tcam.2016.08.007 valverde, a., gianotti, g., rioja-garcia, e. & hathway, a. (2012). effects of high-volume, rapid-fluid therapy on cardiovascular function and hematological values during isoflurane-induced hypotension in healthy dogs. canadian journal of veterinary research (revue canadienne de recherche veterinaire), 76(2), 99–108. voldby, a. w. & brandstrup, b. (2016). fluid therapy in the perioperative setting-a clinical review. journal of intensive care, 4(1). doi: https://doi.org/10.1186/s40560-016-0154-3 wang, n., jiang, l., zhu, b., wen, y. & xi, x.-m. (2015). fluid balance and mortality in critically ill patients with acute kidney injury: a multicenter prospective epidemiological study the beijing acute kidney injury trial (bakit) workgroup. critical care (london, england), 19(371). doi: https://doi.org/10.1186/s13054-015-1085-4 yozova, i. d., howard, j., sigrist, n. e. & adamik, k.-n. (2017). current trends in volume replacement therapy and the use of synthetic colloids in small animals-an internet-based survey (2016). frontiers in veterinary science, 4, 140. doi: https://doi.org/10.3389/fvets.2017.00140 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. the evidence base for developing a veterinary business management curriculum elizabeth l. jackson bag (hons) mba phd sfhea1* sarah hauser bsc (hons) mpa mpp1 1royal veterinary college, hawkshead lane, north mymms, hatfield, hertfordshire, al9 7ta, united kingdom *corresponding author (eljackson@rvc.ac.uk) vol 1, issue 2 (2016) published: 02 june 2016 reviewed by: hannah perrin (bsc ma pgche pgdiphe fhea phd) doi: 10.18849/ve.v1i2.38 section index:    abstract | introduction | methods | results | discussion | conflict of interest | references abstract objective: this paper sets out to highlight the ongoing need for integrated teaching of business skills in the veterinary curriculum. background: in response to the changing environment of the veterinary profession, it is important to understand the future needs of veterinary practitioners. while changes to the veterinary curriculum have been made in recent years, they have been highly varied across schools and little evidence is available on how these have improved students’ non-technical skills, knowledge, aptitudes, and attitudes.  evidentiary value: this literature review of 23 papers provides a solid basis for the further development of knowledge on business management issues in veterinary curricula. the impact on practice from our findings is substantial. the role of clinicians in academia is recognised as a primary source of engaging students with business management through their day-to-day teaching. furthermore, the role of first-opinion vets who take on placement students (known as extra mural studies or ‘ems’ in the uk) cannot be underestimated as they play an essential role in ensuring that students perceive business skills with the same importance as clinical skills. methods: this research draws on the findings of 23 papers that emerged as relevant from the structured literature search.  the search yielded 124 papers but many were excluded because they focused on issues beyond the search strategy, did not report empirical findings so were based largely on discussion and conjecture, were not about the undergraduate veterinary curriculum, were not written in english or were not related to business teaching. results:  employers of recent graduates highly value business skills, and often base their hiring decision on non-technical skills, rather than clinical skills. while changes to the veterinary curriculum have been made to include more non-technical training by individual veterinary schools, it is unclear how effective these programmes have been. conclusion:  veterinarians have identified a need for greater inclusion of business skills in the veterinary curriculum, however successfully integrating business skills into the curriculum will mean that students learn business principles in non-traditional, non-lecture-style environments with materials inter-twining with clinical teaching. this will mean a significant shift from traditional classroom based delivery of business lectures to an integrated approach. this can only be achieved if business and clinical teaching staff work together in delivering business education to the next generation of veterinarians. that said, the evidence regarding the importance of business within the veterinary medical curriculum, coupled with increasing competition in the market for first-opinion veterinary services, means that changes in the approach to teaching business may be easier to achieve than ever before. application: the results of this research are applicable to practicing veterinarians in both academic and private practice. it is clear that business management needs to be integrated throughout the veterinary curriculum and thus ‘owned’ by academics with both clinical and non-clinical roles. veterinarians in private practice also have a critical role to play as these people are the gatekeepers to the real-world experience that placement students encounter. introduction in response to the changing environment of the us veterinary profession, significant advancements were made in understanding the future needs of the veterinary profession by brown and silverman (1999).  one of the resounding findings, later supported by volk et al. (2011) and harris and lloyd (2011), was related to the skills, knowledge, aptitude and attitude of vets in terms of business, management and communication skills. the qualitative phase of harris and lloyd’s (2011) research showed that their research participants were not prepared for the management requirements of private practice and that they did not receive enough training in management, communications and other skills necessary for non-private practice. in terms of veterinary graduates being able to fulfil roles beyond the practice, it was found that vets would be in a better position to fill non-clinical roles if they had better training in speaking/writing, business, administration, personnel management, sales/marketing, finance and computing. volk et al. (2011) went on to identify eight business practices as the leading predictors of higher personal income: business orientation, frequency of financial data review, employee development, negotiating skills, client loyalty, leadership, client retention and new client development. an important caveat to this list is that it is applicable to all types of vets (i.e. companion animal, equine, food animal and mixed-practice). lloyd et al. (2007) further developed the work of brown and silverman (1999) with an emphasis on the importance of leadership skills for vets. their findings highlighted the important role veterinary medical schools and faculties play in providing a pool of candidates for future tertiary administrators of the profession.  they espouse that funding for leadership development programmes should be part of every veterinary education institution’s budget.  similarly, hodgson et al. (2013) identified leadership as one of the nine essential competencies for veterinary graduates and, like lloyd et al. (2007), recommended the inclusion of this skill in veterinary curricula. even more recently, henry and jackson (2015) recognised the imbalance of leadership roles held by women in the uk veterinary profession. they posited the importance of leadership training for women in the face of their dominance in the profession and warned of the profession being led by people unrepresentative of its major demographic. in terms of preparing vets to deal with erratic changes in the economic climate and ensure their businesses are resilient enough to cope with the ebbs and flows of clients’ incomes, volk et al. (2011) concur with the findings of bachynsky et al. (2013) and brown and silverman (1999). they suggest three factors that would make it more likely for vets to be visited more often – all are related to business and none are related to clinical skills: more predictability in the cost of veterinary care, competitive prices for products available through competing channels (e.g. dietary supplements and parasite control products) and improved convenience of the service offering by extending opening hours and pet drop-off appointments. harris and lloyd (2011) recognise the substantial changes that have been made to veterinary curricula in the usa since the publication of brown and silverman’s (1999) work. they identified increases in communications training and more, but highly-varied, options to improve their students’ non-technical skills, knowledge, aptitudes, and attitudes. however, the question remained regarding the effectiveness of these changes to curricula and how they have been converted into graduates who possess skills for economic success. on the other hand, hodgson et al. (2013) have the opinion that veterinary schools are lagging behind their practitioner colleagues in grasping the importance of skills in personnel management, business management and leadership. these authors report on “a recent survey of [north american] faculty regarding the teaching of professional competencies almost half the faculty respondents did not perceive a responsibility to teach or assess business skills.” (hodgson et al., 2013, p. 110).  in addition, volket al. (2011) drew two alarming conclusions in relation to the uptake of business practices amongst vets.  they found that, irrespective of the numerous opportunities to improve performance, there is a low use of widely-accepted business practice amongst vets.  despite annual incomes increasing substantially, companion animal vets did not increase their use of 19 standard business practices. the conclusion was that results point to the fact that incomes were increasing due to the unsustainable practice of increasing fees rather than other improvements to business knowledge. veterinarians are often not adequately prepared for the management requirements of private practice due to a lack of training in management, communications and other non-clinical skills. there is a need to understand what makes veterinarians more prepared to deal with changes in the economic climate and ensure their businesses are resilient enough to cope with the ebbs and flows of clients’ incomes. state hypotheses: as this is a literature review determining the evidence base for developing a veterinary business management curriculum, a statement of hypothesis is not relevant. methods this research reports on the results of a structured literature review. the royal veterinary college’s scout database was used to search for papers. this search engine simultaneously searches the following databases: biomed central journals, bioone, british library public catalogue, cab direct, cabi ahpc, animal health and production compendium, cochrane library, compendium on continuing education for the practicing veterinarian, copac national, academic, and specialist library catalogue, consultant veterinary diagnostic database, defra, directory of open access journals (doaj), ethos, internet center for wildlife damage management, ivis: international veterinary information service, national institutes of health (nih), noah datasheets, pubmed, researchgate scientific network, sciencedirect, springer protocols, suncat, veterinary information network (vin), veterinary medicine, veterinary practice news, vetnetbase, vetsonline, vetstream, web of science, wellcome library, wikivet, wildpro, wiley online library, zetoc electronic table of contents. after some trial and error, the following search terms were used to search the database: veterinar* and business* and (educat* or curricul*) it should be noted that this literature review does not include published commentaries on the subject of integrating business into the veterinary medical curriculum. as these pieces were based on opinion and conjecture, they were excluded from the analysis.  research into integrating business skills in veterinary medical curricula is approached in disparate fashions to include methodological approaches that span inductive approaches whereby conclusions are drawn from thematic coding of focus group data (e.g. lloyd et al., 2005) to deductive research where logistic regression is used to analyse survey data (e.g. adam et al., 2015).  as such, sample sizes for research considered in this review vary considerably. a lot of published research also consists of literature reviews on the topic and therefore offer opportunities for further exploration, rather than definitive conclusions based on empirical research.  results a high demand for non-technical skills among the veterinary community many veterinary practitioners are aware that clients do not choose a veterinarian based on his or her clinical skills and knowledge alone. in many cases clients are not aware of these skills and cannot judge them adequately, instead the veterinarian-client relationship, and as a result client trust and client retention is built through non-technical skills. employers of veterinarians are now looking for more than a sound clinical background. non-technical veterinary skills significantly contribute to employer satisfaction, as is found by danielson et al. (2012). non-technical skills assessed in their survey included interpersonal-skills, making referrals, ability to deal with legal issues, business skills and problem solving. the three skills most significantly correlated to employer satisfaction were found to be: interpersonal skills, business skills and problem solving. while the authors present a clear, statistically significant link, there are limitations to the paper, such as small sample size and the sample being only graduates of the iowa state university college of veterinary medicine. in addition, the term “business skills” is not clearly defined, and no conclusion can be drawn about what kind of business skills employers value. when answering the survey employers could have had a number of business related skills in mind, such as practice management, time management, effective handling of administrative tasks, or something else entirely. this issue is partially addressed by butler (2003), in a survey of employers and new graduates where the term business skills is broken into conflict management skills, time management, financial management, file management, retrieving, compiling and analysing data, professional writing skills, presentation and public speaking skills and awareness of public concerns challenging business/industry’s future. these skills were perceived differently by employers and employees, which is an interesting outcome in itself, and leads to the question on what graduates’ expectations of the workplace look like. however, the author fails to analyse or comment on the results in more detail and shed light on the consequences of these findings. bachynsky et al. (2013) were the most recent authors to publish work on the business skills of veterinary practitioners. their research focused on opinions of recent graduates (n = 150) and employers (n = 150) and revealed six areas that new graduates should have cognisance: financial performance appraisal, communications to clients of charging and payment, recognising the commercial consequences of under-charging, understanding sources of profit in developing pricing estimates for clinical services and equipment investment decisions. while these factors were statistically significant, evidence is lacking in regards to the breadth of employees contributing to the study (i.e. were they only veterinary practices or were a broader range of employers considered e.g. corporate practices, government agencies, abattoirs, official veterinarians (ovs)?) and the source of the questions (i.e. were the right questions being asked? what evidence is there to suggest that the questions contributing to this survey were well-founded and discipline-specific?). the emphasis on communication it is widely accepted by the veterinary profession, that veterinary medicine is more than treating animals. one of the most important skills to have as a veterinarian is the ability to communicate and effectively share information and knowledge with clients, the public and colleagues. this was also found in a study by rhind et al. (2011) where most final year students (n=161) and recent graduates (n=90) ranked communication skills with clients and the public followed by communication skills with colleagues as ‘very important’. despite significant advances being made in the education of veterinary students in client communications, this theme still features strongly as a non-technical competency that needs to be included in veterinary medical education. it is mostly discussed in papers published in the early 2000s but the need to improve client communications remains a key non-technical competency addressed by the literature. in a survey of recent graduates and senior partners routly et al. (2002) found that, in addition to more practical experience, many senior veterinarians listed a greater commitment in undergraduate training to financial/legal skills and communication skills. this sentiment was echoed by the recent graduates surveyed. non-clinical skills as a path to employment non-clinical skills are valued highly by employers of veterinarians, who often choose their employees from a pool of graduates with a very similar level of clinical skills. while in-theory grades and academic performance may feature in employers’ decision making, roth et al. (2014) found that when examining factors that influence students’ average transactions in a small-animal primary care clinical environment, that there is no statistically significant correlation between grades and class rank and economic performance. this finding is supported by routly et al. (2002), stating that selection during job interviews is often based on personality and communication skills and a perceived empathy for the job. a basic clinical prowess is expected by the fact that the student graduated and, in the uk, is thus a member of the royal college of veterinary surgeons. these findings highlight the need for students and academic institutions to provide classes on business and communication skills. a limitation of the roth et al. (2014) paper is that purely average client transaction was measured rather than also measuring client satisfaction and retention. this is grounds for further research as it has been shown that through client communication, involving clients in the decision making process and getting client buy-in, this can alleviate some of the financial challenges involved in veterinary-client interactions (coe et al, 2009). including business skills in the veterinary curriculum a search of the literature highlights that the early 2000s were a turning-point in teaching veterinarians some business skills. numerous studies show that veterinarians need a strong background in business skills such as practice and financial management, in order to achieve commercial success (kogan et al., 2005; jaarsma et al., 2008; lloyd and covert, 2001). there is mixed evidence concerning students’ and graduates’ attitudes towards business education. when compared to clinical subjects, business or commercial education were not a priority for students of veterinary medicine, when however, employers were asked, business acumen and good communication skills were some of their top priorities. findings from student and recent graduate surveys show that students find clinical subjects to be more important for their career than business management skills (rhind et al., 2011) and, the teaching of practice and business management is one of the top underrepresented non-clinical topics in the veterinary curriculum. veterinarians however are concerned that they do not receive enough training in practice management and client communication, as well as working independently and practical/technical skills, during their time at university (jaarsma et al., 2008). when veterinary students were specifically asked about their interest in non-clinical subjects, kogan et al. (2005) showed that there are high levels of interest in the subjects of veterinary practice management and the fundamentals of management. these authors purely focus on ranking classes related to business management among veterinary students, they do not compare these to other (technical skills), whereas rhind et al. (2011) asked final year students and recent graduates which skills are considered to be ‘very important’. in follow-up interviews and focus groups the same study presents results suggesting the ranking of business acumen and knowledge of veterinary practice management should be higher. this suggests that business skills are perhaps not prominent in the minds of new clinicians, but they acknowledge that when advancing in the veterinary profession, they become more important. the limitations of these studies are that they represent the views of the students and employees, thus does not represent the skills employers’ value. furthermore, first year graduates are likely to be employees rather than being in practice management positions. repeating the survey after five or even 10 years in practice could provide a very different survey outcome. improving the way business skills are taught in vet schools another key theme, highlighted by lloyd and covert (2001), is the way business education is taught in veterinary schools in the us. it was found that a wide variety of course topics, such as marketing, personnel management, financial management, law and ethics and personal management were being taught, however there was very little agreement between schools about where the focus of veterinary practice management (vpm) courses should lie. it was highlighted that graduates from two different schools, despite both having to take at least one vpm module, could have very different learning outcomes. the authors suggest that educational priorities in practice management should be set from the perspective of experts in the field, that an outcomes assessment should be undertaken and that initiation of academic research programs in vpm should be initiated to provide a knowledge base for future educational programs. the approach of lloyd and covert (2001) assesses vpm as an ‘add on’ subject, rather than part of an integrated approach as advocated by henry and jackson (2015) and poon et al. (2014). these authors suggest that there is substantial evidence to support the importance of integrating, rather than inserting, business skills into the veterinary medical curriculum.  a number of methods to achieve this ambition have been outlined herein: teach business skills via student experiences in veterinary hospitals (poon et al., 2014) and ensure all teaching staff are sufficiently trained to mentor students and impart knowledge of non-technical competencies (including business) with students as-and-when required (lane and bogue, 2010). lane and bogue (2010) also highlight that while veterinary faculty share responsibility of teaching critical thinking skills, ethics, communications skills and interpersonal skills, almost half the faculty respondents did not perceive a responsibility to teach business skills. the interpretation of these results are twofold, on the one hand it could suggest that business skills are being taught by business lecturers and designated faculty members, and so others do not see the need to integrate these skills in their subjects, or it could be that business skills are not being prioritised within the curriculum. it does however clearly show that the approach taken by poon et al. (2014) to integrate business skills is unlikely to be the reality of business teaching. education beyond the classroom once in employment, adam et al. (2015) found that in order to retain farm animal veterinarians in practice, the following strategies need to be implemented in business: regular staff appraisals, having the support of an experienced veterinarian, especially in on-call situations, and improve job satisfaction amongst the new employees by better training and support of practice management staff. it is unclear if these findings are applicable to all veterinary practitioners, or if they are specific to farm animal veterinarians. similarly lloyd et al. (2005) suggest that cross training, staff development and other benefits, such as discounted animal health care are important factors of staff satisfaction of a veterinary teaching hospital. in the quest to develop a standardised business model for veterinary teaching hospitals the following key themes were identified: operationalising the mission, financial management, hr management, pricing, marketing, operations, legal and ethical issues and constraints to success. finally, some literature takes a broader view on business skills, than pure financial and client management, it takes into account emotional intelligence (timmis, 2006; lane 2010). this is often included as non-technical competencies, along with communication skills. timmins (2006) highlights the importance of emotional intelligence in veterinary medical education, especially for the field of companion animal medicine, with 85% of pet owners viewing their pet as a family member, with emotional intelligence potentially improving client satisfaction and compliance with therapy. discussion this paper is a literature review of evidence for the development of a veterinary business management curriculum.  it has described the evolution of business management in the veterinary curriculum and highlighted six key themes for curriculum managers to be aware of: a high demand for non-technical skills among the veterinary community the emphasis on communication non-clinical skills as a path to employment including business skills in the veterinary curriculum improving the way business skills are taught in vet schools education beyond the classroom perhaps a less-obvious theme to emerge from this work is the importance of first-opinion practitioners in shaping the views of future veterinarians in accepting business management education. evidence suggests that first-opinion practitioners strongly support the integration and business management into the veterinary curriculum but undergraduate students need encouragement to engage with this learning.  while the literature is abundantly clear on the importance of veterinary business education, few clues exist of how to operationalise this within the curriculum.  as a result, there is much scope for further investigation of this matter. the major limitation of this research is the paucity of recent, empirical findings on which to build an evidence base for developing a veterinary business management curriculum.  the structured literature search yielded numerous commentaries published in leading veterinary journals, such as the veterinary record, however these pieces were rarely based on empirical evidence, rather they were based on experience, opinion and conjecture. such papers may be an easy-read for practitioners and help them to engage in business issues but they are not helpful in developing an evidence base to draw upon for well-structured, well-researched guidance.  a further limitation is the absence of research about the advent of corporate veterinary practices in the uk.  in 1998, legislation changed to allow non-vets to own veterinary practices.  this change eventuated in an explosion of corporate veterinary businesses, which are often characterised as being run by people with acute business skills, rather than the traditional veterinary clinical skills. the consequence is that competition has increased with independent veterinary businesses finding it difficult to compete against commercially-savvy businesses that focus on cost-reduction, client relationship management, supply chain efficiency and overall systems optimisation. as with much of the literature on veterinary business management, there is a lot written about managing competition but we were not able to identify any empirical evidence. the final limitation to recognize herein is the omission of knowledge gained from the animal health economics literature. there are numerous overlaps between economics and business skills such as tools for optimising investment and decision making. this was recently highlighted by jackson et al. (2015) who reported on findings from the neat project (see: http://www.neat-network.eu/). these findings largely concur with the findings of the present literature review: that animal health economics (which includes using economics for general business management and understanding markets) needs to be better embedded into global veterinary curricula. to conclude, there is plenty of convincing evidence to suggest that veterinarians have identified a need for greater and more effective inclusion of business skills in the veterinary medical curriculum. however there are disparate opinions about what the term ‘business skills’ truly means. the consequence of this is that the fundamental requirements of establishing business teaching within a veterinary medical curriculum remain sketchy. evidence points to the idea that successfully integrating business skills into the veterinary medical curriculum will mean that students learn business principles in non-traditional, non-lecture-style environments with materials inter-twining with clinical teaching. this will mean a significant shift in the delivery of teaching materials and will need a great deal of acceptance from clinical teaching staff. that said, the evidence regarding the importance of business within the veterinary medical curriculum, coupled with increasing competition in the market for first-opinion veterinary services, means that changes in the approach to teaching business may be easier to achieve than ever before. conflict of interest the authors declare no conflicts of interest. references adam, k. baillie, s. and rushton, j. 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(2002) support needs of veterinary surgeons during the first few years of practice: perceptions of recent graduates and senior partners. the veterinary record, 150 (6), pp. 167-171. http://dx.doi.org/10.1136/vr.150.6.167 timmins, r. p. (2006) how does emotional intelligence fit into the paradigm of veterinary medical education?. journal of veterinary medical education, 33 (1), pp. 71-75. http://dx.doi.org/10.3138/jvme.33.1.71 volk, j.o. et al. (2011) executive summary of the bayer veterinary care usage study. veterinary medicine today, 238 (10), pp. 1275-1282. http://dx.doi.org/10.2460/javma.238.10.1275 intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. are sand or composted bedding cubicles suitable alternatives to rubber matting for housing dairy cows? a knowledge summary by mike steele bsc(hons), bvsc, mrcvs 1* 1inspire cattle solutions, granborough road, winslow, buckinghamshire, mk18 3bp uk *corresponding author (mike@dairyconsulting.vet) vol 3, issue 4 (2018) published: 31 oct 2018 reviewed by: nick bell (ma vetmb phd pgcert vet ed fhea) and jo hockenhull (bsc, msc, phd) next review date: 31 oct 2020 doi: 10.18849/ve.v3i4.148 pico question in [dairy cow management] do [sand or composted bedding] compared with [rubber matting] result in [fewer disease incidence] consequences? clinical bottom line clean, deep-bedded sand appears to be associated with the best outcomes in clinical mastitis, cow cleanliness, subclinical mastitis, cow lying times, hock lesions and cow preference. recycled sand, composted manure and other deep-bedded systems also appear to have increased cow comfort and hygiene indices versus mattress systems. deep-bedded, composted manure systems can also have better outcomes concerning gram positive and negative bacterial growth versus straw and mattress systems as long as they are kept clean and renewed frequently. clinical scenario many veterinarians are faced with dairy clients asking their advice for the best bedding medium to install in new housing upgrades for their indoor barns. of course, the advisor has to consider cost, practicality in suitable housing design and willingness of the client to pursue the ideal path. however, there are many outcomes to consider: “welfare” (which can have many facets), mastitis, skin lesions, lameness, optimum lying times as well as an economic and productivity benefit. producers also have to consider logistical practicalities in slurry handling and quality assurance issues: some milk processors will not accept recycled manure solids (rms) due to the risk of spore contamination of milk and there may be a risk of thermoduric bacterial growth in milk. there are relatively few examples in literature that address these questions and it will be useful to review the evidence before advising on specific guidelines. the evidence table 1: outline summary of bedding type by disease event and behaviour outcomes thi=temperature humidity index; bcs=body condition score; scn=streptococcus catalase negative; dim= days in milk; scc=somatic cell count; cns=coagulase-negative staphylococcus; imi=intra-mammary infection; se/sp=sensitivity/specificity; pcr=polymerase chain reaction; btscc=bulk tank somatic cell count; cfu=culture forming units rms: recycled manure substrate dbms=deep bedded manure substrate sbms=shallow bedded manure substrate nes=new sand rs=recycled sand summary of the evidence gao (2017) population: dairy cows and quarter milk samples sample size: 3190 dairy cows in 161 herds, 3288 quarter milk samples over a 2.5 year study period intervention details: sand or organic bedding materials (organic = compost, rice husk or saw dust) study design: case series outcome studied: clinical mastitis and culture results from each bedding type main findings (relevant to pico question): sand bedding was cleaned 3 times per day (during milking) to remove all organic materials. in general, fresh new sand was added to the bedding once per week, according to the bedding thickness mean herd cumulative incidence of clinical mastitis (cicm) was 3.3% per month in the herds and median cicm was 3.0% per month (range = 1.7 to 8.1 per herd) coli was most frequently isolated (14.4%), followed by klebsiella spp. (13.0%), cns (11.3%), strep. dysgalactiae (10.5%), staph. aureus (10.2%), and other streptococci (8.0%). enterobacter spp.,strep. agalactiae, and strep. uberis were isolated in 5.5, 2.8, and 2.1% of samples, respectively of 3,288 clinical mastitis (cm) samples, 1,750 were collected from herds using sand bedding, whereas 1,538 samples were from herds using organic bedding materials mean monthly cicm was 2.9 and 3.7% for herds using sand and organic bedding material, respectively. streptococcus dysgalactiae was more frequently isolated in herds using sand bedding than those using organic bedding, whereas klebsiella spp. and other streptococci were more prevalent in herds using organic bedding. limitations: restricted to farms in china much variation in management possible between farms and over time. mastitis outcome can be influenced by many other factors than bedding, so trends can be reported and associations but solid conclusions are tentative there are many seasonal and geographical environment factors that vary across such a wide region as china that may also affect mastitis outcomes culturing on agar may not always show growth of causative organisms no mastitis samples were recorded in february due to the spring festival guarín (2017) population: dairy cows housed indoors in wisconsin sample size: 128 primarily primiparous dairy cows, 32 cows in a 4 x 4 design intervention details: 4 types of bedding: new sand (nes), recycled sand (rs), deep bedded manure solids (dbms) and shallow bedded manure solids (sbms) on matting study design: cohort study outcome studied: udder cleanliness score (1-4) and teat hyperkeratosis score and teat culture main findings (relevant to pico question): the proportion of udders that were classified as clean (score 1 or 2) was 68%, 82%, 54%, and 95% for cows housed in pens containing nes, rs, sbms, and dbms, respectively no association was found between hk score and teat skin bacterial count. higher hygiene scores (dirtier teats) were associated with higher bacterial counts bacterial counts of teat skin swabs from front teats of cows in pens containing rs and sbms were significantly less than those of rear teats of cows in pens containing dbms or nes limitations: low population numbers mostly from primiparous cows manual observations may be subjective kayitsinga (2017) population: dairy cows sample size: survey to 1,700 dairy farms in michigan, pennsylvania, and florida in january and february 2013 intervention details: questionnaire study design: case series outcome studied: questions related to 7 major areas: sociodemographic and farm characteristics, milking proficiency, milking systems, cow environment, infected cow monitoring and treatment, farm labor, and attitudes toward mastitis and related antimicrobial use amount of antimicrobial drug use for clinical mastitis by intramammary or systemic administration main findings (relevant to pico question): use of sand or mattresses for bedding, rather than older styles of housing, were associated with decreased systemic antimicrobial use but also there is an association of less systemic use on higher managed farm types limitations: survey was only to grade a certified dairy farms, so may not be representative of the whole dairy population responses were dependent on farmer opinion and self-reported frequency of antimicrobial use there was a huge amount of variation in management practices across the surveyed population bedding use was only a very small part of the survey and was based on sand or mattress (not specific other bedding types) bedding associations based on multivariate regression analysis on low-level evidence foundation (survey and self opinion) black (2016) population: dry dairy cows sample size: 28 cows intervention details: n=14 in each group . sand (deep bedded) or pasture study design: cohort study outcome studied: accelerometer measuring steps and lying times, respiration rates and feeding displacement rates (studied for 2hours post feeding, once per week), thi from aug 2013 to jan 2014. bcs, locomotion and hygiene (overall cow cleanliness) all scored at 1-5. main findings (relevant to pico question): freestall housed cows lay down for 2 hours longer during far-off and close-up periods (p < 0.01; df: 76), but no differences occurred during calving and postpartum compared to pastured cows no difference in bacteria cultured from either group limitations: low cow numbers overproportion of primiparous cows (>60%) only studied in autumn/early winter feedspace per cow was 60cm in headlocks for indoor and free in pasture (lower than recommended 75cm in literature and possible for bullying in pasture system, potentially reducing feed intake) comparing sand and pasture, not bedding types in same system, so confusing results for general indoor management and pasture manual observations may be subjective rowbowtham (2016) population: lactating dairy cows in freestall pens sample size: 128 cows in 4 identical pens in one barn (n=32 cows per group) over 42 weeks. intervention details: each pen had either nes (new sand), rs (recycled sand), dbms (deep bedded manure solids), sbms (shallow bedded manure solids on mattresses) study design: cohort study outcome studied: bacterial culture of bedding teat swabs from one teat per cow from each cow, once a week, preand post-preparation for milking linear regression modelling main findings (relevant to pico question): the median number of total gram-negative bacteria in dbms was 13 times as great as the median number in sbms and 60 and 216 times as great as the median numbers in rs and nes not much difference between recycled and new sand in numbers of coliforms numbers of total gram-negative bacteria, coliforms, and klebsiella were significantly greater in the summer than in other seasons 12 times as many streptococci in shallow-bedded manure solids as in recycled sand across all bacteria and bedding types, the mean number of bacteria recovered from pre-milking swabs (cfu/swab) were approximately 2 to 3 logs less than the corresponding number of bacteria in bedding 4, 8, and 19 times as many total gram-negative bacteria recovered from cows bedded on sbms, rs, and dbms versus ns. post-prep swabs revealed less bacteria in all spp. and all bedding types coliform bacteria (escherichia spp., klebsiella spp., and enterobacter spp.) were only 2 to 7% of total gram-negative bacteria in bedding limitations: primarily primiparous cows (96 vs 15 multiparous) other cows entered the pens when cows ended their lactations rowbotham r.f., associations of selected bedding types with incidence rates of subclinical and clinical mastitis in primiparous holstein dairy cows (2016) population: dairy cows in lactation sample size: 109 cows for 12 months intervention details: primarily primiparous cows randomly assigned to pens containing freestalls with 1 of 4 bedding materials: (1) deep-bedded new sand (nes, n = 27 cows), (2) deep-bedded recycled sand (rs, n = 25 cows), (3) deep-bedded manure solids (dbms, n = 31 cows), and (4) shallow-bedded manure solids over foam-core mattresses (sbms, n = 26 cows) study design: cohort study outcome studied: incidence of subclinical mastitis (sm): >200k cells per quarter, sampled every 28 days from every quarter incidence of clinical mastitis (cm): abnormal milk appearance. all affected cases were cultured on agar main findings (relevant to pico question): the proportion of sm samples that were culture negative was numerically greater in quarters of primiparous cows bedded with nes and dbms as compared with those bedded with rs and sbms far fewer cases of cm were caused by gm –ve bacteria for primiparous cows housed in pens containing nes than in other bedding types majority of sm cases were cultured negative (71%), meaning that there was no association with cultured species and bedding type for sm. almost half of milk samples from cm cases did not result in the identification of a pathogen the overall incidence of cm was 0.26 cases/1,000 and was not associated with bedding types there was a tendency for longer survival times to first case of cm for quarters of cows in pens containing nes as compared with quarters of cows bedded with rs (p = 0.056) or dbms (p = 0.086) limitations: primarily primiparous cows (96 vs 15 multiparous) other cows entered the pens when cows ended their lactations time in pen for rs and dbms was significantly longer than ns and sbms groups bak (2016) population: lame lactating and dry dairy cows sample size: 42 obviously or severely lame cows (3 were dry) intervention details: 19mm thick rubber mattresses in freestalls or 30cm deep bedded sand. each cow spent 24 hours on one type and then 24 hours on the other. then they had access to both surfaces for a further 6 days and lameness scored at the end. concrete slatted flooring in aisles. study design: cohort, cross-over study outcome studied: scales were the experimenters’ own and defined in the methods section of the paper: lameness on 1-5 scale hoof lesions from trimming and manual id lying times and frequency of changing position cctv and manual observation main findings (relevant to pico question): for cows kept on deep-bedded sand, the total lying time, the number of cows observed to lie in the lateral position, and the frequency of lying bouts were higher than when kept on the rubber mats on sand, the lying time ranged from 28 min to 16 h, and while on rubber, it ranged from 6 min to 14 h the number of cows performing interruptions of lying down did not differ between the 2 surfaces, but while kept on sand, the cows lay down and got up faster than the rubber mats limitations: only 4 months of study and prior to this, cows were on loose housing. as lameness lesions take time to manifest clinically, this study cannot imply that bedding types reduce onset of lameness cows treated with medication including nsaid were excluded cows with sole haemorrhage and no other lesion were excluded cows that improved to lameness score 1 or 2 were excluded from the trial (10 cows in total excluded) manual observations may be subjective solano (2016) population: lactating dairy cows sample size: 5135 cows from 10-120 dim, 40 cows (sample) each from 141 farms across canada intervention details: lying behavior modelled using variables: bedding type, quantity (< or > 2cm depth) and cleanliness study design: case series outcome studied: automated accelerometer readings lying times lameness on 1-5 scale number of hock and knee injuries main findings (relevant to pico question): mean herd-level daily lying time ranged from 8.2 to 13.2 h/d and individual daily lying time for cows ranged from 1.3 to 22.1 h/d. daily lying time was associated with the same risk factors as the other measures of lying behavior bout duration was shorter for cows with injured hocks at the herd level, cows housed in stalls with sand had an increased average daily lying time of 1.44 h/d compared with cows housed in stalls with wood shavings limitations: logistic regression and multivariate modelling on many farm and management factors farms had to have >=7000l/lactation average so may not be representative of all farms in country lameness by manual assessment manual observations may be subjective cole (2016) population: lactating dairy cows sample size: 18 mid-late lactation, multiparous dairy cows intervention details: lorem ipsum dolor study design: fresh manure bedding vs recycled, composted manure bedding over 6 weeks, 3 weeks on each type of bedding in a cross-over study outcome studied: bacterial counts of mastitis pathogens present in bedding main findings (relevant to pico question): gram-negative bacteria, coliform, and streptococcal counts in rms windrows were reduced after 4 wk composting compared with counts in windrows before composting. klebsiella counts and dm did not differ composting recycled manure solids (rms) offered minimal advantages over fresh rms in reducing bacterial counts of common mastitis pathogens in bedding for dairy cows in freestalls limitations: low cow numbers multiparous cows only mid-late lactation cows (most studies report more lameness in early to mid lactation) jensen (2015) population: lame lactating and dry dairy cows sample size: 42 obviously or severely lame cows (3 were dry) intervention details: 19mm thick rubber mattresses in freestalls or 30cm deep bedded sand. each cow spent 24 hours on one type and then 24 hours on the other. then they had access to both surfaces for a further 6 days and lameness scored at the end. concrete slatted flooring in aisles study design: cohort, cross-over study outcome studied: scales were lameness on 1-5 scale (according to thomsen p.t., munksgaard l., togersen f.a., (2008), evaluation of a lameness scoring system for dairy cows, journal of dairy science, 91, 116-126) hoof lesions from trimming and manual id lying times and frequency of changing position cctv and manual observation main findings (relevant to pico question): the cows spent more time on the deep-bedded sand than on the rubber surface. on sand, cows spent the majority of the time lying, whereas on the rubber surface, they spent most of the time upright limitations: only 4 months of study and prior to this, cows were on loose housing. as lameness lesions take time to manifest clinically, this study cannot imply that bedding types reduce onset of lameness cows treated with medication including nsaid were excluded cows with sole haemorrhage and no other lesion were excluded cows that improved to lameness score 1 or 2 were excluded from the trial (10 cows in total excluded) manual observations may be subjective black (2014) population: compost bedded pack barns sample size: 42 barns with compost bedded pack systems (cbp) intervention details: correlation models with bacterial count as standard and outcomes as variables bacterial samples taken from 9 sites in each barn, cultured on agar study design: case series outcome studied: temperature, moisture, carbon-to-nitrogen (c:n) ratio, space per cow, and bacterial counts from bedding material collected from compost bedded pack (cbp) barns main findings (relevant to pico question): of the total bacteria sampled coliform, streptococci, staphylococci, and bacillus comprised 1.86%, 20.61%, 52.28%, and 25.25% of all bacteria, respectively coliforms and staphylococci measured a strong correlation with composite temperature (increasing with increasing temp.) and negatively with moisture managing the cbp system for moisture, temperature, c:n ratio, and space per cow may help to reduce some bacterial species counts, but the bacterial load in the bedding will likely remain high. limitations: many different stocking densities and management conditions between barns, especially concerning hygiene 32 barns were for lactating cows and 13 for hospital pens, so comparing healthy with sick cows may bring confounding variables ito (2014) population: lactating, high producing dairy cows sample size: total sample size 3160. 40 cows on each of 40 farms in the northeastern united states (ne) and 39 farms in california (ca) intervention details: lying time and frequency of bouts were correlated to management and bedding factors study design: cross sectional study outcome studied: lying times and lameness scores (1-5) correlated to: management measures, including stall design, bedding, and flooring type within the pen main findings (relevant to pico question): daily lying time decreased with increasing barn age and increased with the use of deep and sand bedding daily lying time decreased as stall stocking density increased, daily lying time increased in the presence of rubber flooring in part of the pen, pen space per cow, and the percentage of stalls with fecal contamination, frequency of lying bouts decreased and average bout duration increased with the use of deep and sand bedding limitations: all farms in the study were from a quality-assurance management program, of which 40 cows were chosen from each farm. as these were already on an assurance scheme, they may not be representative of usa population of dairy farms/cows. surveys retrospective study manual observation of lameness usa data, not canadian data collected in selected months (mar-may and jul-oct 2010) manual observations may be subjective adhikari (2013) population: in vitro study: inoculations of prototheca gt1 (mastitis causing) and gt2 (non-mastitis causing) in broth control or bedding material sample size: four bedding types were tested: kiln-dried spruce shavings, “green” (not kiln dried) hemlock sawdust, processed manure-pack, and sand as well as broth control. 3 samples taken per type. intervention details: growth of prototheca study design: in vitro study outcome studied: quantitative bacterial growth main findings (relevant to pico question): bedding type had a significant effect on prototheca growth in vitro, and this effect was associated with increased growth in manure, sawdust, and sand beddings. kiln-dried spruce shavings may inhibit prototheca growth limitations: in vitro only bedding samples taken from manufacturing sites and not dairies low sample numbers meant large error bars in results dufour (2012) population: lactating dairy cows sample size: 91 farms from 4 regions of canada. 15 cows from each farm. 3 milk samples were collected from each quarter of the selected cows at intervals of 3 wk for 2 years. total of 59,167 quarter samples collected farm observations questionnaire on farm management intervention details: scc and culture results vs farm management practices study design: farmer survey outcome studied: scc, culture, questionnaire and observation results on management practices of farm main findings (relevant to pico question): cns imi incidence of 0.29 new imi/quarter-month but this was 0.36 when misclassification (due to se/sp of culture and other factors) was considered use of sand or wood-based product bedding was associated with lower odds of acquiring a cns imi compared with straw bedding limitations: milk samples growing >3 types of bacteria were considered contaminated and excluded, meaning > 7,000 samples were excluded mastitis incidence is highly related to management practices and these varied between each farm, so multiple confounding factors were not taken into account lobeck (2011) population: lactating dairy cows sample size: 18 farms, 6 of each housing type, jan-nov 2008. 11,400 cows were scored each season across all farms intervention details: cross negative ventilated freestall barns – all deep sand (cv) and compost-bedded-pack barns – 5 wood sawdust, 1 wheat straw (cb), compared with conventional, naturally ventilated freestall barns (nv) study design: case series outcome studied: scales were the experimenters’ own and defined in the methods of the paper. locomotion (1-5 scale), hock lesions (1-3 scale), body condition score (1-5 scale), hygiene, respiration rates, mortality, and mastitis prevalence, culling and mortality rates main findings (relevant to pico question): no difference in lameness incidence or severity by each barn type compost-bedded barns had lower prevalence of hock lesions (3.8%) than cv and nv barns (31.2% and 23.9%, respectively) no significant differences between barn systems for mastitis, culling or mortality limitations: small region of usa manual observations are subjective in nature 4 visits in 9 months per farm respiration rates only measured in summer much variation in farm management types and sizes van gastelen (2011) population: lactating dairy cows sample size: 2927 cows on 24 farms with freestall systems in netherlands. 9 farms used box compost, 6 used sand, 6 used foam mattresses and 3 farms used horse manure as bedding material. feb-may 2010 intervention details: box compost, sand, horse manure, and foam mattresses study design: case series outcome studied: the way cows entered the stalls, the duration and smoothness of the descent movement, and the duration of the lying bout. the cleanliness of the cows was evaluated on 3 different body parts: (1) udder, (2) flank, and (3) lower rear legs (1-4 scale), according to the dutch udder health centre hock lesions (1-4 scale) according to rutherford k.m.d., langford f.m., jack m.c., sherwood l., lawrence a.b., haskell m.j., (2008), hock injury prevalence and associated risk factors on organic and nonorganic dairy farms in the uk, journal of dairy science, 91, 2265-2274 bacteriological counts of the bedding materials bacterial count in milk main findings (relevant to pico question): the percentage of cows having damaged hocks was lower on farms using box compost compared with farms using sand and foam mattresses no differences were found between the different types of bedding materials in all the cleanliness variables the lying bout tended to be longer when using horse manure vs foam mattresses. the first lying bout tended to be longer on sand vs mattresses or box compost less colony-forming units on sand vs box compost manual observations are subjective in nature limitations: only assessed in one season (spring) each farm visited once for 1 day westphal (2011) population: in vitro study sample size: cultures from samples of sand bedding from 1, 2500 cow dairy farm in ohio intervention details: growth and typing of e. coli o157:h7 found in sand bedding from: new sand, in-use sand, washed sand, recycled sand study design: in vitro study outcome studied: growth and types of e. coli o157:h7 main findings (relevant to pico question): median numbers of cfu in all types of bedding declined with time, suggesting that suppressive constituents of sand are not inhibited by processing during recycling heating to 80degc reduced counts of coli vs in-use and fresh sand ambient temperature affected non-heat treated sand contamination the heating process allows heat-sensitive microorganisms to suppress the e. coli limitations: only from one farm sand only and no comparisons with other types of bedding only cultured and studied e. coli o157:h7 dufour (2011) population: articles relevant to scc related to herd health management sample size: 36 manuscripts included in this study: the majority used a cross-sectional study design (n = 28) or a combination of cross-sectional and before-and-after designs (n = 6). one study used strictly a before-and-after study design  and only one study used a longitudinal cohort design intervention details: five databases (pubmed, medline, cab, agricola, and web of science) were searched on april 22, 2009 forest plots review study design: systematic review outcome studied: intervention studied was a management practice applied or observed at the herd level and used as an udder health control strategy; scc was measured using cell counting methods rather than california mastitis test (cmt) or rapid mastitis test mean 305-d milk production of the herds studied was ≥7,000 kg; and mean herd size of the herds studied was ≥40 milking cows main findings (relevant to pico question): freestalls had lower sccs than pasture and bedded pack sand > mattresses > decreased bedding moisture on their impact on decreasing scc manure packed systems had lower scc than other types (from one paper) limitations: focused on many other management practices and impact on scc rather than focusing on bedding type over time, technologies have allowed dairies to have better automated systems and recycling of bedding etc. so when reviewing articles, this has been a challenge to choose what has more weighting. gomez (2010) population: lactating dairy cows sample size: 205 cows in 16 freestall barns in wisconsin intervention details: rubber mattress or sand cubicles study design: case series outcome studied: continuous video surveillance collected the following data: time lying in the stall, time standing in the stall, time standing in the alleys (including drinking), time feeding, and time milking (time out of the pen for milking and transit) during a 24-h period were measured for each cow relationships of components of the time budget with herd-level and cow-level fixed effects main findings (relevant to pico question): lameness affected time feeding, with the greatest feeding times observed in non-lame cows as lameness severity increased, time standing in the alley decreased time standing in the stalls was greater in the mattress herds than sand herds cows in mat herds spent significantly less time lying, with shorter lying bouts than did cows in sand herds limitations: not randomised, small sample size not including summer (hot) data manual observations are subjective in nature lombard (2010) population: lactating dairy cows on a national management program sample size: 491 farms, 297 were holstein herds with cows housed in freestalls average of 96 cows per farm and a total of 25,358 cows intervention details: bedding type, bedding quantity, stall length and width, presence of a neck rail or brisket locator, and relevant distances from the rear and bed of the stall from mar 5 to sept 5, 2007 study design: case series outcome studied: hygiene and hock scores (1-3 scale) (up to 100 cows/herd), number of cows housed in the pen, the number of cows standing with only the front feet in a stall, standing fully in a stall, and lying in a stall main findings (relevant to pico question): rubber mats or mattresses as the stall base had a higher percentage of cows with severe hock lesions vs dirt base compared with farms with dirt base stalls, farms with rubber mats and mattresses had more cows standing fully in the stall 50% of cows were lying down on farms using sand bedding compared with 40% on farms using straw, sawdust, or dry or composted manure limitations: only herds on a national management program were selected, creating potential bias in the results questionnaire allows for subjective assessment >140 manual assessors, so high risk of subjective observations and opinions justice-allen (2010) population: barns sample size: 9 farms in utah. intervention details: samples of bedding taken from back third of 6-10 stall per pen and 6 areas of hospital pens sand from one dairy heat and chemical treated to see whether or not mycoplasma spp. survived study design: case series outcome studied: growth and identification (culture and pcr) of mycoplasma spp. main findings (relevant to pico question): mycoplasma was identified from bedding sand, dirt and recycled sand in 3 of the 9 farms and most samples from those farms mycoplasma appeared to survive in deep bedding samples for up to 8 months, peaking in cycles relating negatively to temperature and positively to moisture (deep samples were always moist) treatment with higher concentrations of disinfectants, 2% chlorhexidine and 0.5% sodium hypochlorite, eliminated 100% of mycoplasma from contaminated bedding sand limitations: only one pathogen studied farms mostly used sand with only a few on straw different pen systems investigated (stalls, pack and dry lots) norring (2010) population: lactating dairy cows sample size: 18 multiparous friesian cows on one farm intervention details: 3 types of bedding material: concrete, sand (particle diameter 0.1 to 0.6 mm), and soft rubber mats each group of cows was allowed to choose between 2 of the 3 different types of materials, rotating around all material types. they were allowed 10 days for preference testing after a 5 day enforcement period so they were used to all materials. study design: cohort study outcome studied: lying time as seen by observers from video footage main findings (relevant to pico question): cows were observed lying down more often on rubber mats than in concrete stalls no overall preferences observed between rubber mats and sand stalls or between sand and concrete-based stalls limitations: low population number cook (2008) population: lactating dairy cows sample size: 59 cows from 4 farms. non-lame, slightly lame or moderately lame cows (5 cows per category) intervention details: either rubber-crumb-filled mattress stall surfaces bedded with a small amount of sawdust (2 herds) or a pack mat design, which consisted of a rubber-crumb-filled mattress pad installed 5 cm below a raised rear kerb, bedded with 5 to 8 cm of sand bedding. study design: cohort study outcome studied: time-lapse video footage lying times and number of lying bouts time budgets for other activities main findings (relevant to pico question): cows on mattress stalls had significantly lower lying bout durations than cows on pack mat stalls stall standing time increased with increased lameness on all bed types stall standing for non-lame cows was longer in mattress stalls than pack mat (sand) limitations: small sample size for 3 groups of cows 4 farms mean management differences may affect results hard for observers to define slightly and moderately lame cows as separate groups norring (2008) population: lactating and dry dairy cows sample size: 52 cows, proportions of parities adjusted per group intervention details: kept on either straw bedded concrete stalls or sand stalls study design: cohort study outcome studied: resting time by video footage, cleanliness, hock injuries, and hoof health main findings (relevant to pico question): lying times and frequency of lying bouts on sand were longer and more frequent than straw there were no differences in the dirtiness of stalls between the materials cows housed on straw were dirtier than those on sand the severity of hock lesions was lower for cows on sand than for cows on straw though not the incidence (no difference) overall hoof health was greater for cows on sand limitations: small sample size leg and hoof injuries inspected only at beginning and end of experiment (1-2 years in between) godden (2008) population: culture samples of bedding from lactating dairy cow barns sample size: 71 samples from 49 farms intervention details: clean sand (cs), recycled sand (rs), digested manure solids (dms), shavings (sh) were sterilized and inoculated with klebsiella pneumoniae and enterococcus faecium, and incubated at 37degc for 24, 48 and 72 hours study design: cohort study outcome studied: bacterial growth nutrients within bedding types main findings (relevant to pico question): for pneumoniae, peak growth occurred within 24 hours in all types of bedding and was stationary afterwards for growth of pneumoniae, the order was as follows: cs < sh < rs < ds for enterococcus, growth appeared to decrease over the 72 hours in all types, decreasing greatest in shavings growth of faecium was greater in rs and ds than growth for cs or sh ph in bedding types: ranging from lowest to highest as sh (4.27) < cs (8.15) < rs (8.37) < ds (8.90) high carbon or ph may be associated with better conditions for bacterial growth limitations: only two species of bacteria studied wenz (2007) population: dairy farms across all usa sample size: of 3876 questionnaires sent out, 3466 were completed, with 1013 completing a further questionnaire and 741 able to collect milk samples and provide bulk tank scc intervention details: questionnaire on farm management and btscc study design: case series outcome studied: bulk tank scc (btscc) at <200k cells/ml, 200-400k, > 400k main findings (relevant to pico question): twenty-six percent and 17.8% of operations reported a btscc <200,000 cells/ml and >400,000 cells/ml, respectively farms with >500 cows and higher milk production than 9000kg/cow 305d lactation had lower btscc values mattress, sand and newspaper bedding were associated with lower btscc. composted manure was associated with higher btscc limitations: herds in national monitoring scheme so may have included bias to better managed herds questionnaire method increases risk of subjective assessment kristula (2005) population: bedding samples from dairy farms in usa sample size: 6 farm samples used for cs and 6 for rs in winter 4 samples for rs and 7 for cs in summer samples taken for 6-8 days, twice intervention details: samples taken from clean sand (cs) or recycled sand (rs) study design: cohort study outcome studied: the number of colony-forming units per gram of bedding of gram-negative bacteria, coliforms, streptococcus spp., and klebsiella spp. were estimated for each sand sample dry matter and organic matter were also assessed main findings (relevant to pico question): rs and cs had the same bacterial counts when compared at any sampling time (winter or summer) cs had higher dm than rs in winter and summer rs had higher organic matter than cs in winter and summer limitations: paper not clear whether the same farms were chosen to compare winter and summer samples (suspected that they were not as different numbers of farms were used) huge variations in types of bacteria by farm indicate large variations by facility cook (2005) population: lactating dairy cows sample size: 12 herds of 150-450 cows were observed but 6 herds using mattresses and 6 herds using sand were chosen for lameness and lying time observations. 602 cows in total were observed with 304 on mattresses and 298 on sand. intervention details: sand or rubber crumb filled mattresses. study design: cohort study outcome studied: number of cows that were lying down in a stall, standing in a stall with all 4 feet, standing in a stall with the rear 2 feet in the alley (perching), and standing in the alley drinking and feeding were recorded main findings (relevant to pico question): lameness prevalence in mat herds was more than 3 times that observed in sand herds no significant difference was found between cow comfort indices and lying times in different systems limitations: herds representative of local area but not of usa variations in stocking density were identified across the sample population variations in lameness across herds may have affected lying times drissler (2005) population: lactating dairy cows sample size: 24 cows in 2 groups of 12, each with 12 freestalls intervention details: sand depth of cubicles in time study design: cohort study outcome studied: lying time, number and length of lying bouts and sand depth main findings (relevant to pico question): over time, the stall surface took on a concave shape, and bedding depth was lowest at the center of the stall and highest at the edges. the loss of bedding was greatest after new bedding was added, and sand levels continued to decline during the entire 10-d period for every 1-cm decrease in bedding, cows spent approximately 11 min less lying during each 24-h period duration of lying bouts was shorter when the stalls contained less sand limitations: small sample size different observers may show inconsistencies in results zdanowicz (2004) population: lactating dairy cows sample size: 16 lactating holstein cows intervention details: housed on either sand or sawdust-bedded free stalls using a crossover design with 3 weeks per bedding type study design: cohort study outcome studied: bacterial count and culture on teat ends and bedding main findings (relevant to pico question): there were 2 times more coliforms and 6 times more pneumoniae bacteria on teat ends of cows housed on sawdust compared with those housed on sand there were 10 times more streptococcus bacteria on teat ends of cows when housed on sand compared with sawdust udder cleanliness was no different on either bedding type there was no clear relationship between teat end counts and bedding counts limitations: small sample size jayarao (2004) population: lactating dairy cows sample size: 126 dairy herds surveyed in pennsylvania state intervention details: questionnaire on farm management practices study design: case series outcome studied: bulk tank scc (btscc) and bacterial culture modelled against questionnaire answers main findings (relevant to pico question): fifty percent of the btscc samples had a btscc <348,000 cells/ml btscc samples > 200,000cells/ml were 5 times more likely to have a high cns (coagulase negative staphylococcus) count sand as bedding had significantly lower btscc in their btscc compared with organic bedding such as shavings, newspaper, and straw limitations: farms restricted to nmc milk testing program (therefore may be biased to better management systems) producers that used sand (quite innovative in 2004) may have had better management practices than older-style bedding, indicating that sand itself may not be better than other bedding materials cook (2004) population: lactating dairy cows sample size: 12 herds of between 150-450 cows each, producing > 9545kg/cow average intervention details: deep sand bedding or rubber mattress with organic bedding material covering study design: cohort study outcome studied: lying times, time per lying bout, lameness (1-4 scale), video footage main findings (relevant to pico question): there was no significant difference in time lying down in stall time standing in stall was significantly lower in sand cubicles cows in sand herds had a significantly greater proportion of long lying bouts than did cows in mattresses lame cows stand for longer in stalls than healthy limitations: selected herds with high production and potentially better management than overall population manual observations may be subjective wagner-storch (2003) population: lactating dairy cows sample size: 104 cows housed in one barn at 100% stocking density. 961 observations of stall usage over a period of 9 months in 2001 intervention details: rubber mattresses, waterbed, concrete + sawdust, sand, around 25 of each type in mixed positions in barn study design: cohort study outcome studied: video footage time budgets main findings (relevant to pico question): preference was sand > mattress > waterbed > concrete cows spent more time lying in sand but more time occupying rubber mattresses (standing in them) limitations: cows had no prior time to get “used” to the bedding types at 100% stocking, some cows had no choice on cubicles and lower social hierarchy cows may have been forced to lie on worse bedding some cows may have visited multiple types of bedding so modelling lameness of lesions would have been affected a robot milked herd, so position of bed in relation to robot may have confused the data manual observations may be subjective hogan (1989) population: lactating dairy cows sample size: 9 farms of 60-200 cows per farm for 1 year intervention details: mattresses with sawdust, straw or sand/crushed limestone cubicles study design: cohort study outcome studied: bacterial counts from bedding materials main findings (relevant to pico question): bacterial counts in organic materials (sawdust, straw) were higher than inorganic (sand) materials klebsiella counts were higher in sawdust vs straw streptococcal counts were higher on straw than sawdust gram –ve counts were higher in summer limitations: herds were selected with lower incidence of aureus and strep. agalactiaea mixed breeds: 8/9 farms had holsteins, one had jerseys. there may be breed preferences due to cow size vs stall size. carroll (1978) population: lactating dairy cows sample size: approximately 800 cows on one farm in california intervention details: fresh or used recycled manure bedding study design: case series outcome studied: bacterial counts from bedding klebsiella and enterobacter, citrobacter and coliform spp. cultured main findings (relevant to pico question): composting manure (when fresh) effectively reduces the coliform counts to near zero when the manure becomes moist and warm, these counts can return to levels found on contaminated bedding. limitations: samples only from one farm and unknown over which period only klebsiella and enterobacter spp. measured fulwider (2007) population: lactating dairy cows sample size: 90,162 from 113 farms in usa intervention details: the bedding materials most commonly used by waterbed and mattress dairies included sawdust, rice hulls, chopped straw, or lime. five free-stall dairies reused (recycled) sand, whereas all others bedded with new sand study design: cohort study outcome studied: hock and leg skin lesions cow hygiene (1-5 scoring system) from reneau j.k., seykora a.j., heins b.j., endres m.i., farnsworth, r.j., bey r.f., (2005) association between hygiene scores and somatic cell scores in dairy cattle, journal of american veterinary medical association, 227, 1297-1301 main findings (relevant to pico question): cows on mattress systems and waterbeds had higher skin lesion scores than sand bedding cows on mattress and waterbed systems had lower hygiene scores than sand bedded systems limitations: no dairies used recycled manure or digester solids average herd size was high (>800 cows) and milk production high, so management practices may have been biased towards better, more efficient systems subjective, observer based scoring systems de palo (2006) population: lactating dairy cows sample size: 44 cows in total: 8 cows (preference test). 36 cows (4 groups of 8) for aversion test intervention details: polyethylene (eva) or polypropylene (pva) mats with wood shavings or manure solids study design: cohort study outcome studied: bed occupation time of the free stalls per day; average duration of each lying event per day; duration of periods spent standing in the free stall, with 2 or 4 feet per day (respectively); number of interrupted attempts at lying down per hour ; mean duration of a single lying bout in minutes; and time spent ruminating in the free stall, during the lying down time per day. cow hygiene milk bacterial count main findings (relevant to pico question): cows appeared to occupy the eva mats more than other types lying times decreased with increasing temperature-humidity index (thi) in eva mats cow comfort index showed greatest consistency over all thi recordings with wood shavings cows tended to stand more, rather than lie, in mattresses, especially the pva type limitations: very small sample number may be some bias from company selling eva mattresses as results tend to differ significantly from other literature reports (lying times on sand and manure vs. mattresses) calamari (2009) population: lactating dairy cows sample size: 56 cows intervention details: straw bedded pack (st), rubber mat (rm), mattress (ma) and sand (sa) study design: cohort study outcome studied: lying times and frequency/length of lying bouts milk yield and milk bacterial count main findings (relevant to pico question): more time was spent lying on sand and straw yard than mattresses time of lying bout was no different between bedding types mattress stalls were used for standing and sand for lying greater milk yield in sand vs mattress bedding manual observations may be subjective limitations: small sample population eckelkamp (2016) population: lactating dairy cows sample size: 50 cows per farm for scoring and scc for whole herd. 15 farms, 8 compost pack and 7 sand intervention details: compost bedded pack (yards) and sand cubicle barns study design: cohort study outcome studied: herd clinical mastitis, scc, high scc prevalence (% of herd >200,000 cells/ml scc), and btscc), locomotion, hygiene, and hock scores main findings (relevant to pico question): no differences between 8 compost and 7 sand bedded farms, based on clinical mastitis, scc, herd locomotion, hygiene score, or hock health limitations: only 50 cows per farm scored observer, subjective scoring rudd (2010) population: lactating dairy cows sample size: 1923 farms, 29,326 lactations for milk yield distributed over 363 free-stalled herds in norway.  the study uses a 305 day lactation as the focus: yield volume and bedding type as variables, so cow number is not relevant to this data mining exercise: one cow may live for 3 lactations and each is considered a single investigative point against the variables. intervention details: questionnaire filled in by producer on management and stall covering: 1 = concrete, softness of 0 mm; 2 = rubber, softness of 1 to 8 mm; 3 = soft mats, softness of 9 to 16 mm; 4 = multilayer mats, softness of 17 to 24 mm; 5 = mattresses, softness over 24 mm study design: case series outcome studied: milk yield by flooring type main findings (relevant to pico question): herds on concrete free-stall bases yielded 6,727 ± 146 kg of milk from 5 to 305 days in milk. in comparison, herds showed a decrease of 0.3% on rubber, an increase of 2.4% on soft mats, an increase of 4.5% on multilayer mats, and an increase of 3.9% on mattresses compared with concrete, the hazard ratio of teat lesions was less on rubber, soft mats, multilayer mats, and mattresses limitations: farmer-lead, subjective questionnaire milk yields modelled using woods equation rather than actual data farms with lower yields may have genetic and breed differences, affecting both production and locomotion adams (2017) population: lactating dairy cows sample size: 191 dairies, 22,622 cows in 17 states of usa intervention details: farm visits by trained personnel to assess lameness and hock lesions and bcs study design: case series outcome studied: bcs, locomotion and hock scores (1-3 scale) main findings (relevant to pico question): 4% cows were sound (locomotion score=1), 6.9% were mild/moderately lame (locomotion score=2), and 2.7% were severely lame (locomotion score=3). 3%) had no hock lesions (hock score=1), 10.1% had mild lesions (hock score=2), and 2.6% had severe hock lesions (hock score=3) 2% were bcs <=2.25 on a 1-5 scale lower locomotion scores (2 or lower) were associated with larger operations, pasture and sand stalls vs straw, compost or matting lower hock scores were associated with dry lot systems limitations: multiple assessors using subjective scoring systems but trained to single scoring system jones (2017) population: lactating dairy cows sample size: 97 cows in a freestall barn intervention details: 46 cows in dual chamber waterbeds and 51 cows on rubber mattresses study design: cohort study outcome studied: milk yield, lying time, rumination time, hock scores main findings (relevant to pico question): greater lying times and lower hock scores were associated with waterbed mattresses rumination time was greater on rubber mattresses milk yield was not significantly different between the two systems limitations: small cow numbers unable to determine whether or not conflicting interests are present upadhyay (2017) population: lactating, indian cross-bred dairy cows sample size: 24 cows in 4 groups of 6 intervention details: concrete floor (covered feeding area) and brick paved (open) concrete (covered feeding area) and sand bed (open) rubber mat (covered feeding area) and sand bed (open) rubber mat (covered feeding area) and brick paved (open) study design: cohort study outcome studied: lameness (1-5 scale) walking speed main findings (relevant to pico question): walking speed was greater in sand bedded groups lameness score was greater in brick paved groups, with greater severity also limitations: very small group numbers conclusions made from underpowered findings subjective scoring scale burgstaller (2016) population: lactating dairy cows sample size: 498 datasets from 10 barns, 201 (5 barns) in compost bedded yards and 297 (5 barns) in cubicles intervention details: compost bedded yards or cubicle barns study design: case series outcome studied: lameness score and severity claw lesions score and severity main findings (relevant to pico question): no significant differences in locomotion between different types of bedding material, flooring system, breed, visit number, observer and time since last trimming statistically significant differences in the prevalence of claw disorders between compost bedded and freestall cubicle barns were found for white line disease (wld; 20.4% and 46.6%, respectively), heel horn erosion (hhe; 26.9% and 59.9%, respectively), concave dorsal wall as a result of chronic laminitis (6.5% and 15.9%, respectively) and for interdigital hyperplasia (0.2% and 3.1%, respectively) limitations: subjective scoring systems comparing bedding types when flooring systems would differ and barn design may have influenced the study outcomes (whether or not there were sharp turns, steep grades, flooring flaws etc.) lim (2015) population: lactating dairy cows sample size: 3691 cows from 76 farms intervention details: cubicles with concrete base and whole straw or rape straw bedding compared with cubicles with concrete bases with sand or chopped straw bedding study design: case series outcome studied: farm data analysis hair loss on lateral aspect of hock (using hock map), hock lesion (score) and lameness (score) bcs, milk yield, duration of housing /td> main findings (relevant to pico question): cows on concrete based cubicles with sand or chopped straw-based bedding had lower hair loss on hock than those on concrete with whole straw/rape straw dressing cows on concrete based cubicles with sand or chopped straw-based bedding had lower hair loss on hock than those on mattresses with whole straw/rape straw dressing limitations: purpose of the paper was to compare the hock map versus the scoring system for analyzing hock lesions rather than the bedding material itself astiz (2014) population: dry cows sample size: 423 holstein dry cows on one farm intervention details: compost bedded loose-yard compared (242 cows) to straw bedded loose yard (181 cows) study design: randomised control trial outcome studied:   dairy data records: milk yield, pregnancy after first insemination (p/fai), somatic cell counts (scc), incidence of clinical mastitis, incidence of metritis and cytological endometritis, and mortality/culling rate main findings (relevant to pico question): no differences in mortality, fertility parameters or uterine health lower clinical mastitis rates in compost bedding cows yielded avg. 760kg more milk in the first 100dim from the compost bedded system limitations: higher milk yield could be double-counted from the lack of mastitis (therefore less dumped/future milk losses) milk yield error limits crosses over between the two bedding types, making the result less significant low numbers to get sufficient power for good conclusions on yield and fertility parameters (altering things in the dry period are a long way in time from getting cows pregnant and many other factors can influence the outcomes, so making conclusions would be extremely difficult) eckelkamp (2014) population: lactating dairy cows sample size: 10 cows intervention details: freestall barn with pasture access transitioning to compost bedded loose-yard study design: case report outcome studied: lying times by activity monitor main findings (relevant to pico question): hours of lying were longer on compost than freestalls sound cows and lame cows lay for the same times on compost but sound cows lay longer than lame cows in freestalls. limitations: very small numbers many environmental changes if going from freestall + pasture to compost, loose-housing. feeding areas, water access, design of barn, heat abatement could all affect outcomes cows were on the freestall system for 495 days and compost for 132 days chapinal (2013) population: lactating dairy cows sample size: 79 farms (unknown number of cow records) intervention details: lameness scoring and relationships between management systems and housing study design: case series outcome studied: lameness (1-5 scale) dairy software records main findings (relevant to pico question): severe lameness increased with the percentage of stalls with fecal contamination and with use of sawdust bedding, and decreased with deep bedding, sand bedding, herd size, and rearing of replacement heifers on site as well as frequency of manure removal in the pen per day deep bedding and sand were highly correlated as most systems used both on the same site. limitations: subjective scoring by multiple assessors modelled data from records mitev (2012) population: lactating dairy cows sample size: 36 cows intervention details: rubber mats, manure-straw bedding and sand study design: cohort study outcome studied: preference to bedding type hygiene (cleanliness score) lying times main findings (relevant to pico question): lying times and number lying down were longer on matting than manure straw bedding and sand limitations: very small cow numbers no information on heat abatement, as this could have affected lying times (thin, rubber matting may be cooler than manure or sand). turkey has a climatically high thi. kara (2011) population: lactating dairy cows sample size: 709 cows from 39 herds intervention details: concrete, sand and rubber mattress bedding in freestalls and tie-stalls study design: case series outcome studied: lameness score main findings (relevant to pico question): there were no significant differences between mean of locomotion scores on concrete, sand or rubber bedding in this study limitations: subjective scoring system varying herds with very variable environments and management systems comparing bedding types with more than one barn type (freestall and tie-stall) means that it is difficult to make conclusions with so much variation shane (2010) population: lactating dairy cows in minnesota sample size: 6 dairy farms (unknown number of cows) intervention details: all farms have compost bedded pack but used as a substrate either sawdust wood chips, flax straw, wheat straw, oat hulls, straw dust, and soybean straw study design: case series outcome studied: organic and inorganic composition of bedding bacterial contamination of bedding lameness, bcs, hock lesions and hygiene main findings (relevant to pico question): bedding pack material averaged 15.8% for total c, 0.93% for total n, 17.8 for c:n ratio, 37.3% for dry matter, 8.83 for ph, 4.25 mg/kg for nitrate, 955 mg/kg for ammonium, 15 g/kg for total potassium, 2.8 g/kg for total phosphorus, 8.5 ds/m for ec, 31.7 degrees c for pack temperature, 7.6 degrees c for outside temperature, and 9.42 million cfu/ml for total bacterial counts in the bedding all types of substrate were considered suitable but regular tilling and replacing were recommended limitations: no information on cow factors doherr (2007) population: lactating dairy cows sample size: 970 cows on 120 farms (60 organic and 60 conventional) intervention details: rubber mat/concrete beds or “otherâ€� study design: case series outcome studied: subclinical mastitis risk factors california milk test (cmt) main findings (relevant to pico question): decreased odds ratios for subclinical mastitis were found on farms using systems other than rubber mat/concrete beds limitations: authors admitted that many of the associated factors and odds ratios were likely to be related to system management variation between farms rather than the factors in the paper themselves. espejo (2006) population: lactating dairy cows in minnesota sample size: 5,626 cows in 53 high-production groups intervention details: freestall herds with sand stalls and freestall herds with mattresses study design: case series outcome studied: records from dairy software lameness score (1-5 scale) main findings (relevant to pico question): the mean prevalence of clinical lameness was 24.6% prevalence of lameness in parity one averaged 12.8% and increased by 8 percentage points each parity. lameness was lower in freestall herds with sand stalls (17.1%) than in freestall herds with mattress stall surfaces (27.9%) limitations: lameness scored by multiple assessors and a subjective system tucker (2003) population: lactating holstein dairy cows sample size: 12 cows were housed individually in separate pens intervention details: each pen contained three free stalls with a different surface: deep-bedded sawdust, deep-bedded sand, and a geotextile mattress covered with 2 to 3 cm of sawdust study design: cohort study outcome studied: preference was determined, based on lying times main findings (relevant to pico question): of the 12 cows used in experiment 1, 10 preferred sawdust before and nine after the restriction phase. during the restriction phase, average lying times and number of lying events during the restriction phase were significantly lower for the sand-bedded stalls (p<=0.05), and standing times were higher on mattresses (p<=0.05), compared with sawdust after restriction, half of cows preferred sawdust and half sand. limitations: all cows had been housed on sawdust for their previous lactation (although they were given experience of all types of bedding before the experiment) very small population number manninen (2002) population: lactating dairy cows sample size: 44 friesian cows, 24 in winter and 20 in summer intervention details: experiment 1: concrete with large amount of straw, soft rubber mat with a thin layer of straw and sand (2-3 mm) without straw experiment 2: 2cm deep rough or fine sand study design: cohort study outcome studied: preference (occupation of cubicles of different types and lying times) observed by video main findings (relevant to pico question): lying times were shorter and fewer lying bouts were observed on sand than on either straw or rubber matting in experiment 1 in winter, cows preferred to lie on straw rather than rubber matting when forced to lie on sand, cows had no preference to either rough or fine sand or lying in the concrete alleyway. limitations: before the experiment, all cows were housed on rubber matting covered with peat and straw, so some may have had previous preferences very small population numbers stocking density was different in winter (100%) to summer (50%) sand layer was 20cm deep which seems low compared with other papers reviewed in this knowledge summary manual observations may be subjective weary (2000) population: lactating dairy cows sample size: 1752 cows on 20 farms intervention details: prevalence study on hock lesions from sawdust, sand, and geotextile mattresses study design: case series outcome studied: hock lesions by scoring and severity scoring main findings (relevant to pico question): 73% of cows had at least one hock lesion 91% cows had lesions on mattresses 24% cows had lesion on sand limitations: subjective scoring methods only 4 farms out of 20 had sand, 10 on mattresses and 6 on sawdust, with 185/1752 cows on sand. hayasaka (2000) population: lactating dairy cows sample size: 15 cows on 16 cubicles intervention details: preference study comparing soil or rubber chip mattress bedding with hardness of 90 vs 52 respectively on a rubber hardness tester study design: cohort study outcome studied: lying time and number of lying bouts on video main findings (relevant to pico question): cows on matts had longer lying times with more frequent bouts of lying cows on matts had lower standing times and less time spent eating than soil based bedded cows manual observations may be subjective limitations: very low sample numbers gamroth (1992) population: bacterial growth of coliforms sample size: bacterial samples grown from bedding materials intervention details: growth of coliforms on days 0, 2, 5, 8 and 11 on dried wood sawdust, composted washed manure solids (cs), chopped ryegrass straw, and shredded paper covering gypsum wall board in freestalls under farm conditions, then: treating recycled manure solids with hydrated lime, copper, zinc and germicide to control coliform growth study design: case series outcome studied: coliform growth on untreated and treated bedding main findings (relevant to pico question): coliform growth on all types of bedding materials reached faecal output levels within 2 days. treatment of bedding with any of the applied materials did not affect bacterial growth in the bedding material limitations: growth from coliforms only brim (1989) population: bacterial growth of bedding material samples sample size: growth of bacteria from samples intervention details: growth on samples of following types of bedding materials: sand, 12-mesh limestone and treated with pine disinfectant, oat straw and cedar sawdust. mulched newspaper study design: case series outcome studied: bacterial growth main findings (relevant to pico question): sand, limestone (including treated) both had significantly higher growth after 6-54 hours incubation than organic bedding (straw, sawdust, newspaper). organic materials (sawdust, newspaper and straw) showed bimodal growth patterns, declining at 30-54 hours and increasing again beyond inorganic levels after 96-120 hours limitations: unknown which bacteria grown and what season, temperature, humidity and levels of contamination beforehand. from table 3, it is inferred that there were 10 samples taken from unused pens and 30 from used, totaling 40 samples but this was for e. coli specifically. the paper is not clear on methodology how many samples were taken for all bacterial species. appraisal, application and reflection at the point of writing, the most recent report from united states dairy association (usda) shows the following proportions of bedding materials used on us dairies: sand (45%), sawdust (21%), straw (14%), and manure (7%) are the 4 most common bedding materials in us freestall barns, with 87% of freestall barns using these bedding types (usda, 2008). no more recent evidence is available at the time of publication. from the evidence reported here, 34 publications originate from the usa, compared with 7 from canada, 3 from finland, 2 each from italy, netherlands, uk and denmark and 1 each from austria, norway, india, turkey, czech republic, japan and china. the majority of research has been concentrated on the bedding systems of lactating dairy cows, with only 3 publications specifically mentioning dry cow accommodation. levels of evidence have ranged from one systematic review (dufour s. 2012) through a majority of cohort studies to many case series and one randomized control trial. as farm management practices and observers can vary from one site to another, there has been potential for subjective errors in input data in most of the papers reviewed.  efforts in multivariate regression modelling and analysis of statistical data has led many authors to attempt to reduce this in many cases. scoring systems for lameness, cleanliness, skin lesions and teat cleanliness have all been assessed on subjective observation systems. attempts have been made to mitigate subjective errors by using consistent guidelines to the assessors or using one single assessor have often been explained in the methodology of each paper. evidence for bedding material and associations with mastitis outcomes reported in the reviewed papers have covered many aspects of mastitis, including clinical incidence, subclinical incidence and bulk tank somatic cell counts, udder cleanliness, teat cleanliness, bacterial culture of milk and teats and bacterial culture/pcr analysis of bedding material. the following general observations can be made from the reviewed studies that can support the clinical bottom line: clinical mastitis incidence was lower in herds bedded on deep sand, freestall systems (dufour s. 2012)(gao j. 2017) (rowbowtham r.f., 2016). lower somatic cell counts and bulk tank somatic cell counts have been reported in clean sand, recycled sand (wenz j.r. 2007)(jayarao b.m. 2004), mattresses (f. a. dufour s. 2011) (wenz j.r. 2007), manure (dufour s. 2011) but higher scc in composted manure (wenz j.r. 2007). such variations in results reflect the enormous variation in potential for management differences farm by farm. many of these papers obtained their information from farm questionnaires on stall management and farmers may not be accurately reporting frequency of cleaning, renewal frequency of bedding, stocking density, cow cleanliness, parlour routines and many other aspects. the only objective measurement in these studies was the btscc or scc values obtained from the dairy records. at the time of writing, many geographical regions are reporting a requirement to reduce the use of antimicrobials on farm. only one paper has reported a reduction in the use of antimicrobials on sand systems specifically (kayitsinga j. 2017). however, it may be prudent to point out that this may not be caused by the use of sand but merely associated with farms that use sand (these farms may be more innovative or better managed generally than farms using other types of bedding). cows have been reported to have lower cleanliness scores on sand systems (cleaner cows) (guarín j.f. 2017) (fulwider w.k. 2007) than straw (norring m. 2008). considering microbial contamination, many papers have studied the growth of bacteria in bedding materials, the relationship between dry matter and moisture content in these materials in different seasons and cultured bacteria on teats or in milk. from these, some general consistencies can be found: less bacterial counts have been reported from inorganic (sand/crushed limestone) bedding material versus organic (straw, manure) (hogan j.s. 1989) (godden s. 2008). more bacterial counts have been found on teats on mattress systems versus sand (zdanowicz m. 2004) and lower counts found on clean, new sand versus manure (guarín j.f. 2017) (rowbowtham r.f., 2016),(van gastelen s. 2011). however, two reports found no differences in bacterial growth on bedding media types (black r.f. 2014) (rowbowtham r.f. 2016). heat treating or composting sand or manure have been found to reduce contamination in two studies (cole k.j. 2016)(westphal a. 2011) the dry matter content and amount of organic material in the bedding as well as moisture have been found to affect bacterial growth within bedding of all types, so summer conditions appear to favour growth (rowbowtham r.f., 2016). when it comes to specific bedding types and their associations with specific bacterial species, associations have been found between increased streptococcus spp. in manure and sand systems vs. more coliforms and klebsiella found in straw, manure and sawdust systems (rowbowtham r.f., 2016)(zdanowicz m. 2004) (carroll e.j. 1978) (godden s. 2008).. it is worth mentioning that fresh versions of any bedding material can easily support higher bacterial growth with increasing time of usage in the barn (carroll e.j. 1978). this is supported by (gamroth m.j. 1992) who showed that bacterial coliform levels on bedding equaled fecal output within 2 days and treatment with inorganic compounds in an attempt to delay this did not reduce further bacterial growth in bedding. an attempt has been made to associate higher milk yields to softer flooring types but the data inputs were not reliable enough for convincing results (too much possibility for variation between farms and management practices to confidently predict differences by bedding type alone) in the author’s opinion (calamari l. 2009)(rudd l.e. 2010) (astiz s. 2014) evidence for associations between bedding types on cow comfort and lameness when considering a subject such as “welfare” and cow comfort, it is difficult to actually define a measurement that can reflect a true picture of cow welfare. because of this, the focus of this knowledge summary has been on comparisons of objective observations between bedding types and such variables as lying times, frequency and length of lying bouts, hock lesions, time spent standing in stalls and preference testing. the following general observations can be made from the reviewed literature: in preference tests, cows appear to choose bedding types in the following order: sand > mattresses > waterbeds > concrete/straw (wagner-storch a.m. 2003) with one paper showing no difference between sand and mattresses but mattresses are preferred to concrete/straw (low sample numbers) (norring m. 2016). one preference test in finland showed strong preferences to mattresses over sand but it is worth mentioning that the cows were used to mattresses before the trial and sample population was very small (manninen e. 2002). sand-bedded systems appear to have fewer lame cows (cook n.b. 2005), (cook n.b. 2004) although as mentioned before, this may be biased by farms with higher production/better management. however, multivariate analysis has attempted to account for this and results have been consistent among observations. time spent lying in stalls is increased in sand bedded systems versus others, with increased length of time of the first lying bout also (bak a.s. 2016)(solano l. 2016) (jensen m.b. 2015) (cook n.b. 2004) (ito k. 2014) (gomez a. 2010) (lombard j.e. 2010) (calamari l. 2009). cows may be seen spending more time in mattress stalls but they are standing rather than lying (cook n.b. 2005)(jensen m.b. 2015) (cook n.b. 2004). compost manure and sand systems can both be shown to have reduced hock lesions versus mattress bedding (fulwider w.k. 2007) (lobeck k.m. 2011)(van gastelen s. 2011) (lombard j.e. 2010) (norring m. 2008) . also, when kept clean, there may be no differences in mastitis, scc, locomotion score and hock lesions between compost pack systems and deep sand freestall systems (eckelkamp e.f. 2014) when using straw for bedding material, it appears that chopping the straw can be associated with less hock hair loss than whole straw (lim p.y. 2015) one paper concentrated on preference testing between sand, straw and rubber matted bedding and found contrary results to other papers, concluding that cows strongly preferred to lie on straw and rubber, avoiding sand where possible (manninen e. 2002). although stocking densities were different in these tests and numbers were low, with cows having previous experience of matting systems before the experiment. (hayasaka k. 2000) mentioned that cows showed longer lying times on mattresses versus soil bedding but spent less time eating. one paper was specific enough to quantify the length of lying time with the depth of the sand bedding and showed that this depth decreases with increased time of use in the barn. lying time decreased by 11 minutes in a 24 hour period per 1cm depth of sand bedding (drissler m. 2005). summary in conclusion, clean sand appears to be associated with the best outcomes in clinical mastitis, cow cleanliness, subclinical mastitis, cow lying times, hock lesions and cow preference. recycled sand, composted manure and other deep-bedded systems also appear to have increased cow comfort indices versus mattress systems. manure systems can also have better outcomes with bacterial growth over straw and mattress systems as long as they are kept clean and renewed frequently. mattress systems and concrete/straw bedding tend to have the worst outcomes for both mastitis and lameness parameters. methodology section search strategy databases searched and dates covered: pubmed search 1910 july 2017 google scholar cab abstracts 1973 to 2017 week 30 search terms: search 1 ((((((cattle or cow$ or bovi*))) and ((bed* or mattress))) and ((sand or compost* or rubber)))) and mastitis search 2 ((((((cattle or cow$ or bovi*))) and ((bed* or mattress))) and ((sand or compost* or rubber)))) and (([hock lesion] or lame*)) search 3 ((((((cattle or cow$ or bovi*))) and ((bed* or mattress))) and ((sand or compost* or rubber)))) and [lying time$] search 4 ((((((cattle or cow$ or bovi*))) and ((bed* or mattress))) and ((sand or compost* or rubber)))) and (([dry matter intake] or dmi)) dates searches performed: 28 july 2017 (pubmed), 3rd august, 2017 (google scholar), 8th august, 2017 (cab abstracts) exclusion / inclusion criteria exclusion: references on grazing (when not compared with the included pico titles), tie-stall barns, feedlots, beef animals or calves. papers that did not directly compare bedding types with clear outcomes. papers that compared different types of the same medium (e.g. comparing 2 types of rubber mattresses) non peer-reviewed information sheets articles covering sheep or buffalo articles covering flooring or whole-barn systems rather than bedding specifically (e.g. compost or straw yards vs cubicle systems). this is because the influences of bedding would be mixed with flooring and barn design and confuse outcomes. inclusion: comparisons of lactating and dry dairy cow types of bedding with any search outcomes in search string peer-reviewed articles search outcome database total number of results from the search strategies after deduplication excluded – not relevant to the pico/not peer reviewed total relevant papers ncbi pubmed 46 11 35 google scholar 454 403 51 cab abstracts 143 118 25 total relevant papers when duplicates removed 59 conflict of interest the author declares no conflicts of interest. references adams a.e., lombard j.e., fossler c.p., roman-muniz i.n., kopral c.a. 2017. 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"comparison of bacteria populations in clean and recycled sand used for bedding in dairy facilities." journal of dairy science 88 (12): 4317-4325. http://dx.doi.org/10.3168/jds.s0022-0302(05)73118-0 lim p.y., huxley j.n., green m.j., othman a.r., potterton s.l., brignell c.j., kaler j. 2015. "area of hock hair loss in dairy cows: risk factors and correlation with a categorical scale." veterinary journal 203 (2): 205-210. http://dx.doi.org/10.1016/j.tvjl.2014.11.005 lobeck k.m., endres m.i., shane e.m., godden s.m., fetrow j. 2011. "animal welfare in cross-ventilated, compost-bedded pack, and naturally ventilated dairy barns in the upper midwest." journal of dairy science 94 (11): 5469-5479. http://dx.doi.org/10.3168/jds.2011-4363 lombard j.e., tucker c.b., von keyserlingk m.a., kopral c.a., weary d.m. 2010. "associations between cow hygiene, hock injuries, and free stall usage on us dairy farms." journal of dairy science 93 (10): 4668-4676. http://dx.doi.org/10.3168/jds.2010-3225 manninen e., passille a.m., de rushen j., norring m., saloniemi h. 2002. "preferences of dairy cows kept in unheated buildings for different kind of cubicle flooring." applied animal behaviour science 75 (4): 281-292. http://dx.doi.org/10.1016/s0168-1591(01)00206-4 mitev j., varlyakov i., miteva t., vasilev n., gergovska j., uzunova k., dimova v. 2012. "preferences of freestall housed dairy cows to different bedding materials." veteriner fakultesi dergisi (istanbul) 38 (2): 135-140. norring m., manninen e., de passillé a.m., rushen j., munksgaard l., saloniemi h. 2008. "effects of sand and straw bedding on the lying behavior, cleanliness, and hoof and hock injuries of dairy cows." journal of dairy science 91 (2): 570-576. http://dx.doi.org/10.3168/jds.2007-0452 norring m., manninen e., de passillé a.m., rushen j., saloniemi h. 2010. "preferences of dairy cows for three stall surface materials with small amounts of bedding." journal of dairy science 93 (1): 2009-2164. rowbotham r.f., ruegg p.l. 2016. "associations of selected bedding types with incidence rates of subclinical and clinical mastitis in primiparous holstein dairy cows." journal of dairy science 99 (6): 4707-4716. http://dx.doi.org/10.3168/jds.2015-10675 rowbotham r.f., ruegg p.l. 2016. "bacterial counts on teat skin and in new sand, recycled sand, and recycled manure solids used as bedding in freestalls." journal of dairy science 99 (8): 6954-6608. http://dx.doi.org/10.3168/jds.2015-10674 rudd l.e., boe k.e., osteras o. 2010. "associations of soft flooring materials in free stalls with milk yield, clinical mastitis, teat lesions, and removal of dairy cows." journal of dairy science 93 (4): 1578-1586. http://dx.doi.org/10.3168/jds.2009-2752 shane e.m., endres m.i., janni k.a. 2010. "alternative bedding materials for compost bedded pack barns in minnesota: a descriptive study." applied engineering in agriculture 26 (3): 465-473. solano l., barkema h.w., pajor e.a., mason s., leblanc s.j., nash c.g., haley d.b., pellerin d., rushen j., de passillé a.m., vasseur e., orsel k. 2016. "associations between lying behavior and lameness in canadian holstein-friesian cows housed in freestall barns." journal of dairy science 99 (3): 2086-2101. http://dx.doi.org/10.3168/jds.2015-10336 tucker c.b., weary d.m., fraser d. 2003. "effects of three types of free-stall surfaces on preferences and stall usage by dairy cows." journal of dairy science 86 (2): 521-529. http://dx.doi.org/10.3168/jds.s0022-0302(03)73630-3 upadhyay d., singh m., gaur g.k., patel b.h.m., verma m.r., bharti p.k., triveni d. 2017. "does floor surface affect locomotion behaviour of crossbred cows under loose housing system?" indian journal of animal sciences 87 (2): 159-162. van gastelen s., westerlaan b., houwers d.j., van eerdenburg f.j. 2011. "a study on cow comfort and risk for lameness and mastitis in relation to different types of bedding materials." journal of dairy science 94 (10): 2878-2888. http://dx.doi.org/10.3168/jds.2010-4019 wagner-storch a.m., palmer r.w., kammel d.w. 2003. "factors affecting stall use for different freestall bases." journal of dairy science 86 (6): 2253-2266. http://dx.doi.org/10.3168/jds.s0022-0302(03)73816-8 weary d.m., taszkun i. 2000. "hock lesions and free-stall design." journal of dairy science 83 (4): 697-702. http://dx.doi.org/10.3168/jds.s0022-0302(00)74931-9 wenz j.r., jensen s.m., lombard j.e., wagner b.a., dinsmore r.p. 2007. "herd management practices and their association with bulk tank somatic cell count on united states dairy operations." journal of dairy science 90 (8): 3652-3659. http://dx.doi.org/10.3168/jds.2006-592 westphal a., williams m.l., baysal-gurel f., lejeune j.t., mcspadden-gardener b.b. 2011. "general suppression of escherichia coli o157:h7 in sand-based dairy livestock bedding." applied environmental microbiology 77 (6): 2113-2121. zdanowicz m., shelford j,a,, tucker c,b,, weary d,m,, von keyserlingk m,a. 2004. "bacterial populations on teat ends of dairy cows housed in free stalls and bedded with either sand or sawdust." journal of dairy science 87 (6): 1694-1701. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in dairy cows with clinical mastitis do systemic antimicrobials in addition to intramammary antimicrobials improve clinical cure rates compared to intramammary antimicrobials only? a knowledge summary by matthew barden bvmedsci (hons) bvm bvs1* 1howells veterinary services ltd, york road, easingwold, yo61 3eb *corresponding author (mattbarden@gmail.com) vol 1, issue 4 (2016) published: 04 oct 2016 reviewed by: michael steele (bsc(hons), bvsc, mrcvs) next review date: 20 oct 2018 doi: 10.18849/ve.v1i4.46 clinical bottom line in spite of limitations to the available studies, in cattle with clinical mastitis and an absence of systemic signs there is no evidence that combined systemic and intramammary antimicrobial therapy improves clinical cure rates compared to intramammary antimicrobial therapy only. in two studies, cattle with severe coliform mastitis showed improved clinical parameters following combined systemic and intramammary antimicrobial therapy compared to intramammary antimicrobial therapy only. question in dairy cattle with clinical mastitis do systemic antimicrobials and intramammary antimicrobials versus intramammary antimicrobials only improve clinical cure rates? the evidence the pico question in this case was not the focus of any of the studies, however the relevant comparisons were available within the results. with the exception of swinkels et al. (2013), the studies generally included small numbers of cows. summary of the evidence erskine (2002) population: dairy cows with severe clinical mastitis (mastitis and at least two indicators of systemic disease) across six herds. sample size: n = 104 intervention details: n = 51 treated with intramammary pirlimycin (50mg, every 24 hours, 3 day duration) and intramuscular ceftiofur (2.2mg/kg, every 24 hours, 5 day duration) n = 53 treated with intramammary pirlimycin (50mg, every 24 hours, max 3 day duration) study design: randomised positive controlled trial outcome studied: clinical cure rate, 30 day survival (culling or death) main findings (relevant to pico question): no significant difference between cure rates in either group. in cases of clinical mastitis caused by coliform organisms there was statistically higher survival in the group treated with combined treatment (intramammary pirlimycin and intramuscular ceftiofur) compared to the group treated with intramammary pirlimycin only. limitations: no blinding adjunctive therapy not standardised across sites, in some situations adjunctive therapy included systemic corticosteroids which are controversial duration of intramammary treatment varied between herds clinical cure assessed subjectively no data regarding bacteriological cure or somatic cell count follow up limited to 30 days post-detection. significant outcomes such as milk yield and long-term culling risk not included. wenz (2005) population: dairy cows on a single site with mild clinical mastitis in one quarter with a positive milk culture sample size: n = 144 intervention details: n = 35 treated with intramammary pirlimycin (50mg, every 24 hours, 2 day duration) n = 36 treated with intramammary pirlimycin (50mg, every 24 hours, 2 day duration) and intramuscular ceftiofur (2.2mg/kg, every 24 hours, 3 day duration) n = 40 treated with intrammammary cephaparin (200mg, every 12 hours, 3 day duration) n = 33 treated with intramammary cephaparin (200mg, every 12 hours, 3 days) and intramuscular ceftiofur (2.2mg/kg, every 24 hours, 3 day duration) study design: randomised positive controlled trial (short communication) outcome studied: clinical cure rates, rate of recurrence 15 – 90 days post-detection, bacteriological cure at 7 days post-treatment, loss of quarter, culling and death. main findings (relevant to pico question): no significant difference in recurrence across groups no significant difference for any outcome across treatment groups. the was a numerical improvement in bacteriological cure at 7 days post-treatment for both groups treated with intramuscular ceftiofur in addition to the intramammary antimicrobial (27% vs 45% and 33% vs 52% for 1 and 2 and  groups 3 and 4 respectively). limitations: small group sizes pre-intervention differences between treatment groups not discussed randomisation technique not stated culling decisions are usually multifactorial and although culling for mastitis is used as a negative outcome for this study, previous mastitis or cell count history and factors not related to udder health will influence the decision to cull only cases with a positive milk culture included which may reduce the applicability of the results to clinical practice (i.e. not applicable for empirical treatment) outcomes such as individual cow somatic cell count data and milk yield not recorded use of mastitis vaccine reduces clinical relevance of study to many herds in uk follow-up limited to 90 days post-detection hillerton and kliem (2002) population: dairy cows on a single site, experimentally infected with streptococcus uberis in two quarters sample size: n = 54 (total of 81 quarters included in study). of these, 39 quarters included that are relevant to pico question. intervention details: (n refers to quarters not cows) n = 11 untreated n = 10 treated with intramammary penthemate (150mg), dihydrostreptomycin (150mg), framycetin (50mg) and prednisolone (5mg); every 12 hours for a 3 day duration n = 11 treated with intramuscular penicillin (8mg/kg) and dihydrostreptomycin (10mg/kg) every 24 hours for a 3 day duration n = 18 treated with intramammary penthemate (150mg), dihydrostreptomycin (150mg), framycetin (50mg) and prednisolone (5mg) ; every 12 hours for a 3 day duration and intramuscular penicillin (8mg/kg) and dihydrostreptomycin (10mg/kg) every 24 hours for a 3 day duration n = 11 treated with intramammary penthemate (150mg), dihydrostreptomycin (150mg), framycetin (50mg) and prednisolone (5mg); every 24 hours for a 3 day duration n = 10 treated with intramuscular oxytocin (80iu at first milking then 20iu at the subsequent 5 milkings) n = 10 treated with 11 treated with intramammary penthemate (150mg), dihydrostreptomycin (150mg), framycetin (50mg) and prednisolone (5mg); every 24 hours for a 3 day duration and intramuscular oxytocin (80iu at first milking then 20iu at the subsequent 5 milkings) study design: prospective cohort study (randomisation abandoned half-way through study) outcome studied: clinical cure bacteriological cure somatic cell count recovery main findings (relevant to pico question): no statistical difference in cure rate or bacteriological cure between groups receiving intramammary antimicrobials compared to group receiving intramammary and intramuscular antimicrobials. limitations: randomisation replaced with allocation during the trial one group (combined intramammary and intramuscular antimicrobials) expanded after initial results different quarters on the same cow included in different treatment groups – systemic treatments avoided but crossover of intramammary treatments between adjacent quarters may affect results. not all cows/quarters accounted for in results – missing data briefly mentioned but no detail relating which treatment groups. no blinding trial over three phases so potential for environmental factors to change between treatment groups group comparisons at start of study not discussed strain of streptococcus uberis used with known antimicrobial sensitivity which limits clinical relevance follow-up limited to 21 days post-infection shipgel (1997) population: dairy cows on a single site, experimentally infected with escherichia coli in two quarters sample size: n = 47 intervention details: n = 12 treated with intramammary cefquinome (75mg, every 12 hours, 3 treatments) n = 12 treated with intramammary cefquinome (75mg, every 12 hours, 3 treatments) and intramuscular cefquinome (1mg/kg, every 24 hours, 2 treatments) n = 12 treated with intramuscular cefquinome (1mg/kg, every 24 hours, 2 treatments) n = 11 treated with amoxicillin  and cloxacillin (75mg and 200mg respectively, every 12 hours, 3 treatments) study design: randomised positive controlled trial outcome studied: clinical mastitis score (based on demeanour, milk appearance, quarter characteristics, rectal temperature, rumen contractions, heart and respiration rate) milk cultures and california mastitis tests haematology and biochemistry main findings (relevant to pico question): no significant difference in clinical cure (measured by clinical mastitis score) or bacteriological cure between groups receiving intramammary cefquinome compared to group receiving intramammary and intramuscular cefquinome. bacterial cure rate numerically higher for intramammary and intramuscular cefquinome group than intramammary cefquinome group (95.2% vs 82.6%) various clinical parameters indicated an improved clinical response in the group treated with intramammary and intramuscular cefquinome compared to cows treated with intramammary cefquinome only. the parameters where a statistical difference was noted were the decrease in rumen contractions, decrease in leukocytes, and peak in urea and creatinine. there was a statistically significant reduction in milk production post-infection in the group treated with intramammary cefquinome compared to the group treated intramammary and intramuscular cefquinome. limitations: trial designed to test different hypothesis to pico question (cefquinome vs amoxicillin/cloxacillin) therefore relevant results and statistical analysis not always easy to extract. clinical assessment with clinical mastitis score individual parameters not given. randomisation technique not stated california mastitis test used in place of quantified somatic cell count data. follow up limited to 14 days post-challenge strain of escherichia coli used with known antimicrobial sensitivity which limits clinical relevance swinkels (2013) population: dairy cows across three herds with high rates of recurrent, environmental clinical mastitis. cows included with clinical mastitis of all grades (mild to severe). sample size: n = 994 of these, 689 treated in a way relevant to pico question intervention details: n = 305 treated with intramammary cefquinome (75mg, two consecutive milkings on day one followed by the morning milking on day two) n = 318 treated with intramammary cefquinome (75mg, two consecutive milkings on day one followed by the morning milking for four consecutive days) n = 371 treated with intramammary cefquinome (75mg, two consecutive milkings on day one followed by the morning milking for four consecutive days) intramuscular cefquinome (1mg/kg, every 24 hours, five day duration) study design: randomised positive controlled trial outcome studied: cure rate assessed subjectively by trained personnel. recurrence monitored until 105 days post-treatment. cows followed for 105 days following initial treatment. recurrence assessed at both cow and quarter level. main findings (relevant to pico question): no statistical difference between cure rate or rate of recurrence between the group treated with intramammary cefquinome for 5 days and the group treated with intramammary cefquinome and intramuscular cefquinome for 5 days. no statistical difference at cow or quarter level. limitations: trial not designed to compare outcomes between groups relevant to pico question (groups 2 and 3) but lack of difference in outcome apparent and discussed. missing data acknowledged but not clear from which treatment groups data are missing. 124 cows received nsaids in addition to antimicrobials; 106 cows received systemic antimicrobials off study protocol these cows were not excluded from the trial and the group allocation is not stated. although randomisation used, herd personnel had discretion to assign cows to treatment groups number of 'non-randomised' cows not clear. appraisal, application and reflection the most pertinent question is whether in cases of clinical mastitis without systemic clinical signs there is a benefit to systemic antimicrobials in addition to intramammary antimicrobials. it may have been more helpful to look at treatment approaches for mild and moderate mastitis separately to severe mastitis, however, this approach would have resulted in the exclusion of at least one study (swinkels et al 2013) where the study population included mixed severities of clinical mastitis. the lack of demonstrable benefits of systemic antimicrobials in addition to intramammary antimicrobials for mild and moderate mastitis is relevant as this is relatively common practice; but the limitations of these studies should be considered. the benefits of combined systemic and intramammary antimicrobials for severe coliform mastitis are interesting although expected as the merits of systemic antimicrobials are more established in these cases. the stated aims from these five studies were not directly focused on answering the pico question, however, all provided the data for necessary comparisons to be made. the studies were of mixed but typically good quality and generally, with the exception of swinkels et al (2013), included a small number of cows. clinical cure rate is a vague parameter with all studies using subjective assessment as the primary indicator of both clinical disease and cure. more objective and reliable outcomes such as bacteriological cure were used in some but not all studies. methodology section search strategy databases searched and dates covered: pubmed and cab abstracts 1973 present search terms: cow or cows or cattle or bovine or bovines or bos and mastitis or intramammary infection and parenteral or systemic or inject* and iotics or antimicrobials dates searches performed: pubmed: 06/05/2016 cab abstracts: 01/09/2015 exclusion / inclusion criteria exclusion: reviews, economic models, in-vivo studies, conference proceedings, book chapters, foreign language articles. inclusion: studies where comparison was possible between two groups treated with systemic antimicrobials in addition to the same intramammary antimicrobial. mainly randomised control trials. search outcome database number of results excluded – not relevant to pico question excluded – statistical model, review, book chapter etc. excluded – not available in the english language total relevant papers ncbi pubmed 238 233 0 0 5 cab abstracts 849 838 6 2 3 total relevant papers when duplicates removed 5 conflict of interest the author declares no conflicts of interest. references erskine, r.j. et al (2002) efficacy of systemic ceftiofur as a therapy for severe clinical mastitis in dairy cattle. journal of dairy science, 85 (10) pp. 2571-2575. http://dx.doi.org/10.3168/jds.s0022-0302(02)74340-3 hillerton, j.e. and kliem, k.e. (2002) effective treatment of streptococcus uberis clinical mastitis to minimize the use of antibiotics. journal of dairy science, 85 (4) pp. 1009-1014. shipgel, n.y. et al (1997) efficacy of cefquinome for treatment of cows with mastitis experimentally induced using escherichia coli. journal of dairy science, 80 (2) pp. 318-323. http://dx.doi.org/10.3168/jds.s0022-0302(97)75941-1 swinkels, j.m. et al (2013) effect of extended cefquinome treatment on clinical persistence or recurrence of environmental clinical mastitis. the veterinary journal, 197 (3) pp. 682-687. http://dx.doi.org/10.1016/j.tvjl.2013.03.010 wenz, j.r. et al (2005) short communication: efficacy of perenteral ceftiofur for treatment of systemically mild clinical mastitis in dairy cattle. journal of dairy science, 88 (10) pp. 3496-3499. http://dx.doi.org/10.3168/jds.s0022-0302(05)73034-4 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. non-steroidal anti-inflammatories: does carprofen or meloxicam have fewer gastrointestinal side effects? a knowledge summary by aaron fletcher bvetmed mrcvs 1* 1heath lodge veterinary group, st bernard's road, st albans, hertfordshire, al3 5ra *corresponding author (afletcher53@gmail.com) vol 5, issue 3 (2020) published: 11 sep 2020 reviewed by: james swann (ma vetmb dacvim decvim mrcvs) and edward hall (ma vetmb phd dipecvim-ca frcvs) next review date: 30 oct 2021 doi: 10.18849/ve.v5i3.301 pico question in canines, does the oral administration of carprofen, when compared to meloxicam, result in fewer gastrointestinal side effects?   clinical bottom line category of research question treatment the number and type of study designs reviewed three prospective randomised controlled trials were critically reviewed strength of evidence weak outcomes reported treatment with carprofen or meloxicam results in no significant difference in gastric lesion scoring, increased intestinal mucosal permeability or diminished small bowel absorptive capacity conclusion there is insufficient evidence supporting preferential administration of carprofen or meloxicam to reduce gastrointestinal side effects   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision-making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care clinical scenario you wish to prescribe non-steroidal anti-inflammatory drugs (nsaids) to a canine patient with arthritic pain. the patient has no contraindications for prescribing an nsaid and has not been prescribed an nsaid before. the owner is concerned about gastrointestinal side effects of nsaids and you wish to find out if there is a scientific basis for the preferential treatment with carprofen or meloxicam for this. the evidence three prospective randomised controlled studies have been found which are partially relevant to the pico (luna et al., 2007; craven et al., 2007; and forsyth et al., 1998). two of the randomised controlled trials studied the effects of carprofen or meloxicam administration on gastrointestinal adverse reactions. both these trials used endoscopic measured gastric mucosal lesion scoring following oral nsaid administration (forsyth et al., 1998; and luna et al., 2007) and in addition one of the trials measured an outcome of faecal occult blood (luna et al. 2007). one randomised controlled trial measured the effects of carprofen or meloxicam administration on the gastric permeability and mucosal absorptive capacity through sugar solution absorption (craven et al., 2007). the strength of the evidence found was very weak for the pico question, and there is insufficient evidence to recommend treatment with either carprofen or meloxicam to limit the frequency of gastrointestinal side effects. summary of the evidence luna et al. (2007) population: female neutered crossbreed canines, aged 1–5 years, weighing 15–20 kg maintained in experimental facilities. sample size: 36/42 potential canines met the inclusion criteria intervention details: the population was divided into six arms following assessment and treated for a maximum of 90 days (only meloxicam and carprofen groups were relevant to this paper): group one – (six canines) lactose (control 1 mg/kg once daily (sid)) group two – (six canines) etodolac (15 mg/kg sid) group three – (six canines) meloxicam (0.1 mg/kg sid) group four – (six canines) ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg sid thereafter) group five – (six canines) carprofen (4 mg/kg sid) group six – (six canines) flunixin meglumine (1 mg/kg sid for 3 consecutive days each week) on day 30, after a quarantine period, urine analysis on a cystocentesis sample, complete blood count, biochemistry, coagulopathy profiles, gross/occult blood in faeces analysis and gastroscopy under general anaesthesia were performed. all canines received intravenous fluids throughout the endoscopic examination. the gastroscopy allowed grading of the canines’ gastric mucosal integrity with an endoscopic grading system (forsyth et al., 1998). all canines were graded 0 before the administration of nsaids. the canines were randomly divided into six arms at day 0, housed collectively and fed food and water ad lib. day 0 (3 months following initial evaluation) each arm received either treatment for 90 days with either: lactose (control 1 mg/kg), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg/d thereafter), carprofen (4 mg/kg) or flunixin meglumine (1 mg/kg for 3 consecutive days each week). a veterinarian performed a general health check daily for any abnormalities. if there were any abnormal clinical findings, the animal underwent a complete clinical and laboratory examination. each animal was then assessed by an investigator, who was blinded to the treatment group. if that investigator deemed the abnormal findings were a result of the administration of the nsaid, the animal was excluded. all animals underwent a complete examination, including clinical and laboratory tests on days 7, 30, 60, 90. veterinarians performing gastroscopies were unaware of the treatments received by the canines. study design: a prospective randomised controlled trial outcome studied: gastric mucosal lesion grading after 90 days of treatment. occult faecal blood test after 90 days of treatment. main findings (relevant to pico question): gastric lesion grading is based on the following scale (higher being worse): grade 0 (no visible haemorrhages, erosions, or ulcers) grade 1 (1 to 5 punctate erosions, haemorrhages, or both) grade 2 (6 to 15 punctate erosions, haemorrhages, or both) grade 3 (16 to 25 punctate erosions, haemorrhages, or both) grade 4 (> 25 punctate erosions, haemorrhages, or both; 1 to 5 invasive erosions; or both) grade 5 (> 6 invasive erosions) grade 6 (ulcers of any size). meloxicam treatment arm gastric lesions recorded after 90 days of treatment: grade 4 (two canines) grade 0 (four canines) the proportion of positive occult faecal blood test after 90 days of treatment: 5/6 carprofen treatment arm gastric lesions recorded in the carprofen arm after 90 days of treatment: grade 5 (one canine) grade 0 (five canines) the proportion with positive occult faecal blood test after 90 days of treatment: 3/6 limitations: not a crossover study, so cannot eliminate variability of reaction to different nsaids. the method of randomisation was not stated. the paper did not explicitly state that the veterinarian assessing the animal was blinded to the study aims. very small arm sizes were used with no sample size calculation provided. large study dropout rate (14.2%), and active exclusion of four patients (9.2%) with adverse effects deemed from nsaid administration (although not from the carprofen or meloxicam groups). nsaid doses did not follow the licensed dosage for common preparations, e.g. metacam (meloxicam) is recommended at an initial 0.2 mg/kg dose on day 1, subsequently reduced to 0.1 mg/kg on day 2 and rimadyl (carprofen) is recommended at an initial 2–4 mg/kg dose for the first 7 days then a reduction to 2 mg/kg. the faecal occult blood test result can be influenced by numerous factors, such as different diet (rice & ihle, 1994). craven et al. (2007) population: canines from a client-owned referral population, with no signs of gastrointestinal or renal disease. no azotaemia as determined up to 7 days before inclusion.  no nsaid or corticosteroid administration during the preceding 8 weeks. sample size: 23 adult canines, with a total of 11 different breeds: 13 females, nine neutered 10 males, seven neutered. three canines were withdrawn due to vomiting. intervention details: the population was divided into two groups: group m (10 canines) administered meloxicam orally 0.2 mg/kg on day 1, and 0.1 mg/kg subsequently sid. group c (10 canines) administered carprofen orally 4 mg/kg on day 1, and 2 mg/kg subsequently sid. a permeability test was administered to the subjects: six sugars; sucrose, lactulose, rhamnose, d-xylose, 3-o-methyl-d-glucose and sucralose formed a sugar solution which was administered to each subject. the sugars are absorbed in different parts of the intestine. canines > 20 kg received 400 ml, canines 10–20 kg received 200 ml and canines <10 kg 100 ml of the sugar solution. after a 12 hour fast, sterile urethral catheterisation and aliquots of urine were stored in sodium azide. for any canines not drinking the sugar solution, it was administered with a 10 fr oroesophageal tube. after 6 hours, the bladder was emptied via sterile urethral catheterisation, and all urine collected during the test period was mixed. all sugars, except sucralose, were analysed by high pressure liquid chromatography at an external laboratory. sucralose was measured by capillary column gas chromatography at the rush university medical center, chicago, illinois. a permeability test was performed before nsaid therapy on day 1 (before nsaid), day 3 and 8. nsaids were administered within 24 hours of performing the first permeability test. study design: a prospective randomised controlled trial outcome studied: objective measurements of urinary; sucrose concentration (s), sucralose concentration (su), the ratio of lactulose: rhamnose (l:r is an approximate measure of small intestinal permeability), and the ratio of d-xylose: 3-o-methyl-d-glucose (x:m is a measure of carbohydrate absorption). main findings (relevant to pico question): sucrose is digested as it enters the small intestine, so permeation and urinary excretion is considered to reflect gastric permeability. sucralose recovery is considered an indirect marker of colonic permeability. group m – no significant changes in urinary concentrations of s, si, or l:r or x:m ratios at any time. group c – urinary s recovery significantly decreased between day 1 and 3 (p = 0.049), significantly increased between day 3 to 8 (p = 0.049) but the increase was not significantly different to the level before treatment (p = 0.695). this was thought to be caused by a decreased gastric permeability. urinary recovery of su, l: r and x: m did not significantly differ. the difference in sucrose recovery on day 3, between groups c and m, might indicate changes in gastric permeability. no significantly increased intestinal mucosal permeability or diminished small bowel absorptive capacity in canines receiving standard doses of carprofen or meloxicam in the acute phase. limitations: very small arm sizes were used with no sample size calculation provided large study dropout, reducing the validity of statistical results. limited evidence showing that sugar absorption deficiency correlates to gastrointestinal side effects. current evidence is based on human medicine only. forsyth et al. (1998) population: mixed-breed colony canines housed in groups of eight, aged 1–12 years old. sample size: 24 canines intervention details: canines were randomly assigned to four treatment groups (6 canines per group): group one received oral carprofen 2 mg/kg bid for 7 days, then 2 mg/kg sid. group two received oral meloxicam 0.2 mg/kg sid. group three received oral ketoprofen 1 mg/kg sid. group four received oral placebo (gelatine) capsule (one capsule daily). each canine underwent anaesthesia for gastric endoscopy 7 days before the start of the study, to assess for evidence of grossly visible lesions. examination of the oesophagus through to the duodenum occurred, which was videotaped. the number of lesions, type of lesion, presence of blood, presence of mucosal granularity and size of the lesions at each site was recorded and graded. repeat endoscopic examination and grading was performed on days 7 and 28. the endoscopist recording the results was blinded to the treatment group. study design: a prospective randomised controlled trial outcome studied: the subjective mucosal grading scale of the oesophagus, gastric cardia/fundus, stomach body, body/antrum junction, antrum and duodenum. main findings (relevant to pico question): no significant difference between the gastric lesion scores between the nsaid groups (1–3) and the gelatine group (4). limitations: very small arm sizes were used with no sample size calculation provided. some canines had gastric lesions before the treatment was given. interestingly, canines treated with ketoprofen had the highest frequency of pre-existing gastric lesions before nsaid administration and had a higher number of gastric lesions at day 28. could the canines have other unaccounted for diseases which caused this? there was no description of clinical signs. method of randomisation not stated. appraisal, application and reflection three prospective randomised controlled trials have been found which provide partially relevant evidence to compare the gastrointestinal side effects of meloxicam and carprofen (luna et al., 2007; craven et al., 2007; and forsyth et al., 1998). the outcomes measured in the research varied. there was one weak piece of research which supported no statistically significant difference in gastric mucosal lesion scoring between carprofen and meloxicam treatment (forsyth et al., 1998), while one weak non-statistically backed piece of research reported that carprofen had lower gastric mucosal lesion scoring than meloxicam (luna et al., 2007). one weak piece of research reported no statistically significant difference in gastric permeability in canines receiving standard doses of carprofen or meloxicam in the acute phase (craven et al., 2007). while two of the studies measured an objective outcome occult faecal blood or sugar permeability testing, none of the studies measurable outcomes have been correlated to an increased frequency of the common gastrointestinal side effects (craven et al., 2007; and luna et al., 2007). what is more, in these studies, subjects were excluded if they developed commonly outwardly detectable gastrointestinal signs. as 38% of research studies report adverse effects from nsaid administration, actively excluding patients who show these reduces the evidence relevancy to the pico question (monteiro-steagall et al., 2013).  the clinical relevance of the outcomes recorded are debatable as they differ from the common gastrointestinal side effects reported in practice following nsaid treatment (vomiting, diarrhoea, anorexia, lethargy and melaena (monteiro-steagall et al., 2013)). even more, gastric endoscopy, and sugar absorption are not commonly used techniques to assess gastrointestinal side effects in first opinion practice. the limitations of all three studies reduce the strength of the presented evidence, with some experimental design issues. in human medicine, there is marked variability in an individual’s reaction to nsaids (bruno et al., 2014). interestingly, the literature search found no crossover studies for the two nsaids in this pico question, which are two of the most frequently prescribed nsaids. crossover studies would be an appropriate study design to assess the side effects of nsaids, and would reduce the impact of any individual drug reactions. no study provided power calculations for the populations they used, or confidence intervals for outcomes measured. this increases the risks of type 1 and type 2 errors when assessing the evidence and further diminishes its strength (banerjee et al., 2009). the nsaid dose and duration administered to the subjects received varied widely between studies. craven et al. (2007) dosed carprofen according to the product datasheet and used a licensed form in the united kingdom (4 mg/kg/d day 1 and 2 then 2 mg/kg/d subsequently, rimadyl). luna et al. (2007) exceeded the long-term maintenance dose of their carprofen preparation but used a licensed form in the united kingdom (4 mg/kg/d, rimadyl). forsyth et al. (1998) used a preparation which is unlicensed for use in the united kingdom (zenecarp, 2 mg/kg bid 7 days, then 2 mg/kg/d for 7 days). in contrast, the dosage of meloxicam, while still variable, was more consistent. forsyth et al. (1998) administered meloxicam at 0.2 mg/kg/d (exceeding the current united kingdom datasheet for metacam by 0.1 mg/d for ongoing usage). luna et al. (2007) administered meloxicam at 0.1 mg/kg ongoing (and did not increase the dose on day 1 as the current united kingdom datasheet for metacam suggests). only craven et al. (2007) followed the datasheet guidelines and administered meloxicam at 0.2mg/kg/d on day 1 and 0.1 mg/kg/d subsequently. while the importance of these variations is not known, it does hinder meaningful clinical comparison as the doses given rarely matched the licensed dosages. there has been an attempt to classify what defines an adverse effect in a systematic review, as ‘outwardly detectable signs’ that are assessed through observational monitoring, physical examination and non-invasive procedures (monteiro-steagall et al., 2013). these are inherently subjective criteria, but have much greater clinical relevance than the outcomes reported by this knowledge summary, and hence the systematic review may be more helpful for clinicians than this knowledge summary. another limitation of this knowledge summary is that as some research found in the literature search did not report any adverse effects, it could have introduced reporting bias, by only including research studies which reported adverse events. also, the inclusion criteria were for primary research which contained both drugs in the pico question, excluding research for each of these drugs in isolation. the justification for this approach was an existing systematic review on evidence for the adverse effects of nsaids in veterinary medicine (monteiro-steagall et al., 2013), and that a knowledge summary of available comparator research would be more externally valid to the pico question. the systematic review concluded that whilst there was high strength research available for carprofen and meloxicam, the strength of evidence regarding adverse drug experience was variable. finally, a language bias may have been introduced by only selecting papers that were published in english. despite these limitations, this knowledge summary is the first comparator looking to assess gastrointestinal side effects of these two frequently used nsaids. nsaids are a widely used analgaesic in veterinary medicine, and while there is high strength evidence documenting for the adverse effects of these drugs (monteiro-steagall et al., 2013), there is a lack in comparative research to guide rational clinical decision making between products. this knowledge summary concluded that there is insufficient evidence to recommend treatment with meloxicam over carprofen to reduce the frequency of gastrointestinal side effects. methodology section search strategy databases searched and dates covered: cab abstracts 1900–2019 pubmed 1910–2019 web of science 1900–2019 search strategy: cab abstracts – (canin* or dog* or dog) and (adverse* or side* or safety*) and meloxicam and carprofen pubmed – (canin* or dog* or dog) and ("adverse*" or "side*" or "safety*") and carprofen and meloxicam web of science – (ts=((canin* or dog* or dog) and (adverse* or side* or safety*) and carprofen and meloxicam)) dates searches performed: 30 oct 2019 exclusion / inclusion criteria exclusion: papers not in english paper cannot be accessed the study: was not relevant to the pico did not contain the two non-steroidal anti-inflammatories did not consider gastrointestinal adverse effects nsaid treatment arm also included other cox enzyme inhibiting drugs (steroids) sequential administration of nsaids without washout administered nsaids in another route other than orally reviews single case reports conference papers book chapters inclusion: any relevant primary research paper which compared the gastrointestinal side effects of the non-steroidal anti-inflammatories, carprofen and meloxicam. search outcome database number of results excluded – case reports, conference papers, reviews, book chapters, correspondence excluded – not relevant to pico excluded – languages other than english excluded – inaccessible total relevant papers cab abstracts 36 14 12 4 3 3 pubmed 13 3 7 0 1 2 web of science 73 16 55 0 0 2 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflicts of interest. references banerjee, a., chitnis, u. b., jadhav, s. l., bhawalkar, j. s., & chaudhury, s. (2009). hypothesis testing, type i and type ii errors. industrial psychiatry journal, 18(2), 127–131. doi: https://doi.org/10.4103/0972-6748.62274 bruno, a., tacconelli, s. & patrignani, p. (2014). variability in the response to non-steroidal anti-inflammatory drugs: mechanisms and perspectives. basic and clinical pharmacology and toxicology, 114(1). doi: http://dx.doi.org/10.1111/bcpt.12117 craven, m., chandler, m. l., steiner, j. m., farhadi, a., welsh, e., pratschke, k., shaw, d. j., & williams, d. a. (2007). acute effects of carprofen and meloxicam on canine gastrointestinal permeability and mucosal absorptive capacity. journal of veterinary internal medicine, 21(5), 917–23. doi: http://dx.doi.org/10.1111/j.1939-1676.2007.tb03043.x forsyth, s. f., guilford, w. g., haslett, s. j., & godfrey, j. (1998). endoscopy of the gastroduodenal mucosa after carprofen, meloxicam and ketoprofen administration in dogs. journal of small animal practice, 39(9), 421–424. doi: http://dx.doi.org/10.1111/j.1748-5827.1998.tb03748.x fox, s.m. & johnston, s.a. (1997). use of carprofen for the treatment of pain and inflammation in dogs. journal of the american veterinary medical association, 210, 1493–8. innes, j., clayton, j. & lascelles, d. (2010). long-term nsaid use for canine oa: is it more effective? proceedings, 3rd world veterinary orthopaedic congress, esvot-vos, 15th esvot congress, bologna, italy, 15–18 september, 341–342. luna, s. p., basílio, a. c., steagall, p. v., machado, l. p., moutinho, f. q., takahira, r. k., & brandão, c. v. (2007). evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. american journal of veterinary research, 68(3), 258–264. doi: http://dx.doi.org/10.2460/ajvr.68.3.258 monteiro-steagall, b.p., steagall, p.v.m. & lascelles, b.d.x. (2013). systematic review of nonsteroidal anti-inflammatory drug-induced adverse effects in dogs. journal of veterinary internal medicine, 27(5), 1011–1019. doi: http://dx.doi.org/10.1111/jvim.12127 pigott, j., cobb, m. & o’rourke, d. (2015). a comprehensive review of adverse events associated with non-steroidal anti-inflammatory drug treatments in dogs in the uk. bsava congress 2015: scientific proceedings, birmingham, uk, 9–12 april 2015. doi: http://dx.doi.org/10.22233/9781910443521.70.12 rice, j.e. & ihle, s.l. (1994). effects of diet on fecal occult blood testing in healthy dogs. canadian journal of veterinary research = revue canadienne de recherche vétérinaire, 58(2), 134–137. valencia sánchez, f., gutiérrez pérez, e. & pérez carral, v. (2008). calcinosis cutis en iguana. argos: informativo veterinario, 58–60. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. can garlic prevent, repel or kill fleas that infest dogs? a knowledge summary by louise buckley phd fhea rvn1* 1edinburgh surgery online, deanery of clinical sciences, college of medicine & veterinary medicine, university of edinburgh, 196 canongate, edinburgh, eh8 8aq *corresponding author (louise.buckley@ed.ac.uk) vol 5, issue 3 (2020) published: 28 aug 2020 reviewed by: virginia fajt (dvm phd dacvcp) and roberta perego (dvm phd) next review date: 08 dec 2021 doi: 10.18849/ve.v5i3.311 pico question in dogs, is oral or topical administration of garlic, compared to no treatment, efficacious at preventing or reducing parasitism by fleas?   clinical bottom line category of research question treatment the number and type of study designs reviewed zero strength of evidence critical appraisal of the selected papers meeting the inclusion criteria collectively provide zero evidence in terms of their experimental design and implementation outcomes reported the outcomes reported were none conclusion it is concluded that there is a lack of peer-reviewed scientific in vivo evidence to address the pico   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision-making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a veterinary nurse is reading through the ectoparasiticide advice being given in a facebook group that encourages a ‘natural’ (non-conventional medicine) approach to preventative medicine in dogs. she notices that garlic is being recommended quite frequently by some pet owners as an alternative to a conventional ectoparasiticide for preventing or treating flea infestation on dogs and wonders what the evidence base is for this recommendation. the evidence no peer-reviewed scientific papers were identified that addressed the pico. widening the inclusion criteria to include garlic applied environmentally (the same search strategy was retained) to address extra dog environmental infestation, or case studies based on oral, topical or environmental application of garlic also yielded no results. summary of the evidence there was no peer-reviewed evidence that met the inclusion criteria to summarise. appraisal, application and reflection no in vivo studies that examine the efficacy of garlic at preventing, killing or repelling any stage of the flea life cycle in dogs were identified from the search strategy applied, and therefore no papers met the inclusion criteria for this knowledge summary. one in vitro study (renapurkar & deshmukh, 1984) was identified which demonstrated that environmental application (on to filter paper) of garlic extract in a hexane solvent was efficacious with the lc50% (the concentrate that kills 50% of the animals tested on) concentration of garlic extracts similar to that for various organochlorine and organophosphorus (dieldrin; malathion; fenthion; dichlorodiphenyltrichloroethane). however, external validity (e.g. oral or topical application of garlic to the dog with, or at risk of, flea parasitism) should not be inferred from these findings due to the numerous differences between laboratory and clinical application. there is some evidence of in vitro efficacy of garlic application across parasitised species and ectoparasites from various phyla, which suggests that it may have its place as a plant-based ectoparasiticide for the ethnoveterinary based treatment of some species. in two cattle-based studies (both abstract only as the full text was in spanish), oral supplementation with garlic (100 g or 200 g per cow; massariol et al., 2009) or garlic residue (3–9 g per cow; de castro alvarenga et al., 2004) resulted in a significant reduction in ticks, similar to those cattle treated with amitraz 0.025% (massariol et al., 2009).  however, no significant effect was seen on horn, stable or house fly burden (massariol et al., 2009). similarly, topical (vent/abdomen; birrenkott et al., 2000) or environmental (hen housing; gorji et al., 2014) application saw a significant decrease in northern fowl mite by week 4 compared to baseline and the control group (birrenkott et al., 2000) and an 85% reduction in red mite infestation after the first application (gorji et al., 2014). topical (gholipour-kanai et al., 2012; and fridman et al., 2014) or oral (fridman et al., 2014) application of garlic extracts have also been shown to effectively reduce or eliminate ectoparasitism by the protozoan ichthyophthirius multifiliis (host was a sail fin molly fish; gholipour-kanai et al., 2012) and various trematode mongean species (host was a guppy fish; fridman et al, 2014). this cross phyla efficacy may suggest a tentative basis for clinical research to investigate the efficacy of garlic as a plant-based ectoparasiticide to prevent, repel or kill fleas in the domestic dog. however, until garlic has been shown to be efficacious against fleas in dogs (and at levels non-toxic to the canine) the veterinary professional cannot make assumptions of external validity based on the studies cited, and clients should be recommended to use instead an ectoparasiticide that has been demonstrated to be so. methodology section search strategy databases searched and dates covered: pubmed on ncbi platform (01/01/1900 – 03/12/2019); web of science (1900 – 03/12/2019); cab abstracts on ovid platform (1973 – 2019, week 47); scopus (1960 – 03/12/2019) search strategy: pubmed: (dog or dogs or canine or canid or canis or bitch or bitches or pup or puppy or puppies) and (garlic or “allium sativum”) and (flea or fleas or ctenocephalides or ectoparasiticide or ectoparasite)   web of science: (dog or dogs or canine or canid or canis or bitch or bitches or pup or puppy or puppies) and (garlic or “allium sativum”) and (flea or fleas or ctenocephalides or ectoparasiticide or ectoparasite)   cab abstracts: (dog or dogs or canine or canid or canis or bitch or bitches or pup or puppy or puppies) and (garlic or allium sativum) and (flea or fleas or ctenocephalides or ectoparasiticide or ectoparasite)   scopus: (dog or dogs or canine or canid or canis or bitch or bitches or pup or puppy or puppies) and (garlic or “allium sativum”) and (flea or fleas or ctenocephalides or ectoparasiticide or ectoparasite) dates searches performed: 03 dec 2019 exclusion / inclusion criteria exclusion: pre-defined exclusion criteria: non-english language, popular press articles, in vitro studies, conference abstracts inclusion: any comparative study in which the effect of orally or topically administered garlic on flea parasitism of the dog was studied search outcome database number of results excluded – did not address the pico excluded – not english language excluded – conference abstract only excluded – duplicates total relevant papers pubmed 1 1 0 0 0 0 web of science 1 1 0 0 0 0 cab abstracts 1 1 0 0 0 0 scopus 2 2 0 0 0 0 total relevant papers 0 conflict of interest the author declares no conflicts of interest. references birrenkott, g. p., brockenfelt, g. e., greer, j. a. & owens, m. d. (2000). topical application of garlic reduces northern fowl mite infestation in laying hens. poultry science 79(11): 1575–1577. doi: http://dx.doi.org/10.1093/ps/79.11.1575 de castra alvarenga, l., de aguiar paiva, p. c., banys, v. l., collao-saenz, e. a., rabelo, a. m. g. & de rezende, a. p. (2004). alternation of the thicks load of bovines under intake of different levels of residuals of the improvement of garlic. ciencia e agrotecnologia 28(4): 906–912. doi: http://dx.doi.org/10.1590/s1413-70542004000400025 gholipour-kanani, h., sahandi, j. & taheri, a. (2012). influence of garlic (allium sativum) and mother worth (matricaria chamomilla) extract on ichthyophtirius multifilus parasite treatment in sail fin molly (poecilia latipinna) ornamental fish. procedia apcbee 4: 6–11. doi: http://dx.doi.org/10.1016/j.apcbee.2012.11.002 gorji, s. f., gorji, s. f. & rajablon, m. (2014). the field efficacy of garlic extract against dermanyssus gallinae in layer farms of babol, iran. parasitology research 113: 1209–1213. doi: http://dx.doi.org/10.1007/s00436-014-3759-2 fridman, s., sinai, t. & zilberg, d. (2014). efficacy of garlic based treatments against monogean parasites infecting the guppy (poecilia reticulata (peters)). veterinary parasitology 203: 51–58. doi: https://doi.org/10.1016/j.vetpar.2014.02.002 massariol, p. b., olivio, c. j., richards, n., agnolin, c. a., meinerz, g. r., both, j. f., faccio, l., hohenreuther, f. & martinelli, s. (2009). ectoparasite load alteration in holstein cows fed with different garlic (allium sativum l.) levels. revista brasileira de plantas medicinais 11(1): 37–42. doi: http://dx.doi.org/10.1590/s1516-05722009000100007 renapurkar, d. m. & deshmukh, p. b. (1984). pulicidal activity of some indigenous plants. insect science and its application 5(2): 101–102. doi: http://dx.doi.org/10.1017/s1742758400001740 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in newborn piglets does drying versus no intervention reduce the risk of mortality pre-weaning? a knowledge summary by nicola blackie bsc (hons) phd 1* 1department of pathobiology and population sciences, royal veterinary college, hatfield, al9 7ta *corresponding author (nblackie@rvc.ac.uk) vol 4, issue 4 (2019) published: 12 nov 2019 reviewed by: john carr (bvsc, phd, dpm, diplecphm, mrcvs. – specialised pig vet), vengai mavangira (bvsc, dacvim) and duncan berkshire (ma vetmb msc certpm mrcvs) next review date: 31 oct 2020 doi: 10.18849/ve.v4i4.245 pico question in newborn piglets, does drying piglets, compared to no intervention, reduce the level of mortality pre-weaning (up to 28 days)? clinical bottom line data specifically evaluating drying piglets are limited. many papers had multiple factors evaluated or were assessments of management in general. there is evidence that drying piglets can reduce mortality and improve thermoregulation of piglets. the cost of such interventions has not been appraised and should be considered on a case-by-case basis. therefore, currently when advising farmers it could be suggested that the drying of piglets may form part of a number of recommendations given to reduce piglet mortality pre-weaning. clinical scenario piglets are born with limited energy reserves and are not licked dry by the sow therefore risk hypothermia around the time of birth. mortality levels pre-weaning on indoor pig farms in the uk average 11.6 % (ahdb, 2019). the practice of drying piglets is more common in the us than in the uk based on anecdotal evidence. conversations with uk pig farmers and veterinarians revealed that there are mixed strategies for managing the newborn piglet indoors, many of which do not include a direct intervention to dry the piglet. indirect methods of drying piglets may include lamps at the rear end of the sow or providing bedding. drying piglets may be a way of reducing the risk of hypothermia and thus reduce the risk of mortality. therefore, an appraisal of the evidence could be used to advise farmers on best practice. the evidence there are three methods of drying piglets from the literature. one is drying with stimulation such as using paper towels, cloth towels or straw, as well as drying the piglets they may also receive stimulation from the act of rubbing them. another method included the use of drying powders and the third method was moving the piglet under a lamp. from the evidence it is clear that drying piglets can result in lower mortality however, a simpler method may be to place the piglet under a heat lamp (andersen et al., 2009). drying piglets with stimulation without combination of other strategies was only assessed in four studies (christison et al., 1997; mcginnis et al., 1981; pan, 1995; and vasdal et al., 2011), of which one study did not record mortality (pan, 1995), one study showed no effects on mortality and two showed an improvement in mortality where piglets were dried (christison et al., 1997; and vasdal et al., 2011). a further two studies included drying as part of an “advanced care” around farrowing which included a number of interventions (dewey et al., 2008; and white et al., 1996). dewey et al. (2008) found no impact of extra care on mortality however, they did have low mortality levels in the study overall (7–8 %). in contrast, white et al. (1996) had less mortality when farrowing was assisted and piglets were dried among other interventions. when comparing with the average level of mortality on uk pig farms 11.6 % (ahdb, 2019); mortality was considerably higher where no intervention was made in one study of 21% (christison et al., 1997) and similar in two studies (andersen et al., 2009; vasdal et al., 2011). summary of the evidence andersen et al. (2009) population: litters from 67 (landrace x yorkshire) healthy sows; parity 2–4 housed in loose farrowing pens (3.2 m x 2.0 m) with solid, concrete floor in the front two thirds of the pen with the rest slatted room temperature 18–20°c natural farrowing sample size: 67 litters (total number of live born piglets not given) intervention details: three treatment groups: control (c) n = 23 litters, no supervision of farrowing, farmer could help with difficult births but not to intervene if he/she heard a piglet being crushed heat lamp (hl) n = 22 litters, piglets placed under heat lamp directly after birth (lamp in the creep area) dried and heat lamp (dhl) n = 22 litters, piglets were dried with straw and paper towel, then placed under heat lamp directly after birth (lamp in the creep area) study design: non-randomised controlled trial outcome studied: mortality reason for death (via post mortem examination) main findings (relevant to pico question): mortality of live born piglets was lower in hl (7.6%) and dhl (6.7%) interventions when compared to control (11.7 %). no significant difference between hl and dhl proportion of starved piglets was significantly lower in the hl treatment than in the dhl and control group dhl group had the lowest number of piglets crushed (13.8%). hl less crushed than control (34.8% and 47.9%, respectively) paper only gives percentage data. limitations: it is not clear if the treatments for each group were carried out in the same room as each other or in different rooms –the room environment could influence the results raw data hard to extrapolate from graphs there was no drying only treatment christison et al. (1997) population: litters from 11 sows (cross-bred); parity not given housed in farrowing crates (conventional 0.45 m x 2.1-m farrowing crates with raised perforated floors) room temperature not given induced farrowing trial conducted from 0 – 21 days of age (weaning age not given) sample size: 98 piglets (litters standardised to nine piglets/sow – additional piglets were fostered off) intervention details: three treatment groups – the three treatments were randomly assigned within birth order trios (first three born, second three born, final three born were trio 1–3, respectively): control n = 33 piglets – piglets were not handled except to dry and colour one ear (method of drying not specified) dried n = 32 piglets – piglets dried at birth with paper towel and returned to where they were born, marked on back heat lamp n = 33 piglets – piglets picked up by back legs and moved under heat lamp, one ear was dried and coloured for identification (method of drying ear not specified) mucus was cleared from the nose and mouth for all groups. umbilical cords were detached or shortened if required to ensure that it did not hinder their movement. study design: randomised controlled trial outcome studied: teat seeking success (made up of latency to udder contact and first suckle) weights at various time points (2 hours, 6 hours, days 1, 3, 7, 14 and 21 mortality main findings (relevant to pico question): no effect of any treatment on mean time to udder contact no effect of any treatment on mean time to suckle no effect of any treatment on weight at 2 hours or average daily gain at 24 hours and 21 days mortality higher in control piglets 7/33 (21%) compared to dried piglets 2/33 (6%) and heat lamp piglets 0% mortality limitations: litters reduced to nine piglets which may mean that the litters were smaller than normal which may be less representative of the population as the piglets had less competition for teat access induced farrowing (this can make piglets less viable however, equal across treatments) marking process may confound results – dried piglets perhaps should have been marked on ear as well relatively small sample size dewey et al. (2008) population: litters from 126 sows (breed not given); parity 2–7+, mean 5.7 housed in farrowing crate – details not given natural farrowing room temperature not given weaning age ranged from 16–28 days with an average of 20.2 days sample size: 1367 piglets intervention details: two treatment groups: standard care litters n = 60 litters – cross-fostering at 24h, day 1 processing = teeth clipping, tail docking, and iron injection. instrument’s not cleaned between pigs, castrated at 10 days and given further iron injection maximal care litters n = 66 litters – as standard care with instruments dipped in antiseptic between uses and castration wound treated with iodine. piglets dried (method not stated) and assisted at farrowing, split suckling undertaken, electrolytes given and chilled piglets received extra care. sows given extra meal study design: randomised controlled trial outcome studied: weight at 16 days mortality morbidity main findings (relevant to pico question): no effect of treatment on mortality (standard = 8.3% and maximal = 7.2%) maximal pigs heavier at 16 days of age only percentage data available limitations: lot of variables changed between treatments, cannot decipher if one or more additional care factor influenced outcomes more than another system comparison rather than treatment/control study drying of piglets was not an independent treatment mcginnis et al. (1981) population: litters from 33 sows (breed and parity not given) housing – farrowing crate concrete floor natural farrowing room temperature 22°c trial conducted from 0 to 5 days of age sample size: 326 piglets from 33 sows intervention details: 2x2x2 factorial design 326 piglets were divided over eight treatment groups (exact number undergoing each treatment was not specified): alternate piglets of each sex were dried with paper towel within 2 minutes of birth two different floor temperatures 20°c and 30°c supplemental heat via 250-watt infrared heat lamp versus light bulb study design: randomised controlled trial outcome studied: skin temperature measured at 30 minutes, 1 hour then hourly to 8 hours after birth using an infrared thermometer rectal temperature was taken hourly to 8 hour then at 1, 2 and 5 days of age body weight measured at birth, 1, 2 and 5 days of age blood samples at birth, 2 and 5 days of age survival rates to 5 days main findings (relevant to pico question): exact numbers of piglets in each treatment group were not specified piglets dried at birth had higher rectal temperatures at 1 hour post birth (37.9 °c) compared to non-dried piglets (37.4°c) all other time points were similar between dried and non-dried piglets supplemental heat treatments had higher skin temperatures from 5–8 hours after birth dried piglets had higher skin temperatures at 30 minutes (34.2°c) after birth compared with non-dried piglets (33.0°c) dried piglets had higher skin temperatures at 1 hour after birth (34.9°c) compared with non-dried piglets (34.5°c). no impact of drying piglets on cortisol levels no treatment effects on survival limitations: since this paper was published genetics have changed dramatically which may influence comparison with other studies average 9.8 piglets per litter so no issues with large litter and subsequent competition for teats exact number of piglets in each treatment group not specified pasca et al. (2008) population: litters from 12 sows (landrace and large white); parity 1 (n=6) and parity 3 (n=6) housing – no details given no details of natural or induced farrowing room temperature not given sample size: 143 piglets from 12 sows intervention details: three treatment groups; two parity 1 and two parity 3 sows in each: control n=53 piglets – no intervention mistral powder n=45 piglets – powder applied to skin mistral powder + injection n=45 piglets – powder applied to skin and injection of dexamethasone (intramuscular 0.1 mg/piglet) study design: randomised controlled trial outcome studied: rectal temperature (1, 3, 6, 12 and 48h after birth) blood glucose levels (1, 12 and 24h after birth) birth and weaning weights main findings (relevant to pico question): results stated that the body surface was dry in 10–15, 1–2 and 1–2 minutes post parturition for control, mistral powder and mistral powder + injection, respectively. however, no definition given as to how the surface of the piglet being dry is defined from the data presented differences in temperature profiles: control piglets saw a decrease of 1.1 to 1.8°c in the first hour following birth. piglets treated with mistral powder had a decrease of 0.5 to 0.8°c in the first hour following birth. piglets treated with mistral powder + injection had a decrease of 5 to 1.8°c. the glycaemia at 1 hour after parturition records the highest values in the piglets treated with mistral powder (58–61 mg/ml) and mistral powder + injection, compared to control group (56–57 mg/ml) birth weights were 1.55 kg, 1.61 kg and 1.53 kg for control, mistral powder and mistral powder + injection respectively. weaning weights were 8.47 kg, 8.77 kg and 8.80 kg for control, mistral powder and mistral powder + injection respectively these data are all calculated by the author of this knowledge summary, from raw data given in the paper mortality was not discussed in the paper however, from the raw data the author of this knowledge summary calculated mortality as 5/53 (9.4%), 1/45 (2.2%) and 2/45 (4.4%) for control, mistral powder and mistral powder + injection respectively, assuming that piglets with no weaning data died limitations: methods lack description of what “mistral” powder is, on investigation it is actually a blend of desiccants (mineral), seaweed, clay and essential oils which the piglets are dipped into. more information on dexamethasome required as well not clear what statistical analysis was undertaken (if any) tables of raw data presented and discussed mortality not measured however, within the discussion dried piglets were stated to be heavier at weaning which may improve survival. this was calculated by the author of this knowledge summary using the assumption that piglets with no weaning weight recorded had died no statistical tests or variation of data stated, just numbers written in the text and tables of raw data presented pan (1995) population: large white x yorkshire piglets, sow numbers; parity not given housed in individual farrowing pen with concrete floor (dimensions not given) – no bedding temperature 23–35°c natural farrowing study conducted for 9 days post-farrowing (weaning age not stated) sample size: 44 piglets intervention details: two treatment groups: control – no intervention piglets allowed to dry naturally (n=22) dried – piglets dried immediately after birth with a clean dry cloth (n=22) study design: randomised controlled trial outcome studied: rectal temperature taken at 0.5, 14, 26, 38 and 50 hours post birth and days 3–9 post birth skin temperature taken at 0.5, 14, 26, 38 and 50 hours post birth and days 3–9 post birth main findings (relevant to pico question): no treatment effects seen on skin or rectal temperatures at any time point with the exception of 26 hours after birth. at 26 hours post birth rectal temperature was 103.37°f for dried piglets compared with 103.23 °f for non-dried piglets. at 26 hours post birth skin temperature was 103.83°f for dried piglets compared with 103.79 °f for non-dried piglets limitations: small sample size limited detail on the sows used quite warm ambient temperature (35°c) during experiment which may explain lack of difference between the groups mortality and growth rates not measured vasdal et al. (2011) population: litters from 67 (yorkshire x norwegian landrace) sows; parity 1–7 (average 2.7 ± 0.2) housed in individual farrowing pens (tunby®) 6.2 m2 in total. sow area = 5.0 m2 with 2.7 m2 slatted plastic floor. sawdust on floor during farrowing farrowing room temperature 20°c on day of farrowing, reduced to 16°c from next day natural farrowing weaning age not given sample size: 872 piglets intervention details: six treatment groups (all piglets had rectal temperature taken and birth order marked after which they were treated according to one of the following): control (n =14 litters) – piglet placed back at birth location creep (n=13 litters) – piglet placed in the creep area udder (n= 10 litters) – piglet placed at udder dry (n=10 litters) – piglet was dried with straw and paper towel for 15 seconds and placed back where it was found dry/creep (n=9 litters) – piglet was dried with straw and paper towel for 15 seconds and placed in the creep area dry/udder (n=11 litters) – piglet was dried with straw and paper towel for 15 seconds and placed at udder study design: randomised controlled trial outcome studied: weight (birth, 2h, 24h) time of birth latency to suckle rectal temperature (birth, 2h, 24h) mortality main findings (relevant to pico question): significantly more piglets died in the udder treatment (i.e. not dried), no other treatment effects on mortality. mortality was: control 7.9% creep 11.5% udder 15.1% dry 9.7% dry/creep 7.1% dry/udder 9.3% drying and placing piglets at the udder reduced mortality in one batch but not in the other two piglets placed near the udder were faster to suckle  only percentage data available limitations: number of litters not equal across the treatment groups. the method of randomisation is not specified white et al. (1996) population: litters from 60 (york x landrace) sows; parity 1–13 housed in diagonal farrowing crates 2.0 m x 0.76 m farrowing room temperature 22°c natural farrowing study conducted up to 21 days post farrowing (assumed weaning age) sample size: 626 piglets intervention details: two treatment groups: control (n=308) – no intervention treatment (attended) (n=318) – automated alert of farrowing followed by attendance by stockperson undertook the following procedures. piglets were dried, umbilicus tied, oral and nasal cavities suctioned, oxygen supplied, bovine colostrum administered and placed on teat study design: randomised controlled trial outcome studied: mortality cause of mortality weight (birth, days 7, 14, 21) haematocrit (birth, days 7, 14, 21) main findings (relevant to pico question): overall mortality significantly lower in attended farrowing 32/318 (10.1%) compared with control 56/308 (18.2%) these data include stillbirths. excluding stillbirths mortality was 27/318 (8.5%) and 38/308 (12.3%) for attended and unattended farrowing respectively. significantly more piglets were stillborn, starved and contracted e-coli in the control group weight of control piglets higher at birth (assumed that they had suckled before weighing) mean weight at 21 days higher for the attended piglets (5.33 kg) versus (5.09 kg) limitations: no drying only group, drying formed part of a number of interventions made at birth large range of parities however, similar between treatment groups appraisal, application and reflection when appraising the evidence on this topic it became clear that there are limited papers which can be used to address this research question. a number had to be excluded due to not being published in english (n= 6) and a large number were not directly related to the pico question as they addressed general management practices; sow management or older piglets. a number were also related to embryo production and development. papers which were not published in english could not be translated for this knowledge summary. we excluded them from the appraisal as only the abstract was available. where sows are loose housed, drying and placing piglets under a heat lamp did reduce death from crushing (andersen et al., 2009), overall however, mortality was similar whether piglets were dried and placed under a lamp or just placed under a lamp in comparison to a control. within this experiment there was no drying only treatment (andersen et al., 2009). whereas christison et al. (1997) compared no intervention or control with drying piglets and moving piglets under a heat lamp without drying them. this was a smaller cohort of piglets than that of (andersen et al., 2009) and the litters were standardised to just nine piglets per litter. mortality was significantly lower in dried piglets and those placed under a heat lamp compared to control piglets (christison et al., 1997). dewey et al., (2008) compared level of care given to piglets at birth through to 16 days of age. drying piglets was just one of many additional procedures undertaken on piglets considered to have had maximal care in comparison to standard levels of care. however, maximal care litters did end up heavier at 16 days with no impact on mortality between groups (dewey et al., 2008). another study with multiple treatments looked at the impacts of drying piglets with a paper towel, the addition of supplemental heat and two different floor temperatures on growth and thermoregulation (mcginnis et al., 1981). within this study piglets which were dried had higher rectal temperatures at 1 hour old and higher skin temperatures at 30 minutes and 1 hour of age (mcginnis et al., 1981). the sows in the study had quite small litters of just under 10 piglets per litter, which is not as comparable to modern sows with large litters. as well as paper towels and straw utilised to dry piglets there is research into using drying powders (goden, 2016; kiehne, 2006; pasca et al., 2008). however, the paper by goden (2016) was not available in english, kiehne (2006) was too general and pasca et al. (2008) did not include statistics. the work of pasca et al. (2008) also showed differences in the thermoregulation pattern when piglets were treated with drying powder, however, this paper did not look at differences in mortality between treatment groups. the development of thermoregulation is key for the piglet to adapt to environmental conditions outside the uterus (herpin et al., 2002). another small scale study compared drying piglets straight after birth with no intervention (pan, 1995). this study again did not look at mortality of growth rates of piglets, they focused on skin and rectal temperatures and there were no treatment effects in this study, however, it should be noted that the ambient temperature during the study was particularly high 23–35°c compared to recommended temperatures of 18–20°c for sow comfort (pan, 1995). a further study was undertaken by vasdal et al. (2011) comparing six treatment groups using different methods of drying piglets. drying piglets and placing piglets at the udder resulted in lower mortality in one but not all batches (vasdal et al., 2011). they did find however, that litter size; birth weight; latency from birth to suckle; and rectal temperature 2 hours post birth had an impact on mortality independent of treatment (vasdal et al., 2011). of the three treatments in the study of vasdal et al. (2011) which involved drying the piglets, the mortality rate was less than 10% which was positive considering the sows were loose-housed. in addition, placing the piglets close to the udder (with or without drying) reduces the latency to suckle (vasdal et al., 2011). rosvold et al. (2017) looked at overall management effort within 52 herds in norway, where higher levels of management included drying piglets. farms which dried piglets as well as supervised farrowing, practiced split suckling as well as other management practices were rewarded with lower levels of piglet mortality (rosvold et al., 2017) although drying piglets was not an independent treatment. another study which included drying as part of an overall enhanced management strategy at farrowing showed significant improvements in mortality (white et al., 1996). the extra interventions were estimated to take around 2 minutes of extra processing time with a reasonable amount of time waiting for piglets to be born with at least 15 minutes between piglets (mean 156 minutes per litter in total) (white et al., 1996). a number of the excluded papers focused on general management around farrowing and its impact on mortality. ogunbameru et al. (1991) evaluated different configurations of supplementary heat given during farrowing; their study found no benefits of treatment on piglet survival or growth, however, it was not clear what temperature the rooms were during the experiment. one issue which influences piglet performance including mortality is difficult to separate out, this is stockmanship. self-discipline and a warm nature were positively correlated with good performance on farrowing units in canada (ravel et al., 1996). more evidence is still required to determine which is the best method of drying piglets, particularly that of a peer reviewed nature with robust statistical evaluation to answer the pico addressed through this report. there is evidence that drying piglets results in less mortality. although there are a number of methods utilised across the studies of drying piglets which makes direct comparison difficult. there is evidence however, that drying piglets does influence thermoregulation with less of a drop post farrowing in core body temperature. there is also evidence that the temperature of the farrowing room itself has an impact on piglet mortality and sow performance. drying of piglets would appear to be of value within the general area of farrowing management and as such is not always a standalone treatment. the consideration of creep configuration and type of heating was outside the scope of this knowledge summary. these may have an impact along with the environmental conditions as mentioned above. farms will vary hugely in terms of creep management and as such this was considered out of the scope of this review. methodology section search strategy databases searched and dates covered: cab abstracts on the ovid interface 1973 to 2018 week 42 pubmed accessed via the ncbi website 1910–october 2018 search strategy: cab abstracts: piglets or exp piglets/ or ((newborn or birth or baby or neonatal or infant) and (pig* or swine)) (dry* or warm* or towel* or 'heat lamp') (mortal* or death or surviva* or viabil* or shiver* or chilling or chill or chills or hypothermia or thermoregulation or 'body temperature') or exp mortality/ or exp hypothermia/ or exp thermoregulation/ 1 and 2 and 3   pubmed: piglets or ((newborn or birth or baby or neonatal or infant) and (pig or pigs or swine)) drying or warming or towel or towelling or heat lamp mortality or death or survival or viability or shiver or shivering or chilling or hypothermia or thermoregulation or body temperature 1 and 2 and 3 dates searches performed: 31/10/2018 exclusion / inclusion criteria exclusion: most common reasons for exclusion was age of pigs, work focused on sows, embryos or older piglets (not pico) non-english papers could not be apprised fully as we could only see the abstract and therefore assessments of methods and experimental design could not be made papers which we could not get access to were following extensive online search and following contacting the british library (by clare boulton rcvs knowledge) inclusion: peer-reviewed articles/td> search outcome database number of results excluded – did not answer the pico excluded – non-english excluded – could not get access total relevant papers cab abstracts 262 230 6 7 19 pubmed 35 31 0 0 4 total relevant papers when duplicates removed 8 conflict of interest the author declares no conflicts of interest. the author would like to gratefully acknowledge clare boulton (rcvs knowledge) for help with the search strategy and obtaining papers that were not available. references (2019). prices & stats \ costings & herd performance \ indoor breeding herd. andersen, i. l., haukvik, i. a., & boe, k. e. (2009). drying and warming immediately after birth may reduce piglet mortality in loose-housed sows. animal, 3(4), 592–597. doi: http://dx.doi.org/10.1017/s1751731108003650 christison, g. i., wenger, i. i., & follensbee, m. e. (1997). teat seeking success of newborn piglets after drying or warming. canadian journal of animal science, 77(2), 317–319. doi:  https://doi.org/10.4141/a96-119 dewey, c. e., gomes, t., & richardson, k. (2008). field trial to determine the impact of providing additional care to litters on weaning weight of pigs. canadian journal of veterinary research, 72(5), 390–395. goden, b. (2016). how to get more piglets at weaning? svinovodstvo (moskva)(8), 22–23. herpin, p., damon, m., & le dividich, j. (2002). development of thermoregulation and neonatal survival in pigs. livestock production science, 78(1), 25–45. doi: https://doi.org/10.1016/s0301-6226(02)00183-5 kiehne, r. (2006). quick dry: warming up by drying piglets off conserving piglet energy. large animal. proceedings of the north american veterinary conference, volume 20, orlando, florida, usa, 7-11 january, 2006, 329. mcginnis, r. m., marple, d. n., ganjam, v. k., prince, t. j., & pritchett, j. f. (1981). the effects of floor temperature, supplemental heat and drying at birth on neonatal swine. journal of animal science, 53(6), 1424–1431. doi: https://doi.org/10.2527/jas1982.5361424x ogunbameru, b. o., kornegay, e. t., & wood, c. m. (1991). evaluation of methods of providing supplemental heat to newborn pigs during and after farrowing. journal of animal science, 69(10), 3939–3944. doi: https://doi.org/10.2527/1991.69103939x pan, s. (1995). effect of mop-drying on body temperature of porcine neonates. journal of veterinary and animal sciences, 26(1), 62–63. pasca, i., pusta, d., morar, r., cimpean, a., sobolu, r., oroian, r., dalea, i., & bagita, c. 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(1996). increasing piglet survival through an improved farrowing management protocol. canadian journal of animal science, 76(4), 491–495. doi: https://doi.org/10.4141/cjas96-075  intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in dogs undergoing elective procedures is medetomidine superior to acepromazine when used as a premedication? a knowledge summary by rebecca littlehales bvsc mrcvs 1* 1university of liverpool, chester high road, neston, ch64 7te *corresponding author (beckylittlehales@gmail.com) vol 5, issue 4 (2020) published: 02 dec 2020 reviewed by: jodie hughes (bvsc certavp(va) fhea dip.ecvaa mrcvs) and william mcfadzean (bvetmed certavp(va) dipecvaa mrcvs) next review date: 23 apr 2022 doi: 10.18849/ve.v5i4.318 pico question in dogs undergoing elective procedures does the use of medetomidine during premedication result in an increase in anaesthetic complication rates, when compared to acepromazine?   clinical bottom line category of research question treatment the number and type of study designs reviewed four papers were critically reviewed, all of which were randomised controlled trials strength of evidence strong outcomes reported there were some statistically significant differences between using medetomidine and acepromazine as premedications in the outcomes measured, but as the clinical parameters including blood pressure were still within acceptable clinical limits, the clinical benefits of these findings remain undetermined. there is also evidence to suggest that patients premedicated with medetomidine have less of a perioperative stress response than those receiving acepromazine, but in addition may have increased risk of cardiac conduction disturbances, but the clinical importance of these findings is also unknown conclusion the overall findings showed that either drug can be used as a suitable premedication, but the differences in pain score postoperatively shown in one small study mean that due to its poor analgesic properties it is recommended when using acepromazine instead of medetomidine, that additional analgesia should be given to reduce postoperative pain for better animal welfare   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario premedications are often used in anaesthetic protocols for dogs undergoing elective procedures, with acepromazine and medetomidine being commonly used in combination with other drugs. these two drugs belong to different classes of anaesthetic drugs, with acepromazine being a phenothiazine whilst medetomidine is an alpha-2 adrenergic receptor agonist. this summary aims to determine if there are any differences in anaesthetic complication rates between these two drugs, so that veterinary surgeons in practice are more informed on which would be best to use in their anaesthetic protocols for the best patient outcome. the evidence four blinded controlled trials (grint et al., 2010; väisänen et al., 2002; väisänen et al., 2005; and wamaitha et al., 2019) were found to be relevant to the pico question, which have strong study designs. the wamaitha et al. (2019) study compared the two drugs when used as a premedication in combination with an induction using ketamine and propofol. the outcomes measured in the study that were relevant to the pico question were postoperative pain scoring and smoothness of recovery based on time to standing and whether they had tremors when recovering, and post induction apnoea. the grint et al. (2010) study provided a larger, more representative sample size and compared the two drugs when used in combination with buprenorphine as a premedication. the outcomes measured in this study were more based around cardiopulmonary parameters as a measure of anaesthetic complications, which were considered less in the wamaitha et al. (2019) study. the two studies by väisänen et al. (2002 & 2005) were conducted concurrently using the same study design, one (2002) to compare the perioperative stress response between acepromazine and medetomidine as a premedication based on anaesthesia monitoring data, blood hormone concentrations, heart rates and mean arterial pressure and assessment of pain and distress. the other study (2005), compares the electrocardiography data of the same cohort focusing on heart rate, cardiac conduction disturbances and heartbeat variability data. summary of the evidence grint et al. (2010) population: dogs were enrolled in the study at the university of liverpool’s small animal hospital in a 2-year period who were undergoing routine surgical or diagnostic procedures that involved only a mild to moderate stimulus such as neutering, arthroscopy, endoscopy, radiography and other similar minor procedures. only dogs with an american society of anaestheologists (asa) status of 1 (healthy) or 2 (mild systemic disease) were included in the study. sample size: 90 dogs (two dogs from group 1 were lost so were not analysed, and no explanation is given for this) intervention details: the dogs were randomly assigned (by block randomisation and sealed envelopes) to one of three groups. group 1 (28 dogs) were given acepromazine (0.03 mg/kg) and buprenorphine (0.02 mg/kg) intramuscularly. group 2 (30 dogs) were given medetomidine (5 µg/kg) and buprenorphine (0.02 mg/kg) intramuscularly. group 3 (30 dogs) were given medetomidine (10 µg/kg) and buprenorphine (0.02 mg/kg) intramuscularly.   experimental procedure: before administration of any premedications, a full clinical examination was performed, and sedation score was recorded for each dog. the premedications were given in a single syringe according to the treatment group that the dog was assigned to and were administered into the dog’s cervical epaxial muscle by a veterinary surgeon or veterinary nurse. the dogs were then observed for any adverse effects. after 15 minutes (group 1) or 30 minutes (groups 2 and 3) in line with the peak sedation effect time of the drugs used, respiratory rate, pulse rate and sedation score were then recorded. a cephalic catheter was placed in all dogs and anaesthesia was induced using iv propofol until the dogs’ jaw tone was relaxed and the tongue could be held without retraction. previous research was used to predict the required dose of propofol needed for induction. group 1 were administered propofol using a syringe driver at 2.25 mg/kg/min, group 2 at 1.5 mg/kg/min and group 3 at 0.75 mg/kg/min. an endotracheal tube was placed and anaesthesia was maintained using isoflurane in oxygen with a specified appropriate breathing system (parallel lack anaesthetic circuit for dogs weighing >10 kg with fresh gas flow equal to minute ventilation and a jackson-rees modified ayre’s t-piece for dogs weighing <10 kg with fresh gas flow equal to at least 2x minute ventilation). anaesthesia was maintained at a specified standard depth throughout. intravenous fluid therapy (hartmann’s) was administered throughout at 10 ml/kg/hour, and additional analgesia of carprofen at 4 mg/kg was administered intravenously if required. monitoring throughout the anaesthetic period involved oxygen saturation (using a pulse oximeter and lingual probe), end tidal partial pressure carbon dioxide concentration (using a capnograph), oscillometric blood pressure measurements (using dorsal pedal or palmar carpal arteries), pulse rate and respiratory rate. these values were all recorded at 5 minute intervals. there were protocols in place should dogs develop hypotension or bradycardia, but none of the dogs required this treatment. at the end of the procedure, isoflurane was stopped. for groups 2 and 3 if the procedure length was <120 minutes atipamezole was given intramuscularly at the same time as stopping the isoflurane (group 2 at 0.025 mg/kg and group 3 at 0.05 mg/kg). dogs were continually monitored during recovery, where times from discontinuing isoflurane to extubation, movement to sternal recumbency and standing and walking were recorded. study design: randomised, blinded, controlled trial outcome studied: sedation scores median dose of propofol used mean vaporiser setting duration of anaesthesia adverse effects post premedication mean, diastolic and systolic blood pressure heart and respiratory rates mean end tidal partial pressure of carbon dioxide oxygen saturation time from isoflurane discontinuation to extubation, moving to sternal recumbency, standing and walking main findings (relevant to pico question): adverse effects post premedication group 1: salivation (1/28), signs of pain on injection (1/28) group 2: salivation (2/30), signs of pain on injection (1/30), muscle twitching (1/30) group 3: signs of pain on injection (4/30), salivation (3/30), vomiting (3/30), muscle twitching (2/30) blood pressure mean and diastolic blood pressure was significantly lower for dogs in group 1 compared to those in groups 2 and 3 heart and respiratory rates mean and lowest heart rates were significantly higher for dogs in group 1 compared to those in groups 2 and 3 respiratory rates were significantly higher for dogs in group 1 compared to those in groups 2 and 3 mean end partial pressures of carbon dioxide mean values were significantly lower for dogs in group 1 compared to the other groups, but all values were within normal range limitations: no record of how dogs were assessed as to whether they needed additional analgesia, or how many of the dogs were given carprofen as a treatment for this. the difference in the amounts of propofol and isoflurane administered depending on the group may have confounded the mean arterial pressure values. tissue perfusion was not measured which may have helped to explain the clinical significance of the differences in mean arterial blood pressures. the dose of medetomidine used in group 2 is lower than the licenced dose range as stated by the datasheet, so at this dose it used off-licence. there are two dogs’ data which was not analysed as it was lost and no explanation is given for this. väisänen et al. (2002) population: dogs that underwent routine elective ovariohysterectomy at helsinki university veterinary teaching hospital between january and august 2000. inclusion criteria required the dogs to have a good body condition score, weigh between 15 and 40 kg, be 2–7 years old and not on any medications. brachycephalic and greyhound-type breeds were excluded. the dogs were determined to be in good health based on a thorough clinical examination, and haematology and biochemistry blood analysis. the age and body weights of the dogs in the two different groups did not differ significantly. sample size: 42 dogs (this was initially 44 dogs, but two dogs were omitted in the results due to technical difficulties) intervention details: the method of allocating the dogs into the two treatment groups was using sealed envelopes. group med (21 dogs) were given medetomidine (20 µg/kg) and butorphanol tartrate (0.2 mg/kg), intramuscularly. group ace (21 dogs) were given acepromazine maleate (0.05 mg/kg) and butorphanol (0.2 mg/kg), intramuscularly.  experimental procedure on the day of the procedures, the dogs arrived at or before noon and stayed in the clinic for 24 hours. on arrival each dog was placed in a separate cage in a quiet area and were only handled by the experimental team. after around 1 hour of time spent in the cage, the premedication was administered. the premedications were all in covered syringes of equal volumes, and were administered into the biceps femoris muscle by the same trained investigator who was unaware of the medication given to each dog, but was aware of the two possibilities. the dog was then left undisturbed for 15–20 minutes. then a jugular catheter (for blood sample collection) and femoral artery catheter (for continuous direct measurement of blood pressure) were placed using local anaesthetic. cephalothin (30 mg/kg, iv) and carprofen (4 mg/kg, iv) were administered before induction of anaesthesia. an infusion of lactated ringer’s solution (10 ml/kg/h, iv) was started, and the infusion was continued until the end of surgery. anaesthesia was then induced using propofol in small increments over a 90 second period to allow orotracheal intubation, and the amount required was recorded. anaesthesia was maintained by using isoflurane in oxygen (flow rate of 1 l/min) through a semi-closed circle. at least 10 minutes elapsed from induction to commencing the surgery. ovariohysterectomy was performed via a routine standard ventral midline approach by one of three experienced veterinary surgeons. during anaesthesia, heart rate, direct arterial blood pressure, end-tidal co2 (etco2), and end-tidal isofluorane concentrations, respiratory rate, and arterial haemoglobin saturation (via an oxygen saturation (spo2) measurement using a probe on the dog’s tongue) were measured continuously. arterial blood samples were obtained just prior to induction and at the end of surgery for measurement of partial pressure of oxygen (pao2), partial pressure of carbon dioxide (paco2), and ph. dogs could breathe spontaneously, but respiration was assisted manually when necessary to maintain etco2 <60 mm hg. additional boluses of fluids (5–10 ml/kg, iv) were administered to prevent hypotension (mean arterial blood pressure [map] <60 mmhg). heating blankets were used to maintain rectal temperature at ≥ 37 c. after finishing the surgery, buprenorphine (0.010 mg/kg) was administered iv, then the dogs were maintained in a light plane of anaesthesia for 15 minutes while the femoral artery catheter was removed. the vaporiser was then turned off, and the dogs could breathe pure oxygen for 5 minutes. the duration of preoperative sedation, anaesthesia, and surgery was recorded. the dogs were recovered in their cages and time until extubation was recorded. dogs that became excited during recovery were given propofol (2–4 mg/kg, iv) and buprenorphine (0.005 mg/kg, iv). physical examinations were performed at predetermined time points, and additional warming was provided when needed, to maintain rectal temperature ≥ 37o buprenorphine (0.010 mg/kg, iv) was used for postoperative analgesia when required. throughout the study, each dog wore an ambulatory electrocardiographic monitor (holter monitor), and the behavior was video recorded. results of the holter monitoring and behavioural analysis were not evaluated in this study. hormone concentration measurements were obtained from the jugular vein and collected in edta (ethylenediaminetetraacetic acid) tubes. plasma was separated by refrigerated centrifugation within 30 minutes of collection. concentrations of epinephrine, norepinephrine, cortisol, and β-endorphin were measured via methods described in the paper. samples that had catecholamine concentrations less than the limit of detection were assigned a value equal to the limit of detection. the first blood samples were obtained at time of arrival via jugular venipuncture. the subsequent samples immediately prior to induction, within 2 minutes of removal of the second ovary, end of the surgery, 1, 3 and 6 hours post surgery and 24 hours after the initial sample were taken via the indwelling catheter. blood volume was replaced by giving a bolus of 20 ml of lactated ringer’s solution and heparinised saline solution was used to prevent clotting of the catheter between samples. heart rate was measured by pulse palpation immediately before administration of preanaesthetic medication and 1, 3, and 6 hours after surgery. in addition, intraoperative heart rate and map (directly measured) were recorded immediately prior to induction, 10 minutes after induction, at the time of the abdominal incision, at time of removal of each ovary, during closure of the incision, and at the end of surgery. response of each dog to handling was recorded during the entire perioperative period. sedation and pain and distress scores were determined immediately before administration of preanaesthetic medication and after surgery at the same times as collection of blood samples for hormonal analysis. assessments were performed for each dog after other measurements and collection of samples were completed. sedation was assessed initially by monitoring each dog’s response to opening of the door to the cage, hand clapping, and speaking to the dog. for pain and distress evaluation, vocalisation, restlessness, freedom of movement, and finally, response to firm pressure applied to the region of the incision were observed. the protocol used was a modification of scoring systems that are described elsewhere in literature. study design: randomised, blinded, controlled trial outcome studied: anaesthetic variables (duration of perioperative sedation, duration of anaesthesia, mean duration of surgery, and mean interval from the end of surgery until extubation, amount of propofol required, end-tidal isoflurane concentration, ph and spo2, pao2 and paco2, additional fluids required, additional propofol and buprenorphine required to treat excitation during recovery). blood hormone concentrations (concentrations of epinephrine, norepinephrine, cortisol, and β-endorphin). heart rate and map throughout. assessment of pain and distress (by response to handling, sedation assessment, pain and distress score via a described protocol). main findings (relevant to pico question): anaesthetic variables group ace required significantly more propofol for induction of anaesthesia (mean of 3.6 ± 0.7 mg/kg), compared with group med (mean of 1.3 ± 0.2 mg/kg). mean end-tidal isoflurane concentration (etiso) was significantly higher during anaesthesia for the group ace (mean of 1.6 ± 0.2%), compared with group med (mean of 1.4 ± 0.3%). 11 dogs in group ace were given additional fluids (ranging from 5–10 ml/kg; mean of 6 ml/kg) at the beginning of anaesthesia; none of the dogs in the med group received any additional fluids. blood hormone concentrations plasma concentrations of epinephrine and norepinephrine were significantly lower in group med, than group ace. the values for group med decreased to a lower concentration and increased at a later time point than group ace also. concentration of cortisol was significantly lower for group med, compared with group ace; however, the cortisol concentration increased during surgery in both groups and remained at or above the concentration of the initial sample until collection of the sample at 24 hours.  heart rate and map heart rate was significantly lower and map significantly higher in group med, compared with values for group ace. the map decreased significantly after induction of anaesthesia in both groups, but values did not differ between groups during surgery.  assessment of pain and distress signs of sedation were apparent for a longer period in group ace, with the sedation scores being significantly higher for group ace than for group med 3 and 6 hours after completion of surgery. group med had higher pain and distress scores throughout the entire assessment period, compared with group ace, but the values were only significantly different 6 hours after surgery. limitations: small sample size of 42 dogs split into two groups, which may not be representative of the total dog population, and it was not stated by the researchers what the required sample size should be for adequate study power. therefore, this may affect the reliability of the conclusions made. the difference in the amounts of propofol and isoflurane administered depending on the group may have confounded the mean arterial pressure values. tissue perfusion was not measured which may have helped to explain the clinical significance of the differences in mean arterial blood pressures. väisänen et al. (2005) population: dogs that underwent routine elective ovariohysterectomy at helsinki university veterinary teaching hospital between january and august 2000. inclusion criteria required the dogs to have good body condition, weigh between 15 and 40 kg, be 2­–7 years old and not on any medications. brachycephalic and greyhound-type breeds were excluded. the dogs were determined to be in good health based on a thorough clinical examination, and haematology and biochemistry blood analysis. the age and body weights of the dogs in the two different groups did not differ significantly. sample size: 43 dogs (although there were technical errors which led to some data from both groups not being analysed; this is fully explained in the results section of the study) intervention details: the dogs were randomly allocated to the two treatment groups by the method of sealed envelopes. group med (21 dogs) were given medetomidine (0.02 mg/kg) and butorphanol tartrate (0.2 mg/kg), intramuscularly. group ace (22 dogs) were given acepromazine maleate (0.05 mg/kg) and butorphanol (0.2 mg/kg), intramuscularly.  experimental procedure on the day of the procedures, the dogs arrived at or before noon and stayed in the clinic for 24 hours. on arrival each dog was fitted with an ecg (echocardiogram) holter monitor and placed in a separate cage in a quiet area and were only handled by the experimental team. after around 1 hour of time spent in the cage, the premedication was administered. the dog was then left undisturbed for 15–20 minutes. then a jugular catheter (for blood sample collection) and femoral artery catheter (for continuous direct measurement of blood pressure) were placed whilst the dogs were in lateral or dorsal recumbency with minimal or no restraint. carprofen (4 mg/kg, iv) was administered before induction of anaesthesia. anaesthesia was then induced 85 minutes post premedication, using propofol. mean ± sd dosage of propofol was 1.3 ± 0.2 mg/kg iv, for dogs premedicated with medetomidine and 3.6 ± 0.7 mg/kg iv, for dogs premedicated with acepromazine. anaesthesia was maintained by using isoflurane in oxygen, mean ± sd (standard deviation) end-tidal isoflurane concentration during anaesthesia was 1.4 ± 0.3% for dogs premedicated with medetomidine and 1.6 ± 0.2% for dogs premedicated with acepromazine. ovariohysterectomy was performed via a routine standard ventral midline approach by one of three experienced veterinary surgeons. during anaesthesia, end-tidal partial pressure of co2 (etco2) was maintained at < 60 mmhg by use of intermittent manual ventilation. oxygen saturation as measured by pulse oximetry remained between 99% and 100% and mean arterial blood pressure remained > 60 mm hg throughout surgery in all dogs. rectal temperature was maintained at ≥ 37oc by use of heating blankets. after finishing the surgery, buprenorphine (0.010 mg/kg) was administered iv and the duration of preoperative sedation, anaesthesia, and surgery was recorded. the dogs recovered in their cages and time until extubation was recorded. dogs that became excited during recovery were given propofol (2–4 mg/kg, iv) and buprenorphine (0.005 mg/kg, iv). in seven dogs (two in group ace and five in group med), an additional dose of buprenorphine (0.01 mg/kg, iv) was administered 6 hours after surgery. physical examinations were performed at predetermined time points, and additional warming was provided when needed, to maintain rectal temperature ≥ 37o. 6 hours post surgery the dogs were given food and water and taken for a walk. after this, the dogs were taken for walks and physical examinations were performed at predetermined intervals. around 24 hours after admission, ambulatory electrocardiography was discontinued, and dogs were discharged. the ambulatory electrocardiography equipment used involved five adhesive electrodes that were used to obtain two transthoracic leads. to allow an assessment of the relationship between cardiac activities and perioperative events, the clock of the holter monitor was synchronised with one worn by one of the members of the investigative team and with the clock on the video recorder used to record the dogs’ behaviour when in their cages. a standard holter analysis system was used to analyse ambulatory ecgs and determine hourly minimum, maximum, and average heart rates; number of episodes of secondand third-degree atrioventricular block; number of ventricular premature complexes (vpcs); and number of sinus pauses > 2.0 seconds long. to more closely evaluate heart rate behaviour, printouts of heart rates recorded every 2 minutes were also obtained. analyses were conducted by a physician accustomed to reading canine ecgs. full disclosure printouts were checked by a veterinarian and verified by a veterinary cardiologist to ascertain correct labelling of arrhythmic events. the in-depth methods of ecg analysis are detailed in full in the study methods. study design: randomised controlled trial outcome studied: heart rate cardiac conduction disturbances heartbeat variability additional observations (lying down time) main findings (relevant to pico question): heart rate minimum heart rate during the 24 hour recording period was significantly lower among dogs in group med (mean of 38 beats/min; 95% ci, 35–40 beats/min) than in group ace (mean of 48 beats/min; 95% ci, 45–51 beats/min). this was mainly attributed to low heart rates during the preoperative sedation phase and within the first few hours after surgery in dogs given medetomidine. cardiac conduction disturbances the number of episodes of second-degree atrioventricular (av) block was significantly greater among dogs in group med than in group ace. in the dogs in group med the episodes of atrioventricular block were mostly in the 30 minutes following premedication. both mobitz type i and ii types of second-degree av block were seen, but third-degree atrioventricular block was not identified in any of the dogs (kashou et al., 2020). the number of dogs that had sinus pauses > 2.0 seconds and median duration of the longest pauses were significantly greater among group med (20 dogs; median duration of longest pause, 3.5 seconds; range, 2.2–7.5 seconds) than in group ace (14 dogs; median duration of longest pause, 2.5 seconds; range, 2.1–5.5 seconds). in group med, pauses occurred most often during the preoperative sedation or early recovery period. in group ace, pauses occurred most often during the night. heartbeat variability in the time up until 6 hours post surgery, the time domain hrv (heart rate variability) indices (sd of all normal-to-normal r-r intervals, square root of the mean squared differences of successive normal-to-normal r-r intervals, and proportion of interval differences for successive normal-to-normal r-r intervals > 50 milliseconds) were significantly higher among group med than in group ace. however, intraoperative time domain hrv indices were lower and the lf:hf (low frequency: high frequency) ratio was significantly higher among  group ace than group med. limitations: it is stated that this study was conducted alongside a previous study conducted by the author (väisänen et al., 2002), however there are differences in the described experimental procedure, this leads to ambiguity. most importantly in relation to this, in this study it does not suggest that the study was blinded, whereas väisänen et al. (2002) suggests that the investigator was blinded. small sample size of 43 dogs split into two groups, which may not be representative of the total dog population, and it was not stated by the researchers what the required sample size should be for adequate study power. therefore, this may affect the reliability of the conclusions made. the difference in the amounts of propofol and isoflurane administered depending on the group may have confounded the mean arterial pressure values. tissue perfusion was not measured which may have helped to explain the clinical significance of the differences in mean arterial blood pressures. there is a lack of control 24-hour electrocardiography recordings available to compare these results to, especially when considering the arrhythmias that occurred during the night in the study. the calculations of heartbeat variability included measurements during the periods of arrhythmia which affects their accurate estimation. wamaitha et al. (2019) population: dogs were recruited from willing owners within the area of the faculty of veterinary medicine, university of nairobi, kenya and had to be free of clinical disease. sample size: 12 male mongrel dogs intervention details: 12 dogs split into group a (six dogs) and group b (six dogs) randomly by computer random number generator. group a involved intramuscular sedation using acepromazine (0.1 mg/kg bodyweight) then induction and maintenance of anaesthesia using intravenous 4 mg/kg ketofol (1:1 ratio of ketamine and propofol). group b involved intramuscular sedation using medetomidine (0.02 mg/kg bodyweight) then induction and maintenance of anaesthesia using intravenous 4 mg/kg ketofol (1:1 ratio of ketamine and propofol). experimental procedure: dogs were housed at the department of clinical studies in individual kennels for 2 weeks of acclimatisation before the study began and were fed a commercial dog food once daily with ad libitum water. they were all wormed using a combined praziquantel, pyrantel pamoate, fenbental product (vermic total®) plus given ectoparasite control consisting of chlorfenvinphos (steladone®) once per week. during this 2-week acclimatisation period the dogs were regularly handled, and clinical examinations performed weekly. food and water were withheld 12 hours prior to the procedure. each dog was weighed using digital scales and sedation and pain scores, pedal and palpebral reflexes were assessed before they were sedated. the dogs were then sedated according to whether they were in group a or b and the investigator was blinded to this process to reduce bias. at 10 minutes post sedation, a cephalic intravenous catheter was placed, then the scrotal area was shaved, scrubbed and disinfected with 70% ethyl alcohol. at 30 minutes post sedation, anaesthesia was induced using ketofol and an endotracheal tube was placed. the anaesthetic monitoring was supported using a multi-parameter machine. a standard dose of ketofol (50% of induction dose) was administered when the laryngeal reflex was restored, indicated by coughing. another dose (25% of induction dose) was drawn up for use if needed throughout the anaesthetic period. orchidectomy was performed routinely, with warmed lactated ringer’s solution administered intravenously through the catheter at 10 ml/kg/hr throughout the surgery until extubation. the sedation score was measured every 5 minutes from the injection of sedation using a protocol described by tsai et al. (2013) and were measured for post induction apnoea. palpebral (by running a finger along the dog’s eyelashes) and pedal (by firm pressure on interdigital skin of either hindlimb) reflexes were measured throughout the anaesthetic period. the endotracheal tube was removed when the laryngeal reflex (indicated by coughing) returned and dogs were monitored in recovery. study design: randomised, blinded, controlled trial outcome studied: postoperative pain score – assessed using the short form glasgow composite pain scale (reid et al., 2007). it was measured at 1, 2, 4, 8 and 24 hours postoperatively. if the pain score was ≥13 out of a total of 24 at any point, the dog was excluded from the study and given intramuscular phenylbutazone at 8 mg/kg. sedation score (using protocol described by tsai et al., 2013). duration of anaesthesia. smoothness of recovery – based on number of attempts to stand and presence of tremors or not. main findings (relevant to pico question): postoperative pain score in the second hour postoperatively, dogs in group a had significantly (p=0.01) higher pain scores (median of 8) compared to dogs in group b (median of 6). in the fourth hour postoperatively, dogs in group a had significantly (p=0.01) higher pain scores (median of 7) compared to dogs in group b (median of 6). in the eighth hour postoperatively, dogs in group a significantly (p=0.004) higher pain scores (median of 6.5) compared to dogs in group b (median of 4.5). at the end of the monitoring period (24 hours postoperatively), dogs in group a had significantly (p=0.01) higher pain scores (median of 5.5) compared to dogs in group b (median of 2.5). smoothness of recovery dogs in group b had a significantly longer (p<0.01) extubation time compared to those in group a. dogs in group a took longer to stand (37.2 minutes ±7) than those in group b (17 minutes ± 7.1) which was statistically significant (p=0.04). the pedal reflex was absent for a longer period in the dogs in group b (50 minutes) compared to those in group a (10 minutes), which was statistically significant (p=0.01). the palpebral reflex was absent for a longer period in the dogs in group b (30 minutes) compared to those in group a (5 minutes), which was statistically significant (p=0.04). 83% (5/6) of dogs in group a exhibited tremors on recovery compared to 33% (2/6) of dogs in group b. cardiorespiratory assessment 67% of dogs given medetomidine showed post induction apnoea, compared to 33% of dogs given acp. no individual numbers of dogs used to calculate these percentages are stated in the study. limitations: the paper did not analyse any variations in age or weight of the dogs in the two groups. small sample size of 12 dogs split into two groups, which may not be representative of the total dog population, and it was not stated by the researchers what the required sample size should be for adequate study power. therefore, this may affect the reliability of the conclusions made. no values given for extubation time for both treatment groups. no evaluation of cardiorespiratory parameters pre, peri or postoperatively. many of the comparisons of values that show differences in outcomes are not statistically significant. some outcomes have percentages given but it is not specified as whether they were found to be statistically significant or not. the pain score cut off used for rescue analgesia in this study was greater than or equal to 13/24, whereas in clinical practice a much lower cut off may be used. it is not clear whether the investigator conducting the observations/pain scores was consistent throughout, or whether there were multiple observers as this could lead to inconsistent assessment of the dogs. appraisal, application and reflection when appraising the evidence on this topic it became clear that there were only four papers that directly compare the use of medetomidine and acepromazine in a randomised control trial study design. any other study design was deemed not relevant to the pico question as studies with different intervention protocols cannot be directly compared. it is also important to consider what is defined as an ‘anaesthetic complication’, as this may vary based on different studies. according to one study looking into the incidence of cardiorespiratory anaesthetic complications, (in descending order of incidence) bradycardia, hypotension, hypoventilation, hypoxia, hypothermia and death were the most common (redondo et al., 2007). a rapid, smooth and complete recovery is advantageous in veterinary patients, especially in outpatient procedures such as neutering (laing et al., 2009). an important aspect of this is peri and postoperative pain which can contribute to a poor recovery, and cardiorespiratory complications also occur in recovery (lerche et al, 2000). in the first study evaluated (grint et al., 2010) it was shown that medetomidine maintained blood pressure better than acepromazine, but whether this has any clinical benefit was not studied. this could have potentially been assessed by measuring tissue perfusion which was not done in the study and would have improved the clinical relevance. however, the practicalities of this would be difficult in a clinical setting with there being no readily available clinical equipment to measure this or available normal values for comparison; and it would have to be determined which tissue or tissues were relevant to study. it was also found that mean and lowest heart rates perioperatively were significantly higher for dogs given acepromazine, compared to those given medetomidine, which may be because acepromazine has no analgesic properties (thurmon et al., 1996; and smith et al., 2001). this may also be due to alpha-2 adrenergic receptor agonist drugs such as medetomidine often causing a decrease in heart rate of patients due to its pharmacological effects on blood pressure (murrell, 2016). overall, the study had strong methodology due to the randomised controlled trial design with a large sample size and had minimal limitations because of this, therefore the results are highly applicable to the overall dog population. however, the study did not fully explain the clinical conditions of the dogs who were judged to have an asa status of 2 (mild systemic disease) but this may have had a confounding effect on the outcomes (abouleish et al., 2015). there were also differences in the amounts of propofol and isoflurane administered between the groups which could have confounded the mean arterial pressure values as propofol has hypotensive effects due to resetting of baroreceptor sensitivity so reflex tachycardia often does not occur (grood et al., 1987) plus isoflurane causes dose-dependent cardiovascular depression and a reduction of blood pressure (lynch, 1986). in the second study evaluated (väisänen et al. (2002), it was found that plasma concentrations of epinephrine, norepinephrine and cortisol levels were significantly lower in the group receiving medetomidine than those given acepromazine. this would suggest that medetomidine elicits a reduced perioperative stress response when administered compared to acepromazine, however the medetomidine group did have significantly higher pain and distress scores than the acepromazine group 6 hours post surgery. it is proposed that an increased stress response could be a factor in patient morbidity during anaesthesia (desborough, 2000), so this study suggests that medetomidine would be better as reducing this risk. a limitation of this study was the sample size; by using only 42 dogs split into the two groups, it may not be representative of the normal dog population. it was also not stated by the researchers if any statistical power calculations were carried out in order to work out an adequate sample size to use. it is also worth noting that the authors used either acepromazine or medetomidine in combination with butorphanol as the premedication in the study; butorphanol is a opioid with only mild analgesic effects at the doses given in the study (grimm et al., 2000). therefore, acepromazine and butorphanol as a premedication would provide very little analgesia to the patient. due to this, opioids with more potent analgesic properties should ideally be used for surgical procedures, such as methadone or buprenorphine. it has been suggested by research that pre-emptive analgesia is much more effective than giving peri or postoperative analgesia like this study did (dahl et al., 2005). this may have affected the results, as having more appropriate increased analgesia may have had a differing effect on the variables measured, especially heart rate. in the third study evaluated (väisänen et al. (2005), it was found that heart rates were significantly lower during the 24-hour monitoring period for those dogs administered medetomidine compared to those given acepromazine, however this is not surprising given the pharmacological effects of medetomidine as alpha2-agonists often cause bradycardia due to their effects on blood pressure (murrell, 2016). in those given medetomidine, there were significantly greater number of episodes of second-degree atrioventricular block compared to those given acepromazine, and mostly these were in the 30 minutes after premedication, which suggests medetomidine may be the cause. the medetomidine group also had a significantly greater number of dogs with sinus pauses greater than 2 seconds and the median duration of the longest were also significantly longer. it is also important to recognise that the methods that the study used to calculate heartbeat variability values can be affected by unstable experimental conditions, which would have unavoidably happened in this study as the patients were left unattended, especially overnight. overall, the study does provide data on the cardiac electrical activity and autonomic modulation in dogs undergoing routine surgery when acepromazine or medetomidine is used as part of a premedication, and showed that greater influences on cardiac efferent vagal activities were documented for dogs premedicated with medetomidine than with acepromazine. the clinical importance of this is currently unknown, and further research on this relevance should be conducted. in the fourth study evaluated (wamaitha et al., 2019), at four of the five time points when postoperative pain was assessed by pain scoring, the dogs given acepromazine had statistically significantly higher pain scores than those given medetomidine. again, acepromazine has no analgesic effects (thurmon et al., 1996; and smith et al., 2001) which could explain these differences. it may also be important to consider the pain score cut off that studies use for rescue analgesia, as in this study the dogs were given additional analgesia if the pain score was greater than or equal to 13/24, whereas in clinical practice a much lower cut off may be used. the short-form glasgow composite measure pain scale (cmps-sf) is commonly used to pain score animals in clinical practice, as it is a shortened version of the highly validated glasgow composite measure pain scale. the clinical intervention point for additional analgesia is 6/24 in the cmps-sf (reid et al., 2007), so is considerably lower than the cut off used in this study. this suggests that many more of the dogs in the study may have required additional analgesia if the cmps-sf cut off value was used to pain score the dogs, and raises potential welfare concerns. the paper also does not report the distribution of the pain score data and presents the median as decimals when the score is an integer. the study reports that the dogs given medetomidine had a smoother recovery based on the finding that dogs given medetomidine took significantly less time to stand, appeared to struggle less and exhibited less tremors on recovery. however, the extubation time was significantly longer than those given acepromazine along with fewer attempts to stand, plus the pedal and palpebral reflexes were absent for longer than those given acepromazine. it is not clear whether the investigator conducting the observations/pain scores was consistent throughout, or whether there were multiple observers as this could lead to inconsistent assessment of the dogs, plus some of the outcomes such as ‘appearing to struggle less’ are subjective measures. a key limitation of this study was the sample size; by using only 12dogs split into the two groups, it may not be representative of the normal dog population. it was also not stated by the researchers if any statistical power calculations were carried out in order to work out an adequate sample size to use. therefore, this may have affected the reliability of the conclusions based on the statistical significance values suggested by the researchers. the researchers also did not analyse any variations in age or weight of the dogs between those allocated to the two different groups and this could have led to individual differences in the dogs confounding the outcome results. another limitation of the study is that no evaluation of cardiorespiratory parameters especially perioperatively such as blood pressure, heart rate etc. was performed. these are important measures of potential anaesthetic complications and should have been monitored as part of routine anaesthetic monitoring by the researchers so could have been stated and analysed in the study. the use of ketofol (ketamine mixed with propofol) is not commonly used in the uk veterinary industry as an induction agent in dogs in combination with propofol, however the use of ketamine in combination induction protocols is routinely used. this induction using ketamine could explain the incidence of muscle tremors during recovery, as ketamine is known to cause muscle tremors, increased muscle tone and spontaneous movement in dogs (kovalcuka et al., 2013). alfaxalone is also commonly used as an induction agent in the uk and none of the papers found had evaluated this drug in any of their protocols which could be an area of future research. the study suggested that the reason that the dogs receiving acepromazine exhibited more muscle tremors than those given medetomidine was due to the medetomidine causing muscle relaxation, whereas the acepromazine is not as effective at counteracting the muscle effects of ketamine. therefore, as ketamine is not often used by vets as a co-induction agent, muscle tremors are less likely to occur in recovery anyway so the clinical benefits of using medetomidine to reduce these may not be relevant. it is also important to consider that the premedication used involved a single drug (acepromazine or medetomidine), whereas in general veterinary practice in the uk a combination using an opioid agent alongside the sedative agent is often used. this sedative and opioid combination may have potentially led to less side effects, than using the sedative agent alone with a ketofol induction. all of the studies appraised showed some statistically significant differences between using medetomidine and acepromazine as premedications in the outcomes measured, but as the clinical parameters such as blood pressure still were within acceptable clinical limits, the clinical benefits of these findings remain undetermined. there is also evidence to suggest that patients premedicated with medetomidine have less of a perioperative stress response than those receiving acepromazine, but may have increased risk of cardiac conduction disturbances, but the clinical importance of these findings is also unknown. the overall findings showed that either drug can be used as a suitable premedication.  however, the differences in pain score postoperatively shown in the small wamaitha et al. study (2019) and due to its poor analgesic properties, it is suggested that when using acepromazine additional analgesia should be given to reduce postoperative pain for better animal welfare. another key point to consider is that human error is the most common causes of problems during anaesthetic monitoring (egger, 2016), therefore being vigilant when monitoring through the anaesthetic period is of paramount importance. to reduce complications, irrespective of the drugs used to premedicate dogs, the patient should be adequately stabilised before beginning procedures and attentive perioperative and postoperative monitoring is vital. it is also important to consider the patients as individuals and adapt anaesthetic protocols to their individual status, to avoid inaccurate drug doses, and to have protocols in place for when complications do arise. methodology section search strategy databases searched and dates covered: cab abstract 1973 – 23rd april 2020 pubmed (ncbi) 1973 – 2020 web of science 1900 – 2020 search strategy: this search strategy was used in all databases: (elective or routine or anesthetized or anaesthetized or anesthetized or anaesthetised or anaesthesia or anesthesia or anaesthetic or anesthetic or pre-medication or premedication or pre-anaesthetic or pre-anesthetic or preanaesthetic or preanesthetic) and (dog or dogs or bitch* or canine or canines) and (acp or acepromazine and medetomidine) dates searches performed: 23 apr 2020 exclusion / inclusion criteria exclusion: articles not available in english, unsuitable paper types including book chapters, single case reports conference proceedings, irrelevant to the pico question, inaccessible articles. inclusion: any relevant research relating to the pico question. search outcome database number of results excluded – [not available in english language] excluded – [case report/book chapter/irrelevant paper type] excluded – [irrelevant to pico question] excluded – [duplicate article] total relevant papers cab abstracts 62 5 8 45 0 4 pubmed 38 0 0 34 0 4 web of science 119 7 1 106 1 4 total relevant papers when duplicates removed 4 conflict of interest the author declares no conflicts of interest. references abouleish, a.e., leib, m.l. and cohen, n.h. (2015). asa provides examples to each asa physical status class. asa newsletter. 79, 38–49. dahl, j.b. and møiniche s. (2005). pre-emptive analgesia. british medical bulletin. 71(1), 13–27. doi: https://doi.org/10.1093/bmb/ldh030 desborough, j.p. (2000). the stress response to trauma and surgery. british journal of anaesthesia. 85, 109–117. doi: https://doi.org/10.1093/bja/85.1.109 egger, c.m. (2016). bsava manual of canine and feline anaesthesia and analgesia. british small animal veterinary association (bsava manuals series). grimm, k.a., tranquilli, w.j., thurmon, j.c. and benson, g.j. (2000). duration of nonresponse to noxious stimulation after intramuscular administration of butorphanol, medetomidine, or a butorphanol-medetomidine combination during isoflurane administration in dogs. american journal of veterinary research. 61(1), 42–7. doi: https://doi.org/10.2460/ajvr.2000.61.42 grint, n.j., alderson, b. and dugdale, a.h. (2010). a comparison of acepromazine-buprenorphine and medetomidine-buprenorphine for preanesthetic medication of dogs. journal of the american veterinary medical association. 237(12), 1431–7. doi: http://dx.doi.org/10.2460/javma.237.12.1431 grood, p.m.r.m.d., coenen, l.g.j., egmond, j.v., booij, l.h.d.j. and crul, j.f. (1987). propofol emulsion for induction and maintenance of anaesthesia. a combined technique of general and regional anaesthesia. acta anaesthesiologica scandinavica, 31(3), 219–223. doi: http://dx.doi.org/10.1111/j.1399-6576.1987.tb02554.x kashou, a.h., goyal, a., nguyen, t. and chhabra, l. (2020). atrioventricular block. statpearls publishing. kovalcuka, l., birgele, e., bandere, d. and williams, d.l. (2013). the effects of ketamine hydrochloride and diazepam on the intraocular pressure and pupil diameter of the dog’s eye. veterinary ophthalmology. 16(1), 29–34. doi: https://doi.org/10.1111/j.1463-5224.2012.01015.x laing, s., paul, v. and murison, p.j. (2009). the effects of nitrous oxide on recovery from isoflurane anaesthesia in dogs. journal of small animal practice. 50(2), 82–86. doi: https://doi.org/10.1111/j.1748-5827.2008.00689.x lerche, p., reid, j. and nolan, am. (2000). comparative study of propofol or propofol and ketamine for the induction of anaesthesia in dogs. veterinary record. 146, 571–574. doi: http://dx.doi.org/10.1136/vr.146.20.571 lynch, c. (1986). differential depression of myocardial contractility by halothane and isoflurane in vitro. anesthesiology. 64, 620–631. doi: http://dx.doi.org/10.1097/00000542-198605000-00013 murrell, j.c. (2016). bsava manual of canine and feline anaesthesia and analgesia. british small animal veterinary association (bsava manuals series). redondo, j.i., rubio, m., soler, g., serra, i., soler, c. and gómezâ€�villamandos, r.j. (2007). normal values and incidence of cardiorespiratory complications in dogs during general anaesthesia. a review of 1281 cases. journal of veterinary medicine series a. 54(9), 470–477. doi: https://doi.org/10.1111/j.1439-0442.2007.00987.x reid, j., nolan, a., hughes, j., lascelles, d., pawson, p. and scott, e. (2007). development of the short-form glasgow composite measure pain scale (cmps-sf) and derivation of an analgesic intervention score. animal welfare. 16, 97–104. smith, l.j., yu, j.k., bjorling, d.e. and waller, k. (2001). effects of hydromorphone or oxymorphone, with or without acepromazine, on preanesthetic sedation, physiologic values, and histamine release in dogs. journal of the american veterinary medical association. 218, 1101–1105. doi: https://doi.org/10.2460/javma.2001.218.1101 thurmon, j.c., tranquilli, w.j. and benson, g.j. (1996). preanesthetics and anesthetics adjuncts. veterinary anesthesia (3rd ed.). thurmon jc, tranquilli wj, benson gj (eds). williams & wilkins, baltimore, usa, pp. 183–189. tsai, t.y., chang, s.k., chon, p.y., yeh, l.s. (2013). comparison of postoperative effects between lidocaine infusion, meloxicam and their combination in dogs undergoing ovariohysterectomy. veterinary anaesthesia analgesia. 40, 615–22. doi: https://doi.org/10.1111/vaa.12064 väisänen, m.,  raekallio, m., kuusela, e., huttunen, p., leppäluoto, j., kirves p. and vainio, o. (2002). evaluation of the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication. american journal of veterinary research. 63(7), 969–975. doi: https://doi.org/10.2460/ajvr.2002.63.969 väisänen, m., vainio, o., raekallio, m., hietanen, h., and huikuri, h. (2005). results of 24-hour ambulatory electrocardiography in dogs undergoing ovariohysterectomy following premedication with medetomidine or acepromazine. journal of the american veterinary medical association. 226(5), 738–745. doi: https://doi.org/10.2460/javma.2005.226.738 wamaitha, m.n., mogoa, e.m. and mande, j.d. (2019). evaluation of anesthesia produced by ketofol in acepromazineor medetomidine-sedated dogs. journal of advanced veterinary and animal research. 6(2), 215–221. doi: http://doi.org/10.5455/javar.2019.f335 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. does pet remedy reduce stress in dogs? a knowledge summary by louise buckley phd, rvn 1* 1the royal (dick) school of veterinary studies, university of edinburgh *corresponding author (louise.buckley@bristol.ac.uk) vol 4, issue 3 (2019) published: 16 sept 2019 reviewed by: sienna taylor (msc, bsc (hons), fdsc; fhea) and debbie emmerson (bsc (hons), msc cabc) next review date: 12 jun 2021 doi: 10.18849/ve.v4i3.219 pico question in stressed dogs, does using a pet remedy diffuser, compared to not using one, result in lowered stress levels? clinical bottom line three studies were reviewed, two that investigated pet remedy and one that investigated valerian (an active ingredient in pet remedy) on aspects of canine behaviour associated with stress. the highest quality study was a randomised controlled trial that found that pet remedy had no significant effect on particularly stress-susceptible dogs exposed to an acute stressor. the weakest quality study was a randomised controlled trial that found a significant positive effect, but had high levels of industry involvement, weak and incomplete scientific reporting and methodology, and was not peer-reviewed prior to publication. thus, the findings are unreliable. the final study, which was a quasi-experimental, fixed treatment order, controlled trial, found a positive effect of environmentally applied valerian (on its own) on behaviour in shelter dogs. however, experimental design limited interpretation of the findings in relation to canine stress reduction, and external validity in relation to applicability to pet remedy use is weak. where used as an adjunct, pet remedy is unlikely to do any direct animal welfare harm and may have a positive effect, based on studies that have unreliable findings and/or low external validity. however, unless further high quality research demonstrates a positive effect of pet remedy, veterinary professionals should be cautious about recommending it as an alternative to options with a stronger evidentiary basis, or as a delay to seeking more extensive professional support where needed. there is a need for further research to examine the efficacy of pet remedy on behavioural and physiological indices of canine stress reduction across a range of common stressful scenarios to further support veterinary professional decision making. clinical scenario during veterinary clinics, you find that clients are asking you about a herbal diffuser, pet remedy, that they have seen marketed in pet shops and online, as a method to reduce stress levels in dogs and make them calmer. they notice that the product has been endorsed by a human psychiatrist as efficacious in dogs but wonder what you, the veterinary professional, think about this product. you pause, think, and realise that you do not know anything at all about this product so decide to undertake a review of the published scientific literature in order to be able to provide the client with evidence-based advice. you also note that the manufacturer reports having studies to support the product’s use so decide to contact them direct for further details. the evidence three studies were included in this knowledge summary, of which one found no efficacy of pet remedy in a stressed dog sample (taylor and madden, 2016), one found that it was efficacious at improving behaviour/reducing excitability in a sample of dogs that might be stressed (unex designs ltd., 2014), and one found a significant positive effect of valerian alone (not as part of the pet remedy product) that might reflect lowered stress levels (binks et al., 2018). two of the studies (taylor and madden, 2016; unex designs ltd. 2014) used the product pet remedy in their clinical trial, and were supported financially by the producers of pet remedy (unex designs ltd., torquay, devon, uk). the binks et al. (2018) was tentatively included due to valerian being a key component of pet remedy, shelter dogs being a population of dogs identified as experiencing stress (hermiston et al., 2018) and the mode of administration (environmental application, but not diffuser). however, when interpreting the efficacy of pet remedy based on these findings this should be borne in mind. one study (taylor and madden, 2016) purposively selected dogs subjectively assessed as stressed by the owners for inclusion in the study, and one study provides insufficient detail to assess this aspect (unex designs ltd., 2014). all of the studies focused on behavioural parameters, and there are currently no studies that examined the effects of pet remedy (or its constituent parts applied environmentally/topically) on physiological indicators of stress. two studies (taylor and madden, 2016; unex designs ltd., 2014) used a randomised controlled trial design and the other (binks et al., 2018) used a fixed treatment order, quasi-experimental, controlled trial design. two of the studies were published in peer-reviewed scientific journals (binks et al., 2018; taylor and madden, 2016). the other (unex designs ltd. 2014) was obtained by public request from the producer of pet remedy and has not been through the peer review process but is supplied direct to veterinary professionals asking for evidence as to the efficacy of the product. this study contained insufficient experimental detail to fully appraise key aspects of the study design (including the method of delivering pet remedy or what the placebo was, essential sample population details or behavioural protocols used), and the findings for most outcome measures were not reported. summary of the evidence taylor and madden (2016) population: adult (1–11-years-old, mean: 4.6 years) pet dogs of any breed, sex or neuter status that had previously exhibited signs of stress, plus anxiety in new situations (as reported by the owner in a pre-selection interview). dogs that were aggressive to strangers or too anxious to handle safely were excluded from the trial. sample size: 28 dogs intervention details: this study was a cross over design, with each dog used as its own control. dogs were randomly allocated their order of treatment (how is not specified). the two interventions were: placebo control pet remedy the pet remedy product was a commercially available preparation that includes a 5.37% essential oil blend (valerian, vetiver, basil and sage) in a volatile base, delivered via a diffuser. the placebo used the same diffuser type containing only the volatile base. dogs were randomly allocated in which they experienced the two treatments to control for order effects (1. placebo first, followed by pet remedy: n = 15; 2. pet remedy first, followed by placebo: n = 13), with approximately 7 days between the dog receiving each treatment. a power calculation was used to determine appropriate sample size. the statistical analysis was a multivariate regression analysis, with treatment, individual dog and order of treatment as fixed effects. experimental set up: the test pen was a room novel to the dog (at the start of the study), that measured 3 x 3 m, and contained a bed, bowl, and diffuser. a camera allowed remote recording of the dog. the room had washable walls, floor and internal furniture and a built-in fan, with all being cleaned between subjects/tests and a two day period s to allow any diffuser residual smells to dissipate. testing procedure: the on 30 minutes before the test subject (dog) entered. the dog was placed into the room alone for 30 minutes (the details of this process are missing). a camera filmed the dog’s behavior over the thirty minutes. the dog was then removed. thus, the length of each treatment was 30 minutes, with approximately 7 days between treatments. data analysis: the video footage was renamed by a naïve assistant so that the researcher was blind to the treatment the dog was receiving at the time. the researcher recorded the behaviours according to a pre-prepared ethogram of behaviours (see outcome measures). the university of exeter’s ethical review group approved the study. study design: randomised controlled trial outcome studied: duration of time that the dogs spent performing each of the following behaviours: autogrooming digging drinking lying down nosing locomotion hind legs (standing on hind legs only) sitting standing circling chewing stretching (“time spent standing on hind legs with front legs resting or digging against exit” taylor and madden, 2016) wall bounce frequency with which each of the following behaviours was performed: barking howling nose licking paw lifting sighing whining yawning urination/defecation panting main findings (relevant to pico question): duration of time behaviours performed: there was no effect of treatment on the duration of time with which each of the 14 behaviours recorded were performed. although order of treatment exposure was built into the statistical model, the authors do not report this finding in the results. frequency with which behaviours performed: there was no effect of treatment on the frequency with which the nine behaviours recorded were performed. dogs to sigh less (p = 0.052). limitations: the study was industry funded (by unex designs ltd.) the inclusion criteria were based on subjective assessment by the owners, with no attempt to standardise level of ‘stress’ between dogs (or to control for it statistically). the treatment groups were not evenly allocated to control for order effects. the authors do not report whether the dogs were currently taking any medications or other supplements that might have an anti-stress/anxiolytic effect. insufficient detail is provided with regards to how the dog was handled in the lead up to entering the room e.g. was the owner present immediately prior to testing commencing, was this standardised between dogs, etc.? some of the behaviours measured are not clear measures of stress. binks et al (2018) population: healthy adult (18 months–9-years-old, mean age: 4 years and 4 months) neutered dogs in a uk rescue centre. the sample population was mainly male (= 13), mainly medium sized (= 13) and mainly bull breed or bull breed crosses (n = 10). sample size: 15 dogs intervention details: each dog was used as its own control, with each dog exposed to four different essential oil scented cloths in order to investigate the effect of each odour on canine behavior within a kennel. the experimental and control conditions that each dog was exposed to included: unscented cloth (control 1) coconut vanilla valerian± ginger no cloth (control 2) ±a key herbal component of the pet remedy diffuser. only the controls and the valerian treatment findings will be reported in the main findings section. dogs were all simultaneously exposed to the same treatment condition. each dog was observed for 2 hours per day (11:00–13:00, with shelter visitors/potential adopters viewing dogs for the second hour) for 3 consecutive days per treatment. each dog was then given 2 days “wash out period” (no treatment provided) before being exposed to the next treatment condition. a standardised procedure (5 drops were applied to each cloth – 1 per corner and one in the middle), with and handlers wearing latex gloves to prevent scent contamination during handling. cloths were scented 60 mins before being placed in the centre of the dog’s run, and dogs were provided with the cloth 30 minutes before observations started. the order in which treatments were applied was randomly determined (how is not defined), but the same order was used for each dog (because they were housed relatively close to each other and tested on the same days). the order of exposure was in the same order as the treatments (1–6) listed above. each dog’s behaviour was recorded using instantaneous scan sampling at 10 minutes intervals by an unblinded observer. the study was conducted in accordance with the international society for applied ethology’s ethical guidelines for the use of animals in applied animal behaviour research. study design: fixed order of treatments, controlled trial outcome studied: the frequency of observation points in which the dog was showing the following behaviours/location: standing sitting moving resting sleeping stereotyping vocalising located in the front half of the kennel main findings (relevant to pico question): standing no significant effect of valerian was found on the frequency of standing behaviour observed. sitting no significant effect of valerian was found on the frequency of sitting behaviour observed. moving dogs moved significantly less when exposed to the valerian scent cloth, than when exposed to either the unscented cloth (z = -4.05, p < 0.001) or no cloth control (z = -8.34, p < 0.001). the mean (± standard deviation) of observational points in which the dog was vocalising was: valerian: 1.73 (±2.25) unscented cloth: 5.80 (±4.41) no cloth: 12.07 (±5.74) resting dogs rested significantly more when exposed to the valerian scent cloth, than when exposed to the no cloth control (z = 4.20, p <0.001). no other pairwise combination was significantly different. the mean (± standard deviation) of observational points in which the dog was resting was: valerian: 9.60 (±6.15) unscented cloth: 8.13 (±7.07) no cloth: 4.47 (±4.17) sleeping no significant effect of valerian was found on the frequency of sleeping behaviour observed. stereotyping stereotypical behaviours were performed at such a low frequency that this behavioural parameter was not statistically analysed. vocalising dogs vocalised significantly less when exposed to the valerian scent cloth, than when exposed to either the unscented cloth (z = -8.34, p < 0.001) or no cloth (z = -4.66, p < 0.001) controls. the mean (± standard deviation) of observational points in which the dog was vocalising was: valerian: 2.53 (±2.70) unscented cloth: 8.67 (±6.42) no cloth: 13.87 (±8.84) located in the front half of the kennel no significant effect of valerian was found on the frequency of times the dog was observed to be in the front half of the kennel. limitations: the observer was not blinded to treatment. as the study aim was not specifically to look at the effect of valerian on stress, the pre-existing stress levels of the dogs was not assessed. the dogs considered (by rescue centre employees) to be most susceptible to stress were excluded. all dogs received the same treatment at the same time and in the same order so the study is particularly sensitive to order effects and stochastic events that might influence dog behaviour during a particular treatment condition. none of the behaviours measured in the ethogram are indicators unique to stress. all of the behaviours that were significantly affected by valerian could be used as measures of arousal more generally without reference to the emotional valence (positive or negative) per se. limited range of behaviours observed. unex designs ltd. (2014) population: dogs (various breeds, ages and both sexes) with behavioural issues (for example anxiety, nervousness or aggression). the authors do not provide further demographic detail (e.g. age range). sample size: 66 dogs (33 dogs per treatment group) intervention details: two treatment groups, with each dog used as its own control: behavioural therapy + placebo behavioural therapy + pet remedy on arrival dogs were given a behavioural assessment, the behaviour issue identified and a behavioural programme that was partly tailored to the individual dog was devised. dogs were allocated to the treatment group by the order in which they presented at the clinic (alternated between groups). the handler and trainer was blinded to which treatment group dogs were allocated to. each dog was assessed at four time points: january (baseline measurement) february march april with data collected at time points 2–4 being compared to the baseline measurement for each dog. each dog, and handler, came to the animal behaviour centre on several occasions each month to work with the trainer on a combination of set exercises, plus exercises specific to the individual dog. the owner also undertook training at home. it is not stated whether the number of centre visits, trainer(s) or at home training sessions were standardised between dogs. the set exercises are not fully defined, with only examples (hand feeding, door manners) of the type of exercises provided. it is not clear when or how the dog was exposed to the intervention (placebo or pet remedy, dependent upon the group the dog was in), but it appears to have been within the training centre environment. it is not clear exactly when and how the dogs were scored (excitement/behavior) at each of the four time points. study design: randomised controlled trial outcome studied: subjective measures were used: behaviour score – ordinal scale ranging from 0 (poor/unacceptable) to 5 (normal/good behaviour), with half-points allowed. excitement level – 0 (not excited) to 5 (very excited), with half-points allowed. for both measures, the data was handled as follows: the difference between the score/level awarded in january (baseline) and each subsequent experimental month (individually) was calculated for each dog. this ‘differences’ data for each experimental month was compared statistically inter-treatment groups. other outcome measures: licking of paws – yes/no licking of bedding – yes/no suckling – yes/no paw over lead – yes/no jumping up – yes/no turning in circles – yes/no main findings (relevant to pico question): subjective measures: behaviour score the median (range) behaviour score for the placebo group was: january: 1 (1–1) february: 2 (1–3) march: 3 (2–4) april: 3.5 (2.5–4.5) the median (range) behaviour score for the pet remedy group was: january: 1 ( 1–1) february: 2.5 ( 1–3) march: 3 (1.5–4) april: 4 (2–5) a statistically significant difference was observed between the placebo and pet remedy treatment groups in february (p = 0.0011), march (p = 0.0070) and april (p = 0.0047) however, the 95% confidence interval associated with the change (compared to baseline) in behaviour level seen by each month was 0.0– -1.0   excitement level the median (range) score for excitement for the placebo group was: january: 4 (4–4) february: 3 (1.5–4) march: 2 (1–3) april: 1.5 (0.5–3) the median (range) score for excitement for the pet remedy group was: january: 4 (4–4) february: 2.5 (1.5–4) march: 2 (1–3) april: 1 (0–2.5) a statistically significant difference was observed between the placebo and pet remedy treatment groups in february (p = 0.0036), march (p 0.0069) and april (p = 0.0009) however, the 95% confidence interval associated with the change (compared to baseline) in behaviour level seen by each month was 0.0– -1.0 for the difference between baseline and february and 0.0–0.5 for the january to march, and january to april time points   other measures: licking of paws findings not reported licking of bedding findings not reported suckling findings not reported paw over lead findings not reported turning in circles findings not reported limitations: the study was funded by the producers of pet remedy. the level of other involvement is not stated but a commercial statistical services company was hired by them to help design and analyse the study, and the disseminated report is produced by the statisticians hired to do so. there is no statement to outline the limit of their involvement in this study. the study has not been published in the scientific press and so was not subject to the accepted peer review process prior to its findings being reported publicly. there is insufficient information provided to allow this study to be replicated by independent researchers. there is insufficient information provided to allow the presence of, for example, confounding variables that might also explain the findings to be identified. the authors’ do not state the aim of the study until midway through the methods section. the aim is very broad; to see if behavioural therapy plus pet remedy is more effective than just behavioural therapy alone, but combined with the inclusion criteria this is very broad. the inclusion criteria are inadequately defined. there is no measure of severity of the behaviour problem, and, from the limited information provided, the behavioural problems were diverse. it is not clear from the description of the sample how many of these dogs were stressed (i.e. if the paper addresses the pico). a negative control that did not include behavioural therapy would have been useful here. it is reported that sample size calculations were performed but not what the test was, what parameters were used to estimate minimum necessary sample size (e.g. power, effect size), or what that minimum size was. thus, it is not known whether the eventual sample size was based upon this calculation. dogs were assessed at the start of the study to establish what the problem was and what behavioural therapy was needed. a protocol was then devised that was partially tailored to the individual dog in terms of the training administered. however, insufficient detail is available here in terms of the nature of the exercises/therapy or the frequency with which they were carried out. it is not clear whether these dogs were involved in 1-2-1 training or in group training sessions. if the later, this may have reduced independence of each observation and raised questions about the true sampling unit. there is no information available on what the placebo was or how it was administered. there is no information on what pet remedy is or what formulation or method of dissemination was used (e.g. diffuser, or spray/topical or environmental application?). there is insufficient information on where the dogs were exposed to pet remedy/placebo (training venue, home, both, etc.?) and whether this was standardised between dogs. anecdotally, pet remedy has a distinctive aroma so it seems reasonable to assume that, despite blinding, the presence of the product would be detectable by the dog, owner, and behaviourist/trainer exposed to the product. the manufacturers claim that the product works on all animals. if this product had any effect on the individuals rating the dogs’ behaviour, was the perception affected by exposure to pet remedy? it is impossible to disentangle any effects of pet remedy on the rater with any effects on the dog’s behaviour as they are confounded. the authors report that data was collected for each dog at four time points (january/february/march/april) at monthly intervals, but it is not clear how these time points were separated temporally. was there an equal number of days between time points, and was this the same for each dog? the primary outcome measures were both subjective measures. no attempt to reduce subjectivity (e.g. through detailed descriptors for each category) appears to have been undertaken. it is unclear who undertook the measurement of the primary outcome measures, or when in the session this occurred. there does not appear to be any attempt to assess inter-observer reliability (e.g. would two people award the same score to the same dog measured at the same time point), or intra-observer reliability (the latter would be more problematic to achieve though given the design). the primary outcome measures are very limited in their scope (e.g. what behaviours contribute to a global assessment of the dog’s excitement or behavioural levels?). the study reports also collecting proxy measures for stress but does not then report any analyses for these measures. it refers to these as objective, but in the same sentence refers to them as incidences of “excessive behavior”. “excessive” suggests a subjective assessment, not an objective one. no detail is available as to how the proxy measures for stress were measured. for example, did the researchers use continuous sampling, instantaneous sampling or fixed time intervals (if the latter, at what time points), all occurrences or one–zero measures, etc. when were these measured? during centre behaviour sessions, at home, etc.? neither of the primary outcome measures specifically measure stress, and the authors do not justify by reference to the wider literature the choice of outcome measures selected. it is difficult to comment fully on the suitability of the secondary measures either without more information on how/when these measurements were taken and how they addressed the study aim. however, the authors mention stress so if the aim was to measure stress it is not clear why the authors did not pick more universal or subtle measures of potential stress like yawning. it is not stated whether this study was reviewed by an ethics committee or whether informed consent was obtained from the clients. the researchers do not report whether the data was normally distributed or not, and present both parametric and non-parametric measures for the raw data. the inter-quartile range is not reported. the median is reported in this knowledge summary as this reflects the type of analytical statistics (non-parametric) that the authors undertook. the lower boundary for the 95% confidence interval for all differences data parameters reported was 0.0, which could mean that the true median value for the difference between the two groups was zero (or no difference). nb. it is assumed median due to the values reported and the distribution around the median difference value, but the authors do not state this, and mean and standard deviation values are also reported. the researchers do not acknowledge this possibility in the summary of findings. appraisal, application and reflection three studies were included in this knowledge summary. of the two directly using pet remedy, one found no efficacy of pet remedy in a stressed dog sample (taylor and madden, 2016) and the other found that it was efficacious at improving behaviour/reducing excitability in a sample of dogs that might be stressed (unex designs ltd. 2014). the final study found a significant positive effect of valerian alone (not as part of the pet remedy product) that might reflect lowered stress levels (binks et al., 2018). all three studies focused on behavioural parameters as proxy measures of stress, and there are currently no studies that examine the effects of pet remedy (or its constituent parts applied environmentally/topically) on physiological signs of stress. this is a significant limitation to the current body of evidence examining the efficacy of pet remedy on canine stress. the only study (unex designs ltd., 2014) to show that pet remedy, as a product, had a positive effect on indices of canine behaviour was an industry designed, reported, and funded randomised controlled trial, and obtained direct from the producer of pet remedy, rather than via a peer reviewed journal. industry sponsored pharmaceutical studies have been shown to be more likely to identify a significant positive effect when using their product in the human healthcare industry (e.g. chartres et al., 2016; lexchin et al., 2003). studies associated with a financial tie are 3.23–4.05 times more likely to report a positive significant effect of the sponsor’s product (ahn et al., 2017; lexchin et al., 2003). whilst understudied in the veterinary profession, a similar effect has been observed with commercially funded studies significantly more associated with a positive outcome (wareham et al., 2017). the peer review process, whilst recognised as imperfect (e.g. smith, 2006), is an integral part of the scientific process, that is designed to improve the quality of scientific reporting. however, the producer claimed to have undertaken a scientific study, and historically had used this scientific output in literature supplied to veterinary professionals to support the use of pet remedy. thus it was deemed appropriate to evaluate any relevant study for quality too as it was a resource that might be used to scientifically inform clinical decision making. unfortunately, the level of detail provided in the submission does not permit an adequate evaluation of the quality of the scientific study, which limits evaluation of both internal and external validity. however, the reporting of the study was very low quality, with numerous omissions of information (see limitations section for the evaluation of this individual study) integral to understanding the scientific methodology utilised. finally, if pet remedy is potentially efficacious for all mammals (pet remedy, 2018) then the assessor (as a fellow mammalian species) may also show altered behaviour when exposed to the product. they are also exposed to pet remedy at the same time as the dog and while making the assessment of the dog’s behaviour. therefore, there is a confounding variable here that means that, if there is an effect, it is impossible to disentangle it from an effect on the dog, the human (e.g. that influences their interpretation of the dog’s behaviour) or various hypothetical interactions. thus, it concluded that the study provided by unex designs ltd. is unreliable and should not be used to inform the decision making of veterinary professionals. it underpins the importance of not simply relying on where the study type would sit on the pyramid of evidence when assessing experimental evidence. by contrast, the study by taylor and madden (2016), whilst funded by unex designs ltd. (2016) was otherwise independent of the funder. this study was also a randomised controlled trial that utilised a cross over design to assess the effects of an acute stressor (a novel environment combined with, it is assumed, solitary confinement) for a 30 minute duration. this study was the strongest in terms of addressing the pico. both the population studied and some of the outcomes measures to evaluate the effect of pet remedy most closely matched the requirement for dogs to be stressed and for the reduction in stress to be measured using parameters recognisable as at least partially associated with a stressed (or anxious/fearful) dog. furthermore, the experimental methodology (video recording for later remote analysis by a blinded observer) removed an important source of bias and confound present in the unex designs ltd. (2014) study. this study found no significant effects of pet remedy on 23 indices of canine behaviour. it is suggested that this study is a more reliable source of evidence for veterinary professionals to consult when considering using pet remedy in situations that may cause a susceptible dog to experience an increase in stress levels. finally, the binks et al., 2018 quasi-experimental, fixed treatment order, controlled study was tentatively included, as valerian is one of the primary herbs included in the pet remedy diffuser/spray and both products can be applied environmentally. valerian was applied environmentally (on a scent cloth) in the binks et al., (2018) study. whilst the inclusion criteria was not specifically stress-associated (e.g. history of vet or owner identified susceptibility to stress, anxiety or fear) the rescue kennel environment is considered to be a significant stressor for rescue dogs (e.g. hermiston et al., 2018) so it is reasonable to assume that dogs would be experiencing some stress. it should be noted though that the study excluded dogs considered most likely to be stressed in kennels. a key weakness here in relation to the pico though, is that a baseline measurement to identify dogs that showed signs of stress was not undertaken. whilst the control conditions preceded and concluded the order in which treatments were applied, these controls differed in terms of what they controlled for. the first for scent only (by providing a cloth that was also a novel inclusion within the dog’s environment) so not a true baseline measurement. furthermore, the outcome measures (a limited ethogram) used to evaluate the effects of valerian on canine behaviour do not allow the reader to disentangle positive (e.g. excitement) and negative (e.g. stress) arousal states. however, it is worth noting that they did find a significant effect of valerian on dog behaviour, with dogs showing reduced vocalisation and movement, and increased resting behaviour on days (3 consecutive days) when valerian impregnated cloths were placed in the run. these findings might support the findings of the unex design ltd. (2014) study and provide an alternative explanation (other than stress reduction) for any effect of valerian based products on canine behaviour. however, using these findings to justify a specific product’s use is more problematic given differences in the method of delivery, the concentration of the product, and the presence of synergistic, additive or negative/antagonistic effects that may be present in a product that combines multiple ingredients that may have a clinical effect on canine behaviour. thus, while the findings of binks et al., (2018) are interesting in relation to the potential use of valerian to modify canine behavior, the external validity of this is not strong enough to use as evidence of efficacy of pet remedy, and more research is needed that uses pet remedy the product. in conclusion, there is currently insufficient evidence to show that pet remedy does work as an environmental tool to reduce stress in dogs. the poorest quality evidence using a non-peer reviewed randomised controlled trial found a significant positive effect, but the findings are unreliable due to the quality of experimental design and inadequate reporting of the methodology and results. the strongest quality evidence, using a single blinded, randomised, controlled trial, found no effect of pet remedy on indices of canine behaviour. there is some evidence that valerian (an active ingredient in pet remedy) may affect canine behaviour in a potentially stressful environment in the medium term, though the affective state sitting behind the behavioural change is unclear. given the anecdotal popularity of this product as an over-the-counter product to sell to pet owners, there is a need for further research to investigate the effect of pet remedy on both behavioural and physiological indices of canine stress levels across a range of common scenarios of relevance to the pet owner and veterinary professional. however, there is also no evidence that pet remedy will negatively affect canine stress levels either, with these findings consistent across all studies reviewed so, when used as an adjunct, it is unlikely to do any direct animal welfare harm. however, until further research demonstrates a positive effect of pet remedy, veterinary professionals should be cautious about recommending pet remedy as an alternative to options with a stronger evidentiary basis, or as a delay to seeking more extensive professional support where needed. methodology section search strategy databases searched and dates covered: pubmed on ncbi platform 1970 – 12/06/2019; web of science: 1970 – 12/06/2019; cab abstracts on ovid platform: 1973 – week 22 2019 grey literature search: request sent to the pet remedy supplier for copies of any studies showing that pet remedy was efficacious (no species defined). original request (reply): 31/05/2018 (31/05/2018), request for updates: 25/10/2018, no reply received by the time of submission of this knowledge summary for review (01/11/2018), or by the time the revised draft was submitted (21/02/2019), or by the time the final draft proof was approved by the author for publication (12/06/2019). search terms: pubmed: (dog or dogs or canine or canines or canis or canid or pup or puppy or puppies or bitch or bitches) and (“pet remedy” or valerian or vetiver or “sweet basil” or “clary sage” or herb or herbs or herbal or “chrysopogon zizanioides” or “ocimum basilicum” or “salvia sclaria” or “valeriana officinalis”) and (stress or stressed or stressor or stressful or fear or fearful or anxious or anxiety or phobia or phobic or distress or worried or nervous or panic or fright or scared or alarm or apprehensive or calm or calming or calmed) web of science: (dog or dogs or canine or canines or canis or canid or pup or puppy or puppies or bitch or bitches) and (“pet remedy” or valerian or vetiver or “sweet basil” or “clary sage” or herb or herbs or herbal or “chrysopogon zizanioides” or “ocimum basilicum” or “salvia sclaria” or “valeriana officinalis”) and (stress or stressed or stressor or stressful or fear or fearful or anxious or anxiety or phobia or phobic or distress or worried or nervous or panic or fright or scared or alarm or apprehensive or calm or calming or calmed) cab abstracts: (dog or dogs or canine or canines or canis or canid or pup or puppy or puppies or bitch or bitches) and (pet remedy or valerian or vetiver or sweet basil or clary sage or herb or herbs or herbal or chrysopogon zizanioides or ocimum basilicum or salvia sclaria or valeriana officinalis) and (stress or stressed or stressor or stressful or fear or fearful or anxious or anxiety or phobia or phobic or distress or worried or nervous or panic or fright or scared or alarm or apprehensive or calm or calming or calmed) dates searches performed: pubmed: 12/06/2019; web of science: 12/06/2019; cab abstracts: 12/06/2019 exclusion / inclusion criteria exclusion: pre-defined exclusion criteria: non-english language, popular press articles, conference abstracts inclusion: any comparative (control group utilised) study in which the effect of pet remedy (or its constituent parts, applied environmentally or topically) on stress (or similar) in dogs was studied. search outcome database number of results excluded – did not answer pico question excluded – not english language excluded – conference abstract only excluded – duplicates total relevant papers pubmed 41 40 0 0 0 1 web of science 46 44 0 0 1 1 cab abstracts 88 86 0 0 2 0 pet remedy – direct request for information 6 5 0 0 0 1 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflicts of interest. references ahn, r., woodbridge, a., abraham, a., saba, s., korenstein, d., madden, e., boscardin, w. j. and keyhani, s. 2017. financial ties of principal investigators and randomized controlled trial outcomes: cross sectional study. british medical journal 356:i6770. doi: https://doi.org/10.1136/bmj.i6770 binks, j., taylor, s., wills, a. and montrose, t. 2018. the behavioural effects of olfactory stimulation on dogs at a rescue centre. applied animal behaviour science 202: 69–76. doi: https://doi.org/10.1016/j.applanim.2018.01.009 chartres, n., fabbri, a. and bero, l. a. 2016. association of industry sponsorship with outcomes of nutrition studies: a systematic review and meta-analysis. jama internal medicine 176(12): 1769–1777. doi: https://doi.org/10.1001/jamainternmed.2016.6721 hermiston, c., montrose, v. t., and taylor, s. 2018. the effects of dog-appeasing pheromone spray upon canine vocalizations and stress-related behaviors in a rescue shelter. journal of veterinary behavior: clinical applications and research (26): 11–16. doi: https://doi.org/10.1016/j.jveb.2018.03.013 kelly, j., sadeghieh, t. and adeli, k. 2014. peer review in scientific publications: benefits, critiques, & a survival guide. the journal of the international federation of clinical chemistry and laboratory medicine 25(3): 227–243. lexchin, j., bero, l. a., djulbegovic, b. and clarke, o. 2003. pharmaceutical industry sponsorship and research outcome and quality: systematic review. british medical journal 326:1167. doi: https://doi.org/10.1136/bmj.326.7400.1167 pet remedy. 2018. pet remedy: natural de-stress and calming. [online] unex designs ltd. (accessed: 01/11/2018). smith, r. 2006. peer review: a flawed process at the heart of science and journals. journal of the royal society of medicine 99: 178–182. doi: https://doi.org/10.1177/014107680609900414 taylor, s. and madden, j. 2016. the effect of pet remedy on the behavior of the domestic dog (canis familiaris). animals 6(11), 64. doi: https://doi.org/10.3390/ani6110064 unex designs ltd. (2014) statistical analysis of a new animal behaviour centre dog trial for pet remedy: final analysis – three-month follow-up. select statistical services, exeter, devon. document supplied by unex designs ltd. by email on 31/05/2018. wareham, k. j., hyde, r. m., grindlay, d., brennan, m. l. and dean, r. s. 2017. sponsorship bias and quality of randomised controlled trials in veterinary medicine. bmc veterinary research 13: 234. doi: https://doi.org/10.1186/s12917-017-1146-9 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in bitches, is ovariectomy/ovariohysterectomy by laparoscopy less painful postoperatively than by midline open laparotomy? a knowledge summary by chris webb ma vetmb pgc(sas) pgdip(vcp) mrcvs 1* julia deutsch dipecvaa mrcvs 2 1fitzpatrick referrals ltd., halfway lane, eashing, godalming, gu7 2qq 2langford vets, small animal referral hospital, university of bristol vet school, langford house, north somerset, bs40 5du *corresponding author (cwebb@fitzpatrickreferrals.co.uk) vol 6, issue 1 (2021) published: 05 feb 2021 reviewed by: malcolm ness (bvetmed certsao frcvs ecvs) and catrina pennington (bvm&s mrcvs) next review date: 30 jun 2022 doi: 10.18849/ve.v6i1.356 pico question in bitches, is an ovariectomy/ovariohysterectomy by laparoscopy superior to an ovariectomy/ovariohysterectomy by a midline surgical laparotomy in causing less postoperative pain?   clinical bottom line category of research question treatment the number and type of study designs reviewed seven papers were critically appraised. they comprised of three blinded randomised controlled trials, two non-blinded randomised controlled trials and two non-blinded non-randomised controlled trials strength of evidence weak outcomes reported in bitches, ovariectomy/ovariohysterectomy by laparoscopy is superior to ovariectomy/ovariohysterectomy by a midline laparotomy in causing less postoperative pain conclusion despite the widely held belief that laparoscopic surgery is associated with less postoperative pain, the available veterinary literature only provides weak evidence to support this in bitches undergoing ovariectomy/ovariohysterectomy. there are many uncontrolled variables to consider across these underpowered studies including surgeon number (and experience), the choice of perioperative analgesia, method of pain scoring and the laparoscopic technique. it is therefore clear that laparoscopic procedures cannot be viewed equally and the strength of the answer to the clinical question may change based upon these variables. it is also important to note that the incidence of complications or the effect of the above variables on postoperative pain have not been critically reviewed and warrant careful consideration when deciding on a laparoscopic approach   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario during a rabies vaccination appointment, you discuss with your client about the benefits of spaying her young french bulldog bitch in the near future. she enquires about a keyhole approach as your practice started performing laparoscopic spays last year. her previous practice was not in support of the technique as the veterinary surgeons had many years of great success with small incisions. the client feels her bitch is very sensitive however, so would like to know if there is any evidence that she will be in any less pain following a laparoscopic approach. the evidence seven studies were identified that compared postoperative pain in bitches spayed by laparoscopy with bitches spayed by a traditional midline laparotomy. they comprised of three blinded randomised controlled trials, two non-blinded randomised controlled trials and two non-blinded non-randomised controlled trials. one paper provided weak-moderate evidence and the remaining six papers provided weak evidence to support laparoscopy as being superior to an open midline laparotomy in causing less postoperative pain. summary of the evidence dalmolin et al. (2020) population: female mongrel dogs inclusion criteria: intact bitches, assessed to be healthy on general physical examination and blood evaluation (haematology, creatinine, albumin, alkaline phosphatase and alanine aminotransferase). group characteristics: age 1–4 years weight 16.19 ± 3.73 kg sample size: 14 dogs intervention details: both groups were premedicated intramuscularly with acepromazine 0.05 mg/kg and, following induction, received an intravenous loading dose of fentanyl 1.25 mcg/kg over 5 minutes followed by constant rate infusion at 15 mcg/kg/h. all procedures were performed by the same surgeon. laparoscopic assisted ovariohysterectomy (loh) (n=7): two 11 mm ports were placed on the midline, through the umbilicus and the prepubic area. bipolar cauterisation and transection of the ovarian pedicles and suspensory ligament was performed (powerblade®) and double ligatures applied to the uterine body and vessels. open ovariohysterectomy (ohe) (n=7): a midline incision was performed approximating 1/3 of the umbilicopubic distance. ovarian pedicle and uterine body ligation was performed with double ligation (2-0 polyglactin 910) using a modified three clamp technique. at the end of the procedure, all patients received intravenous dipyrone 25 mg/kg and scopolamine 0.2 mg/kg, and meloxicam 0.2 mg/kg. wounds were dressed similarly for both groups. further doses of dipyrone and scopolomine were given four times daily and meloxicam given once daily, both subcutaneously. study design: prospective, blinded, randomised, controlled trial outcome studied: surgical time. postoperative pain scores using visual analogue scale (vas), university of melbourne pain scale (umps) and short form glasgow composite measure pain scale (cmps-sf) at 2, 4, 6, 8, 12, 18, 24, 36, 48 and 72 hours after surgery by three trained assessors. requirement for rescue analgesia (0.5 mg/kg morphine sulphate) as determined by two or three assessors scoring greater than 50 mm on vas, 7/27 on umps, or 12/24 on cmps-sf. time to first voluntary eating and defaecation. main findings (relevant to pico question): there was no significant difference in pain scores between groups at any point using vas. pain scores were significantly lower in loh group at 6 hours using umps (p=0.01). pain scores were significantly lower in loh group at 36 and 48 hours using cmps-sf (p<0.01). time to first spontaneous food intake was significantly earlier in loh group (p=0.01). time to first spontaneous defaecation was earlier in loh group but but not significant (p=0.14). no rescue analgesia was required at any point. limitations: surgical description was limited. pain scoring was performed by three different assessors with only light (1x2) and moderate (1x3, 2x3) agreement. none of the pain scores capture feeding or defaecation as a parameter of pain. small study size with only seven animals in each group. no reporting of confidence intervals for pain scores. coutinho et al. (2018) population: female dogs from animal protection association of taquaritinga, são paulo, brazil inclusion criteria intact, anoestrus bitches, assessed to be healthy on general physical examination, abdominal ultrasound, and blood (haematology, creatinine and alanine aminotransferase) and urine evaluation. free of intraoperative complications – 4/24 bitches (two from each group) were removed from further analysis due to intraoperative complications. group characteristics mean age 2.4 ± 0 years weight 9.2 ± 2.5 kg sample size: 24 dogs intervention details: both groups premedicated intramuscularly with morphine 0.5 mg/kg and chlorpromazine 0.5 mg/kg. loh (n=12): a midline prepubic 11 mm single port was placed using an open technique and capnoperitoneum performed with a maximum insufflation pressure of 10 mmhg. bipolar cauterisation and transection of the ovarian pedicles were performed (powerblade®). the uterine body was identified and transfixed using poliglecaprone 25 and transected. the abdominal muscles were closed in the same suture and appositional nylon skin sutures were placed. ohe (n=12): a 30 mm midline incision was made from 1 cm caudal to the umbilicus. the ovaries were exteriorised with the help of a snook hook and a transfixing ligature placed in the pedicles prior to transection. the cervix was ligated with a miller’s knot and transected prior to routine abdominal closure. poliglecaprone 25 was used for all internal sutures and the skin was apposed using simple interrupted nylon sutures. wounds were dressed similarly for both groups. study design: prospective, blinded, randomised, controlled trial outcome studied: postoperative pain scores (as soon as animals regained walking ability and 0.5, 1, 2, 4, 8, 12, 16 and 24 hours later) using vas and umps – assessors blinded to the surgical group. requirement for rescue analgesia (vas >50 mm and/or umps >12/27). blood glucose and serum crp concentrations preoperatively and 1, 4, 12 and 24 hours after the end of the surgical procedure. voluntary food ingestion assessed by direct observation during the 24 hour postoperative period. main findings (relevant to pico question): intensity of postoperative pain was lower for the loh group at most time points but not statistically significant (p>0.05). rescue analgesia was required for 3/20 dogs (loh 1/10; ohe 2/10) but was not significant between groups (p>0.05). animals in the loh group ate earlier and in greater proportion than those in the ohe group (p=0.02). serum crp was similar between groups (p>0.05). blood glucose was higher in ohe group from 1 hour until the end of measurements when compared to loh group (p=0.03). limitations: breeds are not reported. the weight and ages are not reported for each group. elimination of complications from further assessment – these are important to consider when performing studies to support laparoscopy. pain scoring was performed by two observers creating inter-observer bias. neither vas nor umps capture feeding behaviour as a parameter of pain. small study size with only 10 animals in each group. no reporting of confidence intervals. vasiljevic et al. (2015) population: client-owned medium and large breed female dogs inclusion criteria intact bitches, assessed to be healthy on general physical examination, haematology and biochemistry. american society of anaesthesiologists category i (asa i). group characteristics age 0.58–3 years weight 5–35 kg sample size: 20 dogs intervention details: both groups premedicated with carprofen 4 mg/kg subcutaneously and medetomidine 0.03 mg/kg intravenously lov (n=10). ove (n=10). patients received ketamine 2 mg/kg intravenously at the time of withdrawal of the left ovary. atipamazole 0.015 mg/kg was given intramuscularly at the end of surgery in both groups. study design: prospective, non-blinded, randomised, controlled trial outcome studied: intraoperative pain estimation at certain time points by measuring changes in heart rate, respiratory rate, arterial blood pressure and body temperature. postoperative pain using a multifactor pain scoring system (0–9 scale) at 0.25, 0.5, 1, 3 and 6 hours postoperatively. main findings (relevant to pico question): ove group: no dogs were free of pain (score 0) at any time point. number of dogs experiencing mild pain (score 1–3) reduced from five to one over the observation period. number of dogs experiencing moderate pain (score 4–6) and severe pain (score 7–10) increased from four to seven, and from one to two over the observation period, respectively.   lov group: up to 0.5 hours, all dogs experienced mild or moderate pain. from 1 to 6 hours, all dogs experienced either no pain or mild pain. a maximum of two dogs experienced moderate pain, and no dogs experienced severe pain at any time point. limitations: breed, mean age and mean weight are not provided. neither surgical technique was described. ove group received additional intraoperative analgesia. no opioid in the premedication. slower postoperative recovery in the ove group may affect pain scores. the observer was not blinded to the surgical group. no statistical analysis of postoperative pain scores, only intraoperative parameters. small study size with only 10 animals in each group. no reporting of confidence intervals. questionable ethics as no intervention was set for rescue analgesia during the 6 hour observation – 2/20 dogs (10%) were in severe pain and only received analgesia at the end of the study. freeman et al. (2010) population: female dogs; combination of research and shelter animals inclusion criteria healthy bitches. haematocrit, total protein and blood glucose measurement. group characteristics lov 18.8 ± 4.4 kg; ove 20.4 ± 3.8 kg sample size: 30 dogs; research animals n=10, shelter animals n=20 intervention details: all animals were subject to the same anaesthetic protocol but this was not described. (n=10 research animals) natural orifice transluminal endoscopic surgery (notes): this was performed via a previously described transgastric approach. abdominal insufflation was provided by air from the endoscope and co2 via a percutaneous catheter from an automated insufflator set to 12–14 mmhg. a 3.0 x 4.5 cm hexagonal snare (acusnare®) with monopolar electrocautery was used to coagulate and cut each ovarian pedicle. after visual inspection to ensure each ovary was completely removed, the gastrotomy was closed with prototype t-fasteners. this technique will not be commented on further as it is not being investigated by this knowledge summary. lov (n=10 shelter animals): a 10 mm port was placed at the umbilicus and a midline 5 mm port placed 5 cm caudal to this. capnoperitoneum was created using an automated insufflator set to 12–14 mmhg. each ovary was elevated with grasping forceps and suspended from the body wall using a percutaneous needle or weighted hook. a 5 mm harmonic scalpel was then used to cut and coagulate the ovarian attachments. ovaries were removed from the umbilical port, followed by ports and the sites closed in three layers (suture and pattern not specified.) ove (n=10 shelter animals): a 40–60 mm midline incision was made 3 cm caudal to the umbilicus. a snook hook was used to assist exteriorisation of an ovary and a three clamp technique was used to place two ligatures on the pedicle. the pedicle was transected, the oviduct ligated and the ovary removed. the midline incision was closed routinely in three layers. all dogs received intramuscular hydromorphone 0.05 mg/kg at 0 and 6 hours postoperatively. study design: prospective, non-blinded, non-randomised, controlled trial outcome studied: surgical time. pain score preoperatively and postoperatively at 2, 4, 6, 12, 18, 24, 36, 48 and 72 hours after extubation using umps. requirement for rescue analgesia (umps >10/27). nociceptive threshold was assessed (same time points) using a previously described abdominal pressure cuff technique. physiological parameters, blood glucose and blood cortisol concentrations (same time points). surgical stress markers (serum il-6 and crp) at 0, 2, 6, 12, 24, 36 and 72 hours postoperatively. main findings (relevant to pico question): mean lov group pain scores equal or lower than ove group at all postoperative time points. cumulative pain scores for lov group were significantly lower (p<0.05) than ove group at 18, 36 and 72 hours postoperatively. rescue analgesia was not required in any of the groups. nociceptive threshold for ove group significantly lower (p<0.05) than lov group at 4 and 12 hours postoperatively. il-6 and crp were not significantly increased over baseline in both lov and ove groups. cortisol increased from baseline at 2 hours in both lov and ove groups. glucose elevated from baseline at many time points in both lov and ove groups. limitations: no data on age or breed of animals. the general anaesthetic protocol was not stated. as ove and lov were separately randomised from the same population, however, their comparison should not be affected. number of surgeons and their experience was not reported. pain scoring was performed by two observers, creating inter-observer bias. it is not clear whether observers were blinded to the treatment group. it is not clear whether the same observers were involved with nociceptive threshold testing, but the same issue of multiple non-blinded assessors would apply. the stress of blood sampling may affect nociceptive threshold testing (the latter was performed immediately after the former). there is no discussion of the statistical significance between lov and ove – they are only presented as symbols in the figures so may be missed by the reader. small study size with only 10 animals in each group. no reporting of confidence intervals. devitt et al. (2005) population: female dogs scheduled for adoption through local animal shelters inclusion criteria intact, bitches, assessed to be healthy on physical examination and blood parameters (haematology and biochemistry) group characteristics mean age 1.5 ± 93 years (ohe) and 1.45 ± 0.78 years (loh) (p=0.444) mean weight 22.0 ± 5.6 kg (ohe) and 22.1 ± 5.0 kg (loh) (p=0.488) sample size: 20 dogs intervention details: both ohe and loh groups premedicated subcutaneously with glycopyrrolate 0.01 mg/kg, acepromazine 0.03 mg/kg and morphine 0.2 mg/kg; bupivacaine 2 mg/kg was infused into the surgical site (ohe) or divided between surgical sites (loh) prior to incision. loh (n=10): patients were positioned in a hinged v-shaped trough to enable rotation to left and right lateral recumbency. capnoperitoneum was created using a veress needle technique and mechanical insufflator set to 10–13 mmhg. the ovarian vasculature was cauterised and transected using multifunction bipolar gasping forceps via a 12 mm cannula at the umbilicus (11 mm laparoscope and 6 mm working channel). a 5 or 12 mm cannula was then inserted in the midline (approximately 4–5 mm cranial to the pubis) under direct visualization to exteriorise the ovaries and uterus. the body of the uterus was ligated, transfixed and divided before returning the uterine stump to the abdomen and monitoring for haemostasis with the laparoscope. port sites were closed in two layers with absorbable monofilament suture and nylon. ohe (n=10): this was performed via midline incision approximating 1/3 of the umbilicopubic distance (no further description provided). all dogs received 0.2 mg/kg morphine subcutaneously before extubation. study design: prospective, non-blinded, randomised, controlled trial outcome studied: surgical time. requirement for mechanical ventilation under anaesthesia. multi-dimensional composite pain score (adapted from a paediatric pain scoring system) at 1, 2, 4, 6, 12 and 24 hours after extubation. requirement for rescue analgesia (pain score 6/19 or higher). serum glucose and cortisol concentration at the same time points above. main findings (relevant to pico question): pain scores were higher at all time points for ohe group compared to loh group (p=0.001). 9/10 ohe cases required additional pain relief based on the pain score compared to 0/10 loh cases (p=0.001; relative risk 10.0 [95%ci, 1.6–64.2]). cortisol concentrations were significantly elevated from baseline in ohe group at 1 and 2 hours but not in loh group. glucose concentrations were significantly elevated from baseline in ohe group at 1, 2, 4 and 6 hours, and in loh group at hour 1 only. limitations: no breed information provided. limited description of open surgery. use of an adapted pain scoring system originally designed for assessing human paediatric pain. pain scoring was performed by two observers, creating inter-observer bias. small study size with only 10 animals in each group. hancock et al. (2005) population: purpose bred female beagles inclusion criteria intact, beagle bitches, with normal physical examination findings, blood parameters (haematology and biochemistry) and urinalysis results. group characteristics mean weight 11 kg (range: 10.1–12.2 kg) sample size: 16 dogs intervention details: both groups premedicated subcutaneously with acepromazine 0.03 mg/kg and morphine sulphate 0.25 mg/kg. loh (n=8): an open technique was used to place a 5 mm cannula and capnoperitoneum created using a mechanical insufflator set to 10 mmhg. babcock forceps and a harmonic scalpel were used (via a 3-port technique) to transect ovarian pedicles and the uterus cranial to the cervix. the umbilical port incision was closed with simple interrupted sutures in the linea alba (2-0 polydiaxanone [pds]), subcutis (3-0 pds) and skin (3-0 nylon). paramedian port incisions were closed with simple interrupted muscular (3-0 pds) and skin (3-0 nylon) sutures. ohe (n=8): a 60 mm midline incision was made starting 1 cm caudal to the umbilicus. a modified three clamp technique for each ovary and pedicle ligation was performed with 2-0 pds. the linear alba was closed in simple continuous pattern (2-0 pds), followed by the subcutis (3-0 pds), and skin (3-0 nylon). all dogs received 0.5 mg/kg morphine sulphate subcutaneously at extubation. study design: prospective, blinded, block randomised, controlled trial outcome studied: surgical time. physiological parameters. pain scores using umps at 2, 6, 12, 24, 48 and 72 hours postoperatively. requirement for rescue analgesia (umps 10/27 or higher). blood glucose, cpk and plasma cortisol concentrations (same time points). nociceptive threshold using an abdominal pressure cuff by the same handler (same time points). main findings (relevant to pico question): mean pain scores were significantly lower for loh group (p=0.0001) at all postoperative time points (although 95% ci overlapped at hour 2 and 48). mean nociceptive threshold was significantly higher for loh group (p=0.0002) at all postoperative times except 72 hours. no dogs required rescue analgesia at any point. though mean loh group surgical time was significantly longer (p=0.0001), this had no significant nuisance effects on any of the measured pain variables at any time. mean cortisol concentration for loh group was significantly lower than for ohe group at hour 2 (p=0.0001). mean blood glucose and cpk concentrations were not significantly different between groups at any time. limitations: three surgeons were responsible for the procedures of varying levels of experience. mean age and weight not reported for each group. small study size with only eight animals in each group. davidson et al. (2004) population: female dogs; combination of client-owned and shelter animals inclusion criteria intact bitches with normal blood glucose, blood urea nitrogen, packed cell volume and total plasma protein concentration. six animals were not included in further analysis as they did not receive ketoprofen at the end of surgery. group characteristics loh: age 4–36 months (mean 10.5 months; median 8 months); weight 10-38kg (mean, 17.9 kg); 1/16 had whelped previously, 15/16 nonparous. vaccinated and negative for heartworm and intestinal parasites. ohe: age 4–96 months (mean 19 months; median 6 months); weight 2.4–24 kg (mean 12.1 kg) sample size: 34 dogs; client-owned n=18, shelter animals n=16 intervention details: premedication in both groups was a combination of either intramuscular morphine 1 mg/kg and glycopyrrolate 0.01 mg/kg, or morphine 1 mg/kg, glycopyrrolate 0.01 mg/kg and acepromazine 0.1 mg/kg. ketamine was included as an induction agent in some animals (loh= 4/16, ohe=1/18). loh (n=16 shelter animals): capnoperitoneum was created to a maximum pressure of 12–14 mmhg via a veress needle placed at the umbilicus. four 5 mm ports were placed in each quadrant and the ovarian pedicles disrupted using bipolar cautery. pedicles were then double ligated using 4–0 surgical wire (touché™ suturing system) prior to complete transection using bipolar electrocautery. the same technique was then used to remove the uterus just cranial to the cervix. pds muscle sutures and nylon skin sutures were then placed at each incisional site. all surgery performed by a single vet. ohe (n=18 client owned): a ventral midline incision was made and the ovarian pedicles and uterus triple clamped and double ligated with 2-0 or 3-0 pds or polyglactin 910 sutures, and transected. abdominal closure was in three layers. all surgery was performed by veterinary students with a faculty vet for assistance. study design: prospective, non-blinded, non-randomised, controlled trial outcome studied: surgical time. pain scores at 0, 2, 8 and 24 hours postoperatively using a subjective pain scoring system and umps in the 28 dogs receiving the same analgesia at the end of surgery. appearance of the wound. main findings (relevant to pico question): mean pain scores for 2/10 dogs subjective descriptors (facial expression and posture) were significantly lower for loh group for at least one time point. mean pain scores for 8/10 categories (umps) were significantly lower for loh group for at least one time point. limitations: aside from normal blood parameters for ohe group, health status is not clear. no breed information provided. groups were not randomised. there is no statistical evaluation of mean weight or age between groups. premedication was not standardised. use of preoperative ketamine was unequal between groups (n=4 loh; n=1 ohe). there was a single lead surgeon for loh group but there were a number of students operating on the ohe group. abnormal laparoscopic technique. observer not blinded to treatment groups when performing the pain scores. six exclusions were made based on the type of postoperative analgesia but it is unclear which groups they originated from. categories within the pain scoring system were compared for significance between the two groups rather than the cumulative score. small study size (n=28) with unknown final group sizes. no reporting of confidence intervals. appraisal, application and reflection a total of seven papers were appraised, comprising three blinded randomised controlled trials, two non-blinded randomised controlled trials and two non-blinded non-randomised controlled trials. whilst they supported the use of laparoscopy (to varying degrees) over traditional laparotomy by causing less postoperative pain, small patient numbers and the large variability between studies (and in some cases, groups) were significant constraints to the strength of evidence. although each may be considered minimally invasive relative to their comparative (control) open procedure, the difference in laparoscopic technique across studies (i.e. port number, trocar size, method of access for pneumoperitoneum, insufflation pressures and variation in method of haemostasis) makes consideration as a single group very difficult. it is also worth noting that none of the referenced pain scoring systems used in these studies are validated for ovariectomy/ovariohysterectomy pain, but are commonly used in canine studies as a measure of postoperative pain. in humans, laparoscopic techniques have been shown to cause less postoperative pain, shorten hospital admissions and ensure faster return to normal daily activity when compared with open surgery. as such, it is currently considered the gold standard approach for many gynaecological surgeries (rajvinderet al. 2018). a common anatomy and physiology in pain processing between vertebrates (pelligand & mora, 2016) would lead us to believe that a laparoscopic approach is also less painful in dogs. it is likely that smaller incisional wounds, as well as reduced tissue handling of sensitive structures, would be responsible for any difference seen in these patients. underpowered studies (all seven studies here may be considered such) are typically associated with increased risk of false negative results (type ii error) but will also increase the likelihood that statistically significant findings are false positives (type i error). though either scenario would render any results misleading in the context of answering the clinical question, prior knowledge of human laparoscopic surgery would suggest that the probability of the null hypothesis (i.e. no significant difference in postoperative pain scores exists between laparoscopic and open ovariectomy/ovariohysterectomy) being true, is low. this would imply that there may still be some utility in significantly improved laparoscopic group pain scores. the lowest risk of bias was found in the well-designed blinded randomised controlled trial by hancock et al. (2005). despite no age data, the purpose-bred population was considered homogeneous ensuring no difference between groups. dogs were housed for 96 hours prior to surgery to limit the effects of stress on postoperative behaviour changes and pain scores. although three different surgeons were responsible for intervention, block randomisation ensured that no surgeon performed an unequal number of surgeries in each group. a multidimensional composite pain scale (university of melbourne pain scale (umps)) was combined with an objective nociceptive threshold measurement technique and assessed by a single (blinded) observer, removing interobserver bias. statistics were performed appropriately, and confidence intervals recorded. results showed significantly lower pain scores and higher nociceptive thresholds in dogs operated by laparoscopy. the strength of evidence is considered weak to moderate and could principally have been strengthened by larger group sizes. dalmolin et al. (2020) used blinded randomised controlled trial design with three pain scoring systems (including two multi parameter systems) but the benefit of multiple assessments was negated by using three pain assessors with only light to moderate agreement between them. anaesthetic protocol was well controlled and a single surgeon was used for all procedures. the only significant differences in pain scores between groups showed the laparoscopic group to be more comfortable. there were, however, individual time points on each of the pain scoring systems where pain scores were lower for the laparotomy group. significantly faster return to voluntary feeding was noted for the laparoscopy group which has previously been suggested as a sign of reduced postoperative pain (sarrau et al., 2007). unlike the other studies, ongoing pain medication was provided throughout the recovery period which would reduce differences in pain scores between groups. the benefit of laparoscopy over laparotomy appears limited using this analgesic combination but, again, this is an underpowered study. as such we believe that this study only provides weak evidence in favour of laparoscopy. devitt et al. (2005) used a non-blinded, randomised controlled trial design but with few other limitations. the main source of bias was in using two non-blinded observers to perform pain scoring. reporting of breeds may have been beneficial but the weight and age of animals were well controlled. standardisation of procedures was particularly rigorous (although there was limited description of the laparotomy technique), with the same surgeon and anaesthetic protocol for all animals. statistical analysis was appropriate, with recording of confidence intervals. pain scores and requirement for rescue analgesia (as well as neuroendocrine markers for some time points) were significantly higher in the dogs operated by laparotomy. the relative risk for rescue analgesia in the laparotomy was 10 fold, but the 95% confidence interval was enormous (1.6 to 64.2) indicating an underpowered study. the pain scoring system was adapted from a system validated for use in human paediatric patients, not dogs. we therefore consider the strength of evidence in favour of laparoscopy to be weak. a non-blinded, non-randomised controlled trial design was used by freeman et al. (2010). animals in both laparotomy and laparoscopy groups were from a local animal shelter and comparable in weight (though breeds and ages were not stated). anaesthetic protocol was reportedly standardised (details of protocol not shown) but surgical team was unclear. like hancock et al. (2005), a combination of umps and nociceptive threshold testing was used, but two observers limit this strength. reporting of statistics between laparoscopy and laparotomy was limited. the power calculation (the only study to report one) significantly overestimated the effect of the intervention group on reduction of il-6, c-reactive protein (crp), cortisol and increase in nociceptive threshold readings, this demonstrates the study is considerably underpowered. significantly lower pain scores and higher nociceptive thresholds were found in the laparoscopy group at certain time points. this may easily be missed as it is not reported in the results or discussion but is derived from the figures. we would consider this to be weak evidence in favour of laparoscopy. coutinho et al. (2018) used a blinded randomised controlled trial design but several limitations were encountered; principally two observers were responsible for pain scoring. both umps and a visual analogue scale (vas) were used, with the latter known to be more subjective (pelligand & mora, 2016). the groups were assessed thoroughly before inclusion to ensure they were healthy, but breeds were not reported. significantly faster return to eating (and in greater proportion) was found in the laparoscopy group, but this behaviour is not captured by any pain scoring system. postoperative glucose concentrations (which walsh et al. (1999) report to be a possible marker of stress caused by discomfort) were also significantly lower in dogs in this group, suggesting they may be more comfortable postoperatively than dogs operated by laparotomy. although it was reported that no physiological parameters changed (suggesting no change in nociception) during the two complications in the laparoscopic group, the elimination of these from follow-up was an additional weakness. given the lack of significant difference in pain scores combined with the above weaknesses, we cannot see this study being used as evidence to support use of laparoscopy over laparotomy to reduce postoperative pain. though vasiljevic et al. (2015) also used a non-blinded, randomised controlled trial design, there was moderately high risk of bias. aside from study design, a significant factor limiting the strength of evidence was the lack of recording. species and approximate breed size of animals were stated, but we have no other information on group characteristics so are unable to confirm if they were comparable. the minimum patient age was 7 months and the smallest patient weight was 5 kg, which does not fit with the description of medium and large breed dogs. surgical team was not specified nor surgical techniques described, but there was a similar induction and maintenance protocol between groups. additional analgesia was used for all patients in the laparotomy group but none in the laparoscopic group, which would bias the laparotomy group to lower postoperative pain scores (which was not the case). a single postoperative pain scoring method was used by one observer, based on four parameters to give a score from 0 to 9 (incorrectly presented in figures as 0 to 10). the parameters had similarities to the short form composite measure pain scale (cmps-sf), but the description was brief and not referenced to other studies so was difficult to compare. statistics were lacking but there is clear difference in pain scores between groups – much higher for dogs operated by laparotomy. this may, however, be a result of the reported slower recovery from general anaesthesia in the laparotomy group. though unrelated to strength of evidence, ethics are of concern. the study was approved by the local ethics committee but no intervention level was set for rescue analgesia during the 6 hour assessment period. two dogs were considered to be in severe pain at 1, 3 and 6 hours but analgesia was withheld until after the final pain score assessment. overall concerns with reporting bias are significant and results must be viewed with skepticism and therefore this study cannot be used to answer the question in the clinical scenario. a truly non-blinded non-randomised study was used by davidson et al. (2004). the groups may not be comparable as there is no breed data, health status was not clear, and they were derived from different populations. in addition, there was no standardisation of anaesthetic protocol or surgical team between groups. the same surgeon was responsible for laparoscopic surgery, but multiple veterinary students (who are likely to have poorer tissue handling) performed open surgery, increasing bias in favour of laparoscopic techniques. we see that surgical times for ohe were as long as 140 minutes which is not consistent with what is typically expected* for this procedure. equally, laparoscopic surgical times were significantly longer than expected, leading us to believe that this is a novel technique for the surgeon and the outcomes therefore unreliable. ketamine (6 mg/kg iv) was used preoperatively for four of the dogs undergoing laparoscopic surgery and only one of the dogs receiving open surgery. preoperative use has been shown to confer significant postoperative analgesic effects (slingsby & watermanâ€�pearson, 2000), so the results here are further biased. unique to this study, a 4-port technique with a surgical wire ligation device was used. these techniques are not applicable for ovariectomy or ovariohysterectomy in general practice. *typical surgical times for laparotomy or laparoscopy would be 30–60 minutes depending on patient size. although they report a number of parameters within the subjective pain scale and umps to be significantly higher for open surgery, this belies the lack of significant difference in overall scores. overall, this study cannot be used to answer the question in the clinical scenario. even in human surgery, we must remember that a laparoscopic approach is not without problems.­ insufflation pressures above 15 mmhg, unnecessary pressure peaks and prolonged insufflation with co2 have been shown to contribute to pain after laparoscopy in humans (moulton et al., 1999). in dogs, there is a suggestion that the rate of complications are reduced for laparoscopic ovariectomy compared with open ovariectomy (charlesworth & sanchez, 2019), but experience in using the technique will affect the outcomes (pope & knowles, 2014) along with surgical time. none of these factors, however, have been critically reviewed here but would require careful consideration when making recommendations for this technique. despite the widely held belief that laparoscopic surgery is associated with less postoperative pain, the available veterinary literature only provides weak evidence to support this in bitches undergoing ovariectomy/ovariohysterectomy. there are many uncontrolled variables to consider across the underpowered studies here including surgeon number (and experience), the choice of perioperative analgesia, method of pain scoring and the laparoscopic technique. it is therefore clear that laparoscopic procedures cannot be viewed equally and the strength of the answer to the clinical question may change based upon these variables. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform 1973–2020 week 15 ovid medline(r) 1946–june 2020 search strategy: search performed was the same for each database: dogs/ (dog* or canine* or pupp* or bitch*).mp 1 or 2 (laparoscop* or celioscop* or coelioscop* or peritoneoscop* or notes or halo or keyhole or “key-hole”).mp (laparotom* or celiotom* or coeliotom* or open or traditional or conventional).mp 4 and 5 (spay* or spey* or ovarectom* or ovariectom* or ovariohysterectom* or oophorectom* or ove or ohe or ovh or neuter* or desex* or sterilis* or steriliz* or gonadectom*).mp 3 and 6 and 7 dates searches performed: 30 june 2020 exclusion / inclusion criteria exclusion: not available in english. reviews, letters, book chapters, case reports or conference proceedings. species other than canines. no report of outcomes relevant to postoperative pain. studies evaluating different laparoscopic techniques only. papers comparing laparoscopy to open flank approaches. the notes technique was not considered as a comparison to open procedures as it is not a technique that is currently widely used for neutering in general practice – papers were not excluded if they still compared a standard laparoscopic technique with open surgery. inclusion: comparison of midline open ovariectomy/ovariohysterectomy with laparoscopic ovariectomy/ovariohysterectomy. laparoscopic techniques and methods considered reasonable in general practice. this included any number of direct abdominal ports for access, as well as the use of harmonic scalpel, monoor bi-polar electro surgery and suture, wire or clip ligation. studies that used a postoperative pain scoring system. search outcome database number of results excluded – [not english] language excluded – [review, case re-port or conference proceedings] excluded – [did not answer pico] total relevant papers cab abstracts 92 29 14 43 6 medline 44 1 5 34 4 total relevant papers when duplicates removed 7 conflict of interest the authors declare no conflicts of interest. references charlesworth, t. m. & sanchez, f. t. (2019). a comparison of the rates of postoperative complications between dogs undergoing laproscopic and open ovariectomy. journal of small animal practice. 60(4), 218–222. doi: https://doi.org/10.1111/jsap.12993 coutinho, a. j., gasser, b., rodriguez, m. g. k., uscategui, a. a. r., santos, v. j. c., tiosso, c. de f., barros, f. f. p. da c. & toniollo, g. h. (2018). comparison between single port videolaparoscopy and miniceliotomy with snook hot ovariohysterectomy techniques in bitches. ciênca rural. 48(10), e20180345. doi: https://doi.org/10.1590/0103-8478cr20180345  dalmolin, f., oliveira, m. t., filho, s. t. l. p., vaz, m. a. b., de cecco, b. s., feranti, j. p. s., carvalho, e. r., silva, m. a. m. & brun, m. v. (2020). dipyrone, scopolamine, and meloxicam for conventional or two-port laparoscopic assisted ovariohysterectomy in female dogs. semina: ciências agrárias (londrina). 41(3), 887–896. doi: https://dx.doi.org/10.5433/1679-0359.2020v41n3p887 davidson, e. b., moll, h. d. & payton, m. e. (2004). comparison of laparoscopic ovariohysterectomy and ovariohysterectomy in dogs. veterinary surgery. 33(1), 62–69. doi: https://doi.org/10.1111/j.1532-950x.2004.04003.x devitt, c. m., cox, r. e. & hailey, j. j. (2005). duration, complications, stress, and pain of open ovariohysterectomy versus a simple method of laparoscopic-assisted ovariohysterectomy in dogs. journal of the american veterinary medical association. 227(6), 921–927. doi: https://doi.org/10.2460/javma.2005.227.921 freeman, l. j., rahmani, e. y., al-haddad, m., sherman, s., chiorean, m. v., selzer, d. j., snyder, p. w. & constable, p. d. (2010). comparison of pain and postoperative stress in dogs undergoing natural orifice transluminal endoscopic surgery, laparoscopic, and open oophorectomy. gastrointestinal endoscopy. 72(2), 373–380. doi: https://doi.org/10.1016/j.gie.2010.01.066 hancock, r. b., lanz, o. i., waldron, d. r., duncan, r. b., broadstone, r. v. & hendrix, p. k. (2005). comparison of postoperative pain after ovariohysterectomy by harmonic scalpel-assisted laparoscopy compared with median celiotomy and ligation in dogs. veterinary surgery. 34(3), 273–282. doi: https://doi.org/10.1111/j.1532-950x.2005.00041.x khasriya, r., vashisht, a. & cutner, a. (2018). laparoscopy in urogynaecology. the obstetrician and gynaecologist. 20(2), 101–108. doi: https://doi.org/10.1111/tog.12449 mouton, w. g., bessell, j. r., otten, k. t. & maddern g. j. (1999). pain after laparoscopy. surgical endoscopy. 13(5), 445–448. doi: http://dx.doi.org/10.1007/s004649901011 pelligand, l. & mora, s. s. (2016). pain assessment methods. in: duke-novakovski t., de vries m. & seymour c. (eds.) bsava manual of canine an feline anaesthesia and analgesia, third edition. gloucester, uk. british small animal veterinary association, pp113–123. pope, j. f. a. & knowles, t. g. (2014). retrospecitve analysis of the learning curve associated with laparoscopic ovariectomy in dogs and associated perioperative complication rates. veterinary surgery. 43, 668–677. doi: https://doi.org/10.1111/j.1532-950x.2014.12216.x sarrau, s., jourdan, j., dupuis-soyris, f. & verwaerde, p. (2007). effects of postoperative ketamine infusion on pain control and feeding behaviour in bitches undergoing mastectomy. journal of small animal practice. 48(12), 670–676. doi: https://doi.org/10.1111/j.1748-5827.2007.00362.x slingsby, l. s. & watermanâ€�pearson, a. e. (2000). the postoperative analgesic effects of ketamine after canine ovariohysterectomy—a comparison between pre and postoperative administration. research in veterinary science. 69(2), 147–152. doi: https://doi.org/10.1053/rvsc.2000.0406 vasiljeviä‡, m., ristanoviä‡, d., jovanoviä‡ m., davitkov, d., bošnjak, i., krstiä‡, v. & stanimiroviä‡, z. (2015) comparative analysis of parameters of intraoperative and postoperative pain in bitches undergoing laparoscopic or conventional ovariectomy. acta veterinaria-beograd. 65(4), 488–495. doi: https://doi.org/10.1515/acve-2015-0041 walsh, p. j., remedios, a. m., ferguson, j. f., walker, d. d., cantwell, s. & duke, t. (1999). thoracoscopic versus open partial pericardectomy in dogs: comparison of postoperative pain and morbidity. veterinary surgery. 28(6), 472–479. doi: https://doi.org/10.1111/j.1532-950x.1999.00472.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. the missing link between practice and research professor peter cockcroft1* editor-in-chief 1university of surrey, school of veterinary medicine, daphne jackson rd, guildford gu2 7al *corresponding author (p.cockcroft@surrey.ac.uk) vol 5, issue 2 (2020) published: 29 apr 2020 doi: 10.18849/ve.v5i2.343 the application of evidence-based veterinary medicine (ebvm) can improve and optimise: diagnosis, prognosis, control, treatment of animals, provide informed choices for owners, enable veterinarians to defend their decisions scientifically, provide the user with a methodology for appropriate,  patient orientated life-long, self-directed learning, identify information deficits in the literature and direct clinical research (cockcroft and holmes 2003). veterinary research is often dictated by top down approaches where funding bodies have specific topics which they are prepared to fund. veterinary practitioners often feel they have little or no influence on the ‘research agenda’ and are simply the end users (holmes and cockcroft, 2008). the practice of evidence-based veterinary medicine, and in particular the creation and publication of knowledge summaries, can provide a bottom up approach to identifying important and useful information needs that influence the quality of care and advice we can provide in clinical practice. identification of important clinical questions from practice settings, and the identification of the strength of evidence to answer the question from the published primary literature, is an overlooked important outcome with regard to directing future research. figure 1: the missing link between practice and research the veterinary evidence journal will now provide an annual list of knowledge summaries where the strength of evidence to answer the question in the primary literature is weak or non-existent. this will provide the veterinary research community with topics that have been identified as requiring further high-quality research to increase the strength of evidence. this page is available here: veterinaryevidence.org/index.php/ve/strength-of-evidence references cockcroft p d and holmes ma (2003) handbook of evidence‐based veterinary medicine, p9, blackwell publishing ltd holmes ma and cockcroft pd (2008) handbook of veterinary clinical research, p, blackwell publishing ltd   there is no evidence for or against the use of non-steroidal anti-inflammatory drugs to reduce the clinical duration of kennel cough (infectious tracheobronchitis). a knowledge summary by marc a. c. silpa bvm&s mrcvs* *corresponding author (m.a.c.silpa@gmail.com) vol 1, issue 1 (2016) published: 27 jan 2016 next review date: 15 aug 2017 doi: 10.18849/ve.v1i1.3 clinical bottom line there is no evidence on which to judge the efficacy of non-steroidal anti-inflammatory drugs for the treatment of kennel cough. question in [canines], does the use of [nsaids] versus [no treatment] reduce the [clinical duration of canine infectious tracheobronchitis (kennel cough)]? clinical scenario mr. smith brought his two year old male labrador retriever, “winston”, to your clinic for a sudden onset hacking cough. winston was housed in a kennel last week while the owners were on holiday. on clinical exam, the dog coughs when the trachea is manipulated, but is well otherwise. you suspect “winston” has infectious tracheobronchitis. you, keeping aware of the latest ebvm publications, know antibiosis is not warranted in this case. but you wonder if a few doses of a non-steroidal anti-inflammatory drug would reduce the time that it takes for “winston’s” cough to resolve. the evidence there are no research studies, case studies, or epidemiological surveys published on the use of non-steroidal anti-inflammatory drugs (nsaids) for the treatment of canine infectious tracheobronchitis. no judgement can be made whether the use of nsaids is justified. further research is needed. appraisal, application and reflection there are no research studies, case studies, or epidemiological surveys published on the use of non-steroidal anti-inflammatory drugs (nsaids) for the treatment of canine infectious tracheobronchitis. no judgement can be made whether the use of nsaids is justified. further research is needed. methodology section search strategy databases searched and dates covered: pubmed accessed via the ncbi website 1900 – 2015, cab abstracts on the ovid platform 1973 – 2015 week 31 search terms: (dog or dogs or canine* or canis or pup*) and ((inflamm* and (bronchi or trachea)) or tracheobronchitis or itb or rhinotracheitis or "kennel cough" or bronchitis or tracheitis or laryngitis or bordetellosis or bordetella) and (nsaid or nsaids or anti-inflammatory or "anti inflammatory" or non-steroidal or "non steroidal" or steroid*) dates searches performed: 15 august 2015 exclusion / inclusion criteria exclusion: non english language, non-systematic reviews or conference papers. inclusion: systematic reviews, randomised controlled trials, case studies, meta-analyses and epidemiological surveys. search outcome database number of results excluded – study design excluded – nonenglish language publication excluded – did not answer pico question total relevant papers ncbi pubmed 66 0 5 61 0 cab abstracts 9 2 0 7 0 total relevant papers when duplicates removed 0 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. the use of mobile devices and online services by german veterinary students cindy kasch1 peggy haimerl1 sebastian arlt1* wolfgang heuwieser1 1clinic for animal reproduction, faculty of veterinary medicine, freie universität, berlin, königsweg 65, 14163 berlin, germany *corresponding author (sebastian.arlt@fu-berlin.de) vol 1, issue 3 (2016) published: 04 july 2016 reviewed by: erik fausak (mslis, ma, cvt, lvt, rlat) doi: 10.18849/ve.v1i3.41 section index:    abstract | introduction | methods | results | discussion | conflict of interest | references | supplementary files abstract objective: the research question of our study was to determine the adoption and use of mobile devices and online services by veterinary students. background: new technologies support learning, communication and information transfer during the pre-professional years and the professional lifetime. hence, mobile devices may also be a feasible tool for information access for the practitioner at any place and any time, and consequently may support better informed clinical decision making. evidentiary value: we conducted a survey among 124 german veterinary medical students in their third year with a median age of 23.0 years. methods: the survey was conducted during a lecture and contained 10 questions with preset answers to be ticked and a free text comment section. participation was voluntary and data processing was performed anonymously.   results: according to the answers of surveyed third year students 84.7% used a smartphone as a mobile device. the vast majority of the veterinary students used google, facebook and whatsapp besides other applications.   conclusion: most students are familiar with mobile devices and the use of social media and information tools. thus, new learning strategies could be developed and applied that encompass mobile online learning and information access. these strategies could help to better address different learning types, provide sufficient interactivity and feedback and enable veterinarians to seek and share information via the internet. however, despite promising results reporting a positive educational effect, these perceptions need to be validated in further research. in addition, it should be assessed in future surveys if veterinarians would use mobile online access to scientific data or knowledge summaries for better informed decision making in practice. application: veterinary students, and thus the next generation of veterinary practitioners, are using mobile devices to a high extent. this paves the way to refine existing and to develop new education strategies. new information tools for mobile devices may help veterinarians to seek and share information. in addition, it might be worthwhile to teach veterinary students and practitioners how to search for and appraise online scientific information. introduction students frequently use mobile devices for everyday activities such as talking and texting (applegate, 2010). in 2013, more than 60 billion instant-messages and sms were communicated every day (informa, 2013), mostly by teenagers and adolescents (goodarzi, 2012; herman, 2007). it is expected that this amount will be doubled by 2017 (juniper research; emarketer, 2013). the rapid development of new communication technologies also has a major influence on veterinary education (short, 2002; valliyate, 2012). already now, veterinary teaching has profited considerably from advances in information communication technology (simões, 2010). for example, computerised testing has made significant inroads into veterinary education (folk, 2006). also, learning management platforms such as blackboard (www.blackboard.com), which enable lecturers to provide teaching materials online, and information tools like wiki systems (kolski, et al. 2015) represent such a technological advance. a well-known advantage of the integration of new technology into education is that it enables students to study independently to location and time (short, 2002). furthermore, technological advance allows the usage of virtual patients as an educational aid, as suggested by trace et al. (2012) or schaper et al. (2011). the most important prerequisite for this type of communication is the availability and actual use of adequate technology. according to cole-lewis and kershaw (2010), across the world (in both developing and developed countries) more and more people are gaining access to the internet via mobile phones. consequently, more and more people do have access to current medical knowledge. since this potentially facilitates clinical decision making, it in turn supports the implementation of evidence-based veterinary medicine. however, this means that students need to gain competence in information search and retrieval via the internet. little research has been published on how veterinary students actually use mobile devices (gikas and grant, 2013). hence, the research question of our study was to determine adoption and use of mobile devices and online services by veterinary students. methods in march 2014, we conducted a survey among veterinary medical students in their third year. in this term of education the students participate in lectures and seminars offered by the clinic for animal reproduction, berlin, germany. at the beginning of a lecture we asked the students to participate in the survey. we developed the questionnaire according to statements and suggestions made by students that participated in earlier courses and seminars. participation was voluntary. students declared informed consent by completing the survey. the project was reviewed and approved by the ethical commission of the charité hospital associated with freie universität berlin (ea 1/126/16). the students had 15 minutes to answer the questionnaire which contained 10 questions with preset answers to be ticked and a free text comment section (figure 1). after a short introduction to the study and demographic questions (i.e. age, semester, and gender) three questions addressed the use of mobile devices. the second part dealt with the students’ habits and preferences concerning the application of mobile devices. we performed descriptive statistical analysis anonymously using the statistic program spss for windows (version 22.0; spss inc., munich, germany). we performed frequency analysis on the obtained quantitative data. furthermore, we used cross tables to analyse the students’ answers considering both genders. finally, we analysed the quantitative data using the two tailed fisher's exact test and the pearson-chi2-test. we set the significance level as α = 0.05. for a statistical analysis of free text comments we considered them as qualitative data. results in total, 124 of 130 students (101 female and 22 male) completed the questionnaire. one participant did not specify gender, age or semester. median age of participating students was 23.0 (iqr 22.0 – 25.0). the majority of the students (84.7%) stated to use a smartphone as a mobile device (table 1). about one fourth of the students (23.4%) additionally utilised tablets, while 8.1% employed a laptop in addition. the given answers revealed that, regarding operating systems, students preferred ios (41.1%) and android (44.3%). the majority of students (78.2%) stated to have an internet flat rate for their mobile device. concerning online services used via mobile devices, most of the participating students (78.2%) used google. moreover, 62.9% of the students accessed the e-learning platform of the fu berlin (blackboard) via mobile devices. similarly, the majority of students (54.0%) frequently used google maps. most of the respondents (61.3%) used online dictionaries occasionally while, respectively, 50.8% and 42.7% stated to consult the information platform wikipedia often and occasionally. in addition to the suggested online services, six students (4.8%) added further options (e.g. veterinary dictionary doccheck) as free text comments. while 15 students (12.1%) reported to have a quick response (qr) code reader, 18 stated to use such a tool, either often (n=1) or occasionally (n=17). with 74.2% and 70.2%, respectively, whatsapp and facebook turned out to be the most frequently used social media services (table 2). in line with that, 44.3% of the students referred to whatsapp as their favourite application software. this was also supported by comments in the free text comment section. moreover, more than half of the students (53.2%) occasionally used skype; a software allowing free instant messaging and voice or video calls. on the contrary, only few students indicated a frequent or occasional use of social media like viber (3.2%), talk (1.6%), twitter (0.8%), instagram (8.9%), telegram (8.9%) or snapchat (2.4%). more than one-third of the students spent 2 to 4 hours per day online via mobile devices. the majority of the students (68.5%) indicated that they answer incoming messages only when they find time to do this. veterinary online applications wished for by the responding students included a “laboratory data app” (4.8%) or learning apps (4.8%), that were not further specified. discussion mobile learning and information retrieval has been growing internationally in visibility and significance (traxler, 2007, 2010, 2012). therefore, we wanted to investigate if german students of veterinary medicine have adopted the use of mobile devices as well. current mobile devices are designed to allow users to enter and access data like contacts and memos, to send and receive messages, to view documents and pictures, or to access the web (kukulska-hulme, 2005). in 2013, 96% of people in germany aged between 12 and 19 owned a smartphone (kutscher, 2014). in our survey, the share of veterinary students who stated to use a smartphone regularly resembled those findings (84.7%). moreover, the fact that the majority of the participants (78.2%) had an internet flat rate was in accordance with the findings of wallace et al. (2012). the finding that the vast majority have mobile access to the internet indicates that online professional tools designed for mobile devices have a great potential to reach the majority of veterinary students and also presumably a growing proportion of practitioners and clinicians in germany. regarding online education, the concept of 'anytime' and 'anyplace' offered by mobile learning may be an important pedagogical aspect (bidin and ziden, 2013). as emphasised by smith (2003), e-learning should accommodate different learning styles and provide sufficient interactivity, testing, and feedback to engage the user. personalised learning can recognise diversity and individuality of the students and account for different learning styles and approaches (traxler, 2007). one way this can be accomplished is by an assortment of tools that learners can combine to best suit their individual learning styles to increase their academic success (rodriguez, 2011). a more recent interview-based survey showed that 90% of the participants used mobile computing devices and that this usage was believed to have a positive educational effect (wallace, et al. 2012). since an interview allows face to face communication and immediate feed-back for both interviewer and interviewee, such an approach might be beneficial for further research in this area. according to our findings, the vast majority of the veterinary students used the search engine google (96.7%), either frequently (78.2%) or occasionally (18.5%). those data deviate from wallace et al. (2012), who found that 50% of those participating in their survey stated to use google. however, their study was conducted in 2012 and the growing popularity of google might at least partly account for these differences. furthermore, the authors did not only interview students in their survey, but also residents and members of the faculty. hence, as shown previously we can assume that the resulting higher average age explains for the lower usage of online media (wolff, 2006) like the search engine (pew research center. n.d., 2011).  those two aspects might also explain why only 15% of their participants used the encyclopedia wikipedia, whereas more than half of our participants (50.8%) stated to do so. since wikipedia is not specific for veterinary medicine, a wiki-system designed for veterinary purposes may be advantageous (kolski, et al. 2015). a special issue connected with this topic is the quality of provided information. it is essential to train students to critically assess information, especially if it is found on webpages or wiki systems with unknown expertise of the author. clinical decisions based on false, incomplete or outdated data may be highly detrimental for the health and well-being of the animals. qr-code readers, a mobile device tool enabling the scanning of bar codes (lorenzi, et al. 2014, ramsden, 2008), were not popular according to our survey. qr-codes enable a quick uptake of data in a compact fashion (lorenzi, et al. 2014) or visiting a specific website without typing the address of the webpage. with regard to our survey, only 12.1% of the veterinary students used such a tool. these data correspond with earlier findings where only 2% of students had scanned a qr code with their device (ramsden, 2008). different promising recommendations for the use of qr-codes within a lecture or course have been published. for example, students may easily get access to handouts, additional online presentations or feedback questions by scanning a qr-code integrated into a presentation (ramsden, 2008). another application may be a direct link to standard operation procedures or specific additional information. surprisingly, in our survey, there were more students stating to use qr-codes (14.5%) than having installed a qr code reader on their device. this discrepancy may indicate that some students did not read the question carefully. on the other hand, some students may have used this tool with the device of someone else or have uninstalled the reader. a majority of the participants stated to frequently use facebook (70.2%) or whatsapp (74.2%). both applications are reported to rank among the most popular ones used by young people in germany (kutscher, 2014; roblyer, 2010). also, 44.3% of the students referred to whatsapp as their favourite application software. whatsapp enables users to send and receive text messages, images, audio and video files (church and de oliveira, 2013). membership of online social networks has recently exploded at an exponential rate (cheung, et al. 2010). according to facebook reports, they had 1.44 billion users in the first three months of 2015, out of which 1.25 billion additionally and 581 million exclusively used mobile access (facebook, 2015a, facebook, 2015b). as reported by pempek et al. (2009), students use facebook approximately 30 min per day for study purposes. via whatsapp, more than 10 billion messages are sent per day and it is one of the most popular paid apps across all mobile platforms (church and de oliveira, 2013). concerning possible benefits of integrating online tools into education, greenhow (2011) emphasised that social utilities do not only have a social effect, but can also have a positive impact on learning outcomes. however, this potential positive impact on learning success should be assessed in future research, especially since current information of practical relevance is increasingly shared via social media. by allowing an almost real-time interaction between students and instructors (gikas and grant, 2013), the integration of social tools may promote a more student-centred course (greenhow, 2011). this live contact with others also allows direct conversations on a topic or issue (gikas and grant, 2013; traxler, 2007), and by that may support the concept of collective learning and critical discussion (levy, 2001). furthermore, using the highly interactive knowledge sharing features of a virtual community can increase the student’s learning motivation (wasko and faraj, 2005). according to a study by wu et al. (2014), the diverse resources provided in virtual communities promoted critical thinking, problem analysis, and problem-solving skills of the researched nursing students. with regard to our survey, more than one-third of the students (36.3%) spent two to four hours per day online with their mobile devices. some students stated that they would like to have a “laboratory data app” or other learning apps. the reason that only a small proportion of surveyed students suggested new tools may be due to the fact that few apps already exist for veterinary purposes or that they are rarely used. therefore, the students may not be aware of the possibilities such apps may provide. this issue should be surveyed in a future project. we assume that the development of such tools, together with the involvement of students in the creative process, might foster their motivation and consequently increase their learning outcome (bidin and ziden, 2013), and at the same time increase the number of applicable learning and information tools. overall, the use of the new technology may offer the possibility to consider new learning strategies (bidin and ziden, 2013; short, 2002). however, studies which attempted to systematically assess the learning success of online and mobile teaching compared to the traditional approach have hardly been published. in addition, it has to be assessed if information tools would be accepted and used by practitioners. however, it sounds plausible that a practitioner may see benefits in an app that provides dosages or other information and is accessible on-site by a mobile phone while examining the patient. in addition, online tools offering current and easily accessible research syntheses may support transfer of new knowledge into practice and enable an efficient information search. in that regard, it might be worthwhile to train students in how to search and appraise online scientific information. in spite of various interesting findings, we are aware of the limitations of our survey. the small number of male students, for example, caused an uneven gender distribution (22 male vs. 101 female). furthermore, only veterinary students of the free university of berlin in their third year were included. also, the fact that many questions offered the possibility to tick more than one answer may have led to bias. however, the objective of the study was to research the distribution and use of mobile devices, and a survey is likely to be one of the best methods to acquire valuable and evaluable data. considering that objective, we inevitably had to face the uneven gender distribution typical for veterinary schools worldwide (kostelnik, et al. 2010). to sum it up, mobile devices have found their way into the everyday life of veterinary students. as shown in our survey students valued the new possibilities of online communication. hence, the development of online learning tools and information platforms meeting the specific demands of veterinary medicine should be promoted. however, some authors criticise that mobile learning should only represent a supplement since it might imply learning across contexts and at different times, resulting in fragmented knowledge and incomplete schemata (gikas and grant, 2013; tella, 2003; traxler, 2010). overall, the integration of mobile devices in education may assist most students in their learning (gikas and grant, 2013). in conclusion, veterinary students (equivalent to the next generation of veterinary practitioners) are using mobile devices to a high extent. this paves the way to refine already existing and to develop new education and information tools for mobile devices. however, conflicts may arise since not every teacher and student is able or willing to handle mobile devices or other new technologies (gikas and grant, 2013). hence, augmenting the importance of new technologies within education might lead to isolation of those not having access to mobile devices. most importantly, although it is difficult to evaluate mobile learning (traxler, 2007), further studies are warranted to examine the learning success. in addition, courses at universities should address skills in searching and assessing online information. finally, it should be assessed in future surveys if veterinarians would use mobile online access to scientific data or knowledge summaries for better informed decision making in practice. conflict of interest acknowledgments: the authors gratefully thank the participants of the survey. in addition, we thank the students that provided statements and suggestions for the design of the survey. also, many thanks go to özlem cigdem, a student of integrated natural sciences at the freie universität, who stayed with us for two weeks in terms of a work practice for helping to develop the questionnaire. competing interests: none to declare. the manuscript, or parts of it, have not been and will not be submitted elsewhere for publication. none of the authors have any financial or personal relationships that could inappropriately influence or bias the content of the paper. references applegate, js. 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(2014) using smart mobile devices in social-network-based health education practice: a learning behavior analysis. nurse education today, 34 (6), pp. 958-63. http://dx.doi.org/10.1016/j.nedt.2014.01.013     tables & questionnaire tables table 1: use of mobile devices and operating systems by third year veterinary students (n=124) use of mobile devices n %2 smartphone  108  84.7 smartphone and other electronic devices1  47  37.9 conventional cell phone  18  14.5 conventional cell phone and other electronic devices1  9  7.2 operating systems n %2 android 55 44.1 ios 51 41.1 android & windows 15 12.1 ios & windows 12 9.7 1 other electronic devices: tablet, e-book-reader, laptop 2 multiple selection was possible; not all questions were answered by all participants   table 2: use of social media by third year veterinary students (n=124)   facebook1 whatsapp1 telegram1 skype1 twitter1 often 70.2% 74.2% 1.6% 12.9% 0.8% occasional 18.5% 2.4% 8.9% 53.2% 0.0% never 8.9% 19.4% 83.1% 31.5% 92.7% 1 multiple selection was possible; not all questions were answered by all participants   fig. 1. questionnaire to assess the use of mobile devices by german veterinary students click to toggle questionnaire personal data: age: _______ semester: _________ sex: __________ please tick the boxes which operating system(s) do you use? conventional cell phone smartphone tablet e-book-reader other________ which operating system do you use? android ios (apple) blackberry windows other________ do you have an internet flat rate for your mobile device? yes no which online services do you use via your mobile device?   often occasionally never google       dictionary       wikipedia       google maps       blackboard       other________ do you have a qr code reader? yes no …if yes, how often do you use a qr code? often occasionally never which social media do you use? please indicate for all that apply!   often occasionally never facebook       whatsapp       skype       tango       snapchat       telegram       twitter       threema       viber       talk       instagram       other________ how much time per day do you spend online with your mobile device(s)? less than 1 hour 1-2 hours 2-4 hours more than 4 hours in average, after what time interval do you answer a received message? immediately within 5 min when i have time what is your favorite app? .......................................... which veterinary online tools would you like to have? .......................................... the tables and questionnaire can also be found in the downloadable pdf. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. are glucocorticoids or nsaids more effective in reducing idiopathic feline urinary tract disease signs than no treatment or placebo? a knowledge summary by lesca monica sofyan baavbs(honsii) mvs dvm 1* 1orchard hills veterinary hospital, 49–63 wentworth rd, orchard hills nsw 2748, australia *corresponding author (lesca.sofyan.xx@hotmail.com) there is an erratum to this paper published in veterinary evidence vol 6, issue 4 (2021): https://doi.org/10.18849/ve.v6i4.532 vol 6, issue 3 (2021) published: 12 aug 2021 reviewed by: nicolette joosting (bsc bvsc) and constance neville white (dvm phd) next review date: 08 mar 2023 doi: 10.18849/ve.v6i3.439 pico question in cats with idiopathic feline urinary tract disease (flutd), are glucocorticoid or non-steroidal anti-inflammatory drugs more effective than placebo or no treatment in reducing clinical signs attributable to cystitis?   clinical bottom line category of research question treatment the number and type of study designs reviewed three randomised controlled trials have examined the efficacy of prednisolone or non-steroidal anti-inflammatory drugs (nsaids) in reducing the clinical signs of feline lower urinary tract disease compared to a placebo whilst one retrospective cohort study compared the reoccurrence of flutd in cats treated with meloxicam and without meloxicam strength of evidence weak outcomes reported one small controlled trial compared prednisolone to a placebo and found no clinical differences in dysuria, microscopic haematuria, and occult blood for cats diagnosed with idiopathic non-obstructive feline lower urinary tract disease (flutd) hospitalised for 10 days. the study however had a very small sample size. furthermore, the external validity of the study to similar patients discharged to their home environment is unclear. the second small controlled trial compared meloxicam to a placebo in cats diagnosed with obstructive flutd. statistical analysis was applied to determine if there were significant differences in voiding behaviour, general demeanour, haematuria, food intake and abdominal pain as assessed by the veterinarians in charge during hospitalisation and owners at discharge. no statistically significant differences (p>0.05) were calculated between the two treatment groups based on the owner questionnaire and veterinarian assessment but small samples in each treatment probably limited statistical power. the third small controlled trial compared the reoccurrence of feline idiopathic cystitis (fic), related clinical signs and recurrent urinary obstruction in cats at 10 days, 1, 2 and 6 months after discharge when treated with phenoxybenzamine and alprazolam, with or without the addition of meloxicam. no statistically significant differences were found in the reoccurrence of obstructed or non-obstructed fic for cats treated with either meloxicam or no meloxicam. however, full details of each intervention group were not sufficient to assess for balance of prognostic factors, subjective scoring of clinical signs was not detailed, and the study was underpowered for the actual obstruction rates reported. the fourth paper was a retrospective cohort study that examined the association of different treatment factors with 30 days reobstruction. the study found no significant association between the use of meloxicam and the rate of reobstruction but a number of confounders were present conclusion three small randomised controlled trials and a single retrospective cohort study failed to find a significant association between the use of glucocorticoids or nsaids with severity of flutd clinical signs or risk of reobstruction. clinical outcome measures were heterogeneous and studies were significantly underpowered and/or at risk for bias and/or confounding. there is insufficient evidence to recommend the use of either drug category in decreasing time to resolution or severity of clinical signs in cases of idiopathic flutd or fic   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are presented with a 2 year old, female spayed long hair tortoiseshell with her third episode of frequent and painful urinations and gross haematuria. her first episode occurred when the owners acquired a new puppy who she hides from. prior ultrasound was negative for uroliths and her urine was culture negative. haematology, serum biochemistry, and urinalysis are unremarkable aside from the finding of large numbers of red blood cells in her urine sediment. after explaining your suspicion for feline idiopathic lower urinary tract disease (flutd) (aka feline idiopathic cystitis (fic)) and her probable bladder inflammation, her owners ask about the use of anti-inflammatory medications to alleviate her clinical signs. you discuss that both non-steroidal (nsaids) and steroidal anti-inflammatories (glucocorticoids) have been used in the past and the owners ask which, of any, you would recommend. the evidence there are four studies available that assesses the efficacy of prednisolone and/or non-steroidal anti-inflammatory meloxicam for fic. summary of the evidence osborne et al. (1996)1 population: criteria for eligibility and inclusion: felines diagnosed with idiopathic flutd.   criteria for exclusion and rejection: felines diagnosed with a major illness/illnesses of other body systems. obstructed felines requiring an indwelling catheter. sample size: 12 cats: eight males four females intervention details: random allocation into two treatment groups: prednisolone treatment group n=6 placebo treatment group n=6   dosage and administration of treatment: prednisolone treatment group: prednisolone was administered as a capsule by mouth twice daily at a dose rate of 1.0 mg/kg body weight. placebo treatment group: a capsule containing no prednisolone was administered by mouth twice daily.   duration of therapeutic intervention: 10 days treatment; all cats remained hospitalised during treatment.   diet: all cats were fed on hills science diet feline maintenance throughout the duration of the study.   collection of urine on days 0, 5, 10, 14, 28: urine was collected either via void or cystocentesis for assessment. study design: prospective double blinded and randomised clinical study outcome studied: dysuria urinalysis during hospitalisation, 2 weeks, 4 weeks: mean urine specific gravity urine dipstick (bayer multistix®) ph and occult blood struvite crystalluria microscopic haematuria urine culture: baseline, 2 weeks, 4 weeks main findings (relevant to pico question): dysuria reduced in an average of 1.5 days across both treatment groups. microscopic haematuria reduced in an average of 3.2 days in the prednisolone treatment group and 3.5 days in the placebo treatment group. trace to 1+ occult blood was detected across both groups during and after therapy. urine culture was negative in all cats. no significant reduction in urine specific gravity was observed in the prednisolone group. limitations: no information about method, source, or time of patient recruitment. no statement of ethical review. evaluative criteria for dysuria not stated. generalisability is unclear: hospitalisation and diet change represent significant potential stress triggers for fic and results should be interpreted with caution for owned cats in their home environment. two differing methods of urine collection (cystocentesis and voided) likely confound comparison of haematuria between groups and over time points. small sample study size with no statistical analysis. had authors performed statistical analysis, probable insufficient study power. dorsch et al. (2016)2 population: criteria for eligibility and inclusion: cats with clinical signs of stranguria, haematuria, pollakiuria or painful voiding diagnosed with obstructive fic.   criteria for exclusion and rejection: imaging evidence of urolithiasis or/and neoplasia. positive feline immunodeficiency virus (fiv) and/or feline leukaemia virus (felv) test. positive fiv. diabetes mellitus, hyperthyroidism. cats that had been treated with steroids, other nsaids or antimicrobial drugs within 2 weeks prior to presentation of the study. positive urine culture.   recruitment and treatment all cats were treated at the clinic of small animal medicine, ludwig-maximilian universität, munich from november 2006 to august 2008. sample size: 37 cats intervention details: random allocation into two treatment groups: meloxicam treatment group n=18 placebo treatment group n=19   dosage and administration of treatment: meloxicam treatment group: meloxicam was administered orally (per os) at a dose rate of 0.1 mg/kg on day 1 and 0.05 mg/kg on days 2–5. placebo treatment group: a liquid formulation containing no meloxicam was administered per os for 5 consecutive days.   duration of therapeutic intervention: 5 days treatment.   day 0 interventions: subjects were administered an intravenous crystalloid fluid therapy (lactated ringer’s solution). administered 0.01 mg/kg buprenorphine and then every 8 hours subcutaneously for 2 days. under general anaesthesia, all cats were inserted an indwelling urinary catheter (silicon feeding tube – charriere (ch) 4.5, 1.0 x 1.5mm, braun). cats presented with post-renal azotaemia, metabolic acidosis or hyperkalaemia had repeated serum chemistry and blood gas analysis prior to starting treatment (day 0).   day 1 interventions: meloxicam or placebo commenced 24 hours after presentation to ensure correction of hydration status and re-establishment of urine flow.   day 2 interventions: urinary catheter removed. urine sample via cystocentesis for aerobic bacterial culture. cats that were observed for having difficult voiding behaviour remained hospitalised until able to void spontaneously for 24 hours.   day 2–5 interventions: upon discharge, owners were provided written instructions to complete the 5 days treatment course. study design: prospective double blinded and randomised clinical study outcome studied: occurrence of recurrent urinary obstruction within the first 7 days. objective exam parameters during hospitalisation and 10–14 day post-discharge recheck (temperature, body weight, respiratory rate, heart rate, haematuria). subjective clinician scoring during hospitalisation and 10–14 day post-discharge recheck (general demeanour, pain on abdominal palpation, food intake). subjective owner scoring for 5 days post-discharge (general condition, voiding behaviour/pain, macroscopic haematuria, food intake).   statistical analysis: mann-whitney u test to evaluate differences in age and body weight across treatment groups. kruskal-wallis test and dunn’s multiple comparison tests to evaluate differences in continuous parameters between groups at different time points and within groups between different time points. χ2 was used for all categorical parameters within and between groups (without correction for multiple comparisons). results were regarded as significant if p<0.05. main findings (relevant to pico question): 4/18 cats (22.2%) in the meloxicam group and 5/19 cats (26.3%) in the placebo group suffered from recurrent urinary obstruction within the first week. no statistical significance test is reported for this result and these cats were censored after day 2 from subsequent analysis. no statistically significant differences between treatment groups on exam parameters during hospitalisation and 10–14 day post-discharge recheck (temperature, body weight, respiratory rate, heart rate, haematuria). no statistically significant differences between groups on subjective clinician scoring during hospitalisation and 10–14 day post-discharge recheck (general demeanour, pain on abdominal palpation, food intake). no significant differences between the two treatment groups at any time point based on the owner questionnaire. limitations: no explicit details on method of randomisation. unblinded mid-study. potential confounding by group imbalance for prior history of fic: meloxicam group had statistically significantly higher (p=0.046) proportion of cats with ≥3 prior episodes (5/18) versus the placebo group (0/19). this may have obscured a positive effect in the meloxicam group if these cats had greater severity of fic versus the placebo group. potential confounding by catheterisation: clinical signs attributable to fic versus catheter-associated discomfort cannot be disentangled, at least for the initial 2–3 days of data collection. small sample size with probable low statistical power; no sample size or power calculation is presented. subjective clinician evaluation of abdominal pain, general demeanour, food intake did not use a validated instrument and was not assessed for inter-rater reliability; it is unclear how many clinicians contributed to data collection. owner questionnaire not validated. medication adherence not controlled for or assessed after discharge. unaccounted loss to follow-up. nivy et al. (2019)3 population: recruitment and treatment: the study was conducted in a referral teaching hospital between the years 2016 and 2018.   criteria for eligibility and inclusion: male cats admitted with obstructive fic which had not received medication prior to admission. resolution of azotaemia during hospitalisation. ability to empty the urinary bladder before discharge.   criteria for exclusion and rejection: not outlined in detail. sample size: 51 cats: seven intact males 44 neutered males intervention details: prior to urinary catheterisation to relieve urinary obstruction: all cats underwent blood sampling for serum chemistry and/or /total solids/electrolytes, abdominal sonography, urinalysis and urine culture as part of their initial diagnostic evaluation; a subset (20/51) also underwent additional survey and contrast radiography where owner financial resources allowed. all cats were medically stabilised and the obstruction relieved; iv fluid therapy, treatment of hyperkalemia, choice of urinary catheter and timing of removal were at the clinician’s discretion.   random allocation into two treatment groups: cats were allocated to a treatment after discharge by draw from a sealed envelope for 14 days. study group n=24: phenoxybenzamine (2 mg/kg po q 12 hours) with alprazolam (0.125 mg/kg po q 12 hours) and meloxicam (0.025 mg/kg po q 24 hours). control group n=27: phenoxybenzamine (2 mg/kg po q 12 hours) with alprazolam (0.125 mg/kg po q 12 hours) alone for 14 days.   strict dietary intake: owners were instructed to feed a therapeutic urinary diet. study design: prospective randomised study outcome studied: reoccurrence of fic related clinical signs and/or recurrent urinary obstruction were recorded at 10 days, 1, 2 and 6 months after discharge.   statistical analysis: primary hypothesis was that meloxicam would reduce the rate of reobstruction but many other associations were examined. fisher’s exact test used to assess for association of categorical variables with recurrence. logistic regression used to assess for association of continuous variables with recurrence. receiver operator characteristic (roc) analysis was used to assess the predictive value of heart rate for presence of hyperkalaemia. results were regarded as significant if p<0.05; no mention of correction for multiple comparisons with the assumption that the control group has a 50% reoccurrence rate and that meloxicam reduces the risk by five fold. sample size calculated with g*power 3.0.10 software; powered at 0.8 to detect a risk ratio of 0.2 in the study group assuming 50% recurrence in control group. main findings (relevant to pico question): overall, recurrent fic signs occurred in a total of 12 cats (6/24 (25%) cats from the study group and 6/27 cats (22%) from the control group) over 6 months after discharge. no significant difference in obstructive or non-obstructive fic signs between the study (meloxicam) and control groups (no meloxicam) at any time point in the 6 month period. limitations: unclear how recurrent non-obstructed fic signs were assessed; no mention of blinding of assessors. unclear whether groups balanced for potentially important measurable prognostic variables (no baseline table of groups characteristics). low statistical power; sample size not powered to detect relative risk reduction <80% assuming baseline risk for recurrence of 50% per the reported power calculation. hetrick & davidow (2013)4 population: recruitment and treatment: male cats diagnosed with urinary tract obstruction from january 2004 to december 2010 at private practice emergency referral hospital (animal critical care and emergency, seattle, wa, usa).   criteria for eligibility and inclusion: medical records of male cats treated as in-patients for uncomplicated urinary obstruction (uo) with an indwelling polyvinyl chloride catheter (infant feeding tube) and for which bladder imaging was available (ultrasound and/or radiography). cases needed at least 1 day of follow-up information post-catheter removal for inclusion in the study.   criteria for exclusion and rejection: cats with uo secondary to urolithiasis or neoplasia or acetaminophen toxicosis. cats in which urethral catheterisation was attempted or accomplished prior to referral. prior urinary catheterisation within the last 7 days. cats transferred to the care of the referring veterinarian prior to urinary catheter removal. discharge from the hospital <24 hours after urinary catheter removal and without follow-up. ability to urinate within the first hour of administration of initial medications. urinary bladder rupture or urethral obstruction secondary to trauma or urethral tear. surgery after unsuccessful attempts to pass a urinary catheter. prior perineal urethrostomy. sample size: 192 cases intervention details: records were reviewed for baseline characteristics (age, weight, body temperature, blood urea nitrogen (bun)/electrolytes) at admission and treatments administered in hospital. 24 cases included cats treated with meloxicam and 27 cases cases included cats without meloxicam. no details provided about stabilisation, that is the use of intravenous fluid therapy (ivf), repeat of hyperkalaemia, anesthesia/sedative use. primary aim of the study assessed the association of specific treatment factors with rate of reobstruction.   treatment data extracted: analgesia (buprenorphine or meloxicam). use of alpha-adrenergic antagonist (prazosin or phenoxybenzamine). antibiotic therapy after catheter removal duration of urinary catheterisation. size of indwelling urinary catheter.   treatment details from included cases: mean initial dose of meloxicam 0.09 mg/kg, mean of 3.7 doses administered to cats receiving meloxicam. mean dose of buprenorphine was 0.01 mg/kg twice a day (bid) or three times a day (tid) with mean duration of therapy 4.2 days. mean duration of therapy for cats receiving prazosin 7.8 days with most receiving 0.5 mg bid. mean duration of therapy for cats receiving phenoxybenzamine was 7.2 days. most cats received 2.5 mg bid. treatment protocol shifted over time: prior to 2006, meloxicam, phenoxybenzamine, and a 5 french catheter were more commonly used. protocol changed after that time point with proportionately more cats treated with buprenorphine, prazosin, and a 3.5 french catheter from june 2006 to december 2010.   statistical analysis: x2 test (with yates correction when indicated) was used to test for association of categorical treatment variables with recurrence of obstruction at 1 and 30 days. wilcoxson-rank sum or t-test for to assess for association of catheter duration with recurrence (unclear in methods which test was applied to this variable but appropriate test for normality and use of non-parametric and parametric testing is discussed). results considered significant at value of p<0.05. study design: retrospective cohort study outcome studied: recurrence of obstruction at 24 hours and 30 days. main findings (relevant to pico question): there was no statistically significant difference between the reoccurrence of uo in cats administered meloxicam as compared to no meloxicam at 24 hours (5/46 versus 16/146) or 30 days (10/39 versus 27/118). this was due to loss or incomplete follow-up. limitations: high risk of confounding error by changing protocol which altered three variables (use of meloxicam, use of prazosin, catheter size) over the same time period; multivariable analysis would be required to assess for independent effects of each treatment. a graphical stratified analysis of the effects of catheter size and alpha antagonist is presented but no similar analysis is presented for analgesic agents. selection bias due to clinicians preferably selecting a treatment based on characteristics of a patient information bias with the selection of either choosing to report or not follow-up. temporal bias due to possibility of dietary or housing changes for cats from 2006 to 2010 affecting baseline risk of re-obstruction in cats. appraisal, application and reflection three studies examined whether clinical signs of flutd can be improved with glucocorticoids or nsaids whilst one study examined if the use of meloxicam significantly reduced the reoccurrence of flutd. none found a statistically significant difference of either drug class in reducing the clinical signs of idiopathic flutd/fic. all had significant limitations in terms of statistical power and/or external validity and/or risk of bias. external validity is defined as to whether casual relationships may be generalised and applicable to different measures5. internal validity in contrast represents whether the variables operated adequately represent the theories and hypothesis proposed5. whilst it is useful to know if there is a difference between glucocorticoid or nsaids versus no treatment at all for controlling the signs of flutd, the treatment options tested should be validated and applicable to the general flutd population. clinical signs of feline cystitis may be elicited or exacerbated by stressful circumstances, which may include hospitalisation and/or diet change6,7 thus the conditions for patients in the osborne et al. (1996) paper may not be applicable to cats discharged from hospital to their home environment. there was no mention of whether there was a sudden food change for the hospitalised patients. steckler & mcleroy (2008) emphasise the importance of knowing that a program is likely to be effective in other settings and populations. through this, the results of not only osborne et al. (1996) but also the others should be interpreted with caution as it is unclear how the risk of reoccurrence and the lack of resolution reported in any hospital setting may relate to the risk of reoccurrence and persistence in a home population. adequate sample size is essential in avoiding type ii error (failure to detect a statistically significant effect when one exists)8. osborne et al. (1996), dorsch et al. (2016), and hetrick & davidow, (2013) did not provide details of sample size calculation nor did they present a power analysis but we can infer that statistical power was likely low. nivy et al. (2019) and colleagues performed a sample size calculation assuming a population with a much higher risk for fic recurrence actually occurred in their trial, thus high risk for type ii error was also present. randomisation and blinding are key features of most controlled trials to balance groups for important prognostic variables and to minimise biased outcome ascertainment (e.g. randomisation to avoid selection bias and blinding to avoid information bias). in the paper by dorsch et al. (2016) the study was unblinded midway, leading to risk of ascertainment bias. in the paper by nivy et al. (2019) it is unclear whether group balance for prognostic variables was achieved.  although cohort studies are often at higher risk for selection bias, this is less likely to be true of the study by hetrick & davidow (2013) since hospital protocol, rather than clinician choice, appeared to determine treatments for obstructed flutd. however, because three interventions in the hospital protocol were altered over the same time period and no adjusted analysis was reported for the effects of analgesic agent, results are at high risk for unmeasured confounding. finally, the heterogeneous outcomes reported limit evidence synthesis: each publication differed in methods of assessment of fic. for nivy et al. (2014) and hetrick & davidow (2013), recurrence of obstruction was a primary and intuitively valid objective outcome. however, method of subjective scoring of non-obstructive cystitis signs was not transparent in two publications (osborne et al., 1996; and nivy et al., 2019); in the third publication (dorsch et al., 2016), subjective scoring method was transparent but lacked detail on inter-rater reliability and validation; moreover, it is unclear how the raters were blinded.   further study is needed to delineate what role, if any, glucocorticoids or nsaids have in the treatment of flutd/fic. adequately powered randomised controlled trials and/or meta-analysis are required; standardised and validated outcomes to assess bladder pain/dysuria are required. in conclusion, there are no studies which appear to provide evidence for the use of steroidal or nsaids in decreasing symptoms or duration of clinical signs associated with flutd. glucocorticoids are not considered analgesics and there is insufficient evidence to suggest they provide a profound benefit in human interstitial cystitis. glucocorticoids may elevate risk for diabetes mellitus in certain cats and carry some risk for secondary bacterial infection thus also cannot currently be recommended for fic10.  although nsaids are considered a mainstay for management of chronic pain, they are not considered a first line treatment for the use in feline urinary cystitis-related cases11. the leading risk and adverse effects of nsaids includes nephrotoxicity, gastric ulcers, gastric perforations, and anorexia in cats11. given the risk of adverse gastro-intestinal and renal side effects of nsaids in cats, the current evidence does not propose that the use of nsaids shortens the clinical signs of fic and it is critical that veterinarians report and notify the risk factors if they choose to use nsaids as an adjunctive treatment to owners, colleagues and future proposing studies alike. opioids have been considered effective first-line analgesia for pain in cats11 but currently in regards to the use of glucocorticoids and nsaids, pending higher quality studies with greater statistical power is required as there is no high-quality evidence for the use of glucocorticoid or nsaids in the treatment of fic. the plethora of emerging and numerous research on the aetiology of fic has focused on multi-factorial factors including but not limited to behaviour, housing, environmental, dietary, litter type, cohabitation of with other cats or pets in the household, enrichment availability, anatomical formation, age, obesity, neuter states and even neurohormonal pathways12,13,14. the most effective treatment outcomes should be focusing on these factors as the foremost and then the use of pharmacological drugs as an additional secondary action if required. methodology section search strategy databases searched and dates covered: cab abstract database via web of science (1973–2021) pubmed database accessed via the ncbi platform (1910–2021) search strategy: ((feline or felines or cat or cats) and (idiopathic cystitis or feline idiopathic cystitis or feline lower urinary tract disease or cystitis or lower urinary tract disease or urinary tract infection) and (nsaid or nsaids or anti-inflammatories or meloxicam or metacam or loxicom or non-steroidal anti-inflammatories or prednisolone or prednisone or glucocorticoids or glucocorticoid)) dates searches performed: 08 mar 2021 exclusion / inclusion criteria exclusion: articles not written in english articles not associated with the efficacy of prednisolone or glucocorticoids or nsaid products for treating feline lower urinary tract disease case reports case studies book chapters conferences systematic reviews inclusion: meta-analysis randomised controlled study clinical studies search outcome database number of results excluded – systematic reviews excluded – did not relate directly to the factors of pico excluded – case reports and studies excluded – book chapters excluded – not written in english excluded – conferences total relevant papers cab abstracts 28 0 25 0 0 0 0 3 pubmed 37 1 31 1 0 0 0 4 total relevant papers when duplicates removed 4 conflict of interest the author declares no conflicts of interest. however, the author would like to greatly thank bridget sheppard and jennifer morris, the reviewers – ms clare boulton, constance neville white and nicolette joosting and the team of the veterinary evidence for providing this opportunity, and dedicate this paper to her own furry feline pets – jasmine, nala and king sofyan to hopefully help future patients alike. references osborne, c.a., kruger, j.m., lulich, j.p., johnston, g.r., polzin, d.j., ulrich, l.k. & sanna, j. (1996). prednisolone therapy of idiopathic feline lower urinary tract disease. veterinary clinics of north america: small animal practice. 26(3), 563–569. doi: http://dx.doi.org/1016/s0195-5616(96)50085-9 dorsch, r., zellner, f., schulz, b., sauter-louis, c. & hartmann, k. (2016). evaluation of meloxicam for the treatment of obstructive feline idiopathic cystitis. journal of feline medicine and surgery. 18(11), 925–933. doi: https://doi.org/10.1177%2f1098612x15621603 nivy, r., segev, g., rimer, d., bruchim, y., aroch, i. & mazaki-tovi, m. (2019). a prospective randomized study of efficacy of 2 treatment protocols in preventing recurrence of clinical signs in 51 male cats with obstructive idiopathic cystitis. journal of veterinary internal medicine. 33(5), 2117–2123. doi: http://doi.org/10.1111/jvim.15594 hetrick, p. & davidow, e.b. (2013). initial treatment factors associated with feline urethral obstruction recurrence rate: 192 cases (2004–2021). journal of american veterinary medical association. 243(4), 512–519. doi: http://dx.doi.org/2460/javma.243.4.512 steckler, a. & mcleroy, k.r. (2008). the importance of external validity. american journal of public health. 98(10), 09–10. doi: http://dx.doi.org/10.2105/ajph.2007.126847 westropp, j.l., kass, p.h. & buffington, c.a.t. (2006). evaluation of the effects of stress in cats with idiopathic cystitis. american journal of veterinary research. 67(4), 731–736. doi: http://dx.doi.org/ 2460/ajvr.67.4.731 mccobb, e.c., patronek, g.j., marder, a., dinnage, j.d. & stone, m.s. (2005). assessment of stress levels among cats in four animal shelters. journal of the american veterinary medical association. 226(4), 548–555. doi: http://dx.doi.org/ 2460/javma.2005.226.548 jones, s.r., carley, s. & harrison, m. (2004). an introduction to power and sample size estimation. emergency medicine journal. 20(5), 126. doi: http://dx.doi.org/1136/emj.20.5.453 banerjee, a., chitnis, u.b., jadhav, s.l., bhawalkar, j.s. & chaudhury, s. (2009). hypothesis testing, type i and type ii errors. indian psychiatry journal. 18(2), 127–131. doi: https://doi.org/10.4103/0972-6748.62274 barasanti, j.a., shotts, e.b., crowell, w.a., finco, d.r. & brown, j. (1992). effect of therapy on susceptibility to urinary tract infection in male cats with indwelling urethral catheters. journal of veterinary internal medicine. 6(2), 64–70. doi: http://dx.doi.org/1111/j.1939-1676.1992.tb03153.x epstein, m.e., rodanm, i., griffenhagen, g., kadrlik, j., petty, m.c., robertson, s.a. & simpson, w. (2015). 2015 aaha/aafp pain management guidelines for dogs and cats. journal of feline medicine and surgery. 17(3), 251–272. doi: http://dx.doi.org/1177/1098612x15572062 segev, g., livne, h., ranen, e. & lavy, e. (2011). urethral obstruction in cats: /predisposing factors, clinical, clinicopathological characteristics and prognosis. journal of feline medicine and surgery. 13(2), 101–108. doi: http://dx.doi.org/1016/j.jfms.2010.10.006 kim, y., kim, h., pfeiffer, d. & brodbelt, d. (2018). epidemiological study of feline idiopathic cystitis in seoul, south korea. journal of feline medicine and surgery. 20(10), 913–921. doi: http:/dx.doi.org/1177/1098612x17734067 cameron, m.e., casey, r.a., bradshaw, j.w.s., waran, n.k. & gunn-moore, d.a. (2004). a study of environmental and behavioural factors that may be associated with feline idiopathic cystitis. journal of small animal practice. 45(3), 144–47. doi: http://dx.doi.org/10.1111/j.1748-5827.2004.tb00216.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. promoting evidence-based veterinary medicine through the online resource ‘ebvm learning’: user feedback ellie sellers bvsc mrcvs1 sarah baillie bvsc msc phd pfhea mrcvs1* rachel dean bvms phd msc dsam sfhea mrcvs2 sheena warman bsc bvms dsam dipecvim edd sfhea mrcvs1 heidi janicke vetmed phd mrcvs dipl. ecvs sfhea3 sebastian p. arlt dvm phd dipl ecar4 clare boulton diplib dip mgmt (open) mclip5 marnie brennan bsc(vb) bvms phd dipecvph(pm) mrcvs fhea6 david brodbelt ma vetmb phd dva dipecvaa mrcvs fhea7 fiona brown ma bsc fhea8a louise buckley phd fhea rvn8b myai du bsc ma mclip5 emma gallop bvsc mrcvs1 george goran dvm msc phd9 douglas j.c. grindlay ma phd mclip10 laura haddock bvsc mrcvs pgce1 jo ireland bvms phd certavp(em) fhea mrcvs11 catherine mcgowan bvsc phd dipeceim fhea frcvs11 heather k. moberly msls ahip fhea pgcert (vet ed)12 emma place bsc ma1 md mizanur rahman dvm ms phd13 gwen rees bvsc phd mrcvs1 kristen reyher bsc(hons) dvm phd fhea mrcvs1 javier sanchez dvm phd14 johan p. schoeman bvsc mmedvet phd dsam dipl. ecvim-ca15 laura urdes phd dvm pgdip certaqv9 john vanleeuwen dvm msc phd14 kristien verheyen dvm msc phd fhea mrcvs7 1bristol veterinary school, university of bristol, langford, bristol, bs40 5du, uk 2vet partners, spitfire house, aviator ct, york, yo30 4uz, uk 3st. george’s university, school of veterinary medicine, true blue, grenada, west indies 4clinic for animal reproduction, faculty of veterinary medicine, freie universität berlin, germany 5rcvs knowledge, belgravia house, 62–64 horseferry road, london, sw1p 2af, uk 6school of veterinary medicine and science, university of nottingham, sutton bonington campus, leicestershire, le12 5rd, uk 7veterinary epidemiology, economics and public health group, the royal veterinary college, hawkshead lane, north mymms, hatfield, hertfordshire, al9 7ta, uk 8ainformation services group, university of edinburgh, easter bush, midlothian, eh25 9rg, uk 8bdeanery of clinical sciences, college of medicine & veterinary medicine, university of edinburgh, edinburgh, eh16 4sb, uk 9university of agricultural sciences and veterinary medicine of bucharest, 59 marasti bd., 011464, 1st district, bucharest, romania 10centre of evidence based dermatology, university of nottingham, king's meadow campus, nottingham, ng7 2nr, uk 11school of veterinary science, university of liverpool, leahurst campus, neston, ch64 7te, uk 12medical sciences library, university libraries, texas a&m university, college station, tx 77843–4462, usa 13dept. of medicine and surgery, chattogram veterinary and animal sciences university, zakir hossain road, chattogram–4225, chattogram, bangladesh 14atlantic veterinary college, university of prince edward island, 550 university ave, charlottetown, pei, c1a 4p3, canada 15faculty of veterinary science, university of pretoria, onderstepoort, 0110, south africa *corresponding author (sarah.baillie@bristol.ac.uk) vol 6, issue 1 (2021) published: 25 feb 2021 reviewed by: peter denys cockcroft (ma vetmb msc dchp dvm&s dipecbhm mba mrcvs), virginia fajt (dvm phd dacvcp) and mike steele (bsc(hons) bvsc mrcvs) doi: 10.18849/ve.v6i1.392 section index:    abstract | introduction | methods | results | discussion | conflict of interest | references abstract ‘ebvm learning’ is a freely available resource created in 2015 by an international team with the support of rcvs knowledge. the resource comprises a series of online modules teaching the fundamental concepts of evidence-based veterinary medicine (ebvm) (ask, acquire, appraise, apply & assess) supported by case studies, exercises, worked examples and quizzes. the aim of the current study (undertaken in 2019) was to review ‘ebvm learning’ to ensure its ongoing relevance and usefulness to the range of learners engaged in ebvm. feedback was gathered from stakeholder groups using website statistics and feedback forms, a survey and semi-structured interviews to provide a combination of quantitative and qualitative data. website statistics revealed an international audience and a steady increase in visitors exceeding 1,000 per month in august 2020. feedback via the online form (n=35) and survey (n=71) indicated that the resource was well structured, with an appropriate level and amount of content, useful examples and quizzes and the majority of respondents would use it again. semi-structured interviews of educators (n=5) and veterinarians (n=8) identified three themes: features of the ‘ebvm learning’ resource (strengths, suggestions for improvement), embedding the resource in education (undergraduate, postgraduate) and promoting ebvm (challenges, motivation for engagement). at a project team workshop the results were used to plan updates to the existing content and to identify new ways to promote learning and engagement. an updated version of ‘ebvm learning’ was developed. ‘ebvm learning’ is helping to produce the next generation of evidence-based practitioners and enabling to engage in the concepts of ebvm as part of their clinical practice.   introduction there is a clear need to include research evidence in veterinary practice to ensure clinical guidelines and decision-making are informed by the latest findings and continue to evolve and adapt (doig, 2008; holmes & cockcroft, 2004; feetham & raffan, 2014; dean et al., 2017; and dean & heneghan, 2019). however, in medicine it has been shown that there can be a significant time lag between the publication of clinically important research and a change in treatment recommendations made by experts (antman et al., 1992; glaziou 2005; and walker et al., 2019). evidence has become more easily accessible to all health practitioners including veterinarians, for example, through publication of evidence syntheses and open access publishing. patients and owners also have access to some of this information. as a result, there has been growing pressure from the public, professional bodies, practitioners and students to ensure all professions, including veterinary medicine, continue to be science-driven and evidence-based (dean et al., 2017; huntley et al., 2017; and rcvs code of professional conduct for veterinary surgeons, 2020). the practice of evidence-based veterinary medicine (ebvm) can be defined as the ability to choose the best clinical approach for patients through rational decision-making supported by sound clinical reasoning, the current best scientific evidence, and an understanding of risk management (arlt et al., 2012). the circumstances of the patient and owner also need to be taken into consideration (armitage-chan, 2020). however, there are recognised challenges to performing evidence-based (veterinary) medicine (eb(v)m) when in clinical practice including limited access to databases, lack of time to search for key literature, lack of skills to effectively appraise the quality of identified research, and difficulties in applying the evidence and assessing the impact (mccoll et al., 1998; kastelic, 2006; and vandeweerd et al., 2012). the situation has been improved by the production of evidence syntheses, a systemic structured search of the evidence which is then summarised for clinicians in an easily accessible format (a knowledge summary or critically appraised topic (cat)). a number of such initiatives have been introduced in recent years (bestbets for vets; rcvs knowledge; kasch et al., 2017; and brennan et al., 2020). the use of ebvm will further improve over time if the necessary skills are taught in the veterinary curriculum to enable future practitioners to perform ebvm in a busy practice environment (janicke et al., 2020). it is recognised that teaching everything (“just in case knowledge”) in curricula is no longer possible and there is a need for a change in direction towards teaching students the skills to find, appraise and utilise evidence in practice (“just in time knowledge”) (dean et al., 2017). however, the challenges in teaching these skills e.g. recognising uncertainty, understanding how evidence does or does not fill the gaps in our knowledge, can be considerable. in ebvm, the decision-making process is complicated by a variety of types of evidence e.g. primary research versus narrative text or expert opinion; in turn, there is a greater need for students to understand how to make decisions to accommodate greater levels of uncertainty (holmes & cockcroft, 2004). another barrier is finding the time to incorporate teaching these skills into already overcrowded curricula (shurtz et al., 2017) and contextualising the process, so it is presented as an integral part of clinical decision-making and not just a theoretical concept (dean et al., 2017). learning is enhanced by embedding the task into realistic clinical scenarios, similar to those that would occur in veterinary practice (arlt et al., 2012). a number of initiatives have been introduced in veterinary curricula often culminating in students creating a critically appraised topic; for example, in first year (hardin & robertson, 2006), as a clinical pharmacology assignment (fajt et al., 2009) and as part of clinical reproduction (arlt et al., 2012) and farm animal rotations (steele et al., 2013). a toolbox has been developed for veterinary educators to consult when reviewing or introducing ebvm in a curriculum (janicke et al., 2019). in 2013, a workshop was held at the centre for evidence-based veterinary medicine (cevm), university of nottingham to bring together those involved in teaching ebvm at each of the uk veterinary schools (dean et al., 2017). following the workshop, the team was extended to include international partners in a project (‘ebvm learning i’) to produce an open-access coherent online resource with a series of modules for teaching the fundamental concepts of ebvm. over 20 people were involved in developing the resource, including veterinarians who teach ebvm, librarians and a website designer. the team represented 10 veterinary schools and four countries (uk, germany, romania and canada). the resource was divided into distinct sections based on the steps of eb(v)m: the five as (heneghan & badenoch, 2006). first, constructing a relevant patient question (ask) and then searching for the evidence to answer the question (acquire). next, critically evaluating the resulting evidence for quality and applicability to the question (appraise) and then using the evidence, as appropriate, in the clinical context (apply). finally, monitoring and evaluating the outcomes and impact on practice (assess). each section included interactive content and provided context through case-studies, exercises, clinical examples, videos and quizzes. the resource ‘ebvm learning’ was launched by rcvs knowledge in november 2015. the aim of the current project ‘ebvm learning ii’ (undertaken in 2019) was to review the online resource ‘ebvm learning’ to ensure its ongoing relevance and usefulness to the range of learners engaged in ebvm. the project team was extended to include more international partners from universities in grenada, usa, south africa and bangladesh, representation from veterinary nursing and several uk-based practitioners. feedback was gathered from stakeholder groups using website statistics, a survey and semi-structured interviews to provide a combination of quantitative and qualitative data. the information was used to update the existing content and identify areas for development and innovative approaches to promote learning and engagement.   methods online resource usage and user feedback basic information about visits to the ‘ebvm learning’ website was collected by rcvs knowledge using google analytics. the data from the time the website was launched in mid-november 2015 to the end of january 2019 were analysed and included visitor numbers, country of origin and the percentage of return visits. on completion of the resource, users were invited to provide feedback via an online form and were asked to provide free-text responses to questions about what they liked, did not like, what could be improved and their reason for using the tutorial. the data were analysed to identify recurring comments (by author sb). users were also asked if they would use the resource again and recommend it to others (yes, no, or unsure).   survey of user experience a more in-depth survey was developed, informed by the questions and feedback data from the online form, to investigate further the user experiences of the resource to date. following a successful pilot by academic colleagues to check clarity of questions and online functionality, the survey was delivered through online surveys (www.onlinesurveys.ac.uk) to veterinary students and veterinarians who had used ‘ebvm learning’. the survey included basic demographic data (gender, country) and veterinarians were asked for their year of graduation, area of work and context for using the resource. a likert scale (strongly disagree, disagree, undecided, agree, strongly agree) was used for questions about the resource’s content, usefulness, aspects of functionality, time commitment, if participants would use it again and recommend it to others. free-text questions asked what they liked the most, the least and for any suggested improvements, including ways to make the ‘ebvm learning’ resource more engaging and relevant. two groups of veterinary students were identified, both of which had recently completed a course incorporating the resource: the year 4 cohort of the 5 year bvsc programme at the university of bristol, uk and the semester 2 cohort of the 4 year dvm program at st george’s university, grenada. administrative staff contacted the students via email including a link to the survey and a project information sheet. student responses were anonymous. the veterinarian survey was promoted to the veterinary profession through rcvs knowledge media outlets and an email sent to those registered on a postgraduate ebvm module at the university of liverpool, uk. at the end of the survey, participants were asked if they would be willing to be contacted (by email) for a follow-up interview to explore their experiences and suggestions in more detail. in order to maintain anonymity, the email details were excluded from the analysis of the survey response data. the survey was open for a period of 6 weeks. data were exported into excel spreadsheets and the likert items were collated and summarised graphically. the free-text responses were reviewed to identify recurring comments (by author sb).   interviews two groups were selected for interview to gain more insight into ‘ebvm learning’ from the perspective of practitioners and educators using the resource in their teaching. practitioners were approached if they volunteered to be contacted for follow-up interview via the online survey; eight volunteered and all were interviewed, six having previously completed an ebvm module (for the certificate in advanced veterinary practice), another moved into education recently. five educators were interviewed as a convenience sample, identified through project team contacts across four continents. the backgrounds of these educators included veterinary, human health care and epidemiology. they were all using ‘ebvm learning’ in some format within their undergraduate and/or postgraduate ebvm teaching. interviewees were provided with an information sheet describing the purpose of the research study and implications of participation, and returned a signed consent form. a template was developed for the semi-structured interviews with the same questions for the two groups covering: current use and application of the resource, experience of the resource and suggestions for improvements. a pilot interview informed a minor amendment to the order of questions. interviews were conducted via skype or mobile phone, recorded and transcribed, whilst maintaining the interviewee’s anonymity. transcripts were analysed using inductive thematic analysis (braun & clark, 2012). one interview from each group was analysed independently by two researchers (by authors es and sw) before meeting to reach a consensus on the sub-themes. the same sub-themes were identified in both interview groups. the remaining transcripts were coded by es to produce cohesive themes for the two cohorts.   project team workshop a 1 day workshop was hosted by rcvs knowledge in london where the research findings were presented and the updates to ‘ebvm learning’ were discussed. rcvs knowledge demonstrated features of new courseware that will be used to host the updated version of the resource. project team members then worked in author groups for each ‘ebvm learning’ section to plan the specific changes.   ethical approval the study received approval from the faculty of health sciences research ethics committee, university of bristol, uk (# 81624), the veterinary research ethics committee, university of liverpool (# vrec800) and the institutional review board at st george’s university, grenada (# 19020).   results online resource usage data and user feedback over the period monitored (mid-november 2015 – end of january 2019) google analytics recorded 20,925 visitors, of which approximately 15% were returning visitors. there was a steady increase over the first 2 years with an average of just under 500 visitors per month. this upward trend continued and exceeded 1,000 visitors per month for the first time in august 2018. the visitors represented an international audience with most participants in the uk (33%) and north america (30%) followed by australia (5%). visitors from other countries included ireland, france, russia, grenada and brazil (each between 1 and 2%). the online form had been completed by 35 users. most (66%) had used the resource as part of a course (undergraduate or postgraduate) with other reasons being to find out more about using ebvm in practice (9%), to teach students (9%) and to learn how to appraise a paper (6%) while a few did not provide a reason (10%). when asked about using it again: 80% said ‘yes’, 17% ‘unsure’ and one did not answer. when asked about recommending it to others: 89% said ‘yes’, 8% ‘unsure’, 0% ‘no’ and one did not answer. recurring comments in response to the question 'what did you like the most?' were that it was well structured (31%), and had good examples (31%), quizzes (20%) and references/links (17%). the aspects liked the least were that some parts were too wordy (46%) and/or too long (29%). suggestions for improvement mostly related to more interactivity (26%) e.g. case examples, quizzes, videos, and an estimate of time required per section.   survey of user experience the basic demographic information for all participants is displayed in table 1. the student response rates were 26 (18%) and 26 (23%) for the uk and grenada cohorts respectively. eighteen veterinarians responded, 10 (58%) of whom were working primarily in clinical practice; the main reason for accessing the online resource was as part of a university postgraduate ebvm module.     students  (n=53) veterinarians (n=18) gender n % n % male 7 13 2 11 female 44 83 16 89 prefer not to say 2 4 0 0 country uk 26 49 15 83 grenada 27 51  –  – other  –  – 3 17 year of graduation 1991–2000  –  – 1 6 2001–2010  –  – 7 39 after 2010+  –  – 10 56 primary area of work clinical practice: companion animal & exotics  –  – 9 50 clinical practice: equine  –  – 1 6 research and/or education  –  – 8 44 context for using online resource university postgraduate course  –  – 14 78 teaching veterinary students  –  – 2 11 continuing professional development (cpd)  –  – 2 11 table 1: demographic data from the online surveys of students and veterinarians the likert scale responses are shown in figure 1. there were a few missing data points for some questions, but all participants were included. the majority replied positively to questions relating to the usefulness, ease of navigation, clarity of information, time for completion, and use of quizzes and references. most participants (particularly veterinarians) agreed that they would use the resource again and/or recommend it to others. when asked if ‘the content was too much’ and also asked ‘if the content was too little’ most participants disagreed with both statements, suggesting that the volume of content may be about right.   figure 1: likert scale data from the online surveys of students and veterinarians the analysis of the free-text comments identified recurring comments, similar for both students and veterinarians. the ease of navigation and clarity of the layout were appreciated: “well presented. logical. stepwise”, as were the quizzes and examples. a recurring criticism was that some sections were a bit long, wordy and dry: “blocks of text need breaking up”. suggestions for improvement included having more of the existing interactive content (e.g. quizzes), more case examples, and using visual content (e.g. tables, images) to replace text. interviews three major themes, each with sub-themes, were identified through the analysis of interview transcripts. the themes encompassed views about the resource and ebvm more broadly. illustrative quotes have been included from both groups; practitioners (p) and educators (e).   1. features of the ‘ebvm learning’ resource this theme explored the strengths and weaknesses of the resource, with findings aligning closely with those from the user feedback and online survey.   strengths comments in this sub-theme illustrated that the website was easy to use, and the content was at an appropriate level: “everything’s there that needs to be. all the guidance is really, really good” (p4) the examples used throughout the resource added clinical relevance while the quizzes improved engagement and provided learners with feedback on their progress: “it has good examples to really help explain the material” (e2) “i thought having a quiz at the end of each section was quite useful, because it did tell you whether you’d picked up the right information or not” (p1) comments from both groups described that the resource had assisted learners’ skill development and had been helpful for practitioners: [ask, acquire] “i found it really sped me up in terms of, now if i’ve got a question i don’t know the answer to, i’m quite good at finding out that information” (p2) [ask, appraise] “most people with a background in first opinion practice… may not have had much exposure to evaluating evidence, or even things like creation of pico questions… and the resource provided really good explanations” (p4)   suggestions for improvement suggestions for improving the usability included reducing the blocks of text in some sections and increasing interactivity throughout, having a printable version and podcasts. additionally, interviewees mentioned the need to raise awareness as many did not know about the resource before being directed to it through a postgraduate course or as an educator: “i don’t think it’s something i would necessarily have stumbled upon” (p5) educators noted that veterinary librarians appeared to be well acquainted with the resource, as it was disseminated proactively through their networks.   2. embedding the resource in education this theme drew together the experiences of interviewees as they embedded the resource in undergraduate teaching, and as learners or educators at the postgraduate level.   teaching undergraduates educators used the resource in different ways. some provided students with time in the curriculum to work through each section; others provided the resource as a reference tool; and some used the resource to prepare for their own teaching: “we’re actually integrating it into a professional development course” (e2) “it was useful. i certainly went back to look at things, to check things before i had meetings with the students” (p8)        educators were using a mixture of didactic teaching, small group work and self-directed learning. integration throughout the curriculum provided scaffolding for the teaching of ebvm: introducing library skills in early years, progressing to pico formation, evidence gathering and appraisal, and leading to students producing a knowledge summary: “the ebvm course material is arranged vertically through the curriculum. so they build up knowledge and experience through the programme” (e4) those who required students to work through the resource suggested including a way to track student engagement “completion certificate” (e3) and incorporating tips for ways to use it in teaching:  “examples of projects that could be done and ways of incorporating that into a programme” (e3) several challenges were mentioned including time pressure in the curriculum being a reason for not fully incorporating the resource. another challenge was a lack of experience amongst staff, for example, to supervise ebvm related projects: “there was a lot of variability based on whether they had the experience previously or not” (e2) additionally, when using the resource as a reference tool, comments indicated that it was not easy to search and find a relevant subsection. another challenge related to how to engage all students and ensure the teaching is clinically relevant: “some students do it well. some students really struggle... i really thought they would get behind this idea…[i.e.] knowledge summaries. i think the more you make it clinically relevant the better” (e2)    both practitioners and educators commented on the need for repetition of the skills: “feedback from the students is that they do forget things between the years” (e4) “instead of being something that you just get taught… it’s almost something that needs to be incorporated in everything…” (p5)   postgraduate teaching many comments highlighted the usefulness of the resource although finding the time to study was sometimes an issue. a recurring theme across practitioners was the sense of “wishing i’d done it sooner” both as a veterinary student and as part of postgraduate study: “the last module [of the certificate] was the free choice module… i thought it [ebvm] looked really interesting and i really regretted it that i didn’t do it as my first module. i think it would have helped so much, being taught that at the start of my certificate… because i found it so useful” (p2) additionally, access to evidence was much easier from a university environment whereas in practice this could be a significant barrier:   “if they’re free or they’re something that you’ve got access to through doing the certificate module then that’s great. but actually, if you’re a general person in practice who doesn’t have that many professional memberships that would give them access to journals, it’s all very well reading the title of a paper, but then you can’t get access to it” (p1)   3. promoting ebvm both challenges and motivators of ebvm within the context of the wider profession were identified.   challenges  one challenge related to ebvm being in its infancy – an emerging field. there was a sense of a lack of awareness of ebvm within the profession, partly because it is a relatively recent addition to curricula: “i had no idea about all this, you know, [the] evidence-based veterinary medicine thing” (p3) consequently, for educators, a major challenge in promoting ebvm was linked to the lack of experience, their own and that of colleagues: “there was a lot of variability [in staff] based on whether they had the experience previously or not. and that was one of the things we got back from the student feedback was there was a huge variability in the amount of mentoring they were getting, or the quality of mentoring they were getting” (e2) practitioners experienced several challenges for engaging with ebvm, centring around a perceived lack of support for ebvm compounded by a lack of time, lack of access to evidence, variable skills in scientific reading and writing, and difficulties in being able to implement and apply ebvm in clinical practice: “i think time is the biggest one. and then access is the second one. and the third is knowing what to do with it” (p4) “i think the thing that’s hard with ‘apply in a clinical setting’ is that it’s never, [or] it’s rarely relevant. … you go, “oh, no-one’s actually researched it in this population, so i’ll just have to use this population instead”” (p8)   motivators for engagement the reasons that practitioners did engage with the resource related to a desire to develop skills in themselves and others, to understand the connection with clinical practice, and career progression: “it’s not something that necessarily i had all the tools to do effectively. so i did it…to give me a bit of confidence...a way to make it more clinically relevant to me” (p5) for educators, including epidemiologists and clinicians, some of their motivation was to raise awareness in the profession by developing an interest in ebvm amongst undergraduate students. motivated leadership was considered a major influence on the uptake of ebvm in practice, which could be provided by a senior veterinarian or by practices promoting specific ebvm initiatives. in these situations, there was greater prioritisation of ebvm in the practice with, for example, protected time for further education courses and/or facilitating the learning of others: “we had some of the vet nurse clinical coaches in and i went through how we teach ebvm and just tried to give them some ideas of how to incorporate it into practice” (e5) “since doing the ebvm module …. i’ve sat down with individual vets and taught them how to search” (p2) there was a crucial role identified for leaders in the veterinary profession in taking responsibility for the generation of more evidence, which linked to an important point raised by practitioners about the challenges surrounding the lack of evidence (comparing ebvm with ebm): “i could think of lots of questions i wanted to ask and then realised there was zero evidence” (p6) “i remember coming across the cochrane database… wouldn’t that be amazing if we had this for vets, so hopefully in time to come, we’ll get there, yes” (p2) other suggestions for promoting engagement in ebvm related to facilitating learning by creating a “community of learning” (p4), integrating regular clinical club meetings and journal clubs to practise skills, the use of an ebvm network to provide mentorship, online discussion forums, and greater publicity via e-news (e.g. infocus) and social media platforms (e.g. facebook).   updating ‘ebvm learning’ during the workshop, the project team developed a plan to update ‘ebvm learning’ based on the research findings. feedback had been positive about the structure of the resource and therefore the existing sections were maintained. authors representing each section reviewed the content identifying areas that needed updating and checked the validity of hyperlinks. improvements were proposed for each section by, for example, identifying areas that could be shortened and/or consolidated, breaking up or replacing long sections of text with other formats e.g. tables and, images, incorporating more clinically relevant examples and new interactive functionality available via the new courseware. as well as enhancing the overall learner experience such changes would be likely to benefit those for whom english is not a first language. other features included the option to download the complete course and a completion certificate. following the workshop, the groups continued to edit their sections coordinated by the project manager (author es). the updated version of ‘ebvm learning’ is available at https://learn.rcvsknowledge.org/ebvm-learning one point of discussion during the workshop had focused on how to address the challenges practitioners encountered in engaging with ebvm while maintaining a resource that was already used in undergraduate and postgraduate teaching. a decision was made that a ‘one size fits all’ approach was not appropriate and therefore there was a need to create an additional version for practitioners in the future that was more slimline and practitioner-focused.   discussion this article reports on experiences of using the online resource ‘ebvm learning’ in veterinary curricula and practice. there has been increasing awareness of the importance of evidence-based practice and the challenges encountered in translating primary research into better quality healthcare (heneghan et al., 2017; and dean & heneghan, 2019). since the launch of ‘ebvm learning’ in 2015, the resource has been successfully integrated into undergraduate and postgraduate courses and has the potential to provide a sound basis for using ebvm in practice. the further development of ‘ebvm learning’ through this project will help to keep the resource relevant. interestingly, themes emerged through the interviews about ebvm generally not just about experiences using the resource, although the latter was the focus. our findings indicated that the level of engagement in ebvm across the profession has been variable with motivated practitioners keen to upskill. historically, the inclusion of ebvm teaching in undergraduate curricula had been limited and whilst recent research shows that awareness is improving, there is a need for more insight into the wider profession’s understanding of ebvm and how barriers to its practice can be overcome (huntley et al., 2017). a future project being undertaken by the team, ‘ebvm iii’, aims to further investigate the profession’s challenges to inform the development of an additional practitioner-focused resource.   ‘ebvm learning’ – how is it helpful? ‘ebvm learning’ provides educators with a freely available online resource, authored by an international team with experience teaching ebvm. feedback gathered via an online form, surveys and interviews consistently indicated that the resource was easy to use, had a structure that supported a logical and progressive development of skills, with relevant examples and quizzes helping to consolidate learning. feedback also indicated areas for improvement which informed the update of ‘ebvm learning’, including a reduction of large blocks of text and improving interactivity. recent literature suggests that successful teaching of eb(v)m involves embedding the concepts throughout a curriculum and ensuring learning is contextualised within clinical training to reinforce skill development (maggio et al., 2015; and janicke et al., 2020). a blended learning approach, where students were set relevant tasks alongside didactic teaching, has been shown to be effective at improving student attitudes to ebm (ilic et al., 2015). the design of ‘ebvm learning’ supports its integration within a veterinary curriculum with activities designed to support scaffolded active learning, when core knowledge is extended through problem-solving tasks (may & silva-fletcher, 2015), enabling students to build their knowledge and skillset alongside their clinical training. further work is needed to determine the most effective means of providing contextualised ebvm training. comments were raised by educators as to the variable quality of mentoring for such student activities, pointing to a need for more training. in the wider profession there is an increasing appetite for ebvm (huntley et al., 2017) and further understanding is required as to how ebvm training can be brought to a wider audience. in our research, some practitioners remarked on how useful ‘ebvm learning’ had been for their everyday work, wishing they had done it sooner. additionally, some of the perceived and real barriers felt by practitioners in their quest for integrating ebvm into clinical practice were highlighted when discussing ebvm more generally: time in a busy clinical environment, access to databases and journal articles, and difficulties applying ebvm in practice. this is potentially where evidence syntheses such as knowledge summaries, bestbets and cats can assist decision-making for busy clinicians. however, to be able to use them they need to be aware they exist and then understand the purpose and limitations, syntheses of evidence also need to be critiqued. time and busy workloads pose a barrier to practitioners using eb(v)m (vandeweerd et al., 2012; and zwolsman et al., 2013) and our interviewees echoed this point. in coming years, greater emphasis on ebvm is likely to result from the increasing proportion of graduates who will already be familiar with the concepts of ebvm through their training and as ebvm is embedded in postgraduate courses and practice cultures, such as clinical audit. suggestions to increase ebvm uptake included the creation of ebvm podcasts, increasing practice-based journal clubs and support for scientific reading and writing skills. librarians (information specialists) are cited as an underused resource (shurtz et al., 2017) and our data suggest that librarians have a vital role in dissemination of the resource and are often involved in teaching, particularly the ebvm steps ask and acquire. recent initiatives, such as greater access to databases, journal articles and training from rcvs knowledge library and staff, have the potential to provide invaluable assistance to practitioners wanting to engage more with ebvm. a recent manifesto for promoting evidence-based medicine (dean & heneghan, 2019) suggested several groups are required to work together to improve the evidence base, making evidence relevant and producing better guidelines. interviewees commented that they did not know how to apply their newly found evidence in a clinical context and suggested facilitation from “communities of learning” such as online mentorship and discussion forums. although most respondents indicated that they would use the resource again and recommend it to others, google analytics revealed that only approximately 15% were returning visitors suggesting re-use was relatively low. practitioners acknowledged time as an issue and students may not have returned because of other obligations, workload and exams. furthermore, our research primarily gathered feedback on user experiences and additional work is required to determine any long-term benefits and the potential impact on the practice of ebvm.   limitations of the study the response rate through the online feedback form was low. the online surveys were conducted to gather additional feedback although the practitioner numbers remained low. this may reflect practitioners’ reported lack of awareness and time to complete the survey and/or to engage with the resource. most of the practitioners who did respond were involved in an online postgraduate ebvm module, hence our research is relying on feedback from those who were already more actively engaged in ebvm and therefore may not represent the views or knowledge of the wider profession. the small sample size for the interviews limited breadth of inclusion yet added depth to our dataset; the researchers recognised that data saturation was not reached and additional relevant information would be likely to emerge from a larger sample size. educators selected for interview comprised a convenience sample, based on project team contacts, ensuring familiarity and use of the resource within a curriculum. practitioners self-selected for inclusion in the interviews, selecting for those who are actively engaging in and promoting ebvm. additionally, our research primarily gathered feedback on user experiences and further work is required to determine any long-term benefits, learning outcomes and the potential impact on the practice of ebvm.   conclusions ebvm is gaining momentum and ‘ebvm learning’ has the potential to make a valuable contribution to the training of the next generation of ebvm practitioners across the globe. our research indicated that ‘ebvm learning’ in the current format was unsuitable for most busy practitioners, yet there is still a need to support those who do not have easy access to formal ebvm training and courses. therefore, further work is being conducted in a follow-on project ‘ebvm iii’ which aims to identify the needs of practitioners more specifically to enable ebvm to be better integrated into everyday 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(2020). available from: https://www.rcvs.org.uk/setting-standards/advice-and-guidance/code-of-professional-conduct-for-veterinary-surgeons/ rcvs knowledge's knowledge summaries. available from: https://knowledge.rcvs.org.uk/evidence-based-veterinary-medicine/knowledge-summaries shurtz, s., fajt, v., heyns, e.p., norton, h.f. & weingart, s. (2017). teaching evidence-based veterinary medicine in the us and canada. journal of veterinary medical education. 44(4), 660–668. doi: http://dx.doi.org/10.3138/jvme.1215-199r steele, m., crabb, n.p., moore, l.j., reyher, k.k., baillie, s. & eisler, m.c. (2013). online tools for teaching evidence-based veterinary medicine. journal of veterinary medical education. 40(3), 272–277. doi: http://dx.doi.org/10.3138/jvme.0113-010r1 vandeweerd, j-m., kirschvink, n., clegg, p., vandenput, s., gustin, p. & saegerman, c. (2012). is evidence-based medicine so evident in veterinary research and practice? history, obstacles and perspectives. the veterinary journal. 191(1), 28–34. doi: http://dx.doi.org/10.1016/j.tvjl.2011.04.013 walker, a.j., pretis, f., powell-smith, a. & goldacre, b. (2019). variation in responsiveness to warranted behaviour change among nhs clinicians: novel implementation of change detection methods in longitudinal prescribing data. the bmj. 367. doi: http://dx.doi.org/10.1136/bmj.l5205 zwolsman, s.e., van dijk, n., te pas, e. & wieringa-de waard, m. (2013). barriers to the use of evidence-based medicine: knowledge and skills, attitude, and external factors. perspectives on medical education.2(1), 4–13. doi: http://dx.doi.org/10.1007/s40037-013-0039-2 intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. comparing delayed versus on-arrival administration of a modified live viral vaccine in feedlot cattle a knowledge summary by ashlee ambs dvm ms 1 heather k. moberly msls ahip fhea pgcert (vet ed) 2 sarah capik dvm phd 1, 3* 1texas a&m university college of veterinary medicine and biomedical sciences, 660 raymond stotzer pkwy, college station, tx 77843 usa 2202 olsen blvd, university libraries, texas a&m university, college station, tx 77843–4462 usa 3texas a&m agrilife research, 6500 w amarillo blvd, amarillo, tx 79106 usa *corresponding author (sarah.capik@ag.tamu.edu) vol 7, issue 2 (2022) published: 15 jun 2022 reviewed by: john campbell (dvm dvsc) and kiro petrovsky (dvm mvsc pgdipvcsc phd) next review date: 18 dec 2023 doi: 10.18849/ve.v7i2.502 pico question in auction market calves at high risk of developing bovine respiratory disease (brd), does delayed (14–30 days) vaccination with a modified live vaccine (mlv) for viral respiratory pathogens versus administration of mlv on-arrival (within 24 hours of arrival) to the feedlot, result in a decreased percentage of calves with brd morbidity diagnosed based on visual signs and rectal temperature >40 degrees celsius?   clinical bottom line category of research question treatment the number and type of study designs reviewed two papers were critically reviewed. both are randomised complete block designs strength of evidence weak outcomes reported delaying administration of a modified live respiratory vaccine to feedlot cattle may result in lower brd retreatments conclusion in feedlot calves, delaying modified live vaccine administration for viral respiratory pathogens may result in lower brd retreatment rates than cattle receiving the vaccine on arrival to the feedlot. significant statistical data from one study supported this conclusion while another showed numerically less retreatments in calves vaccinated on arrival versus delayed vaccination   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario it is common practice in north american feedlots to use a multivalent modified live vaccine (mlv) for viral respiratory pathogens during arrival processing as a management strategy to reduce bovine respiratory disease (brd) risk. however, brd continues to be a financial and health issue in feedlot cattle despite consistent use of on-arrival mlv for viral respiratory pathogens. recently, modifications to protocols, such as altering vaccine timing, have been considered in the hopes of improving vaccine efficacy and reducing brd morbidity. changing vaccine timing would also allow cattle to acclimate to their new environment before challenging them with a vaccine. feedlot producers and veterinarians must decide on the timing of vaccine administration by reviewing research evidence and considering the financial and production impacts of those decisions. the evidence the strongest evidence for research is presented in systematic reviews and several were identified in our search. however, they did not answer the specifics of the presented question and thus were excluded from the review. the two studies reviewed in this summary are randomised controlled trials*, which produce the strongest evidence of experimental studies (hagenmaier et al., 2018; and rogers et al., 2016). though each of these studies evaluated a large number of cattle, the experimental unit for each study was pen which means the sample sizes for detecting differences in each study are relatively small. small randomised controlled trials have a lower estimate of the true outcome of the treatments if applied outside of the study compared to large randomised controlled trials (o’connor & fajt, 2015). additionally, feedlot pens tend to be much larger (more than 100 calves per pen) which may negatively impact the external validity of these results. for our question, the strength of evidence is weak overall because the reviewed papers are small experimental studies, and each have limitations to answering the presented question (hagenmaier et al., 2018; and rogers et al., 2016). within the details of each study, we have provided a list of limitations either identified directly or limitations that result from a lack of detail in the manuscript. biased results can confound information leading to incorrect findings therefore producers should bear in mind the limitations of each study when considering a change in their vaccine protocol based on this summary.  *the two studies reviewed in this summary are randomised complete block designs, which places them within the classification randomised controlled trials which produce the strongest evidence of experimental studies. summary of the evidence rogers et al. (2016) population: high-risk heifer calves from 274–295 kg; processed within 72 hours of arrival at the feedlot (the paper described the heifers as 'high-risk' and indicated they had one or more risk factors for brd). sample size: n = 5,179, (average 86 calves / pen; 15 pens / treatment). intervention details: treatments: delayed vaccine 30 days (± 5 days) days on feed (dof). vaccine on arrival to feedlot and 30 dof (± 5 days). delayed vaccine plus dna immunostimulant. arrival vaccine plus dna immunostimulant. cattle received tilmicosin during processing for metaphylaxis but no post-metaphylactic interval was described. vaccine: modified-live infectious bovine rhinotracheitis virus (ibrv), parainfluenza-3 virus, bovine viral diarrhea virus (bvdv) types 1 and 2, and bovine respiratory syncytial virus vaccine (pyramid 5, 2 ml subcutaneously in the right neck; boehringer ingelheim vetmedica, inc.). study design: randomised complete block design with a 2x2 treatment factorial. outcome studied: bovine respiratory disease (brd) morbidity (cattle must have a rectal temperature of ≥40 °c and any one of the clinical signs of brd [depression, lowered head carriage, nasal and / or ocular discharge, coughing, stiff gait, or depressed ruminal fossa]) or if advanced signs of illness treatment was initiated even if rectal temperature did not meet cutoff – subjective assessment; blinded personnel. brd treatments 1, 2, and 3 at 60 days on feed (dof) – subjective assessment; blinded personnel. brd 1 treatment rate at approximately 116 dof (104–127 dof). brd retreatment number at approximately 116 dof (104–127 dof). brd 1, 2, and 3 treatment-rate at closeout (average 209 days). brd retreatment risk at closeout. main findings (relevant to pico question): delayed modified live vaccine (mlv) for viral respiratory pathogens statistically significantly reduced the number of calves requiring two treatments at 60 dof (p = 0.04), at approximately 116 dof (data not shown, p = 0.04), and at closeout (p = 0.04), and retreatment risk at approximately 116 dof (p = 0.01) and retreatment risk at closeout (p = 0.01, 37.05% in delayed vs 43.97% in arrival). at 60 dof, approximately 116 dof, and closeout the percentage of calves that received one treatment was the same, statistically, between arrival versus delayed vaccine administration (p = 0.70, p = 0.78, and p = 0.82, respectively). limitations: model-adjusted means and confidence intervals for the overall effect of vaccine were not provided for all outcomes which limits the interpretation of the results as no magnitude of effect can be appreciated. study included pregnant heifers (<90 days) and aborted with prostaglandin at processing, but there was no difference in the number among treatments, and heifers >90 days pregnant were excluded from the study. pen size ranged from 79–98 heifers. dof ranged from 196–221 days (209 days on average). brd treatment details including antimicrobials administered and post-treatment intervals were not described. hagenmaier et al. (2018) population: high-risk beef heifers at 258 ± 12.7 kg (the paper described the heifers as 'high-risk' and indicated they had one or more risk factors for brd). sample size: n = 2,575, (average 86 heifers / pen, 10 pens / treatment). intervention details: treatments: pyramid 5 and presponse sq during arrival: (pre) (860 heifers in 10 pens). nuplura ph and titanium 5 during arrival processing: (tna) (855 heifers in 10 pens). nuplura ph during arrival with titanium 5 delayed until 28 days after arrival processing: (tnd) (860 heifers in 10 pens). no booster vaccines were given during this study. cattle received timicosin as a metaphylactic treatment during arrival processing with a 3 day post-metaphylactic interval during which no animal could be diagnosed with bovine respiratory disease (brd) and receive treatment. vaccines: pyramid 5: modified live infectious bovine rhinotracheitis, bovine viral diarrhea types i and ii, parainfluenza 3, and respiratory syncytial virus vaccine (2 ml subcutaneously; boehringer ingelheim vetmedica, inc.). presponse sq: pasteurella multocida bacterial extract and mannheimia haemolytica toxoid (2 ml subcutaneously; boehringer ingelheim vetmedica, inc.). titanium 5: modified live infectious bovine rhinotracheitis, bovine viral diarrhea virus types 1 and 2, bovine parainfluenza 3, and bovine respiratory syncytial virus vaccine (2 ml subcutaneously; elanco animal health). nuplura ph: toxoid and cellular-associated antigens of mannheimia haemolytica cultures (2 ml subcutaneously; elanco animal health). study design: randomised complete block design. outcome studied: brd treatment 1, 2, and 3 at reimplant (average 111 days) and closeout (average 219 days) subjective assessment; blinded evaluators. in order to be considered a brd case and receive antibiotic treatment, heifers must have had a rectal temperature ≥40°c and at least one of the clinical signs indicative of brd (depression / lethargy, incoordination, dypsnea / abnormal respiration [rate, character, etc.], sunken eyes / dehydration, nasal and / or ocular discharge, lowered head carriage, and / or depressed ruminal fossa). non-febrile heifers with severe clinical presentation of brd according to hospital personnel were also administered therapy without meeting the rectal temperature cutoff.  a 3 day post-treatment interval was observed after brd 1 (enrofloxacin), brd 2 (florfenicol), and brd 3 (oxytetracycline). late day morbidities were treated with danofloxacin to remain within pre-slaughter withdrawal. main findings (relevant to pico question): no statistically significant differences in morbidity assessments were found between vaccine treatments at reimplant or closeout. note: only a p-value for pre, tna, and tnd compared together was reported therefore pairwise comparisons for tna vs tnd were not available. at reimplant (average 111 days on feed [dof]) brd treatment 1, 2, and 3, were numerically greater in those receiving the vaccine at 28 dof (tnd) when compared to tna. brd 1: tnd 14.57% vs tna 12.39% brd 2: tnd 6.45% vs tna 5.73% brd 3: tnd 3.10% vs tna 2.39% at closeout (average 219 dof) brd treatment 1, 2, and 3, were also numerically greater in tnd versus tna. brd 1: tnd 15.77% vs tna 13.24% brd 2: tnd 7.53% vs tna 6.24% brd 3: tnd 3.62% vs tna 3.10% limitations: the treatment interventions tna and tnd were the only ones evaluated because the other intervention had variables inconsistent with the presented question. the timing of processing relative to feedlot arrival was unclear. blocks were created over up to a 4 day period and a minimum of 24 hours rest was given to all cattle after the block was completed. all heifers were given a prostaglandin during arrival processing, but no pregnancy diagnosis was described. standard errors for model-adjusted least square means for tna and tnd for individual outcomes were not reported. pairwise comparisons and confidence intervals between tna and tnd were not reported which limits the ability to interpret the results relative to our question. pen size ranged from 77–91 animals. days on feed ranged from 189–238 days (average 219 days). reimplant ranged from 110–113 days (average 111 days). morbid cattle that were not well enough to thrive remained in the hospital pen while those who could thrive were returned to their home pens after treatment. appraisal, application and reflection rogers et al. (2016) showed calves that received a delayed modified live vaccine (mlv) for viral respiratory pathogens were significantly less likely to require two treatments by 60 days on feed (dof), by 116 dof, and closeout. they also found a significant reduction in retreatment risk at 116 dof and closeout in the delayed vaccine group (rogers et al., 2016). in contrast, hagenmaier et al. (2018) showed only a numerical reduction of bovine respiratory disease (brd) treatments 1, 2, and 3 in calves receiving mlv for viral respiratory pathogens on arrival at reimplant (average 111 days) and closeout (average 219 days) (hagenmaier et al., 2018) and did not statistically evaluate the pairwise comparison between the two treatment groups that were pertinent to our clinical question. these studies have inherent limitations as outlined below and differ in the number of animals evaluated, vaccine studied, timing of delayed vaccination and timing of health outcome measurement, health management, etc., which should be considered when evaluating the results. morbidity assessment is, ultimately, a subjective assessment although some case definitions include a rectal temperature cutoff. however, cattle temperatures are not taken unless respiratory illness signs are observed, so temperature data ultimately relies on that initial subjective assessment of clinical signs. the exact clinical signs used to identify sick cattle can and do vary between studies and operations. additionally, the way an animal is deemed morbid varies between feedlot protocols and between the studies we evaluated. our specific question was about cattle deemed morbid due to clinical signs and a rectal temperature of >40°c.  however, no studies were identified that met that exact question as both of the included studies allowed cattle with advanced clinical signs (per the blinded evaluator) to be treated even if they did not reach a rectal temperature of ≥40°c. allowing treatment of animals that do not meet a rectal temperature threshold could introduce unwanted variation in the morbidity outcomes due to potentially more false positives. it also makes it more difficult to compare morbidity outcomes between studies as the variation related to what one person deems ‘severe’ or ‘advanced’ depends on training, experience, and the type of cattle they are evaluating. due to this variation, animals that were deemed morbid in some studies may not have met criteria to be morbid in another study, so description of criteria for a morbid patient should be compared to a producer’s protocol when deciding whether a study provides good evidence to change practices. additionally, it is important to also consider the way morbid cattle are handled including the antimicrobial therapies applied, any post-treatment intervals that are observed, whether cattle were hospitalised or returned to their home pen, etc., when evaluating studies. hagenmaier et al. (2018) described these aspects of their health program but rogers et al. (2016) did not fully describe treatment regimens which makes it difficult to compare between the health protocols, and thus health-related outcomes, of each study. additionally, origins and prior health backgrounds of cattle represented within these studies differ as do the timing of arrival processing relative to feedlot arrival. this could be a strength of this summary due to our desire to broadly apply these findings to the diverse populations of cattle entering feedlots. however, it also introduces variability into the results of this knowledge summary as much of the prior health data and origin data are unknown. another limitation is that the two studies considered in this knowledge summary only explored delayed vaccination in heifers, therefore the impact of gender, if any, cannot be evaluated (hagenmaier et al., 2018; and rogers et al., 2016). finally, the fact that both studies had less animals per pen than would typically be found in a commercial setting could influence the external validity of the results as respiratory disease dynamics are often different when the pen size is smaller. therefore, the answer to the presented question is, unsurprisingly, not consistent across the two studies we examined. even with the specific criteria for study selection that are outlined below, there is additional variability between studies that should be considered. modified live respiratory vaccines for cattle are made by a variety of pharmaceutical companies and the differences between these vaccines can include: the adjuvant used, number of viruses covered by the vaccine, different pathogen loads, different virus types and strains included, etc. each summary of the studies we evaluated includes a list of the current manufacturer, brand name, and the viruses included in the mlv respiratory vaccine administered. it is important to note that different vaccines and protocols were tested in the two studies we evaluated (hagenmaier et al., 2018; and rogers et al., 2016). therefore, although both studies provide evidence for our question related to delayed vs on-arrival mlv use, they do not provide consistent evidence in terms of products used. producers should use the information provided in this summary to make vaccine protocol decisions in light of the limitations listed above. since the evidence differed among studies, there was considerable variability between the management of the cattle between the two studies, and so few studies were identified, a definite answer cannot be given to the clinical question. methodology section search strategy databases searched and dates covered: cab abstracts via ovid 1910–2021 week 50 limit results to 2000–december 18, 2021   pubmed via ncbi website limit results to 2000–december 18, 2021 limit results to english search strategy: cab abstracts: ((exp cattle/ or (calf or calves or steer or steers or heifer or heifers or bull or bulls or bovine or bovines or cattle or youngstock or young-stock or (young adj2 stock)).mp.) and (exp vaccines/ or vaccin*.mp. or exp immunization/ or immuni*.mp.) and (delay or delays or delayed or arrive or arrives or arrived or arrival or postarrival or "post arrival" or post-arrival).mp. and (pneumon*.mp. or (respiratory adj1 disease*).ti,ab. or "respiratory diseases".sh. or (respiratory adj2 disease*).ti,ab. or ((shipping or undifferentiated) adj1 fever).ti,ab. or (brd or brdc).ti,ab. or (bovine adj1 respiratory adj1 disease*).ti,ab. or (bovine adj1 respiratory adj1 disease* adj1 complex).ti,ab. or (summer adj1 pneumon*).ti,ab. or (enzootic adj1 pneumon*).ti,ab. or pleuropneumon*.mp. or bronchopneumon*.mp. or (respiratory adj1 tract adj1 disease*).mp.))   pubmed: (("pneumonia"[mesh terms] or "pneumonia"[title/abstract] or "pneumoniae"[title/abstract] or "pneumonias"[title/abstract] or "respiratory diseases"[all fields] or "respiratory disease"[title/abstract] or "shipping fever"[title/abstract] or "undifferentiated fever"[title/abstract] or "brd"[title/abstract] or "brdc"[title/abstract] or "bovine respiratory disease"[title/abstract] or "bovine respiratory disease complex"[all fields] or "summer pneumonia"[title/abstract] or "enzootic pneumonia"[title/abstract] or ("pleuropneumonia"[mesh terms] or "pleuropneumonia"[title/abstract] or "pleuropneumonias"[title/abstract] or "pleuropneumoniae"[title/abstract]) or ("bronchopneumonia"[mesh terms] or "bronchopneumonia"[title/abstract] or "bronchopneumonias"[title/abstract] or "bronchopneumoniae"[title/abstract]) or "respiratory tract disease"[title/abstract] or "respiratory tract diseases"[all fields]) and ("calf"[title/abstract] or "calves"[title/abstract] or "steer"[title/abstract] or "steers"[title/abstract] or "heifer"[title/abstract] or "heifers"[title/abstract] or "bull"[title/abstract] or "bulls"[title/abstract] or "bovine"[title/abstract] or "bovines"[title/abstract] or "cattle"[title/abstract] or "cattle"[mesh terms] or "youngstock"[title/abstract] or "young-stock"[title/abstract] or "young-stock"[title/abstract]) and ("immunization"[mesh terms] or "immunization"[title/abstract] or "immunisation"[title/abstract] or "immunizations"[title/abstract] or "immunisations"[title/abstract] or "immunize"[title/abstract] or "immunise"[title/abstract] or "immunized"[title/abstract] or "immunised"[title/abstract] or "vaccination"[mesh terms] or "vaccine"[title/abstract] or "vaccines"[title/abstract] or "vaccination"[title/abstract] or "vaccinating"[title/abstract] or "vaccinated"[title/abstract]) and ("delay"[title/abstract] or "delayed"[title/abstract] or "delays"[title/abstract] or "post-arrival"[title/abstract] or "post-arrival"[title/abstract] or "postarrival"[title/abstract] or "arrive"[title/abstract] or "arrival"[title/abstract] or "arrives"[title/abstract] or "arrived"[title/abstract]) dates searches performed: 18 dec 2021 exclusion / inclusion criteria exclusion: publication date prior to 2000, not a research trial, does not compare arrival versus delayed vaccine administration groups, does not evaluate the same vaccine given on arrival versus delayed administration, does not evaluate the bovine species, or calves not evaluated in a feedlot. inclusion: brd morbidity assessment, comparison of effects delayed modified live vaccine administration and administration of vaccine on arrival to the feedlot, and respiratory vaccine used when evaluating vaccine timing. search outcome database number of results excluded – not a research trial excluded – not an mlv respiratory vaccine study in calves excluded – does not compare arrival versus delayed (14–30 days) administration of the same mlv vaccine excluded – calves not evaluated or administered treatment in the feedlot total relevant papers cab abstracts 115 21 47 40 6 1 pubmed 50 7 16 24 3 0 hand search of reference lists 1 total relevant papers when duplicates removed 2 conflict of interest moberly serves on the cabi publishing north american library advisory board and the vetstream academic advisory board. capik has previously collaborated with a co-author (m. theurer) on the hagenmaier et al. (2018) paper. references hagenmaier, j.a., terhaar, b.l., blue, k., hoffman, b.w., fox, j.t. & theurer, m.e. (2018). a comparison of three vaccine programs on the health, growth performance, and carcass characteristics of high-risk feedlot heifers procured from auction-markets. the bovine practitioner. 52(2), 120–130. doi: https://doi.org/10.21423/bovine-vol52no2p120-130 o’connor, a. & fajt, v. (2015). evaluating treatment options for common bovine diseases using published data and clinical experience. veterinary clinics of north america: food animal practice. 31(1), 1–15. doi: https://doi.org/10.1016/j.cvfa.2014.11.001 rogers, k.c., miles, d.g., renter, d.g., sears, j.e. & woodruff, j.l. (2016). effects of delayed respiratory viral vaccine and/or inclusion of an immunostimulant on feedlot health, performance, and carcass merits of auction-market derived feeder heifers. the bovine practitioner. 50(2), 154–164. doi: https://doi.org/10.21423/bovine-vol50no2p154-164 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. the use of metronidazole in adult dogs with acute onset, uncomplicated, diarrhoea a knowledge summary by emma rogers-smith bsc(hons) ba vetmb mrcvs 1* 1davies veterinary specialists, manor farm business park, higham gobion, hitchin sg5 3hr *corresponding author (emma.rogers-smith@cantab.net) vol 6, issue 4 (2021) published: 22 dec 2021 reviewed by: jennifer garcia (dvm dacvim) and adam swallow (bvsc mrcvs) next review date: 15 jun 2023 doi: 10.18849/ve.v6i4.445 pico question in adult, non-geriatric, dogs with acute onset (<7 days duration) uncomplicated diarrhoea does the addition of metronidazole to a supportive care protocol such as dietary modification or probiotics (excluding other antimicrobials) reduce the time to resolution of diarrhoea compared to supportive care protocols alone?   clinical bottom line category of research question treatment the number and type of study designs reviewed four studies were included in this appraisal. two prospective, double blinded, placebo controlled clinical trials, one prospective treatment trial and one retrospective longitudinal observational study strength of evidence weak outcomes reported one study found a shortened duration of clinical signs (by 1.5 days; p = 0.04) in the metronidazole treated group compared to control. however, a separate study found no significant difference between control and metronidazole groups in the regards to resolution of clinical signs. one study demonstrated a long standing (>28 day) negative impact of metronidazole treatment on gut microbiome with no difference in time to resolution of clinical signs when compared with faecal matter transplant conclusion the current evidence for the superiority of metronidazole compared to supportive treatment alone is weak and at this time there is no evidence-based rationale for its use in cases of uncomplicated, acute, canine diarrhoea. furthermore, the negative implications of metronidazole on the intestinal microbiome have been found to be long standing (>28 days as a minimum) and should not be discounted by the prescribing clinician   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are presented with an 18 month old female neutered labrador retriever with a 3 day history of mixed bowel diarrhoea which includes a small amount of fresh blood following an episode of dietary indiscretion. the patient is up-to-date with routine vaccination and anthelmintic treatment. the dog is bright and your physical examination is completely unremarkable. you wish to provide treatment for this patient and the client is requesting metronidazole treatment as this helped ‘to clear things up quickly’ the last time the patient raided the bins. the evidence until as recently as 2019 the evidence basis for the use of metronidazole in the face of uncomplicated acute canine diarrhoea (uacd) and its superiority to supportive treatment alone (dietary modification, probiotics and more recently faecal matter transplant) has been anecdotal. four papers were found to be fully or partially relevant to the pico question; two randomised, double blinded placebo-controlled trials (shmalberg et al., 2019; and langlois et al., 2020), one prospective controlled treatment trial (chaitman et al., 2020) and one retrospective observational study (singleton et al., 2019). all four studies measured time to resolution of diarrhoea. other factors considered included faecal microbiome and metabolome diversity (chaitman et al, 2020). the evidence for the pico question was found to be weak and at this time there is insufficient evidence to suggest metronidazole is superior in reducing the duration of clinical signs of uacd when compared to supportive measures alone. summary of the evidence shmalberg et al. (2019) population: client owned dogs presenting to two emergency centres (run by a university teaching hospital in the usa) for acute diarrhoea (<7 days duration) with or without concurrent vomiting between march 2017 and august 2018. exclusion criteria: large volume haematochezia, clinical signs compatible with pancreatitis, dogs with high faecal worm egg counts, clinically relevant comorbidities (endocrinopathies, organ dysfunction). sample size: 63 dogs enrolled, 60 completed the study. three dogs were withdrawn and not included in the final analysis due to either a significant parasite burden (n = 1, metronidazole group) or failure of owners to give the assigned study treatment (n = 2, one each in probiotic and placebo group). intervention details: all enrolled dogs had haematology and biochemistry performed in addition to faecal flotation, commercial gastrointestinal (gi) tract polymerase chain reaction (pcr) panel (campylobacter coli, campylobacter jejuni, canine distemper virus, canine enteric coronavirus, canine parvovirus 2, clostridium dificile toxin a/b, clostridium perfringens alpha and enterotoxins, cryptosporidium spp., giardia spp. and salmonella spp.) three treatment groups. all treatments administered twice daily for 10 days. probiotic group: commercial probiotic (vital vet, vital planet®). metronidazole group: metronidazole: 125 mg to dogs 4–10 kg; 250 mg to dogs between 10.1 kg and 20 kg and 400 mg for dogs 20.1–40 kg. (mean metronidazole dose 17.8 mg/kg; range 11.2–24 mg/kg). placebo group: placebo controlled with sucrose at equal volume to probiotic or metronidazole. clinicians were permitted at their own discretion to administer intravenous fluids (subcutaneous [sq] or intravenous [iv]), fenbendazole and/or maropitant. patients were enrolled until there were 20 cases present in each group based on prestudy power calculations. clients were requested to fast the patient for 24 hours before a gradual reintroduction of food over next 24 hours. patients were randomised to a treatment group via pre-study randomisation schedule. both the owner and clinician were blinded to treatment administered. study design: randomised, double-blinded, placebo-controlled clinical trial. the study was unblinded after enrolment of the 60 dogs to perform statistical analysis. outcome studied: time to normal faeces with assessment of faecal consistency, faecal score (based on the waltham™ faeces scoring system), defaecation frequency, straining. main findings (relevant to pico question): dogs were withdrawn from the study due to owner non-compliance, abnormalities noted on post-enrollment laboratory or pcr testing or high faecal worm egg count (total withdrawn = 3) patient age: probiotic group: 5.3 ± 3.2 years; metronidazole group: 5.7 ± 3.7 years; placebo group: 5.7 ± 3.9 years. there was no statistically significant improvement in time to clinical resolution of the clinical signs in any treatment group (p = 0.17). time to normal faecal consistency: probiotic group: 3.5 ± 2.2 days; metronidazole group: 4.6 ± 2 days; placebo group: 4.8 ± 2.9 days. no adverse effects were observed in any treatment group. no dog required rescue treatment. limitations: no standardised treatment protocol so likely multiple confounding effects between cases, although study design and statistical analysis has been structured to minimise this effect. clients were provided a financial incentive which may influence their interpretation. low case numbers in each treatment group, although the treatment group sizes were based on pre-study power calculations. no control of diet. no microbiome or metabolome testing. singleton et al. (2019) population: analysis of electronic health records from 179 volunteer veterinary practices in the uk that participate in the small animal veterinary surveillance network. cases booked in from 1 april 2014 to 31 january 2017, included all canine consultations that had been classified as ‘gastroenteritis’ as the main presenting complaint that also had a completed questionnaire pertaining to clinical signs, diagnostics and advice to the client. inclusion criteria: acute, first presentation diarrhoea of <2 days duration. exclusion criteria: euthanasia on presentation (n = 6) and lost to follow-up (n = 754). sample size: initial review of medical records found a total of 12,455 cases of ‘gastroenteritis’ that also included the augmented questionnaire. of those 3,192 were found to fit the above inclusion criteria.  a further three cases were excluded due to inaccurate date of birth entry. of those 3,189 a further 760 were excluded for aforementioned reasons leaving a total of 2,429 cases used within the modelling dataset. intervention details: information collated on: patient: age, sex, breed, vaccine history, body temperature; interventions classified as: antimicrobials, anti-inflammatories, gastrointestinal agents (antacids, gastroprotectants, antiemetics, anthelmintics) euthanasia agents; gastrointestinal nutraceuticals (products not listed as authorised veterinary or human medicines e.g. pro/prebiotics, kaolin, etc.). study design: retrospective longitudinal observational study. outcome studied: cases considered as resolved if they did not return to the practice for a ‘gastrointestinal’ reason between 11–30 days of initial presentation. any case re-presenting within 10 days of initial presentation was manually checked to ensure no mention of diarrhoea in case notes. main findings (relevant to pico question): total of 763 excluded from the analysis. reasons for this include euthanasia on presentation (n = 6), lost to follow-up (n = 754) and inaccurate birth date (n = 3). large variation in severity of clinical presentation: mild cases (n = 2665) moderate cases (n = 507) and severe cases (n = 17). prescribing of antibiotics: dogs with blood in diarrhoea were more frequently prescribed systemic antibiotics as were those that were pyrexic (haemorrhagic diarrhoea odds ratio [or] 4.1; 95% ci 3.4–5.0) (pyrexia or1.3, 95% 1.1–1.7); in total 49.7% of cases in this series were prescribed antibiotics at initial presentation (95% ci 46.1–53.2). this increased to 52.5% of cases (95% ci 49.1–55.8) when initial presentation and/or cases representing within 10 days of initial presentation were included. of those cases prescribed antibiotics, metronidazole was the most commonly prescribed (47%); when case severity was stratified as mild, moderate or severe, moderate or severe cases were more frequently prescribed a systemic antimicrobial compared to mild cases (or 1.3, 95% ci 1.1–1.7); disease severity was controlled for in univariable mixed effects logisitic regression model (available as supplementary data in singleton, et al. [2019]) and was not significant when considering day 10 resolution (p = 0.95). resolution of clinical signs within 30 days of initial presentation: dietary modification advice and gastrointestinal nutraceuticals were positively associated with resolution of signs (or 2.8, 95% ci 1.3–6.1) no such association was found for pharmaceutical agents including antibiotics. limitations: retrospective study – limitations of retrospective studies are extensive but include lack of control for confounding variables, ability to only infer association not causation, misclassification bias, convenience recruitment which can lead to population not being representative of general population amongst others. calculation of percentage antibiotic prescribing events not expressly documented within the paper. lack of complete clinical records (for example inconsistent body temperature recording) for all cases. large loss to follow-up although this may be associated with a positive outcome (i.e. case does not return to the practice as clinical signs have resolved) this represents an assumption and as such definitive positive or negative associations may be over or under represented. assumption of resolution of clinical signs based on lack of follow-up appointment. lack of standardisation: wide variety of treatments administered leading to potential for significant confounding effects. chaitman et al. (2020) population: 18 client owned dogs presenting between october 2016 and june 2017 to a specialist practice in new york city with acute diarrhoea (lasting under 14 days). dogs in acute diarrhoea treatment group may or may not have had concurrent vomiting. exclusion criteria: pyrexia, tachycardia, tachypnoea, poor general condition, those requiring hospitalisation, known intestinal parasitism, chronic gi history, pretreatment with antibiotics, drugs that may have precipitated condition (i.e. nsaids, corticosteroids) within 2 weeks of presentation. control population were privately owned living in the same geographical area. samples were collected as part of a wider study. none of these controls had a history of gastrointestinal signs. sample size: 32 dogs. intervention details: dogs with acute diarrhoea (n = 18) were divided into faecal microbiota transplantation group (fmt; n = 11) and metronidazole group (met; n = 7) based on owner willingness to agree on one or other treatment. faecal samples were taken from 14 healthy, privately owned, control dogs at a single time point. fmt: 10 dogs received a single fmt with 5 g frozen donor stool/kg bwt. the remaining dog (due to size and availability of donor faeces) received 2.5 g/kg. fmt performed by rectal enema and animals were not fed for 4–6 hours following enema to reduce risk of bowel movement. met: 15 mg/kg metronidazole give per os every 12 hours for 7 days. additional treatment included the use of maropitant (cerenia®, zoetis), 1 mg/kg sq q24 hours in cases that were vomiting. diet was not standardised. no other treatments were given. faecal samples were collected from control dogs at a single time point as part of a wider study evaluating faecal microbiota across different locations. study design: prospective treatment trial. outcome studied: evaluation of clinical signs: by assessment of faecal consistency by a board certified clinician using purina® faecal scoring chart on days 0, 7 and 28 (lower score represents a normal stool consistency). analysis of faecal microbiota: assess by use of quantitative pcr, (qpcr) dysbiosis index and 16s ribosomal rna (rrna) gene sequencing. analysis of faecal metabolome: measurement of unconjugated bile acids and untargeted metabolomics approach. main findings (relevant to pico question): faecal scores: faecal scores decreased significantly from day 0 to day 7 and day 28 in both treatment groups (p <0.01 in both cases). faecal scores significantly lower in fmt group when compared to met group on day 28 (p = 0.04). faecal dysbiosis index (di): no significant difference between treatment groups on day 0. significant difference between acute diarrhoea dogs compared to healthy controls (higher di in acute diarrhoea group; p <0.001). dogs after fmt showed significant decrease in di (p <0.05). dogs in met group showed significant increase in di (p <0.05). abundance of faecalibacteria (associated with health) increased in fmt and significantly higher compared to met at days 7 and 28 (p <0.05). however significantly lower in both acute diarrhoea treatment groups compared to controls (p <0.05). hiranois (a bacterial species important for conversion of primary to secondary bile acids): no significant difference was found between control and fmt group at day 28. met group showed significant decrease in c. hiranois when compared to control dogs at both day 7 and day 28 (p<0.05). 16s rrna gene sequencing: significant decrease in alpha diversity in met group compared to controls (p <0.05). day 28 fmt group and control no significant difference in microbial communities (p = 0.06). day 28 met group still had significantly different microbial communities (based on weighted distances) compared to controls (p = 0.001). faecal bile acid concentrations: fmt led to significant decrease in primary bile acids at day 28 compared to day 0 (p <0.05). these were also lower, but not significantly, at day 7 in this group. met led to significant increase in primary bile acids at day 7 (p <0.05). untargeted faecal metabolomics: fmt dogs clustered closer to controls when compared to met dogs at day 28. limitations: not randomised. not blinded – or at least not reported to be allowing for interpretation bias by the assessor. small treatment groups. lack of placebo. whilst a healthy control population was included a negative control population was not. fmt protocol not standardised for all patients. referral filter bias. no faecal scores provided for healthy control population. langlois et al. (2020) population: client owned dogs presenting to a university veterinary centre (michigan, usa) for acute diarrhoea with or without vomiting. inclusion criteria: age >6 months, bwt between 4 and 50 kg; active diarrhoea <7 days; up to date with core vaccinations. exclusion criteria: dogs receiving probiotics, antibiotics or anti-inflammatory treatments in the preceding 30 days; pregnant or nursing dogs; moderate to severe abdominal pain, complete anorexia; moderate to severe dehydration (>8%). laboratory evaluation: dogs were included providing they did not have evidence of gastrointestinal parasitism, giardia spp. infection or parvoviral enteritis. sample size: 48 dogs initially screened for inclusion. 14 excluded from the study. total of 31 dogs met inclusion criteria and completed the study according to protocol: 14 test population and 17 controls. intervention details: dogs randomly allocated to either placebo n = 17 (capsule containing only microcrystalline cellulose) or metronidazole group n = 14 (10–15 mg/kg po). either intervention given q12 hour for 7days. owners also requested to withhold food for initial 12 hours after enrolment and gradually resume feeding of normal diet over subsequent 12–24 hours. dogs that had vomiting also received a single dose of maropitant (cerenia®, zoetis) 1 mg/kg sq. administration of crystalloid fluids was also permitted. the use of antacids, antidiarrhoeals or any newly prescribed medications was not permitted for the duration of the study unless the patient clinically deteriorated; these cases were subsequently excluded. dogs were returned for repeat evaluation and faecal diagnostic testing on day 7. the study was concluded in all test and control dogs in which diarrhoea had resolved. control dogs that still had ongoing diarrhoea then received 7 days of metronidazole and came back for final evaluation and faecal testing on day 14. study design: prospective, randomised, double blinded placebo-controlled treatment trial. outcome studied: faecal scoring logs kept by the owner (aided by the bristol stool chart). timing and score of each defaecation measured, including pretreatment baseline assessment. main findings (relevant to pico question): population age: test group median age: 4.1 ± 3.4 years. control group median age: 4.9 ± 3.6 years. treatment effects: time until resolution of diarrhoea significantly associated with treatment group in multivariable analysis. time to resolution of clinical signs 1.5 day shorter in metronidazole group (p = 0.04). 29/31 dogs had resolution of clinical signs in <7 days irrespective of treatment group. 13/14 dogs in metronidazole treatment group duration of signs was <4 days. 10/17 control dogs duration of signs was <4 days; 15/17 control dogs duration of signs was <7 days. other treatment interventions: eight dogs in the treatment group and seven control dogs received intravenous fluid therapy (ivft) (duration </=1 day). six dogs in the treatment group and six control dogs received maropitant. limitations: unvalidated method of stool consistency monitoring as a human based chart rather than a veterinary one. referral filter bias. appraisal, application and reflection the available evidence is split between two randomised prospective double blinded clinical trials (shmalberg et al., 2019; and langlois et al., 2020), a prospective treatment trial without blinding or randomisation (chaitman et al., 2020) and a retrospective study (singleton et al., 2019). the retrospective study ranks low on the hierarchy of evidence and so meaningful clinical conclusions are challenging. however, the remaining studies (shmalberg et al., 2019; langloise et al., 2020; and chaitman et al., 2020) are prospective, with two being randomised, double blinded, controlled trials, therefore ranking them at the highest possible level in terms of hierarchy of evidence for individual clinical studies (excluding metanalysis or systematic review). however, both of these studies are limited by small sample sizes albeit with one basing sample size on pre-study power calculation. whilst direct comparisons between the studies cannot be made given the different treatment variables there is approximate consistency in the outcome variable assessed (time to resolution of normal faecal consistency) in all papers bar the singleton et al. (2019) paper which assumed resolution of clinical signs if the patient does not represent to the clinic for gi signs within 30 days. however, there is no standardisation in the assessment of this outcome which, given its subjective nature, does lend towards observer and assessment bias. especially given that in the three studies that utilised a faecal consistency chart (langlois et al., 2020; shmalberg et al., 2019; and chaitman et al., 2020), each used a different tool, which whilst similar in nature does mean that direct study end-point (normalisation of faecal consistency) comparisons must be made with caution. furthermore, despite the availability of veterinary faecal consistency charts, the langlois et al. (2020) paper elected to use the bristol stool chart which has been validated for humans rather than animals. the inclusion/exclusion criteria across the three prospective studies (shmalberg et al., 2019; langloise et al., 2020; and chaitman et al., 2020) allow for comparable population of dogs with what can be described as uncomplicated acute canine diarrhoea (uacd), the population that the pico question addresses. the definition of acute diarrhoea was variable amongst paper including <2 day duration (singleton et al., 2019), <7 days duration (langlois et al., 2020; and shmalberg et al., 2019) and <14 days duration (chaitman et al., 2020). the singleton et al. (2019) paper did not outline whether cases with severe clinical signs, confounding co-morbidities or chronic gastrointestinal histories were excluded/included and so the population evaluated may not be directly comparable to the population outlined in the pico question. three of the studies consider tertiary veterinary centres, two university based practices (langlois et al., 2020; and shmalberg et al., 2019) and one specialist centre (chaitman et al., 2020) which may lead to a referral filter bias whilst the retrospective study is more likely to representative of a general practice population (singleton et al., 2019). the singleton et al. (2019) study assessed the prescribing habits of uk first opinion practitioners when faced with a case of uacd in general practice and of the 2,429 cases that were including in the analysis 52.5% of those were prescribed antibiotics within 10 days of initial presentation. of those cases metronidazole was the most commonly prescribed (47% of antibiotic prescribing cases). furthermore, the study identified 1,050 cases (35.7%) where a patient was normothermic, with mild non-haemorrhagic diarrhoea and still prescribed antibiotics. however, the multivariable analysis of the records in this paper found no positive correlation between the prescribing of pharmaceutical agents (including antibiotics) and resolution of clinical signs. whilst the limitations of this paper, given its retrospective nature, large loss to follow-up and inconsistency in record keeping, are significant, the large population size adds strength to the clinical utility of this information.  this lack of positive correlation between antibiotic use and resolution of clinical signs was mirrored in both the shmalberg et al. (2019) and chaitman et al. (2020) studies, neither of which found a statistically significant superior effect of metronidazole use on the resolution of diarrhoea in when compared to a probiotic and placebo or to faecal matter transplant respectively. both the shmalberg et al. (2019) and chaitman et al. (2020) studies suffer from small treatment groups and the chatiman et al. (2020) paper did not have a placebo-control for comparison, although a healthy control population was present. whilst a significant positive association was found between metronidazole use and duration of clinical signs in the langlois et al. (2020) paper this study is the only one available within the literature and the small treatment group size means that caution should be taken in the clinical conclusions drawn from the data. chaitman et al. (2020) considered both the utility of faecal matter transplant (fmt) when compared to metronidazole on time to resolution of clinical signs as well as the impact of both fmt and metronidazole on diversity of both the microbiome and metabolome of the test subjects. the study is particularly impactful given dogs treated with metronidazole still had altered microbial and metabolic profiles 4 weeks from the start of treatment when compared to those treated with fmt or healthy controls. this study would however have benefited from a placebo control group as, although a healthy control population was assessed at a single time point, the inclusion of a placebo treatment trial would have strengthened the validity of the results of this study. the clinical significance, indeed our understanding of the implications of the findings of this study are uncertain given research into the impact of the gut microbiome is still in its infancy. however, in human medicine the intestinal bile acid pathway has been identified as important in the pathophysiology of diarrhoea (duboc et al., 2013). the chaitman et al. (2020) study found an increase proportion of primary bile acids in the faeces of dogs with acute diarrhoea at day 0 when compared with healthy controls. similarly, the metronidazole treated group had higher levels of primary bile acids (and lower levels of bacteria involved in the conversion of primary bile acids to secondary bile acids) when compared to healthy controls suggestive of ongoing alteration of intestinal function, despite normalisation of faecal consistency. standardisation of treatment protocols was lacking across the three prospective treatment trial papers as well as the retrospective longitudinal study. when considering the shmalberg et al. (2019) paper there was no standardisation in regards to the administration of crystalloid fluids, fenbendazole or maropitant and no standardisation of diet – owners do not appear to have been requested to continue to feed a normal diet and so there is potential for variation from normal diet which may have a confounding effect on duration of clinical signs. the langlois et al. (2020) paper has similar potential for confounding effects with the administration of crystalloid fluids and maropitant although additional oral medications were not prescribed to these patients. there was a lack of standardisation of treatment in the chaitman et al. (2020) paper in regards to both maropitant use and dietary advice. maropitant, a nk1 antagonist is a generally very well tolerated medication but diarrhoea has been described as a rare side effect in dogs (zoetis, 2019). however, a study assessing the use of maropitant in the face of doxorubicin associated delayed vomiting found a reduction in frequency of patients developing diarrhoea, hypothesising that there may be a role of substance p in the development of diarrhoea – or at least diarrhoea associated with chemotherapy (rau et al., 2010) although no further studies have evaluated this link. so, whilst it is unlikely to have a significant impact on the outcome of these studies, its potential as a confounding variable cannot be discounted. however, clinically the use of maropitant is unlikely to be detrimental in a case of acute diarrhoea and given its potent anti-emetic effects its use should not be discounted when faced of a concurrently nauseous patient. there is also considerable variation in the prescribed dose of metronidazole across the studies (shmalberg et al., [2019] 17.8 ± 4.6 mg/kg po bid; langlois et al., [2020] 10–15 mg/kg po bid and chaitman et al., [2020] 15 mg/kg po bid; with no details provided of dosages in the singleton et al. [2019] study) again limiting direct comparison of results across the studies. finally, although out of the scope of this knowledge summary, it feels prudent to touch upon the results pertaining to probiotics in these studies. the utility of probiotics was not found to be superior when compared to either placebo or metronidazole treatment in the shmalberg et al. (2019) study however a positive correlation was found between the utility of nutraceutical products and resolution of clinical signs in the singelton et al. (2019) paper. within the singelton et al. (2019) study multiple different products were included within this one variable, compared with a single formulation within the shmalberg et al. (2019) paper which limits the direct comparison between these two studies. however, this variability in outcome appears consistent with the latest systematic review of the available literature which concludes uncertain clinical benefit to the utility of probiotics in acute gastrointestinal disease (jensen & bjornvad, 2019). whilst the available literature is limited, at this time there is insufficient evidence to conclude a benefit to the prescribing of metronidazole in uacd in favour of supportive measures alone. there is also evidence to suggest that the use of metronidazole can have long-term detrimental implications for the gut microbiome and metabolome. therefore, based on this current review of the available evidence, metronidazole would not be recommended as a first-line treatment in a case of uacd. there would be benefit for further studies of a higher power (prospective, randomised, blinded placebo-controlled treatment trial) with closer standardisation of protocol and larger treatment groups. furthermore, the utility of both subjective, but validated, faecal consistency scoring and quantitative microbiome/metabolome analysis should be considered as well as multivariant analysis in an attempt to control for confounding variables to better ascertain appropriate, evidence-based treatment protocols for the management of uacd. methodology section search strategy databases searched and dates covered: cab abstracts via the ovid platform covering 1972-2021. pubmed 1980–2021 web of science 1992–2021 search strategy: cab abstracts: (dog or dogs or canine) and (metronidazole) and (diarrhoea or diarrhea)   pubmed: (dog or dogs or canine) and (metronidazole) and (diarrhoea or diarrhea)   web of science: (“acute diarrhoea”) and (dog) dates searches performed: 15 jun 2021 exclusion / inclusion criteria exclusion: single case reports. duplicate papers. book chapters. conference proceedings. articles not published in english. articles not relevant to the pico question. inclusion: any relevant primary research paper. search outcome database number of results excluded – not relevant to pico excluded – single case/report/book chapter/conference proceeding/duplicate excluded – not available in english total relevant papers cab abstracts 90 85 2 0 3 pubmed 47 44 0 0 3 web of science 18 17 0 0 1 total relevant papers when duplicates removed 4 conflict of interest the author declares no conflicts of interest. references chaitman, j., ziese, a., pilla, r., minamoto, y., blake, a.b., guard, b.c., isaiah, a., lidbury, j.a., steiner, j.m., unterer, s. & suchodolski, j.s. (2020). faecal microbial and metabolic profiles in dogs with acute diarrhoea receiving either faecal microbiota transplantation or oral metronidazole. frontiers in veterinary science. 7(192). doi: https://doi.org/10.3389/fvets.2020.00192 duboc, h., rajca, s., rainteau, d., benarous, d., maubert, m-a., quervain, e., thomas, g., barbu, v., humbert, l., despras, g., bridonneau, c., dumetz, f., grill, j-p., masliah, j., beaugerie, l., cosnes, j., chazouillères, o., poupon, r., wolf, c., mallet, j-m., langella, p., trugnan, g., sokol, h. & seksik, p. (2013). connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. gut. 62(4), 531–539. doi: https://doi.org/10.1136/gutjnl-2012-302578 jensen, a.p. & bjørnvad, c.r. (2019). clinical effect of probiotics in prevention or treatment of gastrointestinal disease in dogs: a systematic review. journal of veterinary internal medicine. 33(5), 1849–1864. doi: https://doi.org/10.1111/jvim.15554 langlois, d., koenigshof, a.m. & mani, r. (2020). metronidazole treatment of acute diarrhoea in dogs: a randomized doubled blinded placebo-controlled clinical trial. journal of veterinary internal medicine. 34(1), 98–104. doi: https://doi.org/10.1111/jvim.15664 rau, s.e., barber, l.g. & burgess, k.e. (2010). efficacy of maropitant in the prevention of delayed vomiting associated with administration of doxorubicin to dogs. journal of veterinary internal medicine. 24(6), 1452–1457. doi: https://doi.org/10.1111/j.1939-1676.2010.0611.x shmalberg, j., montalbano, c., morelli, g. & buckley, g.j. (2019). a randomized double blinded placebo-controlled clinical trial of a probiotic or metronidazole for acute canine diarrhea. frontiers in veterinary science. 6(163). doi: https://doi.org/10.3389/fvets.2019.00163 singleton, d.a., noble, p.j.m., sánchez-vizcaíno, f., dawson, s., pinchbeck, g.l., williams, n.j., radford, a.d. & jones, p.h. (2019). pharmaceutical prescription in canine acute diarrhoea: a longitudinal electronic health record analysis of first opinion veterinary practices. frontiers in veterinary science. 6(218). doi: https://doi.org/10.3389/fvets.2019.00218 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in horses with secondary sinusitis caused by dental disease, is computed tomography more accurate than radiography for the identification of apical dental pathology? a knowledge summary by rebecca gill-parsons bvmedsci 1 emma shipman bvetmed dipacvim cert va mrcvs 1 kirstie pickles bvms msc phd certeim dipeceim fhea mrcvs 1* 1school of veterinary medicine and science, university of nottingham, sutton bonington, leicestershire, le12 5rd *corresponding author (kirstie.pickles@nottingham.ac.uk) vol 7, issue 2 (2022) published: 07 apr 2022 reviewed by: nicole du toit (bvsc certep msc phd dipevdc dipavdc mrcvs), david ramey (dvm) and neil townsend (bvsc bsc certes[soft tissue] msc dipecvs dipevdc mrcvs) next review date: 13 nov 2023 doi: 10.18849/ve.v7i2.491 pico question in adult horses with secondary sinusitis caused by dental disease, is computed tomography more accurate than radiography for the identification of apical dental pathology?   clinical bottom line category of research question diagnosis the number and type of study designs reviewed the literature search identified four papers that were critically reviewed. the publications consist of two retrospective case controlled studies, one clinical study and one descriptive study strength of evidence weak outcomes reported four studies reported the sensitivity of computed tomography (ct) for the diagnosis of apical dental pathology in horses presented for evaluation of clinical signs of sinus disease with histopathological evidence of apical dental pathology. all studies reported the radiographic changes present in these horses or used absence of definitive radiographic changes consistent with apical dental disease as a reason to undertake further ct evaluation. all four papers found that ct identified teeth with apical pathology that radiography had not conclusion ct is more accurate than radiography for the diagnosis of equine maxillary apical dental pathology; however, clear guidelines on the ct changes associated with apical dental pathology are required. loss of the lamina dura, infundibular changes or pulpal gas as singular findings on ct imaging can be seen in teeth with no underlying histopathological evidence of apical disease, and in maxillary teeth imaged in horses without clinical signs of maxillary cheek tooth pathology   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. the evidence the literature search identified four studies where computed tomography (ct) and radiographic findings of maxillary apical dental pathology were compared. two observational studies reported the accuracy of radiography and ct for diagnosis of maxillary cheek tooth apical infection confirmed by gross and histopathological findings (liuti et al., 2018a; and 2018b). two retrospective case controlled studies investigated radiographic and computed tomographic changes present in maxillary cheek teeth from horses with clinical signs consistent with sinusitis (bühler et al. 2014; and henninger et al. 2003). bühler et al. (2014) reported malodourous nasal discharge, facial swelling or sinus tract formation as clinical evidence of sinusitis in all studies where clinical cases were recruited. henninger et al. (2003) reported clinical signs of 2 weeks to 7 years duration. bühler et al. (2014) and liuti et al. (2018a) did not record the duration of clinical signs. the number of adult horses within these studies ranged from 18–49. liuti et al. (2018a) evaluated radiographic and ct findings of 29 horses with clinical signs of sinusitis. ct findings consistent with apical dental pathology included heterogeneity of the pulp, changes to pulpar volume, gas within or widening of the periapical periodontium, root clubbing and fragmentation and periapical alveolar bone lysis. radiographic changes consistent with apical dental pathology included periapical sclerosis and apical clubbing. histopathological evaluation was performed on the 32 teeth removed from these horses based on the ct findings. 32/32 (100%) of teeth with ct findings consistent with apical dental pathology were found to have histopathological evidence of apical dental pathology and one histologically healthy tooth having abnormal ct findings. in contrast, radiographic abnormalities were detected in only 17/32 (53%) teeth. when a similar study design was used to evaluate cheek teeth from a cadaver population with unknown clinical histories, liuti et al. (2018b) found 27/28 teeth (96%) with histologically identified apical pathology had ct changes consistent with apical disease, whereas radiography identified abnormalities in 14/28 teeth (50%). henninger et al. (2003) reported 16/18 (89%) horses with clinical signs consistent with maxillary sinusitis to have ct changes consistent with apical dental pathology and only 5/18 (28%) having radiographic evidence of apical infection. a retrospective case controlled study (bühler et al., 2014) investigating the prevalence of apical dental pathology in horses with clinical evidence of sinusitis found 27/28 (96%) horses with inconclusive radiographic evaluation had ct changes of apical dental pathology. three or more of the following ct changes were considered indicative of apical dental pathology; clubbing of the tooth root, widening of the periodontal space, nondetectable lamina dura, periapical sclerosis, and changes within the pulp cavity (increased pulp horn volume, irregular margination and heterogenous density) and infundibular changes (hypoattenuating occlusal surfaces, linear hypoattenuation along the infundibular length or linear attenuation with a bulbous shape at its apical extent). an older study (henninger et al., 2003) found ct changes consistent with apical dental pathology in 16/29 (55%) horses presented for evaluation of sinusitis, with only 5/29 (17%) horses showing radiographic evidence of apical infection. the ct findings consistent with apical dental disease included infundibular hypoattenuation, apical bulging of the tooth socket, root fragmentation and hypoattenuating gas within the tooth socket. summary of the evidence liuti et al. (2018a) population: horses (age range 3–15 years) from one hospital presented with chronic unilateral nasal discharge or maxillary swelling. sample size: 32 maxillary cheek teeth from 29 horses and four control cheek teeth from a cadaver. intervention details: to compare the radiographic and ct findings with the gross and histological findings to assess the accuracy of each imaging technique. initial identification of apically infected teeth from clinical examination and oral endoscopy, followed by radiographic and ct imaging. teeth were then extracted based on the outcome of these findings. extracted teeth underwent further ct, gross pathological and histological examinations by two independent examiners. histological slides were anonymised and relabelled before examination and standard radiographic projections used. study design: observational clinical study. outcome studied: the accuracy of radiography and ct in the detection of early apical infection. main findings (relevant to pico question): radiographic apical pathology was present in 17/32 (53%) of teeth. 32/32 (100%) teeth had ct evidence of apical disease with the presence of pulpar changes in all teeth. gross pulpar abnormalities were present in the pulpar of 29/32 (91%) teeth and apical changes in 31/32 (97%) and histological pulpar changes were present in 31/32 (97%) teeth. one tooth had no detectable pulpar abnormalities, including assessment of five additional histological sections. limitations: gold standard histopathological evidence of apical dental pathology was, by study design, available from clinical cases where tooth removal was predetermined due to abnormal ct finding. histopathology results were only available from four control maxillary teeth. the clinical history from the cadaver specimens used as controls was unknown. specific radiographic features indicative of apical infections were decided upon consensus of highly indicative features rather than independent characteristics and same ct findings were agreed upon consensus by both examiners. criteria of radiographic features consistent with apical dental pathology were not specified beforehand. the conclusion that later radiographic examination would likely have shown a higher proportion with definitive radiographic changes was not evidenced in this paper as the duration of clinical signs was not analysed for association with radiographic findings. ct evidence was the sole reason for the extraction of an apparently healthy tooth (as determined by gross and histological examinations) indicating a false positive – discrepancies between ct and pathology were unclear. no control sinusitis population. poor evidence of duration of infection or clinical signs. limited to a small number of cases and predominately descriptive in nature. liuti et al. (2018b) population: 54 cadaver horse heads. sample size: 30 abnormal cheek teeth (26 maxillary and four mandibular) from 26 heads with gross and imaging pathological abnormalities; remaining 28 heads had no abnormalities on gross pathology and imaging and will not be commented on further in this knowledge summary. intervention details: to compare the ct and radiographic findings with the histopathological findings. images were evaluated by two observers with consensus obtained. radiographic changes included root clubbing and alveolar bone sclerosis. ct changes included gas within pulps, irregular pulp horn margins, increased pulpar volume, widened periodontal space, gas within periapical tissues, root clubbing, root fragmentation, periapical halo, periapical bone changes including peripheral sclerosis, alveolar bone thickening, resorption / lysis more axially, and infundibular changes. study design: observational descriptive study. outcome studied: the accuracy of ct and radiography in detecting apical infection of the cheek teeth by comparing these imaging modalities and histopathological findings. main findings (relevant to pico question): gross pulpar abnormalities present in 23/28 (82%) teeth and gross periodontal thickening or swelling of periapical region present in 25/28 (89%) extracted teeth. of 28 teeth that were confirmed by histology to have apical infection, 23 had gross pulpar abnormalities, 26 had apical calcified tissue changes, and 26 had periapical periodontal changes. in all 16 teeth with severe histological alveolar bone changes, perialveolar bone changes were visible on ct, but only four of these 16 cases had identifiable periapical alveolar changes radiographically. ct imaging showed convincing evidence of apical infection on ct imaging in 27/28 teeth (96%). radiographic abnormalities were found in 14/28 (50%) apically infected teeth. limitations: one tooth with pulpar discolouration and histological evidence of apical infection did not have any ct imaging evidence of apical disease (false negative). no previous history of the horses. images were evaluated by two observers but this was not undertaken independently. teeth were initially screened as apically infected by imaging and / or clinical examination before being removed for histopathological evaluation. bühler et al. (2014) population: horses (age range 4–20 years) scanned with ct at one clinic between february 2008 and june 2010. sample size: 1,764 roots and 1,176 infundibula of 588 upper cheek teeth from 49 horses. intervention details: the 49 cases were split into two groups: group 1 (28 horses): horses with clinical signs suggesting primary apically infected maxillary cheek teeth (malodourous, purulent, or sanguineous nasal discharge, facial swelling, and sinus tract formation) but without obvious findings on oral examination and where radiographs were inconclusive. group 2 (21): horses without clinical evidence of apically infected maxillary cheek teeth (examined for unrelated reasons). ct images were observed by a board-certified radiologist and the first author. data sheets evaluating the presence or absence of ct findings were compiled for each cheek tooth, infundibulum, and root in all cases. study design: retrospective case control study. outcome studied: the prevalence and relationship of ct findings in maxillary cheek teeth in horses with and without clinical evidence of apical infection. apical infection was diagnosed if three or more of the ct findings from: changes of the pulp cavity, clubbing of the root, widened periodontal space, nondetectable lamina dura, periapical sclerosis – these features were noted and then subjectively scored as mild, moderate or severe. main findings (relevant to pico question): overall, all horses had ct changes in at least one cheek tooth root – 1,499/1,764 (85%) of all investigated roots had various degrees of ct abnormalities. nondetectable lamina dura was present as the most common single ct abnormality in 1,338 of 1,764 roots imaged. 783/1,338 (59%) roots with no detectable lamina dura were from horses with clinical evidence of apical infection and 555/1,338 (42%) roots from horses with no evidence of apical infection. ct changes more prevalent in horses in group 1: 14 roots had pulpitis in group 1 whereas only one in group 2, clubbing of the root was only present in group 1 (in 29 roots), periapical sclerosis was present in 114 roots in group 1 and six in group 2, widened periodontal space was present in 42 roots in group 1 and one in group 2, and infundibular changes found in 303 infundibula, 182 from group 1. in group 1, mild, moderate, and severe apical infection was diagnosed in 35, 19 and 14 roots and in 15, eight and 10 maxillary cheek teeth, respectively. 27/28 horses with clinical signs of maxillary tooth root pathology were confirmed by ct to have apical infection. one horse from group 2 had ct changes consistent with apical tooth root disease infection but no associated clinical signs. radiographic changes consistent with apical dental pathology were not discussed. limitations: the radiographic features that were examined initially were not specified as to what placed the horses in group 1. ct was only undertaken in horses with inconclusive changes of apical dental pathology on radiographic evaluation. henninger et al. (2003) population: horses (ranging from 1.8–18.1 years) referred between 1998 and 2000. sample size: 18 horses. intervention details: referred for advanced diagnostic imaging and presenting with any of the following clinical signs: unilateral or bilateral nasal discharge, purulent conjunctivitis, facial swelling and / or epiphora. radiography of the head was performed before ct. abnormal ct findings: cavity abnormal findings of hypoattenuation. grade i: loss of enamel/dentine stripes, gas within the infundibulum. grade ii: gas within the dentine / enamel border or within the pulp. grade iii: fractured tooth. root infection – borderline: apical bulging of the socket more than 10 mm off the enamel walls or irregularity. mild: total hypoattenuating spot (gas) within the socket or apical fragmented root. moderate: gas and fragmented root at the same time, increased bulging of 1–3 cm. severe: apical soft tissue changes >3 cm as before and secondary sinusitis, occluded nasomaxillary aperture, hyperattenuation representing a mass. study design: retrospective observational case control study. outcome studied: the usefulness of ct to evaluate dental lesions occurring with nasal and / or paranasal disease. ct changes divided into cavity and root for abnormal findings which were divided into mild, moderate, and severe. main findings (relevant to pico question): 54 maxillary cheek teeth were recognised as diseased between the 18 horses, the most common tooth being 109. the entire rostral maxillary sinus was filled with material of soft tissue opacity in 17/18 horses and ct changes of the nasal cavity were identified in 16/18 horses with nasal discharge. apical infection was identified as the underlying cause of sinusitis in 15 horses. 12/18 horses had changes in the cavity and 16/18 horses had root changes on ct evaluation but only five horses were identified as having apical pathology on radiographic imaging. limitations: older study with less clearly defined ct criteria for the presence of apical dental pathology. all horses were radiographed first, and no comparison is made between radiography and ct yet the study concludes that ct allows a more confident diagnosis over radiography. criteria for radiographic apical changes were not defined nor was it specified if the same teeth were affected radiographically and with ct. only 18 horses. no discussion of whether images were reviewed by one or multiple persons. appraisal, application and reflection no randomised control studies exist within the literature directly comparing ct to radiography in the diagnosis of apical dental pathology in adult horses. three of the four papers in which radiography and ct were undertaken presented data from clinical cases presenting to veterinary hospitals and it is therefore understandable that ct was undertaken in some cases, where radiography was inconclusive and histopathological evaluation of the tooth roots could only be undertaken on teeth deemed to have apical pathology by radiographic or ct evaluation necessitating removal on patient welfare grounds. all four papers comparing ct and radiographic evaluation of apical dental pathology either in horses with clinical signs consistent with sinusitis or in cadaver specimens found ct to identify lesions in horses without radiographic changes of apical dental disease. in all studies, the sensitivity of ct to detect apical dental pathology was greater than the reported sensitivities for radiography alone. there is a wide range of sensitivities reported for radiographic evaluation of apical dental pathology which was likely attributed to differences in radiographic technique and variability in the criteria on which a diagnosis of apical disease was made, as discussed within the literature. radiographic changes consistent with apical dental pathology were listed as apical blunting, periapical halo and crown fracture (liuti et al., 2018a) root blunting and alveolar bone sclerosis (liuti et al., 2018b). other studies that do not directly compare ct to radiography have further stated radiographic findings that indicate criteria for dental pathology as sclerosis, cementosis, clubbing of the tooth root, interruption of the lamina dura, loss of dental density, lucency surrounding the apex of the tooth and fracture lines (weller et al., 2001); and periapical halo formation, periapical sclerosis, clubbing of the root, loss of lamina dura and widening of the periodontal ligament (townsend et al., 2011). the criteria used to make a radiographic diagnosis of apical dental pathology was made was not recorded in two papers (bühler et al., 2014 and henninger et al., 2003). some variations existed in reported ct changes associated with apical dental pathology. changes were generally considered infundibular, pulpal or associated with the alveolar bone. specific ct changes consistent with apical dental pathology were listed as increased pulpal volume, irregular pulp horn margins, periapical gas, widening of the periodontal space, root clubbing, root fragmentation, periapical halo, periapical alveolar bone lysis, dental fracture, and infundibular changes and with the addition of alveolar bone thickening and pulpal gas (liuti 2018a; and 2018b). infundibular gas, pulpal gas, tooth fracture, gas within the socket, apical bulging of the socket were reported (henninger et al., 2003) and increased pulpar volume, irregular pulp horn margins and heterogeneous density, root clubbing, widening of the periodontal space >1 mm, nondetectable lamina dura, periapical sclerosis and infundibular changes (hypoattenuating occlusal surface, linear hypoattenuation along the infundibular length or linear hypoattenuation with a bulbous shape at its apical extent, and tooth fractures (bühler et al,. 2014). bühler et al. (2014) found individual ct abnormalities other than clubbing of the root in dental apices of horses without clinical signs of sinusitis and loss of lamina dura in 1,338 of 1,764 (76%) of tooth roots examined with 555 roots being from the 21 horses without clinical signs of dental disease. likewise, infundibular changes as a solitary ct feature were not significantly associated with other ct signs of apical infection. liuti et al. (2018a) also found one tooth containing gas pockets in the apical aspect of one pulp and adjacent periodontal space where no pathological changes were found following its extraction. single ct changes may therefore be evident in teeth from horses without clinical evidence of dental pathology and in teeth with no histopathological abnormalities and therefore loss of or nondetectable lamina and infundibular changes may be a poor indicator of apical infection as a single pathological change and may need the presence of other changes to be indicative of pathology. the literature supports the use of ct imaging in the diagnosis of apical dental pathology in horses with signs of sinusitis as being more sensitive than radiography. in all four papers comparing ct and radiographic evaluation of apical dental pathology, ct identified lesions in horses without conclusive radiographic evidence of pathological changes consistent with apical dental disease. consequently, all four papers reported a higher sensitivity of ct to detect pathology compared with radiography. however, care should be taken in interpreting individual ct changes, particularly loss of lamina dura, infundibular changes, and gas pockets within the pulp, as these individual changes have been reported in teeth from horses without signs of dental disease and without histopathological evidence of apical pathology. therefore it is recommended that additional pathological changes should be identified to meet the criteria of dental apical pathology. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform 1910–2021 pubmed accessed on ncbi platform 1910–2021 search strategy: cab abstracts: (horse* or equi* or equus or pon*).mp. or exp horses/ or exp equus/ [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (sinus* or paranasal or para-nasal or maxillary).mp. or exp sinuses/ or exp sinusitis/ [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (ct or computed tomography).mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (radiograph* or xray* or x-ray* or radiol*).mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] 1 and 2 and (3 or 4)   pubmed:  horse or horses or equine or equines or equus sinus or sinusitis or paranasal or para-nasal or maxillary or teeth ct or computed tomography radiography or xray or x-ray or radiology #1 and #2 and (#3 or #4) dates searches performed: 13 nov 2021 exclusion / inclusion criteria exclusion: non-relevant to the pico. non-english language. study design was single case report. non-empirical research. duplicates. inclusion: relevant to pico. observational studies. articles published in the english language. retrospective studies. search outcome database number of results excluded – non-english language excluded – not relevant to pico excluded – single case report total relevant papers cab abstracts 389 76 308 1 4 pubmed 369 15 350 0 4 total relevant papers when duplicates removed 4 conflict of interest the authors declare no conflicts of interest. the authors acknowledge the contribution of kirstie pickles and emma shipman in the preparation of this manuscript. references bühler, m., fürst, a., lewis, f. i., kummer, m. & ohlerth s. (2014). computed tomographic features of apical infection of equine maxillary cheek teeth: a retrospective study of 49 horses. equine veterinary journal. 46(4), 468–473. doi: http://dx.doi.org/10.1111/evj.12174 henninger, w., frame, e. m., willman, m., simhofer, h., malleczek, d., kneissl, s. m. & mayrhofer, e. (2003). ct features of alveolitis and sinusitis in horses. veterinary radiology & ultrasound. 44(3), 269–276. doi: https://doi.org/10.1111/j.1740-8261.2003.tb00454.x liuti, t., smith, s. & dixon, p. m. (2018a). a comparison of computed tomographic, radiographic, gross and histological, dental, and alveolar findings in 30 abnormal cheek teeth from equine cadavers. frontiers in veterinary science. 4, 236. doi: https://doi.org/10.3389/fvets.2017.00236 liuti, t., smith, s. & dixon, p. m. (2018b). radiographic, computed tomographic, gross pathological and histological findings with suspected apical infection in 32 equine maxillary cheek teeth (2012–2015). equine veterinary journal. 50(1), 41–47. doi: https://doi.org/10.1111/evj.12729 townsend, n. b., hawkes, c. s., rex, r., boden, l. a. & barakzai, s. z. (2011). investigation of the sensitivity and specificity of radiological signs for diagnosis of periapical infection of equine cheek teeth. equine veterinary journal. 43(2), 170–178. doi: https://doi.org/10.1111/j.2042-3306.2010.00148.x weller, r., livesey, l., maierl, j., nuss, k., bowen, i. m., cauvin, e. r. j., weaver, m., schumacher, j. & may, s. a. (2001). comparison of radiography and scintigraphy in the diagnosis of dental disorders in the horse. equine veterinary journal.  33(1), 49–58. doi: https://doi.org/10.2746/042516401776767458 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. does occurrence of ventricular arrhythmia reduce the survival rate in dogs with gastric dilatation volvulus (gdv)? a knowledge summary by madeleine thomson mrcvs 1* 1university of surrey school of veterinary medicine, vsm building, university of surrey, daphne jackson road, guildford gu2 7al *corresponding author (madeleine.thomson@ntlworld.com) vol 6, issue 4 (2021) published: 25 nov 2021 reviewed by: sam double (bsc(hons) vts dipavn(medical) rvn certed) and dave leicester (bvetmed pgcertsaecc mrcvs) next review date: 30 may 2023 doi: 10.18849/ve.v6i4.476 pico question does occurrence of ventricular arrhythmia reduce the survival rate in dogs with gastric dilatation volvulus (gdv)?   clinical bottom line category of research question prognosis the number and type of study designs reviewed the number and type of study designs that were critically appraised were three retrospective observational case-control studies (brourman et al., 1996; green et al., 2012; and mackenzie et al., 2010) and one prospective, observational study (aona et al., 2017) strength of evidence critical evaluation and appraisal of the papers that met the inclusion criteria provided only weak evidence to support the clinical question. this is due to the lack of recent (within the last 5 years) and specific (do the presence of cardiac arrythmias affect mortality of dogs with gdv) studies conducted on the subject. additionally, more in-depth statistical analysis (e.g. p values and confidence intervals (ci)) may also help to determine the strength of association between the presence of ventricular arrythmia and survival rates. however, there is room for further research to continue investigating the proposed hypothesis. several of the evaluated studies were carried out more than 10 years before this knowledge summary was written, meaning that the knowledge and technology at the time may not be relevant to clinical practice today outcomes reported green et al. (2012) concluded that ‘cardiac arrhythmia was not a prognostic indicator’ for gdv. of the two papers (mackenzie et al., 2010; and brourman et al., 1996) that found a significant association between the development of cardiac arrhythmias (specifically, those of ventricular origin) and an increase in the mortality rates of dogs with gdv, one (brourman et al., 1996) noted that a greater number of dogs that died prior to discharge were diagnosed with preoperative ventricular tachycardia, while the other (mackenzie et al., 2010) found that the greatest mortality rate was among those dogs that developed postoperative ventricular tachycardia. the final study, aona et al. (2017), was the only paper to categorise and grade the ventricular arrhythmias using previously published scales. it was discovered that increased levels of ctn1 (cardiac troponin 1) made a dog more likely to develop a higher grade of arrhythmia, however, no association was found between the type or grade of arrhythmia and patient mortality conclusion taking into account the strength of evidence and the outcomes presented by the appraised studies the following conclusion has been drawn; although there is some evidence to suggest that ventricular tachycardia may be associated with an increase in mortality rates in patients with gdv, further research is required in order to make any further conclusions that may definitively answer the clinical question   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a 7 year old male neutered german shepard presents during emergency ‘out of hours’ practice with gastric dilation volvulus (gdv). while hospitalised he is diagnosed, via electrocardiogram (ecg), with a ventricular arrhythmia secondary to the presenting complaint. will this affect the expected prognosis and survival rate for this animal? subsequently, does it affect the prognosis significantly enough that you would not recommend further treatment to the owner? the evidence from the studies appraised, there is some evidence to suggest that the development of ventricular arrhythmia may be associated with an increase in patient mortality. however, in general, the sample sizes were small and may not be easily extrapolated to a more general population. in addition, the literature reviewed varied significantly in both study objectives and methods. the majority of the reviewed literature was of high academic and clinical quality, however, one paper in particular (mackenzie et al., 2010) contained poorly displayed information and confusing methodology. based solely on the acquired evidence from these four papers, there is insufficient evidence that the presence of ventricular arrhythmia alone may lead to decreased survival rates in dogs with gdv. in conclusion, although there is some evidence to suggest that ventricular arrhythmia and, in particular, ventricular tachycardia, may be associated with increased mortality rates in patients with gdv. further research is required in order to make any further conclusions that may definitively answer the clinical question. summary of the evidence green et al. (2012) population: dogs that were presented and diagnosed with gdv at a small animal university teaching hospital. cases were excluded if standard, preoperative right lateral thoracic radiographs had not been obtained. sample size: 101 dogs. intervention details: for included cases, the following information was obtained from clinic medical records; breed, age, sex, time of presentation to the clinic, respiratory status at presentation, plasma lactate preand post-intravenous fluid therapy (ivft) administration, the presence of preoperative cardiac arrhythmias and the method of decompression used. all radiographs were examined by a board certified radiologist and the subsequent associated reports were considered. these radiographic abnormalities were noted to be absent/present: esophageal dilation, micro-cardia, small cranial vena cava, neoplasia (diffuse metastatic disease/primary lung nodule/extra thoracic), aspiration pneumonia, pulmonary bullae, sternal lymphadenopathy, cardiomegaly, and pulmonary oedema. study design: retrospective, single centre observational study. outcome studied: factors influencing survival to discharge: concurrent radiographic abnormalities; signalment; physiological parameters. main findings (relevant to pico question): in 6/101 (6%) of cases, radiographs were taken due to suspicion of cardiac disease; based on clinical exam findings, auscultation or a previous history of cardiac pathology. upon arrival, 6/101 (6%) of the included dogs had a cardiac arrhythmia. 85/101 (84%) of dogs survived to discharge from the hospital. 16/101 (16%) of dogs did not survive to discharge from the hospital. of these 16/101 dogs (16%): 12/16 (75%) of the dogs were euthanised prior to surgery due to poor prognosis. prognosis was presumably assessed using results of ecg/clinical exam but this was not made clear; 2/16 (12.5%) of the dogs were euthanised prior to surgery due to owner financial constraints on treatment; 2/16 (12.5%) of the dogs died during the postoperative recovery period. 4/85 (5%) of the surviving dogs presented with preoperative ventricular arrhythmia. 2/16 (13%) of the dogs that did not survive presented with preoperative ventricular arrhythmia. presence or absence of preoperative ventricular arrhythmia was not decided to be a major contributing factor in patient postoperative survival rates. limitations: included cases were only taken from a single veterinary hospital so may not be representative of other clinical centres. it was not stated how the presence of ventricular arrhythmia was definitively diagnosed or if all dogs were fully examined for cardiac arrhythmias: it was not stated if any of the dogs underwent ecg, leaving it unclear how the diagnosis of cardiac arrhythmia was reached. it was not stated if the dogs diagnosed with cardiac arrhythmia were the same dogs that also had suspected cardiac disease prior to radiography: these suspicions may have created bias in which only dogs with suspected cardiac disease were fully investigated and led to undiagnosed cardiac arrhythmias in the other dogs. it was not made clear if the two dogs (of the 16 dogs that did not survive to discharge from hospital) diagnosed with ventricular arrhythmia died due to euthanasia or succumbed to their pathologies postoperatively: if these dogs were euthanised due to poor prognosis and subsequently excluded from the results, it could mean that the effect of ventricular arrhythmia on post-operative mortality is higher than recorded in the results of the study. aona et al. (2017) population: any dogs presented to the university hospital with gdv were included. study duration lasted from may 2011 to october 2012. sample size: 22 dogs. intervention details: diagnosis was made based on clinical exam/history, signalment, presenting signs, right lateral radiograph. confirmation was made at point of surgery. exclusion criteria included euthanasia or death prior to surgery. blood samples were taken from every dog within 30 minutes of presentation at the hospital: further samples were taken subsequently every 12 hours until hour 60, or the death of the animal; samples were analysed for ctn1, plasma lactate, and n-terminal pro b-type natriuretic peptide (nt‐probnp) levels. dogs were monitored using ecg upon presentation and throughout their entire surgery. ventricular premature complexes (vpcs) were measured according to a previously published scale that was cited. 6 to 18 hours postoperatively, each dog underwent an ecg performed by a board certified cardiologist. study design: prospective observational study. outcome studied: study outcome was measured as whether the dogs survived to discharge, and if not, whether they died or were euthanised. main findings (relevant to pico question): 4/22 (18%) of dogs were treated with continuous rate infusion (cri) intravenous lidocaine during hospitalization. upon presentation, 4/22 (18%) of dogs had ventricular arrhythmias (it was not stated if these were the same dogs given cri lidocaine, but one would suspect). over the course of their hospital stay, 15/22 (68%) of the dogs developed ventricular arrhythmias. the ventricular arrhythmias identified were categorised as follows: single ventricular premature complex (vpc) in 9/15 (60%) dogs (grade 1); r-on-t phenomenon/ventricular tachycardia in 6/15 (40%) dogs (grade 4). the remaining 7/22 dogs did not have any ventricular arrhythmias during their hospitalisation (grade 0). those dogs with increased levels of ctn1 were found to be more likely to develop grade 4 arrhythmias (highest recorded value during hospitalization). 20/22 (91%) dogs survived to discharge. of the two dogs that did not survive to discharge: one dog was euthanised due to poor prognosis due to the development of septic peritonitis. one dog died from septic peritonitis. arrhythmia grade was not found to be significantly associated with survival. limitations: all cases were presented and treated at a single teaching hospital and therefore may not be representative of dogs in other areas. while the presence of ventricular arrhythmia was noted and categorised, this was not the main goal of the study and their significance (in relation to patient mortality) may have been understated. it was not stated if any but the four dogs that presented with ventricular arrhythmias were treated with cri lidocaine. 2/22 (9%) of the dogs were treated by their primary veterinarian (trocarisation and lactated ringer’s solution bolus), prior to presentation at the hospital, which may have improved their chance of survival irrespective of ventricular arrhythmia. mackenzie et al. (2010) population: dogs diagnosed with gdv between 2000–2004 that were anaesthetised for surgery. study centre not stated. sample size: 306 dogs. intervention details: the medical records of all dogs were assessed for the following factors: signalment (age/breed/sex), time to presentation, time from presentation to surgery, presence of pre and postoperative cardiac arrhythmias, anesthetic/surgical duration and incidence of gastric/splenic injury. a diagnosis of gdv was made based on preoperative, right sided lateral radiographs. biochemistry/hematology, blood count results and any treatments administered preoperatively were not evaluated as part of this study. the presence of cardiac arrhythmias was noted following abnormalities in the patients’ pulse, ecg or both. similar, but not identical, anesthetic protocol was used in all dogs. the overall mortality rate of the study was defined as the number of dogs that died or were euthanised intra or postoperatively, compared to the total number of dogs that were anesthetised. the postoperative mortality rate was defined as the number of dogs that died or were euthanised between the end of anesthesia and discharge from hospital, of all dogs that survived anesthesia. study design: retrospective observational study. outcome studied: do these conditions/factors/procedures affect the overall and postoperative mortality rates: cardiac arrhythmias; splenectomy; partial gastrectomy; time to presentation; anaesthetic time; surgical time. main findings (relevant to pico question): overall mortality rate was 30/306 (9.8%) of the 12/30 (40%) dogs that died intraoperatively: 4/12 (33%) died naturally 8/12 (66%) were euthanised under anesthesia due to poor prognosis. postoperative mortality rate was 18/294 (6.1%). all cardiac arrhythmias recorded during the study were of ventricular origin. 16/147 (11%) of the dogs were diagnosed with preoperative cardiac arrhythmias. of these: 12/16 were intermittent ventricular arrhythmias (iva) 4/16 were ventricular tachycardias. 133/159 (83.6%) of dogs were diagnosed with postoperative cardiac arrhythmias. of these: 105/133 were iva; 28/133 were ventricular tachycardias. 5/133 (3.8%) of the dogs within this population died dogs with preoperative cardiac arrhythmias were associated with a higher overall mortality rate than those without preoperative cardiac arrhythmias. dogs with postoperative ventricular tachycardia were associated with a higher overall mortality rate compared to those without postoperative ventricular tachycardia. limitations: it was not explicitly stated where the medical records were collected from. blood test results (blood count/biochemistry/haematology) were not evaluated as part of the study, and it is therefore unknown if there were any concurrent trends among the results that could have influenced the results of the study. the results were poorly presented, with information missing and it is not clear where some numerical values came from. incomplete medical records and the retrospective nature of the study means that not all aspects of the patients’ treatment could be evaluated. brourman et al. (1996) population: dogs that underwent surgical correction of suspected gdv at two veterinary centres (one university hospital and one private practice) between 1988 and 1993. sample size: 137 dogs. intervention details: surgical correction predominantly involved repositioning and decompression of the stomach. some animals required further surgical procedures such as gastric resection or splenectomies. these factors were evaluated to determine any possible association with patient mortality. all dogs were monitored from admission to discharge, using ecg’s and comprehensive blood analysis (hematology/biochemistry/wbc counts). the presence of cardiac arrhythmia was determined/confirmed by ecg following clinical exam. dogs that died at any point during hospitalisation were included in mortality calculations. fisher’s exact test (handbook of biological statistics, 2014) was used to determine the strength of association between significant factors and mortality. where p < 0.05, there was considered to be a considerable association. study design: retrospective, multi-centre observational study. outcome studied: the association between identified risk factors and mortality in dogs with gdv. differences in treatments between two clinical practices and the effects on patient mortality. main findings (relevant to pico question): 24/137 (18%) dogs died or euthanised due to poor prognosis during hospitalisation: 18/24 dogs died postoperatively; 5/24 dogs were euthanised during surgery; 1/24 was euthanised postoperatively. 113/137 (82%) of cases seen survived to discharge. no blood biochemistry or hematology parameters were found to have significant associations with mortality. 92/137 (67%) of the total cases were found to have developed a cardiac arrhythmia during hospitalisation. 16/92 of these were preoperative, 28/92 occurred intraoperatively and 48/92 were postoperative. of the 16/92 that occurred preoperatively: 6/16 (38%) of those died during hospitalisation; 121/137 (88%) of the dogs did not present with preoperative cardiac arrythmias; comparatively, 18/121 (15%) dogs without preoperative arrhythmias died during hospitalisation. of the 28/92 that occurred intraoperatively, seven dogs died. of the 48/92 that occurred postoperatively, six dogs died. overall mortality for dogs with cardiac arrhythmias was found to be 22%. mortality rates between the two centres were not found to be significantly different. the use of antiarrhythmics was not associated with a significant reduction in mortality at either clinic. limitations: cardiac arrhythmias were not investigated further postdiagnosis, or categorised according to origin. factors such as age, clinical history and prior cardiac disease were not considered during the study. although these was found to be a significant association between dogs that developed preoperative arrhythmias and increased mortality; certain dogs may be predisposed to this condition, as well as more vulnerable to mortality should they develop an arrhythmia. it was not stated how the diagnosis of gdv was made. significant advances in medical technology have been made since this paper was published and as such, the results may not be as relevant to clinical practice today as they were at the time of the study. appraisal, application and reflection relevant to this knowledge summary, four papers were found which investigated the effects of ventricular arrhythmias on the mortality rates of dogs with gdv. of these, three were retrospective, observational, case control studies (brourman et al., 1996; green et al., 2012; and mackenzie et al., 2010) and one was a prospective observational study (aona et al., 2017). the first retrospective observational study (green et al. 2012) reviewed the presence of radiographic abnormalities and their effects on mortality in dogs with gdv. logistic regression analysis was used to evaluate the risk that presenting clinical signs (including presence of ventricular arrythmia) may have on chance of survival to discharge. only 2/16 (13%) of the dogs that died or were euthanised during their hospitalisation were diagnosed with ventricular arrhythmias and it was concluded that the presence of ventricular arrhythmia was not strongly associated with increased patient mortality rates. neither p value or confidence intervals (ci) were stated for ventricular arrhythmia, and it was unknown if they were simply not calculated or that they were not found to be of statistical relevance (e.g. p < 0.05 or ci > 95%). calculating these values would give a better indication of the strength of evidence that the presence of ventricular arrhythmia may affect survival to discharge. ventricular tachycardia can be caused by both extra cardiac pathologies as well as primary heart disease, which can often be seen on thoracic radiographs (rishniw, 2020). in the paper by green et al. (2012), 6/101 (6%) of the cases included in the study were radiographed upon admission due to suspected cardiac disease but it was not stated what proportion, if any, of these dogs presented with or developed ventricular tachycardia during hospitalisation. there may have been bias present, where only dogs with suspected cardiac disease were fully examined for the presence of cardiac arrhythmias, meaning that other dogs may have developed arrhythmias that went undiagnosed. it was also not stated how a diagnosis of ventricular arrhythmia was made in the 6% of dogs that presented with the condition. however, the paper itself was detailed and well-presented, and the results of the study were clear and logical. mackenzie et al. (2010), a retrospective, observational study, evaluated the factors significantly affecting overall and postoperative mortality rates in dogs anaesthetised for surgery to correct gdv. the study found that preoperative cardiac arrhythmias of any origin; as well as postoperative ventricular tachycardia (not concurrently) were associated with a higher overall mortality rate among the 306 cases that were evaluated. statistical analysis was not performed on the collected data, meaning that the strength of association between ventricular arrhythmia and mortality rate was not able to be properly evaluated. furthermore, incomplete medical records and the retrospective nature of the study may mean that some aspects of the included cases could not be properly analysed. additionally, there was confusion as to the origin of some of the figures presented in the results section of the paper as well as the conclusion that was drawn with regards to the incidence of preoperative intermittent ventricular arrhythmias. it was also stated that preoperative iva’s were associated with ‘much higher mortality rates,’ but only provided a p value to support this statement, rather than the number of dogs with preoperative iva that died. the third retrospective observational study that was evaluated (brourman et al., 1996) looked at factors affecting mortality in the perioperative period of dogs admitted to either a university hospital or a private veterinary clinic with gdv. only those cases that underwent surgical correction (which predominantly involved decompression and repositioning of the stomach) were included in the study. fisher’s exact test was used to determine the strength of association between patient factors and mortality, with p < 0.05 indicating that a significant association existed. of the included cases, 92/137 (67%) were found to have developed a cardiac arrhythmia during their hospitalisation; of which 20/92 (22%) died during the perioperative period. the mortality rate for those dogs that developed preoperative cardiac arrhythmias was found to be 35/92 (38%), more than double that of the mortality rate of dogs without preoperative cardiac arrhythmias 18/121 (15%). preoperative cardiac arrhythmias were found to have a p value of greater than 0.05, indicating a considerable association with patient mortality. the results did not differ significantly between the two study centers. although it would have been a useful tool for evaluating the strength of evidence presented by this paper. confidence intervals were not calculated in this study. both hematology and biochemistry parameters were monitored for every dog involved in the study, but none were found to have any impact on patient mortality or the chances of developing cardiac arrhythmias. while all instances of cardiac arrhythmia were diagnosed through clinical exam and electrocardiography, there was no further investigation conducted into the origin or categories of arrhythmia present. additional clinical research could aid in determining which types of cardiac arrhythmia are significantly associated with increased mortality in dogs with gdv.  the remaining paper, a prospective, observational study (aona et al., 2017) was the most recent study conducted on the subject; and evaluated electrocardiography and cardiac biomarker concentrations taken from dogs admitted to a university hospital for suspected gdv from may 2011 to october 2012. dogs that died prior to surgery or were euthanised were excluded from the study. ventricular arrhythmias were identified and graded using a previously published scale of 0–4, with 0 representing the absence of vpcs (ventricular premature complexes) and 4 being ventricular tachycardia. of the 15 dogs that developed ventricular arrhythmias, nine were categorised as grade 1 and six were categorised as grade 4. a strong association was found between increased concentrations of ctn1 and the likelihood of a patient developing a grade 1 or 4 ventricular arrhythmia. the p values for dogs with grade 1 and grade 4 were found to be p < 0.001 and p = 0.002 respectively, showing a strong correlation between these data sets. however, arrhythmia grade was not found to be a significant contributing factor in patient survival following surgical correction of gdv. it is unknown whether p values were calculated to show the strength of correlation between presence of ventricular arrhythmia and mortality rate. doing so may have helped to statistically show the strength of evidence of the study in relation to the pico question. categorical data in more than two categories (arrhythmia grade) was compared using both chi-squared and friedman tests. biomarker concentrations were classed as continuous variables and compared using pearson’s and spearman’s rank correlations. while the design of the study was well laid out and thorough, the sample size was not particularly large, and as such may not have provided results that were as accurate as they could have been. additionally, it was not stated whether the presence of ventricular arrhythmia alone was considered a major factor in overall patient mortality and survival post discharge. large breed, deep-chested dogs have been found to be statistically more likely to develop gdv and indeed, in the papers where breed was recorded, it was these dogs that were overrepresented. it should be noted that smaller dogs may still develop gdv, although not with the same frequency (pdsa, 2020). in conclusion, while some of the evaluated papers provided evidence that may suggest ventricular tachycardia has an association with increased patient mortality in dogs with gdv, there are several weaknesses in the methods and results that prevent conclusive assumptions from being made. primarily, the cases included in the appraised studies, with the exception of brourman et al. (1996), were collected from a single hospital. for the conclusion of this knowledge summary to be applicable to small animal general practice in the uk, it would be preferable that this be drawn from the largest population and geographical area possible. all but one of the papers (mackenzie et al., 2010) used 137 dogs or fewer, with only 22 dogs being included in the study conducted by aona et al. (2017). as such, any confounding factors present are more likely to skew the results obtained by the study, and it is significantly more difficult to extrapolate to the general population on which the outcome of the study was to be applied. it could also be assumed, as a general rule, that veterinary university hospitals are better equipped than most small animal clinics, meaning that the dogs may be more likely to survive to discharge at these hospitals, irrespective of their cardiac status. there is some evidence to suggest that the presence of preoperative ventricular arrhythmias may be associated with reduced survival rate in dogs presented for gdv, but further research on the subject is required to definitively prove this hypothesis. a conclusive answer to this pico question could allow clinicians in practice to better predict survival rates for patients and provide more accurate information to owners regarding the chances of success for continued treatment of their animal. further research on the subject may include larger, multi-centre observational studies with a focus on diagnosing and monitoring cardiac arrythmias in dogs diagnosed with gdv. a larger number of cases included would allow for more accurate and reliable results, while a multi-center study would be more reflective of the wider population, rather than just that of a single centre study. further, in-depth statistical analysis may also be of use in determining strength of correlation between ventricular arrhythmias and mortality rates in dogs with gdv. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform 1973–2021 pubmed accessed via ncbi (1982–2021) search strategy: cab abstracts: (canine or dog or dogs or canis or canines).mp. or exp dogs/ or exp canis/ [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (gastric dilation volvulus* or gdv* or bloat* or gastric torsion* or stomach volvulus*).mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (ventricular arrhythmia* or va* or cardiac arrhythmia* or ventricular fibrillation* or ventricular dysrhythmia* or cardiac dysrhythmia* or cardiac fibrillation* or cardiac arrhythmias* or cardiac dysrhythmias*) .mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (survival or survival rate or survival rates or mortality or mortality rates).mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] pubmed: (canine or dog or dogs or canis or canines) and (gastric dilation volvulus or gdv or bloat or gastric torsion or stomach volvulus) and (ventricular arrhythmia or va or cardiac arrhythmia or ventricular fibrillation or ventricular dysrhythmia or cardiac dysrhythmia or cardiac fibrillation or cardiac arrhythmias or cardiac dysrhythmias) and (survival or survival rate or survival rates or mortality or mortality rates) dates searches performed: 30 may 2021 exclusion / inclusion criteria the main aim was to ensure that the literature used in the knowledge summary was as relevant to the pico question as possible, and that the results would be applicable to the wider population in small animal general practice. since the pico question was specific to dogs, any paper that studied non-canine patients was excluded. differences in surgical technique used was not considered when reviewing the literature for this knowledge summary as it is not within the scope of, or relevant to, the pico question. exclusion: non-canine patients single case reports duplicate non-observational studies full text not available inclusion: canine patients peer reviewed publication english language reporting the survival rates of dogs with gdv with or without ventricular arrhythmia in vivo study search outcome database number of results excluded – non-canine patients excluded – duplicate excluded – non-gdv/cardiac arrhythmia excluded – non-observational studies excluded – full text not available excluded – paper available in english total relevant papers cab abstracts 24 0 4 5 6 1 4 4 pubmed 13 0 2 1 5 1 0 4 total relevant papers 4 conflict of interest the author declares no conflicts of interest. references aona, b.d., rush, j.e., rozanski, e.a., cunningham, s.m., sharp, c.r. & freeman, l.m. (2017). evaluation of echocardiography and cardiac biomarker concentrations in dogs with gastric dilatation volvulus. journal of veterinary emergency and critical care. 27(6), 631–637. doi: https://doi.org/10.1111/vec.12667 brourman, j.d., schertel, e.r., allen, d.a., birchard, s.j. & dehoff, w.d. (1996). factors associated with perioperative mortality in dogs with surgically managed gastric dilatation-volvulus: 137 cases (1988–1993). journal of the american veterinary medical association. available at: https://pubmed.ncbi.nlm.nih.gov/8675474/ [accessed 11 dec 2020]. green, j.l., cimino brown, d. & agnello, k.a. (2012). preoperative thoracic radiographic findings in dogs presenting for gastric dilatation-volvulus (2000–2010): 101 cases. journal of veterinary emergency and critical care. 22(5), 595–600. doi: https://doi.org/10.1111/j.1476-4431.2012.00802.x mackenzie, g., barnhart, m., kennedy, s., dehoff, w. & schertel, e. (2010). a retrospective study of factors influencing survival following surgery for gastric dilatation-volvulus syndrome in 306 dogs. journal of the american animal hospital association. 46(2), 97–102. doi: https://doi.org/10.5326/0460097 pdsa. (2020). gdv (gastric dilation volvulus). [online] available at: https://www.pdsa.org.uk/taking-care-of-your-pet/pet-health-hub/conditions/gdv-gastric-dilatation-volvulus-in-dogs [accessed 1 jan 2021]. rishniw, m. (2020). ventricular tachycardia. vetlexicon canis powered by vetstream. [online] available at: https://www.vetstream.com/treat/canis/diseases/ventricular-tachycardia [accessed 29 dec 2020]. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. tail docking and castrating lambs: does the administration of local anaesthetic or meloxicam reduce the pain response exhibited? a knowledge summary by evangeline dunthorne bvmsci (hons)mrcvs 1* 1the university of surrey school of veterinary medicine, daphne jackson road, guildford, gu2 7al *corresponding author (edunthorne13@gmail.com) vol 6, issue 3 (2021) published: 30 jul 2021 reviewed by: diego moya (dvm msc phd) and iain richards (bvsc mvetsci mrcvs) next review date: 06 oct 2022 doi: 10.18849/ve.v6i3.462 pico question in healthy lambs, does the administration of local anaesthetic reduce the pain response after castration and tail docking compared to the administration of meloxicam?   clinical bottom line category of research question treatment the number and type of study designs reviewed three prospective randomised clinical trials (rct) and one clinical trial without stated randomisation were critically reviewed strength of evidence moderate to strong evidence in terms of their experimental design due to having three rtcs which are all relatively recent research. however, their implementation is moderate to weak as they fail to prove the hypothesis outcomes reported in all four studies there was improvement in the pain related behaviours post administration of anaesthesia or analgesia. there is conflicting evidence on meloxicam’s efficacy, but this could be a result of time spent observing outcomes, which relates to the drugs onset of action and time of peak concentration. lidocaine has consistently shown a reduction in acute abnormal behaviours irrespective of equipment used conclusion based on the studies appraised in this knowledge summary there is not enough evidence to determine whether local anaesthesia is more effective than meloxicam at reducing the pain exhibited by lambs undergoing castration or tail docking. it has been shown that the use of local anaesthesia in the form of injectable lidocaine will reduce acute pain displayed during marking but there remains conflicting evidence for meloxicam with likely benefits occurring after several hours   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are a veterinarian who has been called for advice from a sheep farmer. the farmer is planning on performing all their castrates and tail docking themselves using rubber rings. they noticed last year many sheep exhibited behavioural and physical signs of pain after the procedures. they have asked whether they should use meloxicam or local anaesthesia to reduce this occurrence. due to lack of licensing in the uk for either of these drugs for this purpose you are unsure which one to recommend (bva, 2020). the evidence four studies were found to be relevant to the pico question, three of these were randomised and blinded (kells et al., 2019; smalls et al., 2014; and smalls et al., 2020) reducing levels of selection and observer bias. the variables measured included; time spent performing different behaviours (kells et al., 2019; small et al., 2014; kent et al., 1998) and time taken to ‘mother-up’, meaning time taken for lamb and mother to relocate each other after separation(small et al., 2014; and small et al., 2020). within the behaviour category, acute pain related behaviour was observed alongside postures such as lying and standing. included in the outcomes measured were parameters less relevant to the pico such as cortisol levels (kent et al., 1998) and wound development (small et al., 2014) and therefore these were disregarded. there was one study that contained both meloxicam and lidocaine and therefore fulfilled the inclusion criteria in its entirety; kells et al. (2019). additional to a control, groups were given either lidocaine subcutaneously (sc) or meloxicam intramuscularly (im) or alternatively, given them both in combination. the group given both forms of analgesia was not important to this summary as it does not compare their efficacy. meloxicam was given intramuscularly in the aforementioned study and buccally in the small et al. (2014) study, whilst kent et al. (1998) and small et al. (2020) looked at the effect of lidocaine. all studies differed in route of administration of said anaesthesia and as such are difficult to directly compare. it can be concluded from these studies that both types reduce pain responses post-marking but at different times, with meloxicam unsurprisingly providing more longer-term pain relief and lidocaine benefiting acutely. more evidence is required to directly compare the methods of anaesthesia/analgesia and decide which would be more efficacious in a clinical scenario. summary of the evidence kells et al. (2019) population: new zealand merino, entire, singleton lambs, weighing 15.4 ± 0.23 kg, aged 4–6 weeks old sample size: 90 healthy male lambs intervention details: the 90 lambs were allocated randomly into six treatment groups (allocated via a number generator in microsoft excel): group 1: c+d (castration and tail docking) without analgesia group 2: sham group (handled but not castrated or docked) group 3: c+d with local anaesthesia (la) group 4: c+d with meloxicam group 5: c+d with la and meloxicam administered separately group 6: c+d with la and meloxicam administered together experimental details: day 1: the ewes and lambs were brought down from a hill paddock (1.5 km) and held in a paddock adjacent to the yards. days 2 + 3: the group was moved to the yards. on each of the 3 days: 30 lambs were weighed and randomly assigned to one of the six treatment groups. each lamb was marked on its head and rump according to group and then left in assigned pens for a minimum of 30 minutes. one pen was treated at a time with video data collected. lamb caught and held by researcher, analgesia given by veterinary surgeon and procedure performed by farm staff. lambs were in the pen for a total of 6 hours on their day of testing, no feed or water given. after treatment lambs were ear tagged, vaccinated against contagious pustular dermatitis and given vitamin b12 by the farm staff and returned to their dams. procedure protocols: castration: performed via rubber ring using an elastrator device. tail docking: performed via a gas-heated docking iron. la: 5 ml (1 ml 2% lidocaine diluted to 5 ml in saline) lignocaine sc into scrotal neck, spermatic cord and tail given immediately prior to procedure. meloxicam: 1 ml of 2% meloxicam im immediately prior to procedure. study design: randomised blinded controlled trial outcome studied: behaviours were scored using behavioural observation research interactive software (boris). pain response was measured using time spent performing eight different behaviours (subjective): normal standing/walking abnormal standing/walking twisted lying frequency of foot kicks/stamps turn to hindquarters restlessness hindlimb stretches tail lifts these behaviours were observed at three different points in time relative to the procedure: period a: 30 minutes pretreatment period b: 15–45 minutes post-treatment period c: 4.15–4.75 hours post-treatment main findings (relevant to pico question): groups 1, 3, 4, 5, 6 in period b, the lambs showed a reduction in time spent standing/walking normally compared to pretreatment. spent more time walking/standing abnormally than before treatment. group 4 exhibited behavior similar to those that did not receive analgesia over the 5 hours after treatment. group 3 reduced hl stretching, tail lifting and twisted lying in period b. increased tail wags in period b. little effect on time spent in abnormal standing/walking or restlessness. groups 5 and 6 twisted lying, hindlimb (hl) stretching, and tail lifting reduced. increased head/neck stretches. limitations: first 15 minutes in period b and c was discounted due to disturbances from other pens, this would be when most acute pain behaviours would be exhibited. lambs in the sham group were distinguishable due to being intact so bias was unavoidable. behavior after 4.75 hours was not assessed. meloxicam was given immediately before the procedure; it requires longer for onset time (woodland et al., 2019). period of 3 hours between period b and c were not observed. the lambs were given further treatment such as a vitamin b12 injection which may cause drug interactions. small et al. (2014) population: merino lambs aged 7–10 weeks, weight 19.7 ± 0.38 kg, single born lambs. maintained in field conditions. sample size: 60 healthy lambs intervention details: two groups (randomly allocated by a blinded operator selecting a treatment chip from a box): 30 lambs in placebo group: received 1 ml/10 kg of drug vehicle. 30 lambs in meloxicam group: received a target of 1 mg/kg meloxicam at 10 mg/ml. experimental details: two cohorts of 30 lambs were studied two weeks apart. 6 days before marking: lambs caught and weighed. 5 days before marking: ewes and lambs were run in the observation paddock, during the day an observer walked through the paddock to acclimatise the sheep to humans. day of treatment: lambs separated from ewes and held in a pen adjacent to the paddock. at 2 minutes intervals: lambs caught, weighed to the nearest 100 g and placed in a marking cradle. treatment was calculated and administered via a proprietary dosing gun into the ventral aspect of the buccal sulcus between the molar teeth and the cheek. lamb was then castrated via a marking knife. tail docking carried out by a hot-iron docking knife. lamb was then released into an adjacent paddock with its mother. procedure protocol: treatment was administered via oral mucosa immediately before the procedure castration via a knife tail docking via a hot iron   study design: double blinded randomised study outcome studied: an ethogram was used, whereby the lambs behaviour was observed every 15 minutes for 8 hours and again for 45 minutes at 24 hours (behaviour is subjective): standing (normal, hunched, stretched) lying (ventral or lateral) suckling grazing walking (normal or stiff) running/playing time taken for lamb to mother-up (subjective): time taken to suckle or; time taken for ewe to show interest in the lamb. if >5 minutes categorised as a failure to mother-up. weight change and wound scores at 4 and 7 days after (objective): wounds assessed on a 4-point scale: appearance and swelling. main findings (relevant to pico question): meloxicam results in the 8 hours following marking: reduced time spent (p-values all under 0.05): standing in normal posture standing in hunched posture standing in stretched position walking with a stiff gait in combined abnormal postures and behaviours increased time spent (0.05 <p <0.1): grazing lying suckling overall = statistically significant 7-fold reduction in combined abnormal behaviours from 5.2% in placebo group to 0.7% in meloxicam group (p<0.001) meloxicam results the morning after: increased time spent lying. decreased time spent standing. limitations: the pharmacokinetics of meloxicam efficacy is limited by time for onset of action, tmax is 2.6 hours for buccal transmucosal formulation. the lambs in the first of the two cohorts were marked on the flank which made them difficult to individually identify. there were two observers which could lead to varying results and lack of standardisation. parts of the ethogram used are vague e.g. ‘standing with no apparent abnormalities’. the dose of meloxicam: the lambs were categorised by weights in 5 kg groupings and dose calculated in accordance with the max weight in that group meaning some lambs got more and some got less depending on where they came in the group. kent et al. (1998) population: suffolk x greyface lambs, average weight of 6–7 kg, 5–8 day old sample size: 120 healthy lambs intervention details: assigned eight to a group, each group divided into; with or without local anaesthetic (groups balanced for sex, age and weight): six castration groups five tail docking groups four handled control groups experimental details: 12 hours before treatment the ewes and their lambs were individually penned. procedure protocols: castration: rubber ring applied to the neck of the scrotum proximal to the testes. docking: ring applied to the tail. bloodless castrator: rubber ring applied followed by application of burdizzo for 10 seconds across either the neck of the scrotum proximal to the ring or across the width of the tail. la: lignocaine hydrochloride 2% with adrenaline administered in four different ways: 1 – high pressure needleless injection 0.2 ml intratesticular before ring application 2 – high pressure needleless injection 0.2 ml into left and right dorsolateral side of tail or right and left sides of cranial neck of scrotum after ring application 3 – same as 2 but following bloodless castrator 4 – conventional injection 0.2 ml sc right and left dorsolateral into tail or into spermatic cords study design: non-randomised clinical control study outcome studied: behavioural responses (subjective): lying and standing postures observed every 2 minutes for 96 minutes and every 6 minutes for a further 24 minutes: lying and standing: normal lying, partial, full extension, lying laterally with one shoulder on ground, standing still, walking with swaying and stamping movements. active behaviours recorded continuously for 96 minutes: getting up and down, rolling, jumping, stamping, kicking, easing quarters, head turning and vocalisation. cortisol assays (objective): 20 and 0 minutes pretreatment. 20, 40, 60, 80, 120, 180 minutes post-treatment. main findings (relevant to pico question): the sum of incidences of restlessness, rolling, stamping, kicking and easing quarters (req): la at the time of castration or docking reduced the mean req of all constituents and time spent in abnormal postures: tail docking: 84% reduction in active behaviour and 69% reduction in abnormal postures. castration: 68% reduction in active behaviour, 58% reduction in abnormal postures. la combined with bloodless castrator reduced req further but did not occur in the first 6 minutes after treatment. la during tail docking reduced the req to a similar figure seen in the handled control group. injecting la into the testes was less effective than into the neck of the scrotum, reducing abnormal lying postures by 45% compared to 71%. most effective method: castration: application of ring followed by injection of la and application of burdizzo. tail docking: high pressure needleless injection of la without burdizzo. limitations: too many variables not controlled e.g. different methods used for administration of la and not stated which ones received what. lignocaine used with adrenaline affecting the duration of action. a burdizzo used alongside a rubber ring was also studied, decreasing the sample size relevant to the pico. there was not enough time given for anaesthetic to work. the high-pressure needleless method of injecting la is dependent on volume. the volume in this case was 0.2 ml meaning it may not have reached deep structures such as the superior spermatic nerves. the use of needleless la injection – 1 in 10 injections into the tail needed to be repeated due to it bouncing off the wool fibres. groups were not randomised. observers were not blinded. small et al. (2020) population: lambs aged 4–10 weeks, body weight 9.4–31.9 kg, dorset x merino x border leicester, mixture of single and twin lambs sample size: 150 healthy lambs intervention details: randomly allocated to three groups: handled in a lambing cradle (sham) handled and marked with rubber rings (ring) handled and marked with rubber rings and treated with 30 mg lignocaine using numnuts® instrument (nnla) experimental details: day 0: ewes and lambs separated. lambs were each weighed, sex identified, and ear tagged. the lambs were then randomly allocated to treatment groups and separated into female and male groups. groupings were made up of 30 female and 30 males in nnla and ring groups and a mix of 30 male and female lambs in the sham group. treatment applied and recorded, lambs marked and then released into an observation paddock. three observers recording behaviours using an ethogram. procedure protocols: tail docking: via a rubber ring at the level of the third coccygeal joint of the tail. castration: rubber ring placed at the neck of the scrotum. elastrator pliers for group 2. numnuts® for group 3: injects lignocaine hydrochloride 1.5 ml of 20 mg/ml (sc) at the time of rubber ring placement. midline into dorsal aspect of tail or midline into posterior aspect of scrotal neck. study design: blinded randomised controlled trial outcome studied: time to mother-up: assessed for 180 seconds after release of lambs into the observation paddock. if >180 seconds it was considered a failed to mother-up. acute pain related behaviours at 5, 20, 35, 50 minutes (subjective): restlessness, kicking/stamping, rolling, jumping, pawing, licking/biting wound site, suckling, easing quarters. postures at 10 minutes intervals 60–180 minutes (subjective): normal standing and abnormal standing. standing other, normal walking, abnormal walking, walking other, running, jumping, grazing, suckling, playing, normal lying, abnormal lying, lying intention, lateral lying, ventral lying other, rolling. main findings (relevant to pico question): mothering-up: female lambs had 0.46 times less chance of mothering up with ring treatment compared to nnla treatment (p = 0.015). not significant in male lambs. pain behaviour: nnla was less than ring at 5 minutes (p<0.001) and 20 minutes (p = 0.001). ring and nnla did not differ at 35 or 50 minutes in males, but did differ at 35 minutes in females (p = 0.007). postural behaviours: nnla and ring did not differ at any time point between 60 and 180 minutes. total lying times: males: nnla spent more time lying at 80 minutes. nnla spent more time lying at 90 and 130 minutes. females: nnla differed from ring at 60 minutes. limitations: three observers reducing standardisation. the efficacy is limited to the duration of action of lignocaine 2%. looked at 2 commercial farms reducing the level of control and adding variability. this study is focused on the efficacy of the numnuts® device more so than the efficacy of la itself. reduced volume of 2% lignocaine, should be about 4 mg/ kg into the scrotal neck and spermatic cords (mellema et al., 2006). the behaviours were measured in 1 minute blocks at given time points rather than continuously. appraisal, application and reflection according to the mutilations regulations 2007 (the mutilations act, 2007), if a lamb is aged 3 months or older at the time of tail docking or castration an anaesthetic must be used. tail docking is routinely carried out to prevent faecal or urine contamination around the tail which can lead to flystrike and in worse case scenarios death. castrations are carried out to reduce aggressive behaviours making animal handling easier and prevent unwanted pregnancies of ewes (bva., 2020). this paper looks at the current anaesthesia and analgesia used in lambs during these procedures and compares their efficacy in the hope of encouraging its widespread implementation. the strongest evidence for this pico lies in kells et al. (2019); it contains both meloxicam and lidocaine administration and compares their benefits. this study demonstrates a conventional method of lidocaine infusion subcutaneously (sc) into the scrotal neck, spermatic cord and tail, but the method of meloxicam administration intramuscularly (im) precastration/docking is not highly reported. in a study based on meloxicam efficacy in sheep, it is advised that a dose of 1 mg/kg be given im (woodland et al., 2019), whereas, in kells et al. (2019) the dose worked out at 20 mg/ml making it is more than double the required amount. alongside this; length of time needed for both medications to take effect was not allowed as they were given just before the procedure. it has been demonstrated that 10–15 minutes should be permitted after la administration for it to take effect (wood et al., 1991). in addition, im meloxicam reaches peak plasma concentration (tmax) at 2–3 hours post administration (woodland et al., 2019), therefore longer observation of pain behaviours would have been beneficial. in this study pain related behaviour including reduced time spent lying normally and increased time spent standing/walking abnormally was still seen after 5 hours observation. kells et al. (2019) states no difference between the meloxicam group and the group that did not receive analgesia, but this may be due to the route of administration, time outcome was measured or onset of action. moreover, no p-value was given for these results and so their significance is unknown. there is limited literature about onset of action time for meloxicam in sheep in the uk due to it being given on the cascade. meloxicam was given buccally in small et al. (2014) with its tmax time stated as 2.6 hours for oral administration, despite this it was given immediately before the procedure similarly to kells et al. (2019). the route of administration also differed between studies for lidocaine. in the studies kells et al. (2019) and kent et al. (1998) it was given sc into the scrotal neck, spermatic cord and tail, in the latter, it was sometimes given via a high-pressure needleless injection. in small et al. (2020) it was given by a piece of equipment called numnuts® that injects at the time of castration, it can be argued that the aim of this study was more about the efficacy of the numnuts® device rather than the benefits of lidocaine at marking. numnuts® is for application in 4–8 week old lambs weighing 10–20 kgs and the active ingredient numocaine® is approved in australia and new zealand but not the uk. additionally, lambs tend to be castrated before 4–8 weeks old in the uk and so their use in the uk is limited (numnuts., n.d.). in kent et al. (1998) it was not stated who received which method of lidocaine administration, for example who received high-pressure needleless injection or conventional sc injection and where this injection was given; either intratesticular or in the spermatic cord/neck of the scrotum. this makes the evidence weaker due to little control over the variables. the study later states that there was no significant difference between responses to route of administration, but this is hard to support with such a reduced sample size after subdividing them. additionally, lidocaine was used with adrenalin increasing its duration of action and reducing its use in this pico. overall, the paper provides insufficient evidence as there were too many protocols being tested with little confirmation on groupings, method used or clearly stated aims. timing of measuring outcomes in all instances played a large part in what information was gathered. it could be said that for kent et al. (2019) longer than 4 hours may have given more information on meloxicam and the delay of measurement at 15 minutes could have restricted what outcomes from lidocaine were seen. lidocaine has a variable duration of action in sheep of about 90 minutes and a short onset of action of 2–5 minutes (depenbrock, 2017) so any data collected between 0–30 minutes is imperative. similarly, in small et al. (2020) the behaviours were observed in 1 minute blocks rather than continuously allowing large windows for missing key signs. however, the best timetable for measurements was in both small et al. (2014) and small et al. (2020) which studied pain behaviours at 5, 20, 35, 50 minutes for lidocaine and for 8 hours and then again at 24 hours for meloxicam. it may be difficult to compare the results between the studies due to the range of marking protocols used. kells et al. (2019) used a rubber ring for castration and hot iron for docking, small et al. (2014) used a knife for castration and hot iron for docking, kent et al. (1998) and small et al. (2020) used rubber rings for both procedures which was sometimes followed by a bloodless castrator (kent et al., 1998). it has been shown that the method affects levels of stress and therefore can have an impact on behavioural responses (molony et al., 1993), influencing the results in the trials. all except kent et al. (1998) were randomised and blinded, reducing bias at selection and observation. despite stating that the observer was blinded to treatment groups, in kell et al. (2019) lambs in the sham group were distinguishable from the treated group, but this has little bearing on our review as a comparison is only needed between lambs that were castrated/docked with or without analgesia. most of the studies have an adequate sample size with the smallest being 60 lambs (small et al., 2014). a smaller sample reduces the power of the study directly impacting the studies ability to demonstrate a statistical difference. statistical significance depends on sample size and effect size, so even if the effect size is large if the sample size is small the results are not significant (sullivan & feinn, 2012), hence the data in kent et al. (1998) being of reduced value once the groups had been designated. three of the studies are based outside of the uk making their transferability more difficult. kent et al. (1998) was based in scotland but this paper is of least use. a difference created by location is the breeds examined, which may affect the stoic nature of the lambs. in the uk most lambs are ringed before 7 days old to conform to uk legislation, in australia and new zealand lambs are typically marked between 4–6weeks old. this is demonstrated in these studies whereby the populations of lambs outside the uk exceed 7 days. many lambs in australia and new zealand are born outdoors and require gathering up for marking which is why it is difficult to perform the task in under 7 days (numnuts, n.d.). this means that these studies have a greater resonance with uk farmers with hill sheep flocks. discouraging the non-randomised trial due to its weaknesses outlined above, the other three all show an improvement in aberrant behaviour. lidocaine showed an acute effect after the procedure for example a significant reduction in pain behaviours at 5 (p<0.001) and 20 minutes (p = 0.001) were observed (small et al., 2020). meloxicam showed longer-term effects (small et al., 2014), at 8 hours after marking there was a statistically significant reduction in combined abnormal behaviours (p<0.001) from 5.2% in the placebo group to 0.7% in the meloxicam group. kent et al. (2019) demonstrated that in combination they proved more advantageous, showing a reduction in twisted lying, hindlimb stretching and tail lifting but the p-value was not stated and as such its significance cannot be determined. in small et al. (2014) it was stated that 0.1>p>0.05 still indicates a tendency towards significance but typically p>0.05 supports evidence for the null hypothesis and so results including meloxicam increasing time spent grazing, lying and suckling can be disputed. in conclusion, more evidence is required to compare the benefits of meloxicam to lidocaine when given before castration or tail docking. in the meantime, for lambs over the age of 3 months old anaesthesia must be used. despite meloxicam having conflicting evidence, the use of la or non-steroidal anti-inflammatories (nsaids) have their part to play in reducing pain post-procedure. buccal meloxicam will cause delayed analgesia and sc lidocaine provides acute pain relief; they remain strong methods of pain control and current research is taking place for numnuts® to be introduced in the uk. using both an nsaid and local anaesthesia in combination requires more research to prove its efficacy and safety and is not covered by this pico. as a result of the studies being taken from australian and new zealand flocks, the studies appraised in this paper will have more relevance to uk hill flocks and those castrating/docking late. additionally, lidocaine does not have a maximum residue level (mrl), and both lidocaine and meloxicam are not licensed in the uk for this purpose. subsequently, these papers are limited for practical application in the uk. methodology section search strategy databases searched and dates covered: cab abstracts on ovid interface (1973– oct 2020) pubmed on the ncbi website (1958 – oct 2020) search strategy: cab abstracts and pubmed: (lamb* or sheep) (castrat* or tail docking or marking) (meloxicam or local anaesthesia or analgesia or lidocaine or lignocaine) 1 and 2 and 3 dates searches performed: 6 oct 2020 exclusion / inclusion criteria exclusion: paper not available in english paper cannot be accessed paper was a review or conference paper the study: was not relevant to the pico did not contain meloxicam or local anaesthesia use of a different nsaid use of different local anaesthetic to lidocaine did not look at pain response lidocaine given topically rather than injected looking at mulesing lambs instead of castration or tail docking the study was on sheep not lambs incorrect species inclusion: any relevant primary research paper which compared the pain response with meloxicam or topical anaesthesia search outcome database number of results excluded – not relevant to the pico excluded – inaccessible excluded – conference paper excluded – review total relevant papers cab abstracts 23 13 2 3 2 3 pubmed 44 33 3 0 4 4 total relevant papers when duplicates removed 4 conflict of interest the author declares no conflicts of interest. references british veterinary association. (2020). sheep castration, tail docking, and pain management. 1–7. available at: https://www.bva.co.uk/media/3364/sheep-castration-tail-docking-and-pain-management-final.pdf [accessed 1 november 2020] depenbrock, s. (2017). ruminant field anaesthesia and analgesia. penn conference. 1–5. kells, n.j., beausoleil, n.j., godfrey, a.j.r., littlewood, k.e., ward, r.n. & johnson, c.b. (2019). effect of analgesic strategies on pain behaviour associated with combined ring castration and hot iron tail docking in merino lambs. applied animal behaviour science. 222. doi: http://dx.doi.org/10.1016/j.applanim.2019.104914 kent, j.e., molony, v. & graham, m.j. (1998). comparison of methods for the reduction of acute pain produced by rubber ring castration or tail docking of week-old lambs. the veterinary journal. 155(1), 39–51. doi: https://doi.org/10.1016/s1090-0233(98)80033-6 molony, v., kent, j.e. & robertson, i.s. (1993). behavioural responses of lambs of three ages in the first three hours after three methods castration and tail docking. research in veterinary science. 55(2), 236–245. doi: http://dx.doi.org/10.1016/0034-5288(93)90087-v (n. d.). numnuts® availability in the uk. available at: https://numnuts.store/is-numnuts-available-in-the-uk/ [accessed 27 december 2020] small, a., belson, s., holm, m. & colditz, i.g. (2014). efficacy of a buccal meloxicam formulation for pain relief in merino lambs undergoing knife castration and tail docking in a randomized field trial. australian veterinary journal. 92(10), 318–388. doi: http://dx.doi.org/10.1111/avj.12241 small, a.h., jongman, e.c., niemeyer, d., lee, c. & colditz, i.g. (2020). efficacy of precisely injected single local bolus of lignocaine for alleviation of behavioural responses to pain during tail docking and castration of lambs with rubber rings. research in veterinary science. 133, 210–218. doi: http://dx.doi.org/10.1016/j.rvsc.2020.09.025 sullivan, g.m. & feinn, r. (2012). using effect size – or why the p value is not enough. journal of graduate medical education. 4(3), 279–282. doi: https://dx.doi.org/10.4300%2fjgme-d-12-00156.1 (2007). the mutilations (permitted procedures) (england) regulations 2007. available at: https://www.legislation.gov.uk/ukdsi/2007/9780110757797/contents/data.html [accessed 1 november 2020] wood, g.n., molony, v., fleetwood-walker, s.m., hodgson, j.c. & mellor, d.j. (1991). effects of local anaesthesia and intravenous naloxone on the changes in behaviour and plasma concentrations of cortisol produced by castration and tail docking with tight rubber rings in young lambs. research in veterinary science. 51(2), 193–199. doi: http://dx.doi.org/10.1016/0034-5288(91)90013-e woodland, a.n., van der saag, d., kimble, b., white, p.j., govendir, m. & lomax, s. (2019). plasma pharmacokinetic profile and efficacy of meloxicam administered subcutaneously and intramuscularly to sheep. plos one. doi: http://dx.doi.org/10.1371/journal.pone.0215842 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. does clicker training reduce stress in shelter cats? a knowledge summary by saskia travers bvmsci mrcvs 1* 1university of surrey school of veterinary medicine, vsm building, daphne jackson road, guildford, gu2 7al *corresponding author (saskiatravers@gmail.com) vol 7, issue 4 (2022) submitted: 10 oct 2021 published: 18 nov 2022 next review: 30 jan 2024 doi: add link to doi here pico question in domestic cats in a shelter setting, does clicker training decrease proxy measures of a stressed emotional state (behavioural or physiological) compared to no clicker training?   clinical bottom line category of research question treatment the number and type of study designs reviewed two papers were critically reviewed. one was a prospective quasi-randomised clinical trial, the other was a quasi-experimental before-and-after study with each cat being its own control strength of evidence weak outcomes reported both papers reported a decrease in behavioural stress indicators in shelter cats following a clicker training programme. not all of these decreases were statistically significant and there are large issues with confounding factors in both papers conclusion preliminary evidence suggests that clicker training can be implemented as one form of enrichment to reduce stress in shelter cats alongside other means. further evidence is required to demonstrate superiority to other forms of enrichment to reduce stress in shelter cats, especially given the practical limitations of implementing such a programme in most shelters   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are a shelter medicine veterinarian working in a busy cat adoption centre. you are in a staff meeting discussing novel means of enrichment for the cats. a colleague mentions that she has heard of other shelters clicker training cats to reduce stress and improve adoptability. your initial thoughts are that clicker training would take a significant amount of time in such a busy shelter, but you are intrigued by the idea and the potential benefits. you decide to examine the evidence to assess whether clicker training can decrease stress in shelter cats, before you and your colleagues decide whether to implement it. the evidence a focused search found two papers relevant to the pico question, examining the use of clicker training in the shelter environment alongside measures of stress. one was a prospective, randomised clinical trial (gourkow & phillips, 2016) and the other was a before-and-after study with each cat acting as its own control (grant & warrior, 2019). summary of the evidence gourkow & phillips (2016) population: domestic cats in a shelter in vancouver, canada. all cats had either been surrendered by their owners or found as strays. all cats were aged 6 months or older. they were clinically healthy with no signs of upper respiratory disease or injury on recruitment for the study. this study was part of a larger study reported in three separate articles, assessing the effects of different interventions depending on the assessed mood of the cats using an ethogram (gourkow et al., 2014a). this initially involved classifying 250 cats as ‘frustrated’, ‘anxious’ or ‘content’. the 15 cats deemed ‘frustrated’ were recruited for this study and underwent clicker training, assessing whether cognitive enrichment is beneficial for these cats. the other cats were deemed ‘anxious’ (139 cats) or ‘content’ (96 cats) and their interventions are described elsewhere (gourkow et al., 2014b; and gourkow & phillips, 2015). cats were deemed ‘frustrated’ if they demonstrated any of the following behaviours during more than 10% of their awake time: vocalisation, escape attempts, visual scanning, pushing objects, pacing, or short bouts of aggression during human interaction. sample size: 15 ‘frustrated’ cats. intervention details: this study consisted of two treatment groups: treatment (n = 7): underwent training sessions four times a day for 10 days by one experimenter. the paper does not state whether they also received interaction outside of training sessions. control (n = 8): these cats were completely ignored and did not receive any interaction at all, neither by shelter staff during routine care nor the experimenters. cats were randomly allocated to each group by systematic sampling, through alternating which group an incoming 'frustrated’ cat would be allocated to (treatment or control) in order of admission to the shelter. in this way, every other cat was allocated to the ‘control’ group. the experiment took place in a separate unit to the rest of the shelter. cats were housed in stainless steel cages (76 × 76 × 71 cm) within a separate housing unit to the rest of the shelter. for the treatment group, training took place in a 4 m2 training room adjacent to where the cats were kept. cat behaviour were assessed via daily video footage and classified as ‘content’, ‘frustrated’ or ‘apathetic’ by use of an ethogram, previously developed by the same authors (gourkow et al., 2014a). cats in the treatment group were first conditioned to anticipate a treat with a ‘click’ sound and then trained to perform ‘give me five’ through shaping (rewarding approximations of the behaviour until the desired behaviour was performed). this study examined two responses to stress: behavioural (mood rating using an ethogram) and physiological. the physiological data consisted of secretory iga (s-iga) assays on faeces, and whether cats developed upper respiratory disease (considered to be a proxy measure of stress-induced viral shedding). every stool produced was collected, weighed and immediately stored at -40°c. iga was measured using an enzyme-linked immunosorbent assay following homogenisation of faeces. study design: prospective, quasi-randomised clinical trial. outcome studied: behavioural indicators of stress (subjective). the authors observed cats using focal sampling; 10 minutes per hour for the 10 days. behaviours were categorized according to the ethogram if said behaviours were observed for more than 10% of the awake time. number of cat days, and proportion within each group, rated as ‘frustrated’, ‘content’ or ‘apathetic’. mean time taken to reach a ‘content’ state for each group. whether cats in the treatment group are more likely to remain ‘content’ once attained, compared to the control group, using a cox proportional hazards model (cox, 1972). this is a type of survival analysis which in this context is being used to measure time before the mood rating changes. physiological indicators of stress (objective): daily faecal s-iga levels. incidence of upper respiratory disease, presumed to be a marker of stress-induced viral shedding. main findings (relevant to pico question): behavioural indicators of stress: mood rating per cat day, and proportion within each group: the treatment group were significantly (p = 0.002) more likely to have cat days rated as ‘content’ than cats in the control group. within the control group, 49/67 (73%) of cat days were rated as negative. of these, 41/67 (61.2%) were deemed ‘frustrated’ and 8/67 (11.9%) were considered ‘apathetic’. in the treatment group, 28/55 (51%) of cat days were rated negatively. all were deemed ‘frustrated’. time taken to reach a ‘content’ rating: on average, cats in the treatment group were rated ‘content’ slightly earlier than those in the control group (3.2 days (±1.3 days) vs 4.4 days (±0.3 days)). however, this finding was not statistically significant. hazard ratio (hr): 3.64, confidence interval (ci): 0.85–15.67, p = 0.08 (not statistically significant). whether treated cats are more likely to remain ‘content’ once attained compared to the control cats: treated cats appeared to be 3.6 times more likely to remain ‘content’ once attained compared to the control group, however this result is not statistically significant. hr: 3.64, ci: 0.85–15.67, p = 0.08 (not statistically significant). physiological indicators of stress: daily stool s-iga levels: treated cats had significantly (p = 0.03) greater s-iga levels than those in the control group. 6.73 ± 0.47 µg/g for the treated cats, 6.04 ± 0.68 loge µg/g in the control group. incidence of upper respiratory disease: cats in the control group were significantly (hr: 2.37, ci: 1.35–4.15, p = <0.0001) more likely to develop upper respiratory disease than cats in the treatment group, as determined by the cox proportional hazards model (cox, 1972). limitations: this study had a control group, but the control group is not particularly meaningful because these cats had no interaction at all while the treatment group were let out of their small cages into a larger room and interacted with at least four times a day. the lack of enrichment in the control group creates a severe confounding effect when assessing whether clicker training itself is beneficial, or whether it is simply the interaction or even being outside of a cage. this is an important aspect that must be considered when interpreting the results; the authors are comparing clicker training to no enrichment at all. small sample size (seven cats in the treatment group, eight in the control group). this means that individual differences, such as personality and food motivation, are more likely to influence the results. this study only examined cats deemed to be ‘frustrated’, limiting the applicability of the results. the paper does not state which experimenter assessed the cats’ emotional states based on the video footage, raising the possibility of bias if one experimenter did both the training and behavioural assessment. grant & warrior (2019) population: twelve domestic cats at the rspca’s oxfordshire rehoming centre, uk. the ages of the cats ranged from 1–11 years. ten of these cats were relinquished by their owners and two were former strays. the length of stay prior to the training programme ranged from 2–25 days. sample size: 12 cats. intervention details: all singly housed cats residing in the cattery at the time of the study were subjected to the clicker training programme. behaviour assessments were carried out before the clicker training programme, and after the six clicker training sessions had been completed. all cats underwent the same intervention with no control group. the study utilised a quasi-experimental (i.e. non-randomised, defined as per harris et al., 2006), uncontrolled before-and-after study design. this means that there was no separate control group, as each cat acted as its own control. the term is used to contrast with controlled before-and-after studies, where there is a control group not receiving the intervention allowing for comparison (goodacre, 2015). the experiment was carried out as follows: behavioural observation – before the training programme: each cat had a 10 minute period of observation prior to the training programme beginning. this consisted of: 10 minute video recording (via a smartphone) to allow observation of behaviour and subsequent categorisation. the experimenter recording did not interact with the cats during this time. behaviour was classified as follows, based on an ethogram created by stanton et al. (2015): exploratory: investigate surroundings (such as sniffing objects or manipulating with paws). play: interacting with objects in a playful context. inactivity: stationary in a sitting, lying or standing position. other: neutral behaviours not fitting into the above categories (normal grooming, drinking, eating, defecation). recording the amount of time spent at the front and back of the cage. human approach test (hat), based on the work of arhant & troxler (2017). the experimenter presented their hand to the cat and recorded whether the cat made contact with, investigated or simply did not withdraw from their hand (contact possible [cp]). if the cat withdrew, showed signs of aggression towards or froze in reaction to their hand, this was recorded as no contact possible (ncp). training programme: consisted of 10 minute training sessions, three times a week for 2 weeks (six sessions total). the training was as follows: ‘charging’ the clicker: clicking then presenting a food reward, until the cat began to anticipate food after the click. the distance was increased between the trainer and the cat, so the cat had to travel towards the trainer to obtain the food reward. the trainer added a vocal cue by calling the cat’s name, marking the behaviour when the cat was close to the trainer. for fearful cats, food was tossed near the cat and the clicker marked the cat approaching the food, gradually building up on this until the cat approached the trainer. behavioural observation after the training programme: this was done 2 days after finishing the programme and was done by a person unfamiliar to the cats, in the same way as before training: 10 minute video recording (via a smartphone) to allow observation of behaviour and subsequent categorisation as ‘exploratory’, ‘play’, ‘inactivity’ or ‘other’. recording time spent at the front and back of the cage. hat, recording whether contact was possible or not. each pen had an indoor area and an outdoor area, which the cat accessed via a small opening. the indoor area was not visible to visitors and therefore one of the primary aims of the study was to encourage cats to spend more time in the outdoor area. in addition to clicker training, cats continued to have socialisation sessions with volunteers multiple evenings a week. the cats in the study remained available for rehoming throughout, and as a result several cats were excluded due to rehoming before the clicker training programme had finished (the authors do not state how many). a paired t-test was used for recording the time spent in behavioural categories, and time spent at the front of the cage. a mcnemar’s test with a 2 x 2 contingency table was used for the results of the hat. this test is used in before-and-after studies to determine whether the proportions in two samples from the same individual are equal (morrison, 2010). study design: quasi-experimental, uncontrolled before-and-after study. outcome studied: all outcomes were objective: time spent in the ‘exploratory’ behavioural category, before and after the training programme (subjective, paired t-test). time spent in the ‘inactive’ behavioural category, before and after the training programme. time spent at the front of the cage, before and after the training programme. whether contact was possible following the hat, before and after the training test. main findings (relevant to pico question): results are not displayed numerically in this paper, but rather through bar charts. therefore, all mean values have been rounded to the nearest integer on the charts (denoted with ~) to avoid misreporting of results. the bar charts have error bars but it is unclear whether these refer to the confidence interval or standard deviation, so the variability measures of the means are not reported here. there was a significant (t = 4.33; p = 0.001) increase in mean time spent in the ‘exploratory’ behaviour category after clicker training: before the training programme, the mean time spent in exploratory behaviour was ~2 minutes. after the training programme, the mean time spent in exploratory behaviour was ~5 minutes. there was a significant (t = 4.33; p = 0.001) decrease in mean time spent in the ‘inactive’ behaviour category after the training programme: before the training programme, the mean time spent in inactive behaviour was ~7 minutes. after the training programme, the mean time spent in inactive behaviour was ~1 minute. there was a significant (t = -4.67; p = 0.001) increase in the mean time spent at the front of the cage after clicker training: before the training programme, the man time spent at the front of the cage was ~3 minutes. after the training programme, the mean time spent at the front of the cage was ~8 minutes. while more cats were classified as cp after the clicker training programme, the mcnemar’s test did not find this statistically significant (p = 0.125). before the training programme, 6/12 (50%) of cats had cp with the hat. after the training programme, 10/12 (83.3%) had cp with the hat. limitations: small sample size, meaning that individual differences between cats would have had a greater effect on the results. several cats were excluded from the study because they were adopted before the intervention could be complete. this is understandable from an ethical standpoint but it also lessens the applicability of the intervention. there was no separate control group in this study, as each cat was used as its own control. it is therefore more difficult to ascertain whether the clicker training was responsible for the cats’ improved exploratory behaviours. indeed, in human medicine uncontrolled before-and-after studies have been shown to overestimate the benefits of novel treatments (sacks et al., 1982, cited in goodacre, 2015) and at least one medical journal has limited publication of these studies to exceptional circumstances for this reason (goodacre, 2015). it is worth considering that half of the cats (6/12) were cp in the hat before the training intervention even began. there were several confounding factors, such as the cats continuing to receive interaction with volunteers during the study and the possibility that the cats became more accustomed to their environment over the 2 weeks. the authors acknowledge these limitations, but still interpret the improvement in four cats being cp post-training as being due to clicker training. the video recording post-training involved someone entering the cage to record the video on their smartphone, so it is possible that the cats spent more time on the outside of the pen because they were anticipating training and food. the authors attempted to reduce this effect by having an unfamiliar person record post-training. it is unclear whether the observed increase in exploratory behaviour was seen generally, when alone in the cage. short observation period for behavioural assessment: 20 minutes total over the course of 2 weeks (one before training, one after). does not state which experimenter assessed the cats’ behaviour based on the video footage, raising the possibility of bias. appraisal, application and reflection cats were successfully clicker trained in both studies (gourkow & phillips, 2016; and grant & warrior, 2019), and at least one other paper has demonstrated that cats can be clicker trained in the shelter environment irrespective of other factors such as age (kogan et al., 2017). currently, the evidence suggests that cats can be clicker trained in the shelter environment but the evidence as to whether clicker training decreases stress in the shelter environment compared to other forms of cognitive enrichment is less clear, mainly due to the confounding factors at play in both papers. the main limitations of both studies were the small sample sizes, lack of meaningful control groups and confounding factors. for instance, in the study by grant & warrior (2019), cats received socialisation by staff and volunteers in addition to training, and it is unclear whether the perceived increase in exploratory behaviour post-training was due to the cats anticipating training (and subsequently, food) when a person entered the cage to film the cats on a smartphone. gourkow & phillips (2016) took the approach of having a control group of cats that received no enrichment at all; this calls into question whether the perceived improvements were due to the clicker training or whether any form of enrichment (including the simple act of letting the cats out of the cage for training) would have created similar improvements, given that the control group cats without enrichment are going to be in a compromised emotional state regardless. clicker training animals is a time-consuming venture that many shelters would find difficult to do for every cat. grant & warrior (2019) attempted to make their training method as accessible as possible for that specific shelter environment, namely 10 minutes of training three times per week and aiming for the cats to spend more time in the outside area so visitors could see the cats. the authors speculated that encouraging these behaviours would improve adoptability, a view shared by bollen (2015). grant & warrior (2019) did not have a separate control group and so it is difficult to assess whether clicker training had this desired effect, although research suggests that active and playful cats tend to be viewed more positively by potential adopters (gourkow, 2001; fantuzzi et al., 2010; sinn, 2016; and caeiro et al., 2017). an interesting subject for further research would be to assess whether clicker training cats results in a reduced length of stay in the shelter, although future studies of clicker training in cats could compare it to other means of cognitive enrichment to reduce the confounding factors. the external validity of these findings is limited by the fact that most cat rescue organisations have various resource constraints, and clicker training is a very labour-intensive means of enrichment for shelter cats. because of how labour-intensive a clicker training intervention is, it appears to be more appropriate as a means of enrichment for specific situations rather than a universal measure. grant & warrior (2019) tailored the clicker training programme for the specific cattery design (that is, encouraging cats to spend more time in the outside area), while gourkow & phillips (2016) only recruited cats they deemed ‘frustrated’ for the clicker training intervention. shelter staff should take a tailored approach to feline enrichment as clicker training may not be suitable for every cat. for example, it has been suggested that a fearful cat may find increased human interaction stressful while a frustrated cat would be likely to benefit from it (ellis, 2009). clicker training can be employed alongside a variety of enrichment measures to reduce stress in shelter cats, many of which are less labour-intensive (for instance, puzzle feeders) and allow for cats to express their innate behavioural needs (such as providing scratching posts and play that mimics hunting). to summarise, it is possible to clicker train cats in the shelter environment and there is weak evidence that it may reduce some proxy measures of stress, although confounding factors limit full attribution to clicker training. clicker training can be used as a form of cognitive enrichment alongside other means, depending on the cats personality and presenting problems. however, unless further studies prove that clicker training is a superior form of enrichment to existing forms of enrichment (for example puzzle feeders, or having volunteers play with cats), and given the time requirements that may limit applicability of the studies, it seems more appropriate to suggest clicker training for certain situations and individual cats as part of a multidisciplinary approach, rather than as a universal recommendation for all cats in shelters. methodology section search strategy databases searched and dates covered: cab abstracts, via cab direct (1973–week 4 2022) pubmed, via ncbi interface (1966–week 4 2022) search strategy: cab abstracts: cat or cats or feline or “felis catus” or “felis silvestris catus” or felid* and "clicker train" or train* or "clicker trained" or "clicker training" or “conditioned reinforc*” or “secondary reinforc*” or “successive approximation” or shaping or clicker and shelter or pound or “rescue cent*” or cattery and stress or stress* or behavio* or anxi*   pubmed: ((cat or cats or feline or "felis catus" or "felis silvestris catus" or felid*) and (("clicker train" or train* or "clicker trained" or "clicker training" or “conditioned reinforc*” or “secondary reinforc*” or “successive approximation” or shaping or clicker)) and (shelter or pound or "rescue cent*" or cattery)) and (stress or stress* or anxi* or behavio*) dates searches performed: 30 jan 2022 exclusion / inclusion criteria exclusion: paper not in the english language. abstract only papers, conference proceedings, policy, letters. papers not relevant to the pico. inclusion: peer reviewed research using a comparator of behaviour before and after a period of clicker training. search outcome database number of results excluded – does not answer pico question excluded – paper in a language other than english excluded – abstract-only papers, conference proceedings, policy and letters excluded – duplicates total relevant papers cab abstracts 31 29 0 0 1 1 pubmed 17 16 0 0 0 1 total relevant papers 2 orcid saskia travers: https://orcid.org/0000-0002-8541-969x conflict of interest the author declares no conflicts of interest. references arhant, c. & troxler, j. 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(2009). environmental enrichment: practical strategies for improving feline welfare. journal of feline medicine and surgery. 11(11), 901-912. doi: https://doi.org/10.1016%2fj.jfms.2009.09.011 fantuzzi, j.m., miller, k.a. & weiss, e. (2010). factors relevant to adoption of cats in an animal shelter. journal of applied animal welfare science. 13(2), 174–179. doi: https://doi.org/10.1080/10888700903583467 goodacre, s. (2015). uncontrolled before-after studies: discouraged by cochrane and the emj. emergency medicine journal. 32(7), 507–508. doi: http://dx.doi.org/10.1136/emermed-2015-204761 gourkow, n. (2001). factors affecting the welfare and adoption rate of cats in an animal shelter. master’s thesis, university of british columbia. [online] available at: https://spca.bc.ca/wp-content/uploads/factors_affecting_the_welfare_and_adoption_rate_of_cats_in_an_animal_shelter.pdf (accessed: 03 jan 2021). gourkow, n., lavoy, a., dean, g.a. & phillips, c.j.c. 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(2017). assessment of clicker training for shelter cats. animals. 7(1), 73. doi: https://dx.doi.org/10.3390%2fani7100073 morrison, m. (2010). mcnemar's test. in n. j. salkind (ed.); encyclopedia of research design (780-782). sage publications, inc. doi: https://dx.doi.org/10.4135/9781412961288.n235 sinn, l. (2016). factors affecting the selection of cats by adopters. journal of veterinary behavior. 14, 5–9. doi: https://doi.org/10.1016/j.jveb.2016.06.00 stanton, l.a., sullivan, m.s. & fazio, j.m. (2015). a standardized ethogram for the felidae: a tool for behavioral researchers. applied animal behaviour science. 173, 3–16. doi: https://doi.org/10.1016/j.applanim.2015.04.001 contribute to the evidence there are two main ways you can contribute to the evidence base while also enhancing your cpd: tell us your information need write a knowledge summary either way, you will be helping to add to the evidence base, and strengthen the decisions that veterinary professionals around the world make to give animals the best possible care. learn more here: https://veterinaryevidence.org/index.php/ve/guidelines-for-authors the effect of pre-emptive incisional bupivacaine block on postoperative pain after coeliotomy in dogs a knowledge summary by kiriaki pavlidou dvm phd 1* lysimachos g papazoglou dvm phd mrcvs 1 1companion animal clinic, school of veterinary medicine, department of clinical sciences, aristotle university of thessaloniki, greece *corresponding author (kellypav@gmail.com) vol 6, issue 1 (2021) published: 31 mar 2021 reviewed by: latifa khenissi (dvm mrcvs dipl. ecvaa), christopher norkus (dvm dacvaa cvpp dacvecc) and thomas towers (vetmb ma certavp(va) mrcvs) next review date: 30 sep 2022 doi: 10.18849/ve.v6i1.325 pico question is there an effect on analgesia following coeliotomy in dogs after a block with local anaesthetics?   clinical bottom line category of research question treatment the number and type of study designs reviewed all the available evidence for this pico question comes from clinical trials and one experimental/pharmacology study. all the studies were randomised; 5/7 were blinded clinical studies and 4/7 studies were prospective strength of evidence moderate outcomes reported it is not clear if the use of a local anaesthetic including bupivacaine or lidocaine as incisional blocks minimises the postoperative pain especially in the first 24 hours, as the results are not statistically significant between the groups conclusion in conclusion, bupivacaine or lidocaine can minimise the postoperative pain but more clinical trials are needed   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. the evidence all the available evidence for this pico question comes from clinical trials and one experimental/pharmacology study. all the studies were randomised; 5/7 were blinded clinical studies and 4/7 studies were prospective. the strength of the evidence is not the strongest one as there is no meta-analysis research about this subject, however, it is moderate as most of the included trials were randomised clinical studies. summary of the evidence abbreviations: cmps composite measure pain scale divas dynamic and interactive visual analogue scale etco2 end-tidal carbon dioxide concentration fpia fluorescence polarisation immunoassay technology hr heart rate im intramuscularly iv intravenously mwts mechanical wound thresholds nrs numeric rating scale rr respiratory rate sc subcutaneously spo2 oxygen saturation umps university of melbourne pain scale vas visual analogue scale   wilson et al. (2004) population: various breeds of healthy dogs participating in surgical training exercises sample size: six dogs intervention details: dogs (n=6) were premedicated with: acepromazine at 0.1 ± 0.07 mg/kg im, butorphanol at 0.3 ± 0.1 mg/kg im induction with thiopental at 11.5 ± 2.7 mg/kg iv maintenance with halothane or isoflurane the dose of lidocaine hydrochloride (20 mg/ml) administered intraperitoneally was 8.8 mg/kg. the solution was diluted with an equal volume of isotonic saline resulting in a volume of 0.88 ml/kg. this diluted solution was placed into the peritoneal cavity just prior to closure of the incision in the body wall. 2 mg/kg of 2% lidocaine hydrochloride with epinephrine was placed in the wound after the closure of the abdominal wall. study design: pharmacological experimental study, non-blinded, non-controlled outcome studied: dogs were observed for signs of toxicity (seizures, nausea) at each of the sampling periods and again 18 h after the drug administration. venous blood was collected through a catheter aseptically placed in the cephalic or lateral saphenous vein. the baseline blood sample was collected once the dog was anesthetised and in 5, 10, 15, 20, and 30 mins and 1, 2, 3, 4 and 5 hrs after the intraperitoneal (ip) injection. the lidocaine assay utilised fpia and a commercially available reagent kit. main findings (relevant to pico question): no adverse consequences or signs of toxicity were noted during the postoperative period in these dogs. detectable concentrations of lidocaine were found in all dogs in the sample taken 5 mins after administration. time to peak serum concentration was 0.37 ± 0.26 hr. peak serum concentration was 1.45 ± 0.36 μg/ml. a rapid decrease in serum concentration was shown with an elimination half-life of 1.17 ± 0.11 hr. limitations: small sample size. non-controlled, non-blinded study. no details about which dogs receive halothane and which received isoflurane for the maintenance of anaesthesia. anaesthetic values were not mentioned in the results. carpenter at al. (2004) population: client-owned dogs or from local humane societies and rescue groups presented to veterinary hospital for routine ovariohysterectomy. they were determined to be healthy by physical examination. dogs were excluded if they were less than 1 year of age, weighed less than 4.5 kg, or were having other procedures performed in addition to ovariohysterectomy. sample size: 30 dogs 13 mixed-breed dogs, 17 purebred dogs intervention details: 10 dogs in saline group (sal), 10 dogs in lidocaine group (lid) and 10 dogs in bupivacaine group (bup). premedication with 0.02 mg/kg acepromazine im and 0.22 mg/kg butorphanol im. induction with thiopental sodium at 13.2 mg/kg iv maintenance of anaesthesia with isoflurane in oxygen. intravenous fluids at a rate of 11.0 ml/kg/hr. before closure of the linea alba following the procedure, 10 dogs received 0.88 ml/kg 0.9% saline, 10 dogs received 8.8 mg/kg 2% lidocaine with epinephrine diluted to an equivalent volume with saline and 10 dogs received 4.4 mg/kg 0.75% bupivacaine diluted to an equivalent volume with saline in their ip space at the cranial site of the incision. prior to closure of the skin, the sal dogs received 2.0 ml of 0.9% saline, the lid dogs received 2.0 ml of 2% lidocaine with epinephrine and the bup dogs received 2.0 ml of 0.75% bupivacaine as a splash on linea alba. general anaesthesia was maintained until skin closure. the dogs were placed in sternal recumbency for 10 minutes after the recovery from anaesthesia. dogs with a pain score greater than 50 mm on the vas-pain at any time were given 0.22 mg/kg butorphanol iv or im. dogs that were extremely agitated or they did not respond to butorphanol were given additional doses of butorphanol and/or acepromazine as needed. study design: prospective, randomised, controlled, blinded clinical trial outcome studied: preand post-procedural pain scoring was performed using the cmps and vas by one observer. pain scores at baseline, 0.5, 1, 2, 3, 4, 6, 8 and 18 hrs post extubation. the scorer first observed the dog quietly for 1 min outside the cage. then, he rattled the cage door and entered the cage saying hello. rr was measured at the first minute of observation. behaviour and hr were recorded. palpation of the incision was performed by handler gently three times. position, activity and vocalisation were recorded during quiet observation. position change and behaviour were recorded during the opening of the cage door. a single number from the cmps was recorded at each time period. vas scores were recorded by placing a cross on a 100 mm line between “no pain” and “worst imaginable pain” for pain scores (vas-pain) and between “no sedation” and “very sedate” for sedation scores (vas-sedation). all treated dogs were scored throughout the surgery. the length of the incision was measured upon completion of surgery. observation for signs of local anaesthetic toxicity (sedation, nausea, seizures). main findings (relevant to pico question): 7/10 dogs in sal group, 4/10 in lid group and 2/10 in bup group were given supplemental analgesia (significantly more dogs in sal group than in bup group). 2/7 dogs in sal group were given two doses of analgesics. dogs in lid group were given supplemental analgesia at 0.5, 1, 2 and 3 hrs after extubation. two out of four dogs in lid group were given two doses of supplemental analgesia. in bup group dogs were given supplemental analgesia 1 hr after extubation and only with butorphanol. none of the dogs in bup group were given supplemental analgesia more than once. none of the dogs received supplemental analgesics after 3 hrs post-extubation. vas-pain scores: a mean of 52 ± 24 at 0.5 hrs to 2 ± 3 at 18 hrs for the sal group, a mean of 40 ± 19 at 0.5 hrs to 1 ± 3 at 18 hrs for lid group and 27 ± 4 at 0.5 hrs to 2 ± 1 at 18 hrs for the bup group. no significant difference among groups between vas-pain scores at times 0.5 and 18 hrs. dogs in bup group had statistically significant lower pain scores than dogs in sal group. at 0.5 hrs: bup group had significantly lower pain scores than lid and sal scores. cmps scores: a mean of 7.4 ± 3.9 at 0.5 hrs to 0.1 ± 0.3 at 18 hrs for the sal group, 5.0 ± 2.3 at 0.5 hrs to 0.2 ± 0.4 at 18 hrs for the lid group and 3.5 ± 2.1 at 0.5 hrs to 0.7 ± 0.7 at 18 hrs for the bup group. significantly lower cmps score at 0.5 hrs in bup group than in sal group. vas-sedation scores: a mean of 83 ± 7 at 0.5 hrs to 2 ± 2 at 18 hrs for the sal group, 82 ± 9 to 2 ± 3 for the lid group and 73 ± 14 to 1 ± 1 for bup group. bup dogs were significantly less sedated than the sal dogs. limitations: pain scores were subjective, but the observer was well trained. the exact p-values for the statistically significant differences were not displayed in the results. savvas et al. (2008) population: dogs that were presented for midline coeliotomy. dogs that were in the american society of anesthesiologists (asa) physical status classification system >3, were excluded from the study. sample size: 60 dogs (35 females, 25 males) intervention details: four groups (15 dogs per group randomly assigned: bupivacaine preoperatively (b-pre) bupivacaine postoperatively (b-post) normal saline preoperatively (ns-pre) normal saline postoperatively (ns-post) all animals were fasted for 8 hrs before anaesthesia. premedication with acepromazine 0.05 mg/kg im and meperidine 3 mg/kg im. induction with thiopentone 6–8 mg/kg iv. maintenance of anaesthesia with isoflurane in oxygen. before the start of the incision, 0.8 ml/kg bupivacaine 0.25% or normal saline in the b-pre or ns-pre respectively, was injected sc and im at the incision site. fentanyl at 2 μg/kg iv and morphine at 0.1–3 mg/kg im were given when the pain score was above 5. dogs were monitored from induction to discontinuation of anaesthesia for variables including systolic, diastolic and mean arterial pressure, electrocardiogram, oxygen saturation, inspired and etco2, isoflurane concentration, oxygen percentage and rr. any dogs that required additional analgesia were excluded from the study. study design: blinded, placebo-controlled, randomised clinical trial outcome studied: pain and sedation were scored at 1, 2, 3, 4, 5, 6, 16 to 20 and 24 hrs after surgery. pain was assessed based on a numerical scale from 0 to 10 (0=no pain, 10=full pain) and sedation based on another scoring system (0=fully alert, 1=alert but unable to walk, 2=drowsy and unable to stand and 3=heavily sedated/asleep). after surgery, the dog’s posture, behaviour, vocalisation, and food/water consumption, the willingness to move and the pattern of locomotion and the response to the palpation of the incision area were noted. main findings (relevant to pico question): maximal pain score (mean ± sd) for b-pre: 3.67 ± 1.11, b-post: 5.20 ± 1.30, ns-pre: 6.67 ± 1.59, ns-post: 6.53 ± 1.13. time points of pain scores: 2 hrs after surgery in 48/60 dogs, 3 hrs after surgery in 55/60 dogs and within 4 hrs in 60/60. supplemental postoperative analgesia: b-pre: 0/15, b-post: 7/15, ns-pre: 11/15, ns-post: 11/15. statistically significant difference was the mean maximal pain score between the b-pre group and the other three groups. b-pre group was also statistically different from the other three groups concerning less additional postoperative analgesia (p<0.0005). limitations: no power calculation. the choice of the pain score as it was based on behavioural criteria. the duration of the surgery was not recorded but the duration of anaesthesia was monitored. fitzpatrick et al. (2010) population: shelter-owned, sexually intact, female dogs of various ages and breeds sample size: 92 dogs randomly assigned in four groups intervention details: group i (n=26) – no incisional (inc) injection. group ii (n=12) – pre-incisional saline solution infiltration. group iii (n=21) – pre-incisional bupivacaine infiltration. group iv (n=33) – post-incisional bupivacaine infiltration. premedication with acepromazine at 0.01 mg/kg with morphine 1 mg/kg and atropine 0.02 mg/kg im. induction with thiopentone at 15 mg/kg iv. maintenance with isoflurane. all the inc injections were given at a volume of 0.8 ml/kg. bupivacaine injections at 2 mg/kg dose diluted to the proper volume in saline solution (inc) hydromorphone at 0.1 mg/kg sc was given at extubation in all dogs. buprenorphine at 0.02 mg/kg sc every 6 hrs for 24 hrs in all dogs of all dogs. dogs with glasgow score >10 were given a supplementary rescue dose of buprenorphine at 0.02 mg/kg im. carprofen at 2.2 mg/kg sc or po every 12 hrs for 3 days in all dogs. study design: blinded, randomised, controlled clinical trial outcome studied: pain assessment at 4, 8, 12 and 24 hrs after surgery with glasgow scale and von frey filaments. incision assessment at 4, 8, 12 and 24 hrs after surgery for oedema, erythema, discharge, inc infection or dehiscence. main findings (relevant to pico question): incision length was significantly greater in group iii. glasgow pain scores were significantly decreased from 4 to 24 hrs in groups i, iii and iv. no statistically significant decrease for the same hours in group ii (p=0.125). no dog with glasgow pain score >10. von frey filament score did not differ significantly for group i, iii and iv from 4 to 24 hours. this score was significantly decreased in group ii (p=0.031). there was a higher rate of complications by the time of the suture removal in dogs that received pre-incisional infiltration of bupivacaine compared with dogs that received no injection at the incision site. however, bupivacaine was not indicated for the higher rate of complications in this group. limitations: ovariohysterectomy was performed by non-experienced 4th year veterinary students and this may have affected the results as they had a greater inexperience. no equal number of dogs in each group because of scheduling conflicts and the availability of investigators. high dose of morphine as premedication and thiopental for induction. postoperative analgesia with hydromorphone, buprenorphine and carprofen in all dogs independently of the pain scores may have affected the results as none of the dogs required rescue analgesia. campagnol et al. (2012) population: client owned rescue dogs undergoing ovariohysterectomy sample size: 30 female dogs randomly assigned to three groups intervention details: the treatments consisted of administration of 0.9% nacl and/or 0.5% bupivacaine with epinephrine either by the ip and/or inc route. control group (n=10) – saline solution ip and inc. ip group (n=10) – bupivacaine 5 mg/kg ip and saline solution inc. inc group (n=10) – saline solution ip and bupivacaine 1 mg/kg inc. acepromazine 0.05 mg/kg and butorphanol 0.2 mg/kg as premedication. thiopental 10 mg/kg intravenously for induction. blinded single surgeon performed all the procedures and the administration of the solutions. rescue analgesia with morphine (0.5 mg/kg im) was given if vas or nrs scores were higher than 5 and 10 respectively. study design: prospective, blinded, randomised clinical study outcome studied: during postoperative period, any signs of local anaesthetic toxicity were recorded. postoperative pain and sedation were evaluated 1, 2, 3, 4, 6, 12 and 24 hrs after extubation. it was evaluated through nrs from 0–29 and vas from 0–10. vas scores for both pain and sedation were performed without interaction with the dog. non-interactive parameters were evaluated before interactive parameters during nrs scoring. client-owned rescue dogs continued to be scored throughout the 24 hr observation period and data obtained from these dogs were included in the statistical analysis. main findings (relevant to pico question): 28 mixed-breed and 2 rottweilers were included in the study sedation scores did not differ amongst groups throughout the observational period. sedation was not evident in any of the dogs at 24 hrs. at 1 hr, vas pain scores were lower in ip compared to the control group (p<0.05). medians were: 6.4 in control group, 0.3 in ip group and 0.0 in inc group. from 2–24 hrs, vas and nrs scores did not differ amongst groups. rescue analgesia was given to 7/10, 3/10 and 5/10 dogs in control, ip and inc groups during the first 24 hrs respectively. dogs in control group (7/10) tended to receive rescue analgesia one hr after anaesthesia than in dogs in the ip group (3/10) and inc group (5/10). rescue analgesia was administered more than once in 3/7, 2/3 and 5/5 dogs in the control, ip and inc groups. administration of ip bupivacaine provided adequate analgesia in most dogs. pain scores were lower in dogs given the combination of ip and inc bupivacaine than in the control group. anaesthesia with acepromazine, butorphanol, thiopental and halothane seemed not to provide adequate analgesia in this study as the pain scores in the control group were higher than ip and inc groups and supplemental analgesics were needed during the postoperative period. limitations: small number of subjects in each group without power calculation. client owned rescue dogs usually excluded from the study as this may affect the overall results. large volume of bupivacaine is necessary for the ip administration as the dose of bupivacaine was five times higher than that used in the inc group. morgaz et al. (2014) population: female dogs undergoing ovariohysterectomy sample size: 38 dogs randomly allocated in two groups intervention details: lidocaine group (l) n=19 – received a continuous lidocaine infusion (2 mg/kg/hr) through a wound catheter in the peritoneal control group n=19 – received methadone at 0.2 mg/kg im every 4 hours after premedication. medetomidine at 3 μg/kg im and methadone at 0.3 mg/kg im were given as premedication. induction with propofol and maintenance of anaesthesia with isoflurane. rescue analgesia with methadone at 0.3 mg/kg iv was given when cmps-sf score >6 or divas >50mm. study design: prospective, non-blinded, randomised clinical study outcome studied: hr, rr, etco2, spo2 and non-invasive arterial blood pressure were recorded. pain assessment at baseline, 2, 4, 6, 18 and 24 hrs after the end of anaesthesia. three pain assessment systems: divas, glasgow scale (cmps-sf) and mwts. sedation assessment at baseline, 2, 4, 6, 18 and 24 hrs. lidocaine and cortisol levels were measured at baseline, 2, 6, 18 and 24 hrs after the completion of the surgery. main findings (relevant to pico question): no difference in analgesic parameters between the two groups. in control group, methadone was given at 1 and 5 hrs after the end of the surgery. rescue analgesia was given to 4/19 animals in control group and 0/19 in the l group. mean lidocaine continuous rate infusion (cri) volume was 3.17 ± 0.89 ml/hr. limitations: absence of blinding. two dogs removed the wound catheters before the end of the study. dysphoria was the most frequent adverse effect. no statistically significant differences between the groups. mckune et al. (2014) population: healthy female dogs undergoing ovariohysterectomy sample size: 59 dogs randomly allocated in to three groups intervention details: all three groups were sedated with acepromazine at 0.03 mg/kg sc. induction with propofol and maintenance with isoflurane. l/b (lidocaine/bupivacaine) group (n=20): line block prior to the incision with lidocaine at 4 mg/kg and 1 mg/kg of bupivacaine. saline at 0.05 mg/kg sc was given at the same time with acepromazine. l/bm (lidocaine/bupivacaine-morphine) group (n=19): line block prior to the incision with lidocaine at 4 mg/kg and 1 mg/kg of bupivacaine. morphine at 0.5 mg/kg sc was given at the same time with acepromazine. ss (normal saline/normal saline) group (n=20): 0.275 ml/kg of normal saline prior to surgery in the inc area and 0.05 mg/kg of saline sc at the same time with acepromazine. pain was assessed prior to the sedation (time negative zone), zero time (time of extubation), 2, 4, 6, 8 and 24 hrs post-surgery. one blinded veterinarian. rescue analgesia was morphine at 0.5 mg/kg im and given to: any animal that achieved a maximum score in any one category of the gcps; any animal with a pain score of 8 or greater on the gcps; any animal who did not improve over time as compared to pre-sedation gcps score; any animal developing aggression; or any animal with a combination of these previous factors. study design: prospective, randomised, blinded clinical trial outcome studied: hr, rr and systolic blood pressure were recorded four pain score systems: vas, glasgow scale (gcps), umps and von frey main findings (relevant to pico question): 20/59 dogs required rescue analgesia (7/20 in l/b group, 3/ 19 in l/bm group and 10/20 in ss group). vas, gcps and umps analyses showed no significant differences in pain score systems between groups. no statistically significant difference between the positive (l/bm) and negative group (ss) at any given time point. limitations: no significant difference between pain scores for any treatment group as the sample size was small. the initial sample size calculations hindered the study in two ways. in order to correctly calculate the initial sample size, the p-value should be corrected to 0.017 and this was not done. low pain scores may be due to inherent insensitivity of the measurement techniques preventing a significant difference between negative and positive controls. von frey may not be appropriate for assessing sensitivity of clinical wounds according to previous studies. appraisal, application and reflection the purpose of this knowledge summary was to look at the evidence for the use of bupivacaine through the line block in dogs undergoing midline coeliotomy. seven papers were identified as relevant to this question. five out of seven were blinded clinical trials (carpenter et al., 2004; savvas et al., 2008; fitzpatrick et al., 2010; campagnol et al., 2012; and mckune at al., 2014), four out of seven were prospective clinical studies (carpenter et al., 2004; campagnol et al., 2012; morgaz et al., 2014; and mckune at al., 2014) and one was an experimental, pharmacology, non-blinded, non-controlled study. only one study (savvas et al., 2008) evaluated the effectiveness of pre-emptive incisional block with bupivacaine on postoperative pain and opioid requirements after coeliotomy in dogs. according to this, preoperative wound infiltration with bupivacaine is an effective technique to reduce postoperative pain but further studies are needed. back to 2004, there were two clinical studies. the first one, wilson et al. (2004), determined the safe dose of intraperitoneal and incisional lidocaine applied in dogs undergoing ovariohysterectomy but no evaluation of pain scores was reported. the second was by carpenter et al. (2004) where they found that intraperitoneal and incisional bupivacaine provided effective analgesia following ovariohysterectomy in dogs. in contrast, fitzpatrick at al. (2010) found that there is no any additional analgesic benefit of infiltration with bupivacaine at the incision site, given either pre-emptively or following surgery when used as part of multimodal analgesic protocol for dogs undergoing routine ovariohysterectomy. another study (campagnol et al., 2012) compared the effect of intraperitoneal or incisional bupivacaine on pain and analgesic requirement after ovariohysterectomy in dogs without any statistical difference. there was only one clinical trial (morgaz et al., 2014) where lidocaine was used through the intra-peritoneal continuous wound infusion for pain control following ovariohysterectomy in dogs, but the results were not statistically significant as the postoperative analgesia was similar to the analgesia provided by methadone. lidocaine and bupivacaine were used as a pre-incisional local anaesthetic block in dogs undergoing ovariohysterectomy (mckune et al., 2014). however, even in this prospective, blinded, randomised clinical trial, there were no firm conclusions about whether or not this line block is effective. in conclusion, it is not clear if the use of a local anaesthetic including bupivacaine or lidocaine as incisional blocks minimises the postoperative pain especially in the first 24 hours, as the results are not statistically significant between the groups. as the sample sizes were so small and multiple analgesics were used in the clinical trials, further studies are necessary.   methodology section search strategy databases searched and dates covered: pubmed on ncbi platform, scopus, web of science including cab abstracts, google scholar, accessed via the ncbi website (2000–2019) search strategy: (dog or dogs or canine) and (bupivacaine) and (lidocaine) and (incisional block or pre-incisional or line block) and (coeliotomy or celiotomy) dates searches performed: 30 sep 2020 exclusion / inclusion criteria exclusion: articles not available in english, single case reports, book chapters, articles which were not relevant to the pico question, articles listed on but not provided by the searched databases inclusion: articles available in english which were relevant to the question search outcome database number of results excluded – not relevant to the pico question excluded – other animals total relevant papers pubmed 11 8 0 3 scopus 9 2 0 7 web of science 8 2 0 6 google scholar 91 74 10 7 total relevant papers when duplicates removed 7 conflict of interest the author declares no conflict of interest. references campagnol, d., teixeira-neto, f. j., monteiro, e. r., restitutti, f. & minto, b. w. (2012). effect of intraperitoneal or incisional bupivacaine on pain and the analgesic requirement after ovariohysterectomy in dogs. veterinary anaesthesia and analgesia. 39(4), 426–430. doi: https://doi.org/10.1111/j.1467-2995.2012.00728.x carpenter, r., wilson, d. & evans, a. (2004). evaluation of intraperitoneal and subcutaneous lidocaine and bupivacaine for analgesia following ovariohysterectomy in the dog. veterinary anaesthesia and analgesia. 31(1), 46-52. doi: https://doi.org/ 1111/j.1467-2995.2004.00137.x fitzpatrick, c. l., weir, h. l. & monnet, e. (2010). effects of infiltration of the incision site with bupivacaine on postoperative pain and incisional healing in dogs undergoing ovariohysterectomy. journal of the american veterinary medical association. 237(4), 395–401. doi: https://doi.org/10.2460/javma.237.4.395 mckune, c. m., pascoe, p. j., lascelles, b. d. x. & kass, p. h. (2014). the challenge of evaluating pain and a pre-incisional local anesthetic block. peerj. 2(1), e341. doi: https://doi.org/10.7717/peerj.341 morgaz, j., muñoz-rascón, p., serrano-rodríguez, j. m., navarrete, r., domínguez, j. m., fernández-sarmiento, j. a., gómez-villamandos, r. j., serrano, j. m. & del mar granados, m. (2014). effectiveness of pre-peritoneal continuous wound infusion with lidocaine for pain control following ovariohysterectomy in dogs. veterinary journal. 202(3), 522–526. doi: https://doi.org/10.1016/j.tvjl.2014.08.030 savvas, i., papazoglou, l. g., kazakos, g., anagnostou, t., tsioli, v. & raptopoulos, d. (2008). incisional block with bupivacaine for analgesia after celiotomy in dogs. journal of the american animal hospital association. 44(2), 60–66. doi: https://doi.org/10.5326/0440060 wilson, d. v., barnes, k. s. & hauptman, j. g. (2004). pharmacokinetics of combined intraperitoneal and incisional lidocaine in the dog following ovariohysterectomy. journal of veterinary pharmacology and therapeutics. 27(2), 105–109. doi: https://doi.org/10.1111/j.1365-2885.2004.00552.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. evaluation of factors influencing thigh circumference measurement in dogs ana luisa bascuñán dvm1 nina kieves dvm, dacvs-sa, dacvsmr1 clara goh css bvsc, ms, dacvssa1 juliette hart dvm1 penny regier dvm1 sangeeta rao bvsc, mvsc, phd1 sasha foster mspt1 ross palmer dvm, ms, dacvs1 felix michael duerr dvm, ms, dacvs-sa, decvs, dacvsmr1* 1department of clinical sciences, colorado state university, 300 w drake rd., fort collins, co. 80523 *corresponding author (felix.duerr@colostate.edu) vol 1, issue 2 (2016) published: 05 may 2016 reviewed by: wanda gordon-evans (dvm, phd, dacvs dacvsmr) doi: 10.18849/ve.v1i2.33 section index:    abstract | introduction | methods | results | discussion | footnotes | conflict of interest | references | supplementary files abstract objective: to evaluate interand intra-observer variability, influence of hair clipping and laser guidance on canine thigh circumference (tc) measurements amongst observers. background: it was our goal to further study the reliability of canine tc measurements as currently performed. for this purpose we designed a cadaveric model that allows for controlled inflation of the thigh resembling increase of muscle mass. we also investigated the impact of novel technologies (laser guidance) and hair clipping on tc measurements in this model.  evidentiary value: phase 1 cadaveric study five long-haired, large breed canine cadavers; phase 2 clinical study eight clinically healthy golden retrievers. this study should impact clinical research and practice. methods: phase 1 canine cadaveric thigh girth was manually expanded to three different levels using a custom, submuscular inflation system before and after hair clipping; phase 2 tc of golden retrievers was measured with and without laser guidance. tc measurements for both phases were performed by four observers in triplicate resulting in a total of 552 measurements.  results: phase 1 tc measurements before and after hair clipping were significantly different (3.44cm difference, p<0.001). overall inter-observer and intra-observer variability were 2.26±1.18cm and 0.90±0.61cm, respectively. phase 2 laser guidance nominally improved inter-observer variability (3.34 ±1.09cm versus 4.78 ±2.60cm) but did not affect intra-observer variability (1.14 ±0.66cm versus 1.13 ±0.77cm). conclusion: tc measurement is a low fidelity outcome measure with a large interand intra-observer variability even under controlled conditions in a cadaveric setting. current methods of canine tc measurement may not produce a valid outcome measurement. if utilised, hair coat clipping status should be considered and an intra-observer variability of at least 1cm should be assumed when comparing repeated tc measurements. laser guidance may be helpful to nominally reduce inter-observer variability in settings with multiple observers. further investigation of alternative methods for canine tc measurement should be pursued. application: this information should be considered by everyone utilizing tc measurements as an outcome assessment for clinical or research purposes. introduction assessment of muscle mass in canine patients is a commonly used subjective and objective outcome measure for evaluation of musculoskeletal disease (monk et al., 2006, moeller et al., 2010, eskelinen et al., 2012, gordon-evans et al., 2011, kalis et al., 2012, innes and barr, 1998). definitive measurement of muscle mass involves advanced imaging, making it impractical and cost prohibitive in most clinical cases. limb circumference measurement with a tape measure is frequently used in both human and veterinary patients as an indirect measure of changes in muscle mass over time (doxey, 1987a, doxey, 1987b, jarvela et al., 2002, thomaes et al., 2012). practical and affordable means of outcome measurement are critical to the veterinary field. as an example, cranial cruciate ligament disease (ccld) is a common orthopaedic disease in the canine patient with substantial on-going research evaluating treatment outcomes (kim et al., 2008),(slocum and slocum, 1993). tc has been used to evaluate symmetry in muscle mass between pelvic limbs and hence is often used as an objective evaluation of response to treatment of ccld (gordon-evans et al., 2010, gordon-evans et al., 2011, gordon-evans et al., 2013, moeller et al., 2010). unfortunately previous studies evaluating canine tc measurement using various tape measures have shown significant interand intra-observer variability (smith et al., 2013, baker et al., 2010). use of a spring-tensioned device (gt) is recommended to decrease variability in the force used by the observer when tensioning the tape measure around the limb (millis et al., 1999, millis, 2004). however, this technology is reportedly only reliable for measurements of the proximal antebrachium in canines and its validity for thigh circumference measurement has been questioned (smith et al., 2013). without reliable methods for tc measurement, this assessment may give an incomplete or erroneous evaluation of response to therapy and intervention. the reason for the previously reported poor reliability of canine tc measurement is unclear. potential variables include hair coat length, variation in the site of measurement due to a lack of clearly identifiable landmarks on the limb, limb position, and dog movement. to improve reliability of measurements in human subjectsseveral devices have been created that control height and angle of the measurement along the limb (berard and zuccarelli, 2000, berard et al., 1998, berard et al., 2002, soderberg et al., 1996). however, these devices are difficult to apply to the canine patient due to differences in anatomy. the purpose of this study was to evaluate the impact these potential variables play in tc measurement of the canine. to eliminate the need to rely on palpation of anatomic landmarks, the authors of the present study used a device that projected a laser line across the canine limb, guiding placement of the measuring tape across the thigh. to eliminate dog movement as a factor, we developed a cadaveric model affixing the limb in space while measuring tc. to evaluate hair coat as a factor,  cadavers were measured preand post-hair clipping. our specific aims were to determine if hair coat clipping affects tc measurement, to determine the intraand inter-observer variability of tc under constant conditions using an affixed limb, and to evaluate the effect of laser guidance on interand intra-observer variability of tc measurements in a clinical setting. we hypothesised that hair coat clipping would not significantly affect tc measurements made with a gt, and that using a laser guidance device would decrease both intraand inter-observer variability of tc measurements. methods this study was performed in two phases: first, to evaluate the effect of hair coat length (preand post-clipping) across a range of muscle masses and to determine the interand intra-observer variability of tc measurement under constant conditions, cadaveric limbs were measured in a fixed position. second, to evaluate the effect of laser guidance on tc measurement, live dogs were measured with and without a device that projects a laser line across the canine limb. phase 1: cadaveric study cadavers of long-haired, large breed canines (n=5) euthanized for reasons unrelated to the study were utilised. a custom, submuscular thigh expansion system was developed to  simulate incrementally increasing thigh muscle mass in a cadaveric model. inflation devices were created by attaching surgical gloves (perry orthopaedic, size 7.5, red bank, nj, usa) to red rubber catheters (20 french, tyco healthcare group, mansfield, ma, usa) with a finger trap suture pattern. a standard cranio-lateral approach to the femur of the right hind limb of each cadaver was performed, and one inflation device was inserted in between the femur and quadriceps muscle group, and a second device was inserted between the adductor and biceps femoris muscle bellies. anatomic closure was performed to secure the inflation devices in place under the muscle bellies. the distal limb was secured to a wooden block at the metatarsus to ensure no limb movement occurred between measurements. the cadavers were positioned in lateral recumbency for tc measurement. a 60cc syringe (monoject, covidien, mansfield, ma, usa) was attached to each of the red rubber catheters, and each device was inflated or deflated with water to one of three predetermined volumes (0ml, 60ml, or 120ml total volume split evenly between the two inflation devices) in random order. observers were blinded to the inflation volume. after the measurements were made, the water was removed from the inflation devices and confirmed to be the same total volume (120ml) to detect any leakage within the system. figure 1: this image depicts the left hind limb of a golden retriever with the laser line device positioned midway between the greater trochanter and the lateral femoral condyle to guide measurement each of the observers was instructed in how to measure tc using the gt (country technology, inc. model #67019, gays mills, wi) and given time to practice making measurements until the procedure was routine. observers then measured tc of each limb three times at each level of inflation before and after clipping of fur. fur was clipped in surgical fashion (to the skin) with a number 40 blade in a complete ring around the thigh. to reduce variability in position of the gt on the lateral aspect of the limb between repeated measurements and between observers, a laser line device (cross line self leveling laser, model # gll2-10, bosch, usa) was positioned to project a line at the estimated midpoint between the palpated anatomic landmarks (greater trochanter and the lateral femoral condyle) to guide measurement in all cadavers. the laser device was self-leveling to ensure consistent angle of projection of the beam. cadavers remained in the same position throughout data collection to avoid any variability in the positioning of the laser guidance line while performing serial measurements. the gt used for all measurements was ‘blinded’ to observers by covering the outward facing measurement scale with black electrical tape. an independent observer recorded measurements by carefully pinching the tape without imparting any movement and then rotating it to visualise the inward facing scale. the observer recording the blinded measurements was the same throughout the study to avoid variability incurred while pinching and rotating the tape. the gt was completely removed from around the thigh between each consecutive measurement. phase 2: live dog study live dogs were used to evaluate tc measurements made using the gt and the laser line device in a clinical setting. the same trained observers who participated in the cadaveric portion of the study measured the tc of healthy golden retrievers (n=8) using the blinded gt with and without the laser device for guidance. for non-laser guided measurements, tc was measured as previously described (midway between the palpated greater trochanter and lateral femoral condyle) with the dog in normal weight bearing position (smith et al., 2013). for laser-guided tc measurements, dogs were positioned in a normal weight bearing, square stance on a location marked with an ‘x’ on the floor. this was done to decrease the variability in distance from the laser device. the laser level was placed on a tripod and positioned such that it projected at mid-thigh level on each dog (figure 1). the height of the laser level beam on the wall was recorded for each dog so that the same level of measurement could be replicated between observers and measurements. each observer measured the left pelvic limb three times with and without laser guidance in random order and the gt was removed from around the thigh between each consecutive measurement. when laser guidance was used, tc measurements were performed along the displayed laser line. statistical analysis the data analyses were performed using sas v9.3 (sas institute inc., cary, nc, usa). variability was defined as the mean range in measurements performed under the same circumstance (i.e. the same inflation level or dog); thus a value of 0 would indicate an ideal test with no inherent variability. difference was defined as the mean difference between measurements performed under different circumstances (i.e. different inflation levels or clipped vs. intact hair coat). the data in both live and cadaver dogs were evaluated for normality assumptions. the data on live dogs were analysed using a bivariable linear regression analysis to compare the difference in mean circumference between laser guided and non-laser guided measurements. a bivariable linear regression was also used to evaluate the differences in measurement among the observers. multiple measurements by the same observer on an individual dog were included in the analysis to account for the variability around the mean from repeated observations. the data on cadaver dogs were evaluated using a multivariable linear regression analysis. repeated measures on the same dog were taken into account in the analysis. tc difference was calculated using repeated observations within each dog from all observers. a p-value <0.05 was considered for determining statistical significance. results phase 1: cadaveric data – five long-haired, large breed canine cadavers were used (3 golden retrievers, 1 st. bernard, and 1 malamute). a total of 360 measurements were performed. inter-observer variability in tc measurement when all inflation levels were combined was 2.26±1.18cm. intra-observer variability in tc measurement for all 4 observers when all inflation levels were combined was 0.90±0.61cm (see table 1). mean tc measurement was significantly different between the three inflation levels of the submuscular device (see table 2). tc measurements made on long-haired (unclipped) limbs at all inflation levels were significantly different than those made on the same limbs after clipping the hair (see table 2). inter-observer variability did not improve with clipping of hair coat (see table 1). table 1: phase 1 cadaveric data interand intra-observer variability of tc measurement (in cm) for measurements at all different inflation levels combined table 2: phase 1 cadaveric data comparison of tc measurements made by all observers at different inflation levels and different hair lengths phase 2: live dog data – eight clinically healthy golden retrievers were used. a total of 192 measurements were performed. for measurements made with laser guidance, tc measurements between one pair of observers (observers 1 and 3) differed significantly. in the non-laser guided group three observer comparison pairs were significantly different in their tc measurements (see table 3). the inter-observer variability was smaller in the laser guided group compared to the non-laser guided group (3.34 ±1.09cm compared to 4.78 ±2.60cm). however, no statistically significant difference in either intraor inter-observer variability was found between laser guided and non-laser guided measurement groups (see table 4). table 3: phase 2 live dog data pairwise comparisons between observers of difference in tc measurement (cm) table 4: phase 2 live dog data variability of tc measurement (cm) with and without laser guidance discussion the use of tc measurement is often cited as an objective measure of response to treatment of various pelvic limb injuries and diseases. to our knowledge, no peer-reviewed studies have evaluated the effect of hair coat clipping on tc measurement, or the use of laser guidance to decrease variability of tc measurement. furthermore, no peer-reviewed studies have evaluated the interand intra-observer variability of tc under constant conditions. we developed a cadaveric model that allowed us to mimic progressively increasing muscle mass while eliminating patient motion. this model also allowed us to evaluate hair clipping as the only variable in actual thigh circumference. in the live dog study we attempted to improve consistency of placement of the gt for tc measurement by utilising laser guidance. the results of our study show that tc measurement is a low fidelity outcome measure that should be utilised and interpreted cautiously in clinical practice. even under highly controlled conditions using affixed cadaveric pelvic limbs, large and clinically significant interand intra-observer variability was demonstrated. we found the difference between tc measurements at each of the three inflation levels of the submuscular expansion device to be statistically significant with ~1cm increase in tc per inflation level, suggesting that this custom model is suitable for future application. the difference seen was similar to previous reports using in vivo models of muscle hypertrophy (monk et al., 2006, gordon-evans et al., 2010, gordon-evans et al., 2011, gordon-evans et al., 2013). when considering this value, an inter-observer variability in measurement of more than 2cm demonstrates that the current guidelines for tc measurement are not sufficient to provide reproducible results between observers. this is consistent with previous studies that demonstrated poor intraand inter-observer reliability in canine tc measurement in a clinical setting (smith et al., 2013, baker et al., 2010): baker et al. reported an intra-observer variability of 0.57cm and an inter-observer variability of 1.51cm when measuring canine tc with the gt (baker et al., 2010). smith et al. demonstrated poor reliability in canine tc measurement using intra-class correlation coefficients (icc), with less than 0.59 considered unreliable. the intra-observer iccs ranged from 0.29-0.60, while the inter-observer iccs ranged from 0.23-0.43 (smith et al., 2013). previously published studies have attributed variability in measurement to factors such as limb position, dog movement, and site of measurement along the limb (smith et al., 2013, baker et al., 2010). the results of our study indicate that in addition to these factors, the technique itself is responsible for this poor reliability. despite controlling these factors in the cadaveric portion of this study, variability still existed both within and between observers. this suggests that an unidentified variable may affect measurements of tc with the gt. possible causes of this could be inconsistent placement of the gt on the medial aspect of the thigh, slipping of the gt given the conical shape of the thigh musculature, or differences in clinical experience and skill with the gt. all observers were trained to use the gt prior to data collection; however differences in comfort with or prior exposure to the gt may have contributed to poor reliability in measurement. given that the measured difference in tc between minimum and maximum inflation levels of the submuscular expansion device was less than 2cm, an intra-observer variability of almost 1cm and an inter-observer variability of over 2cm calls to question the ability of the gt to detect true changes in tc even when utilised by a trained observer. though the gt has been validated in previous studies for the measurement of tc on a single occasion, no study has confirmed the sensitivity of the gt to changes in canine tc while also accounting for the inherent variability in measurement (baker et al., 2010, millis, 2004). furthermore, the clinical significance of changes in tc is not well established in the literature. moeller et al. demonstrated that 5 years after unilateral tibial plateau leveling osteotomy, dogs had significantly smaller tcs on the operated limb compared to the non-operated limb, but that no subjective lameness was associated with this difference.(moeller et al., 2010) given the results from the present study, it is possible that the large standard deviation and minimal difference between groups in the moeller study (39.5 ± 5.5cm vs. 40.1 ± 5.6cm) resulted in a type-i statistical error. we found that hair clipping affects measurement of tc performed with a gt. this finding is of particular importance when evaluating tc after surgical procedures or other procedures that require hair clipping. millis et al. studied variables affecting limb circumference measurement with the gt (millis et al., 1999, millis, 2004). it was reported in the non-peer reviewed literature that hair coat length had minimal effect on measurement, however only short-haired dogs were used in that study (millis, 2004, millis et al., 1999). in the current study, hair coat status significantly affected measurements with the gt. this is most likely due to the tensioning device being designed for use in humans rather than canines. since humans have little variation in hair coat, a different degree of tensioning may be needed for canine tc measurement. this is an important consideration in patients that undergo orthopaedic surgery and rehabilitation, as perceived changes in tc may be due to changes in hair coat alone (i.e. hair regrowth after surgery). this is also important when interpreting previously reported tc measurements. several studies report changes in thigh circumference in the months after surgery without specifying the length of hair coat or whether the baseline measurements were taken prior to hair clipping (slocum and slocum, 1993, innes and barr, 1998, lauer et al., 2008). other studies have found significant differences between treatment groups before and after surgical correction, or compared to the contralateral limb. for example, johnson et al. found a significant difference in tc between ccl-deficient dogs treated with electrical muscle stimulation and a control group at weeks 9 and 13 post-operatively (30.8±2.3cm vs. 27.2±2.3cm and 30.6±2.3cm vs 27.4±2.2cm, respectively), but hair coat length was not controlled between groups (johnson et al., 1997). monk et al. demonstrated an increase in tc of 2.75±0.96cm in a surgically corrected limb followed by physical therapy and a decrease in tc of 0.5±0.28cm in surgically corrected limbs without physical therapy, however hair coat length was not described in this paper (monk et al., 2006). measurements evaluating surgical outcome, or response to treatment, should be performed prior to hair clipping, and only after the hair coat has fully returned. alternatively the hair coat should be shaved consistently, which seems impractical in a clinical setting. if immediate post-operative changes are to be evaluated, pre-operative measurements should be made after shaving the limb to decrease the effect of hair coat in measurements. the mid-thigh is the most logical area to be measured when expecting differences in muscle mass due to the bulk of the muscles being located in this area. however, the current descriptions of the pertinent landmarks are imprecise and hence are influenced by the interpretation and palpation skills of each observer. there is no precise way of using anatomic landmarks to determine a repeatable measurement point. the use of laser guidance offers a method of ‘marking’ the area of interest that is feasible to use even during long-term studies with repeated measurements. while, for the study purposes, we could have marked the area by clipping the fur and using a skin marker, this is not realistic in a clinical setting using client-owned dogs. hair coat was not clipped in any of the live dogs, so the presence of an intact hair coat may have resulted in overestimation of tc in the second phase of this study. because we were interested in the reliability of measurement rather than the definitive values, the effect of hair coat on absolute tc in the live dogs was not evaluated. based upon our study results, the use of a laser-guidance tool may slightly improve inter-observer variability when measuring tc in live dogs. this may be of importance in clinical settings in which multiple observers perform tc measurements. previous studies have suggested a single observer improves reliability in measurement(smith et al., 2013, baker et al., 2010) and our study confirms these findings. however if multiple observers are performing tc measurements on the same patient over time, the use of laser guidance may be indicated to provide a consistent marking of mid-thigh level in an individual patient. at the patient’s first tc measurement, the height of the laser line should be recorded and set accordingly at each subsequent measurement (assuming that the position of the dog and the laser device relative to the wall can be repeated). in this study, intra-observer variability in measurement was similar both with and without laser guidance. this is likely associated with the fact that an individual will use the same palpation methods and interpretation of current guidelines. if tc measurement is to be used as an indirect measure of thigh muscle mass, the current study suggests that an intra-observer variability of at least 1.15cm should be assumed. again, this value in comparison to the cadaveric data calls into question the clinical value of tc measurements. one limitation of this study was the use of simulated muscle mass changes in cadavers, rather than natural changes in live dogs. this model was developed by the authors of this study to allow making multiple tc measurements across a range of thigh volumes within an individual patient under highly controlled circumstances. this model also decreased the number of cadavers needed to achieve a meaningful dataset representing a range of thigh volumes. the degree of inflation of the submuscular expansion device was chosen to mimic a clinically appreciable increase in muscle mass. while the model was not validated with advanced imaging, we were able to confirm an increased circumference based on palpation as well as visual confirmation during pilot testing. a fluid-filled expansion device was chosen so that leakage could be detected by comparing initial volume to final volume. under this model it is possible that fluid redistribution within the expansion device contributed to intraand inter-observer variability. because the gt is not tensioned to a high degree around the thigh during measurement, this influence was likely minimal. comparison of tc between device inflation levels demonstrated that the model produced measureable differences in tc and hence should be considered as a useful model for future studies. using the described model, a mean tc difference of 1.96cm was measured between the lowest (0ml total inflation) and highest (120ml total inflation) levels of inflation. this cadaveric model of thigh girth expansion is also supported by previous studies, which state that small changes in tc represent significant changes in muscle mass (doxey, 1987a). a study in men demonstrated that tc changes by only 1.10-1.40cm when a workout regimen targeting the thigh muscles is employed (weiss et al., 2000).23 therefore, minimal changes in tc are likely clinically relevant. ideally a ct scan would have been utilised to confirm true changes in limb circumference under this cadaver model (thomaes et al., 2012), but this was cost prohibitive for the scope of this study. when interpreting our study results, one should also consider that long-haired dogs were used for evaluation of hair clipping, therefore the findings may not be applicable to short-haired dogs.  however, given the large difference preand post-clipping compared to the difference seen with inflation, the authors suggest that sufficient evidence is presented that hair clipping should be considered when utilising this outcome measure. in conclusion, we found there to be a significant difference in tc measurements of the same limb with and without hair coat, therefore evaluation of tc following therapeutic intervention should take into account clipping status of hair coat at the time of measurement. we also found that the use of a laser-guidance system nominally (not statistically) improves inter-observer variability for tc measurements. however the high level of variability even when using laser-guidance essentially negates the clinical usefulness of this method. overall, the high variability in tc measurements made with the gt should be considered when evaluating previous and future studies. novel techniques for indirect assessment of thigh muscle mass, such as ultrasonographic measurement of tc should be evaluated for the use in canines to provide a more reliable and accurate outcome measure (mourtzakis and wischmeyer, 2014). abbreviations tc = thigh circumference ccld = cranial cruciate ligament disease gt = gulick ii tape measure conflict of interest disclosure: the authors do not have any conflicts of interest to declare. acknowledgments: we would like to thank keester and her amazing family for the support and contributions – you will never be forgotten. references baker, s. g. et al. 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(2000) gross measures of exercise-induced muscular hypertrophy. journal of orthopaedic & sports physical therapy, 30 (3), pp. 143-8  http://dx.doi.org/10.2519/jospt.2000.30.3.143 supplementary files, images & tables all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. managing atopic dermatitis in dogs: are antihistamines as effective as glucocorticoids? a knowledge summary by sarah long bvsc certavp mrcvs 1* 1locum veterinary surgeon, united kingdom *corresponding author (sarahmlong@hotmail.co.uk) vol 5, issue 4 (2020) published: 18 nov 2020 reviewed by: louise buckley (phd fhea rvn) and james swann (ma vetmb dacvim decvim mrcvs) next review date: 02 apr 2022 doi: 10.18849/ve.v5i4.335 pico question in dogs with atopic dermatitis, are antihistamines as effective as glucocorticoids at reducing the severity of clinical signs?   clinical bottom line category of research question treatment the number and type of study designs reviewed two randomised control trials and one crossover placebo-controlled trial strength of evidence critical appraisal of the selected papers meeting the inclusion criteria collectively provide weak evidence in terms of their experimental design and implementation outcomes reported the outcomes reported were conflicting. two studies reported that fexofenadine may be as effective as methylprednisolone at reducing the severity of clinical signs after 6 weeks of treatment however, the study size was small in one and there was limited reporting of the data in the other. the third study, the crossover placebo-controlled trial, tested a variety of antihistamines and prednisone with limited reporting of statistical analysis of the data and found that antihistamines did not provide a sufficient reduction in pruritus unless combined with prednisone conclusion in view of the strength of evidence and the outcomes from the studies, there is insufficient quality of evidence to answer the pico question and further comparative study is needed   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are presented with a 3-year-old, male neutered, labrador retriever with a history of non-seasonal pruritus affecting the feet, face, axillae and groin that has recently increased to a moderate level. he has previously been diagnosed with atopic dermatitis and had been treated with topical chlorhexidine shampoo once weekly and oral administration of sarolaner (simparica, zoetis uk ltd) monthly. clinical examination, coat brushing, trichography and cytology show no evidence of ectoparasites, microbial overgrowth or infection. as pruritus has increased to a moderate level, and given the relatively widespread distribution, you would like to prescribe a systemic medication to help manage pruritus in the short-term. the owner’s financial restrictions limit you to either glucocorticoids or antihistamines. glucocorticoids are known to be effective in managing atopic dermatitis but adverse effects are common even with short-term use e.g. polydipsia, polyuria, polyphagia, panting and more uncommonly lethargy, diarrhoea, vomiting or gastric ulceration. antihistamines have far fewer adverse effects, although they may cause sedation. however, are antihistamines as effective as glucocorticoids? the evidence three papers were found that answered the pico question directly; two randomised control trials and one crossover placebo-controlled trial. plevnik et al. (2009) directly compared the effects of methylprednisolone and fexofenadine to control pruritus and clinical lesions in dogs with atopic dermatitis. plevnik et al. (2006) performed a small, non-blinded, preliminary trial comparing the safety and efficacy of fexofenadine against methylprednisolone in dogs with atopic dermatitis. paradis et al. (1991) reported a crossover placebo-controlled trial comparing six medications with placebo. dogs with atopic dermatitis, flea bite hypersensitivity and an undiagnosed cause of pruritus were used in the study. the treatments given were: clemastine, prednisone, astemizole, doxepin, trimeprazine and trimeprazine combined with prednisone. summary of the evidence plevnik et al. (2009) population: client owned dogs of different breeds, age and sex with a clinical diagnosis of atopic dermatitis that showed signs compatible with the criteria set out by willemse (1986). exclusion criteria included: inadequately documented disease or therapy other health conditions that may have affected the study outcome (e.g. cardiac, liver or kidney disease) pregnancy flea bite hypersensitivity food allergy if not well controlled or if insufficient investigations were performed to rule this out ectoparasites, bacterial or fungal infections been prescribed any of the following: glucocorticoids within the last three weeks antihistamines within the last 14 days ciclosporin within the last 30 days essential fatty acids within the last 14 days vitamin e supplements within the last 14 days serotonin reuptake inhibitors and selective serotonin reuptake inhibitors within the last 14 days antimicrobial, antiseborrheic and keratolytic shampoos within the last 14 days immunotherapy sample size: 30 dogs divided equally between groups (15 in each) intervention details: skin scrapings and a treatment trial with stronghold spot-on (zoetis uk ltd.) were used to rule out ectoparasites, including sarcoptic mange, in all dogs prior to study inclusion. all dogs were fed an individualised elimination diet for 3 months prior to and for the duration of the study. dogs were randomly allocated to two treatment groups by alternate allocation. group m (n = 15) were given methylprednisolone orally at 0.5 mg/kg/24hrs for 5 days then 0.5 mg/kg/48hrs. group f (n =15) were given fexofenadine orally at 18 mg/kg/24hrs. patients were evaluated at days 0, 21 and 42. all dogs were treated with fipronil (frontline spot-on, boehringer-ingelheim) topically during the trial period. study design: randomised control trial outcome studied: objective measurements: cadesi-02 (canine atopic dermatitis extent severity index) scores; pvas (pruritus visual analogue scale) scores. cadesi-02 scores were achieved using a scale of photographs of clinical signs to estimate the presence and intensity of erythema, lichenification and excoriation of 40 body parts. these lesions were scored from 0–3 (0 = no skin changes). the assessors were blinded to the patient’s previous scores. pvas scores were provided by owner assessment and ranged from 0 (0 = no pruritus) to 100. statistical evaluation of the data between groups was performed using the one-way t test. evaluation of the data between the visits in each group was performed using analysis of variance (anova). significance was set at p<0.05. main findings (relevant to pico question): there is very limited reporting of the data. individual cadesi-02 scores are provided for each dog at all three time points but pvas scores are not. means of both scores were used for analysis but are only reported in a bar chart and the numbers themselves are not provided. mean cadesi-02 scores can be calculated from the data in table 1 but there is insufficient reporting of the data to calculate mean pvas scores. group m: mean cadesi-02 score was significantly lower on day 21 (22.60, p = 0.002) and day 42 (15.07, p<0.001) compared to day 0 (42.73). mean pvas score was significantly lower at day 21 (p = 0.002) and day 42 (p = 0.004) compared to day 0. group f: mean cadesi-02 score was significantly lower on day 21 (16.33, p = 0.019) and day 42 (8.07, p<0.001) compared to day 0 (40.07). mean pvas score at day 21 was not significantly different from day 0 (p = 0.215) but there was a significant difference by day 42 (p = 0.002). group f had a significantly lower mean cadesi-02 score at day 42 compared to group m (8.07 and 15.07, p = 0.012). group m had a higher mean pvas score compared to group f at day 0 (p=0.048) but not at day 21 or 42. group m dogs showed at least a 50% decrease in cadesi-02 score compared to day 0 in 8/15 dogs (53.3%, 95% ci 30.1-75.2%) and 11/15 dogs (73.3%, 95% ci 48.1–89.1%) at day 21 and 42 respectively. group f dogs showed at least a 50% decrease in cadesi-02 score compared to day 0 in 10/15 dogs (66.7%, 95% ci 41.7–84.4%) and 13/15 dogs (86.7%, 95% ci 62.1–96.3%) at day 21 and 42 respectively. both medications showed significant improvements in clinical assessment and pruritus at the end of the trial. the authors comment that fexofenadine may have a greater effect than methylprednisolone with longer-term use but was less effective at controlling pruritus during the first 3 weeks of treatment. limitations: the dose of fexofenadine used was calculated based on previous safety studies and comparative doses of other antihistamines. a study assessing the effective dose range prior to comparison with methylprednisolone would have been useful. group m had a significantly higher pvas score on day 0 compared to group f which may have introduced bias to the results. as the data is not provided it cannot be determined if this is due to one outlier or an overall group difference. the authors did not discuss if endocrine disease was investigated or excluded with blood and urine testing prior to enrolment. a ‘rash’ was noted in one dog in group f on day 21 that had not resolved by day 42. this dog was in season during that time frame and the authors suggest this may be associated with the lack of resolution of the rash. to help minimise potential variation associated with changes in hormone levels, bitches due in seasons during the trial period should have been excluded. there was very little presentation of the data obtained in the results section in particular for pvas scores. statistical analysis was also not reported in the results and first appears in the discussion. a one sample t-test was not appropriate to compare the means of two groups. it is not clear if repeated measures or one-way anova was used for the evaluation of data between the visits. confidence intervals were not provided and when calculated for at least a 50% decrease in cadesi-02 scores from day 0 to 21 or 42 are wide. there is no visual representation of data dispersion in the bar charts either. there is no information about the power of the study and why a sample size of 30 dogs was chosen. cadesi-02 and pvas are both validated scales; cadesi-02 has now been through two amendments to become cadesi-04 (olivry et al., 2002; olivry et al., 2014; and rybníček et al., 2009). however, their measurements are based on human perception adding a degree of subjectivity to them the lead author is employed by the manufacturer of fexofenadine which may have introduced bias. plevnik et al. (2006) population: client owned dogs over 6 months of age, of varying breeds and both sexes, with a clinical diagnosis of atopic dermatitis showing signs compatible with at least three major and two minor criteria as described by willemse (1986). patients were excluded for the reasons below: inadequately documented disease or therapy other health conditions (e.g. cardiac, liver or kidney disease) pregnancy flea bite hypersensitivity food allergy if not well controlled or if insufficient investigations performed to rule this out ectoparasites, bacterial or fungal infections were prescribed any of the following: glucocorticoids within the last 3 weeks antihistamines within the last 14 days ciclosporin within the last 30 days vitamin e supplements within the last 14 days serotonin reuptake inhibitors and selective serotonin reuptake inhibitors within the last 14 days antimicrobial, antiseborrheic and keratolytic shampoos within the last 14 days immunotherapies sample size: eight dogs randomly allocated to two groups intervention details: four dogs were allocated to each treatment group; the method of randomisation is not reported. group f (n = 4) were treated with 18 mg/kg/24hrs fexofenadine orally and group m (n = 4) with 0.5 mg/kg/24hrs methylprednisolone orally for 5 days, then every other day. treatment was continued for 6 weeks and assessments made at days 0, 21 and 42. study design: randomised control trial (non-blinded) outcome studied: objective measurements for each group were: aspartate aminotransferase (ast); alanine aminotransferase (alt); alkaline phosphatase (alkp) (however as these measurements are not relevant to the pico the results will not be commented in this summary) urea creatinine cadesi (lesion) score performed by clinician pruritus score (pvas) performed by owners (0–100, 0 = no pruritus) statistical evaluation of the data was performed using the one-way student’s t-test and results were considered significant if p<0.0.5. results were compared between each visit at days 0, 21 and 42 and between groups. main findings (relevant to pico question): in group f cadesi was significantly lower at day 42 (mean 4.25) compared to day 0 (mean 30.00, p = 0.011) but not at day 21 (mean 14.00, p = 0.102). in group m cadesi was not significantly different from day 0 (mean 31.25) at day 21 (mean 20.00, p = 0.470) and day 42 (mean 13.00, p = 0.171). in group m pvas score was significantly lower at day 21 (mean 3.75, p = 0.004) and day 42 (mean 17.50 p = 0.022) compared to day 0 (mean 56.25). in group f pvas score was not significantly different from day 0 (50.00) at day 21 (33.75, p = 0.668) or day 42 (23.75, p = 0.374). there was no significant difference between day 0 and days 21 or 42 for ast, alt, alkp, urea or creatinine in either group. cadesi scores were not significantly different between group f and group m at day 0 (p = 0.898), day 21 (p = 0.500) and day 42 (p = 0.111). pvas scores were not significantly different between group f and group m at day 0 (p = 0.625), day 21 (p = 0.078) and day 42 (p = 0.736). both medications reduced mean cadesi and pvas scores by at least 50% at day 42 compared to day 0. individual cadesi and pvas scores or measures of variation are not reported. limitations: fexofenadine dose was calculated based on other antihistamine doses and an acceptable number of tablets to give orally rather than efficacy studies. the method of randomisation is not reported. there was a difference in some baseline biochemistry levels. the method of randomisation was not explained. whilst cadesi and pruritus scores decreased by at least 50% during treatment only methylprednisolone produced a significant reduction in pruritus and fexofenadine a significant reduction in lesion score although this may have been affected by the small group sizes. as only mean cadesi and pvas scores are reported, the level of variance around the mean should have been included. the student’s t-test was not appropriate to compare repeated measurements. the power of the study is not calculated and the sample size of only four dogs per group is likely too small to demonstrate a significant difference. cadesi and pvas are both validated scales; cadesi has now been through three amendments to become cadesi-04 (olivry et al., 2014; and rybníček et al., 2009). however, their measurements are based on human perception adding a degree of subjectivity to them. the lead author is employed by the manufacturer of fexofenadine which may have introduced bias. paradis et al. (1991) population: dogs of variable age, breed and sex that were presented to the university of montreal with a history of pruritic skin disease ranging from 6 months to 5 and a half years in duration.  non-seasonal atopy was diagnosed using history, clinical signs and compatible reactions on intradermal skin testing. a 3 week diet trial with lamb or fish and rice was used to determine if cutaneous adverse food reaction was present. flea bite hypersensitivity was diagnosed using history, clinical signs and compatible reactions on intradermal skin testing. idiopathic pruritus was defined as non-seasonal and not responding to the 3 week elimination diet; these dogs did not receive intradermal testing. none of the dogs had pyoderma at enrolment. sample size: 30 dogs: 21 with non-seasonal atopy two with non-seasonal atopy and cutaneous adverse food reaction two with non-seasonal atopy and flea bite hypersensitivity one with flea bite hypersensitivity four with non-seasonal idiopathic pruritus intervention details: each dog acted as its own control. dogs were treated with each drug individually for 1 week followed by a 2 day wash-out period taking the trial length to 9 weeks in total. the drugs used were (dosages for small (<10kg), medium (10–25kg) and large (>25kg) dogs): astemizole (2.5 mg, 5 mg and 10 mg once daily) clemastine (0.5 mg, 1 mg and 1.5 mg twice daily) doxepin (10 mg, 20 mg and 30 mg thrice daily) trimeprazine (5 mg, 10 mg and 15 mg twice daily) trimeprazine with prednisone (5 mg and 2 mg, 10 mg and 4 mg and 15 mg and 3 mg respectively, twice daily) prednisone (2 mg, 4 mg and 6 mg twice daily) placebo (100 mg lactose tablet once daily for all dogs) the trial was double-blinded with neither the owner nor veterinary surgeon were aware of which treatment was being given at any time. owners were given a data sheet to record daily drug administration and observations. results were evaluated at the end of trial and discussed over the phone or at the hospital. at the end of the 9 week trial, if one or more of the drugs was deemed effective a further 2 week course of each was given to assess if efficacy was sustained. where prednisone was effective, including in combination with trimeprazine, the minimal effective prednisone dose was established. doses of each drug were divided into small dog (<10 kg), medium (10–25 kg) or large (>25 kg) and not calculated on a mg/kg basis. 26/30 dogs were diagnosed with atopic dermatitis; 15/26 atopic dogs started immunotherapy at the end of the study and 4/26 dogs 3 weeks before the end of the study and 7/26 atopic dogs did not start immunotherapy during the study period. study design: double-blinded crossover placebo-controlled trial outcome studied: subjective measurements: improvement in pruritus was recorded by owners as: none-to-worse poor good excellent a satisfactory response was defined as good or excellent with sustained efficacy and unsatisfactory as poor or none-to-worse sustained efficacy. statistical analysis of the data was limited to correlation between improvement or adverse effects with age, breed, sex, weight, clinical diagnosis and duration of clinical signs. the statistical software and methods used are not defined. confidence intervals are not provided but can be calculated from the data. adverse effects for each medication were recorded. main findings (relevant to pico question): prednisone was the most effective drug with a satisfactory response in 17/30 dogs (56.7%, 95% ci 39.2–72.6%) but showed a greater satisfactory response when used in combination with trimeprazine in 23/30 dogs (76.7%, 95% ci 59.1–88.2%). clemastine was the most effective antihistamine with a satisfactory response in 9/30 dogs (30%, 95% ci 16.7–47.9%). all other medications showed very low levels of satisfactory responses; 1/30 dogs (3.3%, 95% ci 0.6–16.7%) for astemizole and trimeprazine, 0/30 dogs (0%, 95% ci 0–11.4%) for doxepin and placebo. all of the above 95% confidence intervals were calculated by the author of this knowledge summary and were not reported in the original paper. no correlation was found between response or adverse effects and age, breed, sex, weight, diagnosis or duration of clinical signs. adverse effects occurred most commonly with doxepin (4/30 dogs, 13.3%) and included vomiting (2/4 dogs), trembling and panting (2/4 dogs) and lethargy (1/4 dogs). doxepin was withdrawn in 2/4 dogs due to these adverse effects. limitations: a more objective measurement of improvement, such as a pruritus visual analogue scale score or veterinary assessment with cadesi scoring, could have added to the study. confidence intervals are not reported and when calculated are wide. it is unclear in what order the medications were given; it is not stated if it is the same order as the table provided or randomised and therefore it is difficult to know if the sequence of medications may have had an influence on results. immunotherapy should not have been started during the study period as it may have had an effect on the owner’s perception of pruritus. it is not clear why a 7 day treatment period and 2 day wash-out period were chosen. the doses of antihistamine used are based partly on manufacturer guidelines, but some are based on empirical clinical consensus and a dose determination trial may have been more useful. including dogs without a diagnosis for the cause of their pruritus may have influenced the response to treatment. a 3 week elimination diet trial was not sufficiently long enough to investigate cutaneous adverse food reaction. an elimination diet should be fed exclusively for 6 to 8 weeks (olivry et al., 2015). there is no information on why a sample size of 30 dogs was chosen nor the power of the study. appraisal, application and reflection there was relatively little evidence available comparing the efficacy of antihistamines against glucocorticoids in dogs with atopic dermatitis. paradis et al. (1991) reported the greatest owner satisfaction with oral prednisone, used either alone or in combination with trimeprazine, for the treatment of pruritus in comparison to any of the four antihistamines used as a sole therapy. however, the lack of objective measurements and minimal statistical analysis limits the value of this study. further subjective bias is added as the outcome was dependent on owner assessment of pruritus and had veterinary assessment of clinical response been performed, this would have strengthened the data. the inclusion of dogs without a confirmed diagnosis will have added another limitation to the data. the choice of a 2 day wash-out period is not explained and is short given that the duration of effect of prednisone is 24–36 hours (miller et al., 2013); as the sequence of drug administration is not specified this could have influenced the results. plevnik et al. (2009) found that methylprednisolone was more effective at reducing pruritus in the short-term than fexofenadine however, at 6 weeks into treatment fexofenadine showed a greater reduction in mean cadesi-02 score than methylprednisolone. the small, non-blinded, preliminary trial carried out by plevnik et al. (2006) demonstrated a similar ability of fexofenadine to reduce cadesi scores at 6 weeks of treatment. the authors state that both medications are efficacious as they reduced mean cadesi and mean pvas scores by at least 50% and are comparable as there was no significant difference between the two groups. however, the results of this study may have been influenced by the small number of dogs used and results should be interpreted with caution. the evidence above is conflicting as whilst two of the studies (plevnik et al., 2009; and plevnik et al., 2006) demonstrate some effect of antihistamines on pruritus and cadesi score, paradis et al. (1991) reported a lack of owner assessed response in pruritus. the international task force on canine atopic dermatitis treatment guidelines (olivry et al., 2010) advise that type-1 histamine receptor antagonists or inverse agonists are unlikely to be beneficial in both acute and chronic atopic dermatitis based on the evidence available. during acute flares antihistamines do not have enough time to block the histamine receptors before histamine is released. antihistamine treatment is also unlikely to be beneficial in chronic cases of atopic dermatitis. this may be due to a lack of relevance of type-1 histamine receptors in canine atopic dermatitis or inappropriate dosing. there is little evidence to determine the efficacy of antihistamines in mild cases of atopic dermatitis or to prevent future flares however, if given daily its use as a preventative may be beneficial. the guidelines note that only hydroxyzine and cetirizine have proven inhibition of histamine when given by intradermal injection in dogs and recommend either of these if antihistamines are to be used (bizikova et al., 2008; olivry et al., 2010; and temizel et al., 2011). the international committee on allergic diseases of animals updated their guidelines on the treatment of canine atopic dermatitis in 2015 (olivry et al., 2015) and reported that their review of the literature found evidence of a limited quality and consistency demonstrating a small benefit of antihistamines in some dogs consisting primarily of a retrospective survey and a randomised placebo-controlled trial. antihistamines may be best suited to mild cases or ideally used as a preventative allowing the drug to block the histamine receptors before histamine is released. they also recommend using antihistamines with proven efficacy or bioavailability. it is worth remembering that atopic dermatitis can be variable in its presentation. some patients may show unvarying severity of lesions all year round however, others may have a seasonal presence or exacerbation of signs. this can make interpreting treatment responses more complicated. two of the studies outlined above compared the same antihistamine however, they were performed at the same institute and the lead author on both papers was employed by the manufacturer of fexofenadine introducing potential for bias (plevnik et al., 2006; and plevnik et al., 2009). studies comparing commonly used antihistamines to glucocorticoids and both their shortand long-term effects would greatly improve the evidence base particularly as atopic dermatitis is a chronic condition that often requires long-term medical therapy. in summary, there is not enough evidence available to answer the pico question and further randomised controlled trials are warranted to demonstrate if there is comparable efficacy of antihistamines to glucocorticoids. methodology section search strategy databases searched and dates covered: cab abstracts 1973-week 14 2020 on cab direct interface pubmed 1900-week 14 2020 on ncbi interface web of science 1900-week 14 2020 search strategy: the search terms below were used on all three databases: (prednisolone or prednisone or glucocorticoid* or steroid* or cortico-steroid* or corticosteroid* or corticoid* or  glucocorticoids or steroids) and (antihistamine* or anti-histamine* or antihistaminics) and (atopy or atopic or allerg* or atopic dermatitis) and (dog or dogs or canine or bitch or bitches or canis) dates searches performed: 02 april 2020 exclusion / inclusion criteria exclusion: review articles, articles not available in english, book chapters and conference proceedings, non-peer-reviewed journals and articles that did not compare antihistamines to glucocorticoids in atopic dogs therefore were not relevant to the pico question. inclusion: peer-reviewed, original control studies comparing antihistamines with glucocorticoids in dogs with allergic skin disease. search outcome database number of results excluded – not available in english excluded – book, conference proceeding or non-peer-reviewed excluded – not relevant to pico question excluded – review articles total relevant papers cab abstracts 84 19 31 19 14 1 pubmed 45 7 0 29 9 0 web of science 39 5 0 24 7 3 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflicts of interest. references bizikova, p., papich, m. g. & olivry, t. 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(1986). bsava education committee commissioned article. journal of small animal practice, 27(11), 771–778. doi: https://doi.org/10.1111/j.1748-5827.1986.tb02119.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. continuous digital hypothermia in the prevention and treatment of acute equine laminitis a knowledge summary by karen pickering bvsc certavp (ed) pgcert vps mrcvs 1* joanne ireland bvms phd certavp(em) fhea mrcvs 2 1the donkey sanctuary, veterinary department, brookfield farm, honiton, ex14 9su 2university of liverpool, institute of veterinary science, leahurst campus, chester high road, neston, ch64 7te *corresponding author (karen.pickering66@gmail.com) vol 5, issue 4 (2020) published: 09 dec 2020 reviewed by: julia dubuc (dmv, dés, dacvs-la, m.sc, afhea, mrcvs) and andrew van eps (bvsc, phd, macvsc, dacvim) next review date: 26 aug 2021 doi: 10.18849/ve.v5i4.307 pico question does continuous digital hypothermia improve clinical outcome in equids with acute laminitis compared to supportive treatment alone?   clinical bottom line category of research question treatment the number and type of study designs reviewed six experimental randomised controlled trials and one multicentre retrospective case series were reviewed strength of evidence moderate outcomes reported the outcomes reported were reduced severity of histopathological lamellar lesions in limbs treated with continuous digital hypothermia (cdh; initiated prior to or soon after the onset of experimentally induced acute laminitis) compared to limbs remaining at an ambient temperature in all five experimental studies where histology was performed. a significant reduction was observed in the prevalence or severity of clinical signs of laminitis in limbs treated with cdh compared to limbs remaining at an ambient temperature. in a single retrospective case series, significantly reduced prevalence of clinical laminitis was reported amongst animals receiving cdh compared to those that did not in a referral hospital population of animals treated for colitis conclusion there is moderate evidence to support that cdh when used prior to or in the early stages of clinical signs, may reduce the severity and progression of lamellar lesions in acute laminitis and no evidence demonstrating that it improves clinical outcome compared to supportive treatment alone. further research into the clinical outcome of equids treated for acute laminitis using cdh is warranted   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. the evidence seven studies were found to provide evidence behind the use of continuous digital hypothermia (cdh) for the prevention or treatment of equine laminitis. three of these are randomised, controlled, blinded, experimental studies with small sample sizes (dern et al., 2018; stokes et al., 2019; and van eps et al., 2014). another three studies were controlled, experimental studies but had further limitations due to not being fully blinded or randomised (van eps et al., 2012; van eps & pollitt; 2004; and van eps & pollitt, 2009). only one study included cases of laminitis induced by the euglycaemic hyperinsulinaemic clamp model (stokes et al., 2019). the other five experimental studies used the oligofructose-induced laminitis model through alimentary carbohydrate overload, mimicking laminitis associated with sepsis. due to the experimental nature of these publications, they provide limited information regarding the clinical outcome of horses receiving cdh and supportive treatment, as opposed to supportive treatment alone. only one study compared the outcomes of colitis cases that received prophylactic cdh with those that did not, in a referral hospital population (kullmann et al., 2014). while including a larger sample size (n=130 horses) compared to the reviewed experimental studies, this observational retrospective case series provides low level evidence and is the only publication providing evidence of cdh in a clinical setting. summary of the evidence stokes et al. (2019) population: clinically normal standardbred geldings (mean age 6.4 ± 1.8 years). all horses had retired from racing within the preceding 4 weeks, and were reported to be sound, with no gross or radiographic abnormalities of the feet. sample size: eight horses intervention details: all horses were stabled for 1 week prior to study and fed lucerne (alfalfa) hay all horses were confined to stocks (a crush) and received ad libitum access to lucerne hay and water 72 hour experimental model: 24 hour control period initially, followed immediately by laminitis induction via euglycaemic hyperinsulinaemic clamp (ehc) model [intravenous bolus of insulin (45 miu/kg bodyweight (bwt)] diluted in 50 ml of saline (0.9% sodium chloride (nacl)) immediately followed by a continuous intravenous infusion of insulin [6 miu/kg bwt/minute; concurrent continuous intravenous infusion of 50% glucose, with the administration rate adjusted to maintain euglycaemia (5 ± 1 mmol/l)] euthanasia performed after 48 hours of ehc for each horse: random allocation of one forelimb per horse for cdh 30 minutes prior to commencing ehc using coin toss cdh forelimb continuously cooled for the remainder of the experiment via 50% ice and 50% water mixture, to a level just distal to the carpus via immersion within a rubber boot other forelimb left at ambient temperature post-euthanasia, dorsal lamellae of both forelimbs dissected from hoof and distal phalanx concurrent treatments: all horses received one dose of phenylbutazone (4 mg/kg bwt iv) between 52–58 hours when obel grade 1 laminitis (obel, 1948) became clinically apparent 5/8 horses received a second dose of phenylbutazone 8–10 hours later. reasons for this were not given. histology, histomorphometry and immunohistochemistry histology performed by single blinded veterinary pathologist on randomised sections from the proximal, middle and distal regions of the forefeet; histological severity of each section was graded using a previously published 0–3 scale (pollitt, 1996) based on basement membrane (bm) separation from the lamellae in increasing severity: grade 0: normal grade 1: mild changes (bm lifted to form teat shaped bubbles) grade 2: moderate changes (absence of bm at the tips of secondary dermal lamellae) grade 3: severe and extensive changes (complete separation of primary epidermal and primary dermal lamellae) histomorphometry performed by single blinded observer on randomised sections from the proximal, middle and distal regions and mean of 5 measurements of primary epidermal lamellae (pel) length (measured from abaxial to axial margins) used for data analysis immunohistochemical staining of middle region sections for the cellular proliferation marker targeting protein for xenopus kinesin-like protein 2 (tpx2), and tpx2-positive cell count performed by single blinded observer with the mean cell counts from both the abaxial and axial regions of 5 pel used for data analysis study design: randomised, controlled (within subject), blinded, experimental outcome studied: pedometer count of each forelimb independently hoof temperature monitored using hoof wall thermistors attached to data logging devices lameness evaluation via obel grading system (obel, 1948) 48 hours post ehc initiation by videoing each horse walking in a straight line for 20 metres, evaluated by a blinded clinician experienced in evaluation of lameness due to laminitis main findings (relevant to pico question): all eight horses developed laminitis within 48 hours of ehc pedometer counts: significant increase in ambient limb pedometer count frequency during ehc (24–72 hours) no significant change in pedometer count in cdh limbs throughout the experimental period weight shifting of ambient limb was clinically apparent from 52–58 hours (28–34 hours after commencing ehc) video analysis at 72 hours showed 6/8 horses lame at walk in the ambient limb (remaining two horses were not detectably lame at walk) hoof wall temperature: in the cdh limbs, temperature decreased after ice boot application (24–72 hours) (median 6.4°c; interquartile range (iqr) 6.0°–6.9°c) in ambient limbs, temperature gradually increased throughout the experimental period (median 29.7°c; iqr 28.6°–31.1°c) histology: secondary epidermal lamellae (sel) elongation and disruption: severe, with obel grade 3 dermoepidermal separation in all ambient eight feet in ≥1 of the 3 section regions and none of the eight cdh feet compared to ambient feet, cdh sections were 98% less likely to exhibit obel grade 2 or 3 histopathological scores (odds ratio 0.02; 95% ci 0.001–0.365; p<0.01) total pel length and non-keratinised pel length significant increase in ambient feet compared to cdh feet (both p<0.01 for all 3 section regions) intense nuclear tpx2 expression frequent in epidermal basal cells in ambient feet and occasional in cdh feet tpx2-positive cell counts significantly lower in the cdh feet compared with ambient feet (p<0.01) limitations: cdh was initiated at the onset of hyperinsulinaemia which limits the direct extrapolation of findings from this study to application in clinical settings horses were combined to stocks for the 72 hours experimental period. this lack of ambulation does not represent a standard clinical scenario whilst the contralateral limb was used as a control, there was no separate control group receiving only supportive treatment small sample size only young, healthy standardbred horses included lameness evaluation was described as being blinded but the way this was ensured was not described. if the cdh limb was obviously wet when video recordings were made, this could have introduced bias into the lameness evaluation. the dose rate and reason for 5/8 horses receiving a second dose of phenylbutazone was not reported lameness evaluation using video analysis is subjective dern et al. (2018) population: clinically normal standardbred geldings (aged 3–11 years). all horses were reported to be sound, with no gross or radiographic abnormalities of the feet. sample size: 15 horses: n=8 controls and n=7 horses administered oligofructose (of) intervention details: horses randomly assigned to control or of group all horses confined to stocks for the duration of the study with constant access to hay and water in the of group, laminitis induction achieved via bolus of 10 g/kg bwt of (up to a maximum dose of 4.2 kg) dissolved in water and administered via nasogastric tube cdh was initiated 12 hours post of administration (of group) or 12 hours after confinement in stocks (control group) for each horse: random allocation of one forelimb per horse for cdh cdh forelimb placed in a rubber boot filled with 50% water and 50% ice to the level of the proximal metacarpus other forelimb left at ambient temperature euthanasia via pentobarbital sodium 36 hours after the beginning of the experimental period the dorsal lamellae dissected from the hoof and distal phalanx, snap frozen or fixed in formalin and processed assessment was via real time quantitative pcr or light microscopy by blinded observers concurrent treatments: all horses received a single dose of phenylbutazone (4.4 mg/kg bwt iv) at onset of lameness signs (obel grade 1 lameness (obel, 1948)) study design: randomised, controlled, blinded experimental study outcome studied: forelimb hoof wall thermistors and pedometer devices: hoof wall temperature frequency of weight shifting histological examination by two blinded observers, bm separation from the lamellae graded using a previously published 0–3 scale (pollitt, 1996) primary study outcomes not directly relevant to pico question (therefore not commented on further): lamellar mrna concentrations of inflammatory mediators lamellar leukocyte numbers main findings (relevant to pico question): all seven horses in the of group developed laminitis (obel grade 1 lameness (obel, 1948)) within 24 hours of of administration hoof wall surface temperature (median and interquartile range): significant decrease in hoof wall temperature compared to ambient from 12–36 hours within both of and control groups (p<0.05) of limb: cdh 6.07°c (5.40°–6.64°c) vs 82°c (26.71°–29.05°c) control limbs: cdh 5.06°c (4.83°–5.92°c) vs ambient 24.67°c (23.25°–26.06°c) no significant difference in temperature between cdh limbs of the control and of groups or between ambient limbs of the control and of groups within the of group: pedometer count showed an increase in limb movement of ambient limbs, peaking at 18 hours, where it was significantly greater than cdh limbs (p<0.05) median histological scores of the middle lamellar sections were significantly lower in cdh limbs (0; iqr 0–0) compared to ambient limbs (2; iqr 1.5–2.5) limitations: method of randomisation not reported small sample size title states that cdh was initiated at a ‘clinically relevant time point’, but it was initiated at 12 hours post of administration before lameness was apparent in all but one horse only standardbred horses included lameness was assessed at one time point only during the 36 hours study period, which was prior to instigating cdh therapy kullmann et al. (2014) population: horses ≥2 years old admitted to two university hospitals between january 2002–august 2012, diagnosed with colitis, enterocolitis or typhlocolitis (45 mares, 78 geldings, seven intact males) sample size: 130 horses: 82 from university a and 48 from university b intervention details: inclusion criteria: diagnosis of colitis, enterocolitis or typhlocolitis plus ≥2 of: fever, tachycardia, tachypnoea, leukocytosis or leukopenia horses included whether or not they received cdh the horses not receiving cdh formed a control group exclusion criteria: horses receiving intermittent digital hypothermia (feet placed intermittently (every 2–6 hours) in ice or ice applied as bags or rectal sleeves wrapped around the hooves) horses admitted to hospital with acute or chronic laminitis or if diagnosis of laminitis at time of hospital admission horses <2 years old as considered to have decreased risk of acute laminitis draught, pony or miniature breed or equine metabolic syndrome diagnosed due to increased risk of acute laminitis treatment data collected included use of cdh (cryotherapy performed on both forelimbs) cdh protocol: submerge distal limbs in ice to level just proximal to metacarpophalangeal joint for a minimum of 48 hours using 5 l fluid bags attached to limb via duct tape. bags filled with ice every 2 hours or more frequently if necessary treatment group: 69 horses received cdh control group: 61 horses did not receive cdh study design: multicentre retrospective case series outcome studied: development of laminitis diagnosis of laminitis based on obel lameness grade (obel, 1948), increased digital pulses, abnormal posture and inability or unwillingness to move long-term outcome on horses that developed laminitis and discharged from hospital included telephone conversations with owners, trainers and referring veterinary surgeon main findings (relevant to pico question): 27/130 horses (21%) developed laminitis, 103/130 horses (79%) did not 7/69 (10%) horses with cdh developed laminitis, 3/7 (43%) were euthanised prior to hospital discharge due to laminitis 20/61 (33%) horses with no cdh developed laminitis, 11/20 (55%) were euthanised prior to hospital discharge due to laminitis horses were less likely to develop laminitis if they received cdh compared with horses that did not receive cdh (odds ratio 0.14; p=0.003). hospital site was significantly associated with development of laminitis. bias may have been introduced in the reporting of potomac horse fever (phf) 15/27 (55%) of horses with laminitis tested positive for phf 25/48 (52%) of horses at university b colitis cases were phf positive, compared to 25/82 (30%) of university a colitis cases only 89/130 (68%) of horses in the study were tested for phf so the variable was not included in the regression analysis 114/130 (88%) horses discharged from hospital 16/130 horses (12%) were euthanised in hospital; of which 14/16 were euthanised due to laminitis. 2/103 horses without laminitis were euthanised due to severity of the gastrointestinal disease and poor response to therapy limitations: only horses that developed laminitis were followed up after hospital discharge ponies, miniature and draught breeds were excluded from the study retrospective study over two sites possible some horses may have been admitted to study with subtle signs of laminitis masked on hospital admission due to receiving analgesia prior to referral no discussion as to why clinical decision was made to use cdh or not in each case, which could have introduced bias via clinician decision-making no data on initiation time point of cdh cdh was initiated for a minimum of 48 hours but whether any horses with cdh continued after this time point is not reported van eps et al. (2014) population: clinically normal standardbred geldings (aged 3–11 years). all horses were reported to be sound, with no gross or radiographic abnormalities of the feet. sample size: eight horses intervention details: all horses housed and fed in stables for 4 weeks prior to the experiment laminitis induction via bolus of 10 g/kg of dissolved in water and administered via nasogastric tube horse confined to stocks and monitored for lameness every 4 hours beginning 12 hours after bolus of of two investigators were required to recognise and agree on obel grade 2 lameness (obel, 1948) to initiate cdh and perineural anaesthesia cdh was initiated 12 hours post of administration (of group) or 12 hours after confinement in stocks (control group) for each horse: random allocation of one forelimb per horse for cdh cdh forelimb placed in a rubber boot filled with 50% water and 50% ice to the level of the proximal metacarpus other forelimb left at ambient temperature euthanasia via pentobarbital sodium 36 hours after the beginning of the experimental period all four hooves on each horse examined histologically, (total of eight cdh forelimbs, plus eight control forelimbs and 16 hindlimbs left at ambient temperature) concurrent treatments: immediately on recognition of lameness, analgesia was initiated via a single phenylbutazone injection (8 mg/kg bwt iv) bilateral forelimb continuous perineural analgesia (palmar nerve block) via catheter placement with 2 ml 2% mepivacaine hydrochloride hourly intermittent perineural analgesia of hindlimbs if a subjective increase in weight shifting was noted study design: randomised, controlled (within subject), blinded, experimental study outcome studied: pedometers taped to antebrachium and recorded every hour, monitoring step count of individual limbs forelimb hoof temperature monitored via thermistors attached to the hoof surface histological examination by two blinded observers was based on basement membrane (bm) separation from the lamellae in increasing severity: grade 0: normal grade 1: mild changes grade 2: moderate changes grade 3: severe and extensive changes grade 4: complete physical separation of lamellar epidermis from dermis, with no association between epidermal and dermal tissues on the section main findings (relevant to pico question): all eight horses developed obel grade 2 lameness within 17–21 hours of of administration pedometer data demonstrated increased frequency of limb movement in the ambient temperature limbs compared to the cooled limbs after the initiation of peripheral nerve blocks and cdh after initiation of the perineural analgesia and cdh, the cdh treated limb pedometer count frequency was significantly decreased at 5–14, 17 and 22 hours compared with the onset of lameness (0 hours) median hoof wall surface temperature was 7.1°c for the cdh feet and 30.2°c for the ambient feet histology: median histological scores significantly greater in the ambient limbs (proximal 2.8 [iqr 2.5–4]; middle 3.5 [iqr 2–4]; distal 2.5 [iqr 2–3.8]) compared to the cdh limbs (proximal 0.5 [iqr 0.5–1.4]; middle 1 [iqr 0.6–1]; distal 0.75 [iqr 0.5–1] cdh initiated at the onset of lameness reduced the severity of lamellar injury complete physical separation of dermal and epidermal lamellae in four ambient temperature feet which was not observed in any of the cdh feet limitations: analgesia via continuous peripheral nerve block is not common practice in many clinical situations – this was done as a humane consideration in this experimental study the study was only continued for 36 hours after the onset of lameness so it is unclear whether the laminitis lesions in the cdh feet may have progressed after discontinuation of the cooling small sample size only standardbred horses included van eps et al. (2012) population: clinically normal standardbred horses (10 geldings and four mares; aged 4–11 years). all horses were reported to be sound, with no gross or radiographic abnormalities of the feet. sample size: 14 horses intervention details: horse confined to stocks laminitis induction via bolus of 10 g/kg of dissolved in water and administered via nasogastric tube for each horse: cdh forelimb placed in a rubber boot filled with 50% water and 50% ice to a level just below the carpus other forelimb left at ambient temperature experiment 1 (eight horses): euthanised 24 hours after of bolus (with no lameness) and tissues collected experiment 2 (six horses): euthanised immediately upon recognition of obel grade 1 lameness between 20–28 hours post of bolus one horse from experiment 1 became lame at 20 hours and was euthanised immediately so included in experiment 2 meaning experiments 1 and 2 both include seven horses euthanasia immediately post anaesthetic induction with immediate harvesting of dorsal lamellae snap frozen in liquid nitrogen control lamellar tissue from a previous study used for comparison study design: controlled experimental study outcome studied: onset of obel grade 1 lameness (obel, 1948) forelimb hoof temperature monitored via thermistors attached to the hoof surface pedometer readings from experiment 2 to monitor weight shifting main findings (relevant to pico question): pedometer counts significantly higher in ambient limbs compared to cdh limbs at 18 and 20 hours, compared to 2 hours time point (p<0.05) in all cases, the pedometer data showed an increase in count frequency in ambient temperature limbs 2–4 hours prior to visual recognition of weight shifting behaviour hoof wall surface temperature (mean ± standard error): cdh limbs 4.2° ± 52°c ambient limbs 23.1° ± 1.4°c limitations: selection bias may have been introduced as study does not mention whether cdh limb was randomly selected or how selection of horses into different experimental groups was achieved control tissue for histology was not from this study although had been harvested in an identical fashion only standardbred horses were included small sample size van eps & pollitt (2009) population: clinically normal standardbred horses (14 geldings, four mares). all horses were reported to be sound, with no gross abnormalities of the feet. sample size: 18 horses intervention details: horses allocated randomly into three groups of six all horses housed and fed in stables for 4 weeks prior to the experiment group 1: cdh controls group 2: laminitis induction by of method and cdh treatment for 72 hours beginning immediately after induction dose of of group 3: laminitis induction by of and no cdh laminitis induction via bolus of 10 g/kg of dissolved in water and administered via nasogastric tube. 10% of the induction dose of of given daily in feed for 3 days prior to administration of bolus dose cdh for groups 1 and 2 administered via a wooden water bath with a rubber mat surrounded by stocks. water added to a level just below the carpus and cooled and recirculated at 1°c using a refrigeration pump and heat exchanger. cubed ice was added initially to reduce the temperature rapidly forelimb internal hoof temperature recorded continuously for groups 1 and 2 as described by van eps & pollitt (2004) group 3 were cross-tied on rubber mats for 72 hours to try to standardise conditions (groups 1 and 2 were confined to the water bath) but did have a limited lameness evaluation every 12 hours during the initial 72 hour period. this consisted of walking the horse in a circle in both directions within the stable. after the 72 hour period, all horses were released into stables for the remainder of the 7 day experimental period and examined at 12 hour intervals concurrent treatments: horses with obel grade 3 or 4 lameness (obel, 1948) were given mixture of phenylbutazone (4.5 mg/kg bwt iv) and sodium salicylate (1.2 mg/kg bwt iv) at every 12 hour examination until lameness was obel grade 2 or less a final lameness exam at 168 hours was video recorded, all footage randomised and evaluated by blinded clinicians experienced in lameness evaluation lateral radiographs taken of each fore foot prior to the experiment and just prior to euthanasia all horses were euthanised after final lameness evaluation study design: controlled experimental study outcome studied: continuous recording of forelimb internal hoof temperature in groups 1 and 2 lateral radiographs of each foot to assess changes during study and between groups histology of dorsal hoof lamellae to measure lamellar length main findings (relevant to pico question): clinical parameters heart rate significantly higher in groups 2 and 3 vs group 1 and significantly higher in group 3 between 44–60 hours, vs group 2 clinical signs of laminitis first noted in group 3 at 24 hours (4/6), and 36 hours (2/6). no signs noted in groups 1 and 2 lameness: horses in groups 1 and 2 were judged to be non-lame (by a single observer) at all time periods between 72 hours and 7 days. median obel grade lameness scores at 7 days were significantly less in group 1 (range 0–1) and group 2 (range 0–2), compared with group 3 (range 2.5–4) no significant difference in obel lameness scores between groups 1 and 2 forelimb internal hoof temperature: there was no significant difference between mean internal hoof temperatures of group 2 (3.8â�° ±6â�°c) and group 1 (3.9â�° ± 0.9â�°c) at any time point radiographs: rotation of the distal phalanx relative to the dorsal hoof wall was not detected in any radiographs a small but significant increase in the dorsal hoof wall to distal phalanx distance was noted in group 3 at 7 days, compared to their baseline radiographs the laminitis preventive effect of distal limb cdh lasted beyond the 72 hours of application limitations: the authors of the study noted the design of wooden water bath was cumbersome, difficult to maintain and required constant supervision. this would not be a practical method of cdh in clinical practice there was no internal hoof temperature monitoring for group 3. depending on ambient temperature at the time of the study this could have meant results for group 3 would have been significantly different to groups 1 and 2. bias may have been introduced in group 3 by allowing some movement where the horses in the water bath had none for 72 hours only standardbred horses included small sample size van eps & pollitt (2004) population: mature, clinically normal standardbred horses (six geldings, four mares). all horses were reported to be sound, with no gross abnormalities of the feet. sample size: 10 animals: four control animals (three geldings, one mare), and six case animals (three geldings, three mares) intervention details: four control horses were immediately euthanised via barbiturate overdose to use as controls for the matrix metalloproteinase-2 (mmp-2) mrna analysis. it is unclear from the study whether they received the same care prior to the experiment six case subjects housed and fed in stables for 3 weeks prior to experiment induction of laminitis via of method: 10 g/kg of of administered in 4 l of water via nasogastric intubation horses confined to stocks for 48 hours with free access to food and water left forelimb placed in rubber boot with 50% ice and 50% water to just below the carpus forelimb hoof temperature monitored continuously via thermistor probes inserted into predrilled hole within dorsal hoof wall. hindlimb hoof temperature monitored 2 hourly via infrared scanning device euthanasia via barbiturate overdose post lameness evaluation at 48 hours sections of dorsal hoof lamellae removed for histological examination by four blinded evaluators using the pollitt (1996) scoring system. the median score was used for each limb lameness evaluation 2 hours prior to of bolus and after removal of the ice boot at 48 hours study design: controlled experimental study outcome studied: hoof temperature monitored via thermistors observation of clinical signs of laminitis (increased digital pulse amplitude, incessant shifting of weight and lameness measured by obel grade) severity of laminitis (histological evaluation) main findings (relevant to pico question): mean hoof temperature of cdh treated limbs (group 1: 3.9° ± 9°c, group 2: 3.8° ± 0.6°c) was significantly less than all the ambient limbs by 2 hours lameness evaluations revealed all horses were obviously lame in the ambient forelimb at walk. lameness was not observed in the cdh limb of any horse histology: histological scores of the ambient forefeet (median scores 1–3) were significantly greater than that of the cdh forefeet (median scores 0–0.5) (p<0.05) detachment of the bm from the secondary epidermal lamellae was present in all ambient feet except hind feet of one subject detachment of the bm was not seen in any of the cdh feet limitations: all horses had the left forelimb cdh treated lameness evaluation was not blinded different devices were used to measure temperature in forelimbs and hindlimbs only standardbred horses included small sample size appraisal, application and reflection laminitis is a common problem affecting equids seen in practice (wylie et al., 2011). it is often debilitating and can cause severe morbidity and mortality. acute laminitis may occur as a complication of various primary systemic diseases (van eps, 2010), excessive unilateral weight bearing (wylie et al., 2015) or, most commonly as a consequence of hyperinsulinaemia (de laat et al., 2010; and patterson-kane et al., 2018). the seven papers summarised all contribute some evidence towards the question of whether cdh can help improve clinical outcome in cases of acute laminitis. all the experimental studies deal with continuous digital hypothermia, and horses receiving intermittent digital hypothermia in the case series by kullmann et al. (2014) were excluded. the study by van eps & pollitt (2009) reported that cdh, when performed for 72 hours on six horses that had not undergone laminitis induction, did not produce any significant lameness or other ill-effects. the horses appeared to tolerate cdh well, although distal limb oedema was reported in all 18 cdh treated horses, which resolved by 7 days following cessation of treatment (van eps & pollitt, 2009). a hypothesis provided by the study’s authors was that this was a consequence of the cryotherapy in conjunction with restricted ambulation for 72 hours. all other included studies reported using cdh for a minimum of 36 hours with no significant side-effects, demonstrating that cdh is safe to use in horses. most of the experimental studies included appear to build on the work of van eps & pollitt (2004), refining the experimental model to often include randomisation and blinding of lameness exams which should serve to increase the quality of evidence. these experimental studies have limitations with regards to generalisability towards general clinical practice as the cdh was initiated prior to or immediately after induction of laminitis both by the oligofructose (of) method (van eps & pollitt, 2004; van eps & pollitt 2009; and van eps et al., 2012) and the euglycaemic hyperinsulinaemic clamp (ehc) method (stokes et al., 2019). however, results obtained using the of method support the prophylactic use of cdh in clinical cases considered to be at risk of sepsis-associated laminitis (van eps & pollitt, 2004; van eps & pollitt 2009; and van eps et al., 2012). in the study by dern et al. (2018), chd was initiated 12 hours after induction of laminitis, however this was still before all but one of the horses showed any signs of lameness. in the van eps et al. (2014) study cdh was initiated in one forelimb only after the onset of lameness was agreed upon by two investigators, providing evaluation of the protective effects of cdh at a more clinically relevant time point, and the most robust evidence relating to clinical practice of all the experimental studies. although still limited by the small sample size, this study provides evidence of a therapeutic effect of cdh when applied after the onset of clinically apparent laminitis. stokes et al. (2019) was the only experimental study of insulin-induced laminitis. the main limitation to clinical application in this study is that cdh was initiated at the time of laminitis induction, before recognition of clinical laminitis. however, the results of the study indicate that overall the protective effects of cdh were similar to those noted in the of studies, with a reduction in the severity of laminitis, both clinically and histologically (stokes et al. 2019). further work would be needed to evaluate whether these protective effects extend beyond the cdh period as shown in the of method by van eps & pollitt (2009). as a retrospective analysis of clinical records, kullmann et al. (2014) falls much lower on the hierarchy of evidence but was included here as it provides evidence of cdh being used in a clinically relevant scenario. in this case series, cdh was performed by submerging the limbs in ice just proximal to the metacarpophalangeal joint, as opposed to the level of the proximal metacarpus which was used in all other studies. there were many limitations to this study which must be borne in mind, particularly surrounding the recording and standardisation of why cdh treatment was initiated, how the cases were selected for cdh treatment, the lack of information regarding when cdh treatment was commenced, and whether cdh continued in any cases beyond the minimum 48 hours specified. the criteria stated that horses admitted to the hospital with acute or chronic laminitis or diagnosed with laminitis at the time of admission were excluded, so an assumption is made that cdh was started after they had arrived at hospital – similar to the timing used in the experimental study by van eps et al. (2014). the authors note however that lameness at time of admission may have been masked in some cases by the administration of analgesics by the referring vet (kullmann et al. 2014). the histopathology results from all the studies must be used to try to extrapolate clinical outcome given that all of the horses in the experimental studies were euthanised before clinical outcome could be assessed. all studies where histological examination was undertaken (stokes et al., 2019; dern et al., 2018; van eps et al., 2014; van eps & pollitt, 2009; and van eps & pollitt, 2004) reported significant reduction in histological scores for laminitic feet treated with cdh compared to untreated laminitic feet. as histological changes due to laminitis are assumed to be non-reversible and the cdh reduced histological lesion progression, the significant difference observed due to the cdh may subsequently improve clinical outcome. clinical significance of the different histology gradings is still unknown and a major limitation to these studies is the severity of laminitis caused by the induction models. in many natural cases, the onset of laminitis is insidious and may not be spotted until well after the time period where cdh was initiated in these studies. all of the horses studied also had no history of laminitis and it would be interesting to compare effects of cdh on horses with pre-existing chronic laminitis. the study by van eps & pollitt (2009) provides the best evidence that the protective effects of cdh in acute laminitis continue after the cdh is discontinued. horses were subjected to 72 hours of cdh immediately following laminitis induction before being euthanised 7 days after induction. results of blinded obel lameness grading just prior to euthanasia showed no significant difference in control horses in group 1 (no laminitis induction but cdh performed) and horses in group 2 (laminitis induction and cdh). however, obel lameness scores in group 3 (laminitis induction but no cdh) were significantly higher than in either group 1 or 2. histopathology revealed significant lamellar changes in group 3, mild changes in group 2 and no lamellar changes in group 1 (van eps & pollitt, 2009). cdh resulted in a decrease in clinical signs of laminitis (decreased pedometer count (weight shifting)) in the cooled forelimb compared to the uncooled forelimb and compared to the pedometer count prior to initiation of cdh (van eps et al., 2014). euthanasia was performed after 36 hours of cdh and histological evaluation identified complete physical separation of dermal lamellae from epidermal lamellae in 4/8 uncooled feet, compared to 0/8 cooled feet (van eps et al., 2014). at the proximal, middle and distal dorsal lamellar sections the median histological scores were significantly decreased in the cdh feet, compared to the uncooled feet (van eps et al., 2014). the van eps et al. (2012) study also reported an increase in pedometer count frequency in ambient temperature limbs 2-4 hours prior to a subjective visual recognition of weight shifting behaviour. given that one limb was encased in a cumbersome ice boot, the subjective data may be subject to significant bias but the objective pedometer data may prove useful for further research into clinically relevant time periods to initiate cdh. reduced frequency of weight shifting was also reported in cdh treated limbs compared to ambient temperature limbs in the two other experimental studies where this was measured objectively using pedometers (dern et al., 2018; stokes et al., 2019). additionally, reduced severity of lameness, as assessed by obel lameness grades (van eps & pollitt, 2009), and a reduced prevalence of lameness (van eps & pollitt, 2004) were reported for cdh treated limbs compared to ambient temperature limbs. given the pico question related to cdh and supportive treatment compared to supportive treatment alone, it should be noted that there are other forms of supportive treatment in the management of laminitis than nsaids. commonly foot supports or corrective foot trimming, deep bedding, dietary management, and other pharmaceuticals such as paracetamol or acepromazine are often employed in the treatment of laminitis. due to the experimental nature of six of the studies, including these variables within the studies would have been difficult to achieve but this should be borne in mind when thinking about the applicability to general clinical practice. further research is required to determine whether the conclusions from the experimental studies included in this knowledge summary are applicable to all equidae and underlying causes of laminitis. it is reasonable to assume that these findings would translate to other large size breeds but future work needs to be done to evaluate the effectiveness of cdh in clinical situations, in equids other than standardbred horses such as ponies or donkeys, and on the effectiveness in animals with a previous history of laminitis, or a history of equine metabolic syndrome and/or pituitary pars intermedia dysfunction. prospective cohort studies of clinical cases utilising strict inclusion criteria could help evaluate application of cdh for treatment of acute laminitis in clinical practice. in conclusion, there is moderate evidence demonstrating that cdh does reduce the severity and/or frequency of clinical signs of pain, such as weight shifting and lameness in experimentally induced laminitis in standardbred horses. histological examination of the lamellae in cases of experimentally induced laminitis demonstrates that cdh reduces epithelial inflammatory events and protects against lamellar separation, especially if initiated before clinical signs are apparent. there is weak evidence to show that cdh provides protective effects in true clinical situations and a lack of evidence to show it improves clinical outcome compared to supportive treatment alone. methodology section search strategy databases searched and dates covered: pubmed accessed via the ncbi website (1910–2019) cab abstracts (1977–2019) search strategy: search terms used in both databases: laminitis and (hypothermia or cold or cryotherapy) dates searches performed: 26 aug 2019 exclusion / inclusion criteria exclusion: review, conference proceedings, book chapter, non-peer reviewed publication not in the english language could not be sourced additionally studies where evaluation of the effect of distal limb cryotherapy on clinical and histological signs of laminitis was not the primary focus were excluded inclusion: studies relating to the use of cryotherapy to treat acute laminitis in equids, regardless of cause of laminitis, where clinical and/or histological signs were the primary outcome measure(s) search outcome database number of results excluded – did not address the pico question excluded – review / book chapter / non-peer reviewed publication excluded – not in english language excluded – could not be sourced total relevant papers pubmed 31 19 5 0 0 7 cab abstracts 68 23 28 8 2 7 total relevant papers when duplicates removed 7 conflict of interest the authors declare no conflict of interest. references de laat, m.a., mcgowan, c.m., sillence, m.n. and pollitt, c.c. (2010). equine laminitis: induced by 48 hr hyperinsulinaemia in standardbred horses. equine veterinary journal. 42(2), 129–135. doi: http://dx.doi.org/10.2746/042516409x475779 dern, k., van eps, a., wittum, t., watts, m., pollitt, c. and belknap, j. (2018). effect of continuous digital hypothermia on lamellar inflammatory signaling when applied at a clinically-relevant time point in the oligofructose laminitis model. journal of veterinary internal medicine. 32(1), 450–458. doi: https://dx.doi.org/10.1111/jvim.15027 kullmann, a., holcombe, s.j., hurcome, s.d., roessner, h.a., hauptman, j.g., geor, r.j. and belknap, j. (2014). prophylactic digital cryotherapy is associated with decreased incidence of laminitis in horses diagnosed with colitis. equine veterinary journal. 46(5), 554–559. doi: https://doi.org/10.1111/evj.12156 obel, n. (1948). studies of the histopathology of acute laminitis. almgvist and wilcsells bottrykeri ab uppsala (thesis). patterson-kane, j.c., karikoski, n.p. and mcgowan, c.m. (2018). paradigm shifts in understanding equine laminitis. the veterinary journal. 231, 33–40. doi: http://dx.doi.org/10.1016/j.tvjl.2017.11.011 pollitt, c.c. (1996). basement membrane pathology: a feature of acute equine laminitis. equine veterinary journal. 28(1), 38–46. doi: https://dx.doi.org/10.1111/j.2042-3306.1996.tb01588.x stokes, s.m., belknap, j.k., engiles, j.b., stefanovski, d., bertin, f.r., medina-torres, c.e., horn, r. and van eps, a.w. (2019). continuous digital hypothermia prevents lamellar failure in the euglycaemic hyperinsulinaemic clamp model of equine laminitis. equine veterinary journal. 51(5), 658–664. doi: https://doi.org/10.1111/evj.13072 van eps, a.w. and pollitt, c.c. (2004). equine laminitis: cryotherapy reduces the severity of the acute lesion. equine veterinary journal. 36(3), 255–260. doi: https://doi.org/10.2746/0425164044877107 van eps, a.w. and pollitt, c.c. (2009). equine laminitis model: cryotherapy reduces the severity of lesions evaluated seven days after induction with oligofructose. equine veterinary journal. 41(8), 741–746. doi: https://doi.org/10.2746/042516409x434116 van eps aw. (2010). therapeutic hypothermia (cryotherapy) to prevent and treat acute laminitis. veterinary clinics of north american equine practice. 26(1), 125–33. doi: https://doi.org/10.1016/j.cveq.2010.01.002 van eps, a.w., leise, b.s., watts, m., pollitt, c.c. and belknap, j.k. (2012). digital hypothermia inhibits early lamellar inflammatory signalling in the oligofructose laminitis model. equine veterinary journal. 44(1), 120–124. doi: https://doi.org/10.1111/j.2042-3306.2011.00416.x van eps, a.w., pollitt, c.c., underwood, c., medina-torres, c.e., goodwin, w.a. and belknap, j.k. (2014). continuous digital hypothermia initiated after the onset of lameness prevents lamellar failure in the oligofructose laminitis model. equine veterinary journal. 46(5), 625–630. doi: https://doi.org/10.1111/evj.12180 wylie, c.e., collins, s.n., verheyen, k.l., and newton, j.r. (2011). frequency of equine laminitis: a systematic review with quality appraisal of published evidence. the veterinary journal. 189(3), 248–256. doi: https://doi.org/10.1016/j.tvjl.2011.04.014 wylie, c.e., newton, j.r., bathe, a.p., and payne, r.j. (2015). prevalence of supporting limb laminitis in a uk equine practice and referral hospital setting between 2005 and 2013: implications for future epidemiological studies. veterinary record. 176(3), 72. doi: https://doi.org/10.1136/vr.102426 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. erratum to: in canine acute diarrhoea with no identifiable cause, does daily oral probiotic improve the clinical outcomes? jacqueline oi ping tong student1* 1university of edinburgh, royal (dick) school of veterinary studies, easter bush campus, midlothian eh25 9rg *corresponding author (jactong48@gmail.com) vol 5, issue 4 (2020) erratum published: 09 dec 2020 doi: 10.18849/ve.v5i4.437 original paper published: 10 oct 2019 the original article was published in veterinary evidence vol 4, issue 4 (2019): https://doi.org/10.18849/ve.v4i4.252 erratum veterinary evidence received a letter 1/10/2020 from walder wyss attorneys, counsel to actial farmaceutica srl (“actial”), owner of the rights to the high-concentration, multi-bacterial strain probiotic product known as vsl#3®. within the published knowledge summary tong, j.o.p. (2019). in canine acute diarrhoea with no identifiable cause, does daily oral probiotic improve the clinical outcomes?. veterinary evidence, 4(4). doi: 10.18849/ve.v4i4.252 the author, jacqueline tong, appraised the paper ziese, a., suchodolski, j., hartmann, k., busch, k., anderson, a., sarwar, f., sindern, n., & unterer, s. (2018). effect of probiotic treatment on the clinical course, intestinal microbiome, and toxigenic clostridium perfringens in dogs with acute hemorrhagic diarrhea. plos one, 13(9), e0204691. doi: 1371/journal.pone.0204691 this paper listed incorrect active ingredients of the product visbiome. the strains referred to with the dsm codes, and that were published in the knowledge summary are as follows: lactobacillus paracasei dsm 24733; lactobacillus plantarum dsm 24730; lactobacillus acidophilus dsm 24735; lactobacillus delbruckeii subspecies bulgaricus dsm 24734; bifidobacterium longum dsm 24736; bifidobacterium infantis dsm 24737; bifidobacterium breve dsm 24732; streptococcus thermophilus dsm 24731. upon a judgement issued by the court of rome confirming that the mentioned deposits did not belong to prof. de simone but to their client, actial was able to secure access to such dsmz accounts and have samples of the bacterial strains in those accounts independently tested by the belgian coordinated collections of microorganisms (bccm) located in ghent, belgium. actial discovered that 5 of the 8 accounts contain bacterial strains different from those referred to in the documentation of the visbiome® product which were mentioned in the publication published in plos which was appraised in our published knowledge summary. in particular, the recent testing has determined that, contrary to representations in such products’ information and marketing materials: – dsm 24731 does not contain streptococcus thermophilus but rather, lactobacillus plantarum; – dsm 24734 does not contain lactobacillus delbruckeii subspieces bulgar-icus but rather pediococcus pentosaceus; – dsm 24735 does not contain lactobacillus acidophilus but rather lacto-bacillus plantarum; – dsm 24736 does not contain bifidobacterium longum but rather bifidobacterium animalis; and – dsm 24737 does not contain bifidobacterium infantis but rather a mix of various bacteria including lactobacillus paracasei, lactobacillus acidophilus and bifidobacterium animalis. thus the details in the published knowledge summary have been corrected from: lactobacillus plantarum dsm 24730 streptococcus thermophilus dsm 24731 bifidobacterium breve dsm 24732 lactobacillus paracasei dsm 24733 lactobacillus delbrueckii bulgaricus dsm 24734 lactobacillus acidophilus dsm 24735 bifidobacterium longum dsm 24736 bifidobacterium infantis dsm 24737 to: lactobacillus plantarum dsm 24730 lactobacillus plantarum dsm 24731 bifidobacterium breve dsm 24732 lactobacillus paracasei dsm 24733 pediococcus pentosaceus dsm 24734 lacto-bacillus plantarum dsm 24735 bifidobacterium animalis dsm 24736 lactobacillus paracasei, lactobacillus acidophilus and bifidobacterium animalis dsm 24737 no fault for this error can be attributed to the knowledge summary author jacqueline tong nor the veterinary evidence journal. the corrections have been made in both the html and pdf versions. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. what prognostic information does flow cytometry provide in canine b-cell lymphoma? a knowledge summary by ben haythornthwaite vetmb ba mrcvs 1* 1medivet st ives, 7 station road, st ives, huntingdon, pe27 5bh *corresponding author (bhaythornthwaite@hotmail.co.uk) vol 7, issue 1 (2022) published: 24 mar 2022 reviewed by: sue murphy (bvm&s msc [clin onc]dip ecvim-ca [onc]mrcvs) and maurice zandvliet (dvm mvr phd dipl. ecvim-ca [med & onc]) next review date: 27 oct 2023 doi: 10.18849/ve.v7i1.381 pico question in dogs with b-cell lymphoma, does the use of flow cytometry provide useful prognostic information?   clinical bottom line category of research question prognosis the number and type of study designs reviewed twelve papers were critically reviewed. all were cohort studies strength of evidence moderate outcomes reported there are multiple potential prognostic indicators in canine b-cell lymphoma that flow cytometry can be used to evaluate, including lymphoma stage, survival time and time to progression. there is promising evidence for the use of percentage expression of cd25 and ki67 cellular markers in providing prognostic information in canine b-cell lymphoma and these should be assessed further in clinical practice. flow cytometry has also been shown to be useful in assessing bone marrow infiltration and providing prognostic information relating to this. there is also evidence for the prognostic value of measuring expression of class ii mhc and ctla-4 cellular markers, peripheral lymphocyte / monocyte ratio, nodal regulatory t-cell populations and the ratio between t and b lymphocytes in extranodal locations. peripheral regulatory t-cell populations and cellular size were also assessed, however further investigations are required before confirming their prognostic value conclusion flow cytometric analysis offers useful measures of prognosis in canine b-cell lymphoma, although further validation is required before introducing their routine use. percentage expression of cd25 and ki67 cellular markers from lymph node aspirates of dogs with b-cell lymphoma appear to be promising prognostic indicators in clinical investigations, however this needs to be translated into clinical practice. while there is evidence for the prognostic value of bone marrow infiltration measured flow cytometrically, expression of class ii mhc and ctla-4, peripheral lymphocyte / monocyte ratio, nodal regulatory t-cell populations and the ratio between t and b lymphocytes in extranodal locations, these need to be further investigated before introducing into clinical practice. as new antibodies against cellular targets in dogs become available, it is likely that flow cytometry will become even more useful in providing prognostic information   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. the evidence twelve studies in total were found relevant to the pico, all of which were cohort studies (baek et al., 2017; joetzke et al., 2012; marconato et al., 2013; marconato et al., 2015; mizutani et al., 2016; pinheiro et al., 2014; poggi et al., 2015, poggi et al., 2017; rao et al., 2011; riondato et al., 2021; tagawa et al., 2018; and wolf-ringwall et al., 2019). eight of the studies looked to correlate flow cytometric analysis with survival data (marconato et al., 2013; marconato et al., 2015; mizutani et al., 2016; pinheiro et al., 2014; poggi et al., 2017; rao et al., 2011; tagawa et al., 2018; and wolf-ringwall et al., 2019). one study looked to correlate stage of b-cell lymphoma with percentage of tregs in peripheral blood measured by flow cytometry (baek et al., 2017).  one study looked to correlate flow cytometric data with involvement of lymphoma in extranodal tissues (joetzke et al., 2012). two studies looked to correlate ki67 expression with grade of lymphoma (poggi et al., 2015; and riondato et al., 2021). all studies were observational in nature which is likely suitable for this pico question, however more prospective studies may be useful in the future to produce more robust studies with fewer sources of potential bias or confounding factors. two studies had more than 100 patients (rao et al., 2011; and riondato et al., 2021). three studies had between 50 and 100 patients (marconato et al., 2015; poggi et al., 2015; and wolf-ringwall et al., 2019). the other seven studies had less than 50 patients (baek et al., 2017; joetzke et al., 2012; marconato et al., 2013; mizutani et al., 2016; pinheiro et al., 2014; poggi et al., 2017; and tagawa et al., 2018).  studies were generally well constructed and provided strong evidence towards the answering of the pico question. this will be discussed in the appraisal. summary of the evidence baek et al. (2017) population: dogs with b-cell lymphoma. sample size: 12 dogs with b-cell lymphoma. five healthy beagles used as a control. intervention details: dogs with b-cell lymphoma were classified based on the world health organization (who) clinical staging system for lymphosarcoma in domestic animals (owen, 1980). 10 dogs with lymphoma were classified as stage iv, and two were classified as stage v. peripheral blood samples were taken from the study patients and peripheral blood mononuclear cells were assessed for the expression of cell markers of regulatory t-cells (tregs) measured by flow cytometry. the extracellular markers cd4 and cd25 were used as well as the intracellular marker foxp3. the percentage of tregs was calculated by dividing the cd4+cd25+foxp3+ t-cells by the total number of cd4+ t-cells. the total number of lymphocytes in the blood samples of each patientwas determined by a routine complete blood count and a differential count on a blood smear ― this was then used to calculate the number of tregs with the percentage of tregs found above. study design: cohort study. outcome studied: percentage of tregs measured by flow cytometry in peripheral blood of the patients. patients with b-cell lymphoma were compared to the average percentage of tregs in the five healthy controls (5.2%). patients with who clinical stage iv lymphoma were compared to patients with who clinical stage v lymphoma. main findings (relevant to pico question): all 12 canine patients with b-cell lymphoma showed significantly increased percentages of tregs (mean 19.6%) compared to the average percentage of tregs in the five healthy controls (5.2%). the absolute numbers of tregs in the peripheral blood of the dogs with b-cell lymphoma (mean 1342 × 103 cells / μl blood) was also significantly increased compared to the five healthy controls (51 × 103 cells / μl blood). dogs in who clinical stage v showed increased relative (57.2% vs 16.2%) and absolute (5809 × 103 / μl vs 936 × 103 / μl) numbers of tregs when compared to dogs in who clinical stage iv. limitations: small sample size. breeds of dogs with lymphoma not described. it is not mentioned how the diagnosis of lymphoma was confirmed in sample patients. who clinical stages sampled only included stages iv and v and it was not explicitly explained how staging was performed and differed between them. stage migration depending on staging technique may impact how these results are interpreted. only two who clinical stage v patients were sampled, compared to ten who clinical stage iv patients. not directly associated with prognosis but indicates a potential prognostic target. joetzke et al. (2012) population: dogs with cytologically confirmed multicentric bor t-cell lymphoma.  a diagnosis of b-cell or t-cell lymphoma was required to be supported by flow cytometric evaluation of fine needle aspirates of lymph nodes with antibodies against cd21 or cd3 respectively. sample size: 44 dogs from 21 different breeds with multicentric b-cell (n = 35) or t-cell (n = 9) lymphoma. five healthy control beagles. intervention details: clinical staging of the dogs with lymphoma was performed according to the world health organization clinical staging system (owen, 1980). samples were taken from blood, bone marrow, liver and spleen. cell counts in all samples were measured with an automated blood cell counter. nucleated cells were then assessed for the cell markers cd45, cd3 and cd21 by flow cytometry. the percentages of cd3+cd21(t-cells) and cd21+cd3(b-cells) were used to calculate t:b values. mean values of the log (t:b) ±2 standard deviations in the healthy control dogs were used to define upper and lower threshold values for each sample type. samples from the patients with t-cell lymphoma would be considered positive for lymphoma involvement if the log (t:b) from the sample was greater than the upper threshold value. samples from the patients with b-cell lymphoma would be considered positive for lymphoma involvement if the log (t:b) from the sample was less than the lower threshold value. study design: cohort study. outcome studied: involvement of lymphoma in extranodal tissues as defined in the intervention details. main findings (relevant to pico question): in dogs with b-cell lymphoma, mean log (t:b) values of lymph node (-1.11 ± 0.47 vs 0.45 ± 0.20), blood (0.12 ± 0.64 vs 0.85 ± 0.15), bone marrow (-0.22 ± 0.59 vs 0.40 ± 0.49), liver (-0.24 ± 0.61 vs 1.08 ± 0.27) and spleen (-0.93 ± 0.44 vs 0.33 ± 0.18) samples were significantly lower than those in samples of the same tissue type from the healthy control dogs (p<0.001 in lymph node, blood, liver and spleen samples; p = 0.017 in bone marrow). on the basis of the defined thresholds results were positive for 25/35 (71.4%) blood samples, 11/34 (32.4%) bone marrow samples, 26/29 (89.7%) of liver samples and 34/34 (100.0%) of spleen samples from dogs with b-cell lymphoma. in 30/35 (86.0%) of the dogs with b-cell lymphoma, a population of presumed neoplastic b-cells was identified at more than one sample site by flow cytometry. in the other five, apparently normal b-cells were depleted in all sample sites or a confluence of presumed neoplastic and non-neoplastic b-cells to one indistinguishable population. in 24/35 (69.0%) of dogs with b-cell lymphoma, relative cd21 expression density was higher in presumed neoplastic than in non-neoplastic lymphocytes in more than one sample. results of cytologic and flow cytometric examination were in agreement for 133/161 (83.0%) of sample collection sites. limitations: dogs from a large range of breeds were used in different numbers. only five normal dogs were used to calculate the upper and lower threshold values for each sample type which may not be fully representative. a small number of antibodies were used to classify lymphocytes. blood contamination may have led to false classifications in cytologic and flow cytometric examinations. lymphocyte populations detected in samples with light scatter and antibody binding characteristics similar to lymphoma cell populations in the lymph nodes of the same patient can only be assumed to be neoplastic – it cannot be ruled out that these are physiologic lymphocyte subpopulations. not directly associated with prognosis but indicates a potential prognostic target. marconato et al. (2013) population: dogs with multicentric large b-cell lymphoma diagnosed by cytology and flow cytometry or histopathology. dogs were enrolled from 2007 to 2012. sample size: 46 dogs total from 21 different breeds. intervention details: all dogs were staged using the world health organization (who) system (owen, 1980). flow cytometric immunophenotyping was carried out on lymph node aspirates, bone marrow aspirates and peripheral blood of each dog at the time of initial staging. a panel of antibodies was used to assess the presence of the following cell markers using a multi-colour approach: cd45, cd3, cd5, cd4, cd8, cd21, cd79a and cd34. the extent of peripheral blood and bone marrow infiltration by large b-cells was evaluated by flow cytometry. this was reported as a percentage of large cd21+ positive cells out of total cd45 positive cells. additionally, in dogs recruited after june 2011 (n = 13) histopathology was performed on the same lymph node that was aspirated for cytology and flow cytometry. the lymph node was examined by a veterinary pathologist and antibodies against cd3, cd5, cd79a and cd20 were used for immunohistochemistry on paraffin embedded sections. treatment was then initiated using the following chemotherapeutic protocol: day 1: l-asparaginase day 8: vincristine days 15–18: cyclophosphamide day 22: doxorubicin the cycle was repeated once after a 1-week interval. a d-actinomycin, cytarabin and melphalan protocol was offered in case of relapse. response to treatment was evaluated by assessment of peripheral lymph nodes 24 hours starting after the first administration of l-asparaginase and at the end of each session of chemotherapy after this. response was classified as complete remission, partial remission, stable disease or progressive disease – responses were required to last for ≥ 28 days. dogs were re-evaluated at the end of chemotherapy. any investigations that previously had abnormal results in the pre-treatment stages were repeated. flow cytometry was repeated on bone marrow and peripheral blood samples in all cases at the end of chemotherapy. study design: cohort study. outcome studied: time to progression was calculated from the start of treatment to progressive disease. lymphoma specific survival was measured as the interval between the start of treatment and death from lymphoma. the authors looked for an association between peripheral blood or bone marrow infiltration assessed by flow cytometry and time to progression or lymphoma specific survival. main findings (relevant to pico question): at the end of the study 6/46 (13.0%) dogs were alive and in complete remission, while 40/46 (87.0%) had died. of these, 38/46 (82.6%) died because of progressive disease and 2/46 (4.3%) died from causes unrelated to lymphoma. bone marrow infiltration significantly influenced time to progression (p = 0.001) on the basis of univariable cox’s proportional hazard regression. bone marrow infiltration significantly influenced lymphoma specific survival (p<0.001) on the basis of univariable cox’s proportional hazard regression. a cut-off of 0% bone marrow infiltration was proposed to identify dogs with an unfavourable prognosis – hazard ratios showed that dogs with ≥3.0% bone marrow infiltration had a 3.3 (95.0% ci 1.4–7.6) times higher probability of progression, and a 3.6 (95.0% ci 1.6–8.0) times higher probability of death, compared to dogs with <3.0% bone marrow infiltration. although significant values were also found when using a cut-off of 1.0% bone marrow infiltration, this is very close to the intrinsic limit of detection of flow cytometry as large b-cells have also been found in healthy dogs at a percentage close to but less than 1.0%. in the multivariate analysis, substage was the only factor associated with time to progression (p = 0.002), while both substage (p < 0.001) and anaemia (p = 0.008) were associated with lymphoma specific survival. bone marrow infiltration was not found to be significant in the multivariable analysis, showing it was not an independent prognostic factor. limitations: histopathology was only performed on 13/46 (28.3%) of the study population. some dogs received corticosteroids before initiation of the study protocol. bone marrow aspiration was routinely unilateral therefore sensitivity for bone marrow involvement may have been decreased. focal bone marrow infiltration may have been missed as trephine bone marrow biopsy was not performed. the decision whether to perform rescue therapy if required was left to the owners which may have biased lymphoma specific survival in some cases. large confidence intervals were found for the hazard ratios. bone marrow infiltration lost significance in the multivariable analysis, showing it is not an independent prognostic factor. although explored in this study, further variables need to be better characterised. marconato et al. (2015) population: dogs with diffuse large b-cell lymphoma diagnosed histologically and immunohistochemically. sample size: 51 dogs from 22 different breeds. intervention details: all dogs were staged using the world health organization (who) system (owen, 1980). flow cytometric analysis of blood was used to assess lymphocyte and monocyte percentages by taking into account morphological scattergrams and the expression of cd45 (pan-leucocyte marker) and cd21 (b-cell marker). absolute lymphocyte count (alc) and absolute monocyte count (amc) were calculated based on the white blood cell count from a complete blood count performed on the day of diagnosis and the percentages of lymphocytes and monocytes obtained by flow cytometric analysis. lymphocyte/monocyte ratio (lmr) was calculated as the ratio of absolute counts between peripheral lymphocytes and monocytes. treatment was then initiated using a cyclophosphamide, doxorubicin, vincristine and prednisolone (chop) based protocol with incorporation of apavac immunotherapy. response to treatment was assessed at each treatment session. response was classified as complete remission, partial remission, stable disease or progressive disease responses were required to last for ≥28 days. dogs were re-evaluated at the end of chemotherapy. any investigations that previously had abnormal results in the pre-treatment stages were repeated. peripheral blood and bone marrow was sample again for flow cytometric analysis in all cases. all dogs were followed up monthly for the first year following this, then every 2 months. rescue treatment was offered in case of relapse. study design: cohort study. outcome studied: time to progression was calculated from the start of treatment to progressive disease. lymphoma specific survival was measured as the interval between the start of treatment and death from lymphoma. the authors looked for an association between lmr and time to progression or lymphoma specific survival. main findings (relevant to pico question): during the study period, 38/51 (74.5%) dogs progressed and 13/51 (25.5%) dogs never relapsed. lmr was found to significantly influence time to progression for the 10th (p = 0.038), 20th (p = 0.003), 25th (p = 0.009) and 30th (p = 0.001) percentiles in the univariable analysis. the probability of progression was 3.691 (1.706–7.985) times higher in dogs with lmr ≤2 compared with dogs with lmr >1.2. lmr was found to significantly influence lymphoma specific survival for the 10th (p = 0.022), 20th (p = 0.004), 25th (p = 0.005) and 30th (p = 0.002) percentiles in the univariable analysis. the probability of death due to lymphoma was 4.131 (1.719–9.931) times higher in dogs with lmr ≤ 1.2 compared with dogs with lmr >1.2. limitations: no healthy control population to compare normal lmr. lymphocytes and monocytes were categorised based only on expression of cd45 and morphological properties, not making use of further markers to help better characterise the cells. the decision whether to perform rescue therapy if required was left to the owners which may have biased lymphoma specific survival in some cases. relatively short median follow-up time. mizutani et al. (2016) population: dogs with lymphoid malignancies diagnosed by cytology and / or histopathology. sample size: 26 dogs with lymphoid malignancies including high-grade b-cell lymphoma (n = 17), t zone lymphoma (n = 5), follicular lymphoma (n = 2), cutaneous lymphoma (n = 2) and acute lymphoblastic leukaemia (n = 3). seven healthy dogs and six dogs with reactive lymphadenopathy were also sampled for comparison. intervention details: samples were taken from peripheral lymph nodes in the 24 nodal lymphoma cases, and from cutaneous masses in the 2 cutaneous lymphoma cases. peripheral blood was separated by ficoll-paque gradient centrifugation from the 3 acute lymphoblastic leukaemia cases. the samples were stained for the cd25 marker, analysed by flow cytometry, and the percentages of cd25 positive cells were calculated from an isotype matched control for each sample. further to this, 15 dogs with high-grade b-cell lymphoma were divided into two groups: >60.0% cd25+ cells (cd25 high) (n = 7) and <60.0% cd25+ cells (cd25 low) (n = 8). dogs in both groups received a chop based protocol and were monitored following treatment for progression of disease or death. progression free survival was calculated from the date of initial treatment to disease progression or death from any cause. overall survival was calculated from the date of initial treatment to death from any cause. study design: cohort study. outcome studied: percentage of cd25+ cells in the samples. the authors also looked to correlate high or low percentage of cd25+ cells in a sample with progression of disease and survival. main findings (relevant to pico question): percentage of cd25+ cells were significantly higher in cases with high-grade b-cell lymphoma than in healthy dogs. cd25 positivity was variable in the patients with high-grade b-cell lymphoma (range 0.4%–97.1%). response to treatment was not significantly different between cd25 high and cd25 low dogs. the median value of progression free survival in cd25 high dogs which was significantly shorter (p < 0.05) than in cd25 low dogs (28 days vs 140 days). kaplan-meier curves appeared to show a decreased overall survival of dogs in the cd25 high group compared to the cd25 low group (median: 115 days vs 244 days), but this did not quite reach statistical significance (p = 0.074). limitations: small sample size, especially for comparing between the cd25 high and cd25 low groups. progression free survival and overall survival calculated from death of any cause, not limited to lymphoma related deaths. it is not explained how frequently dogs were assessed for progression of disease when comparing prognosis. pinheiro et al. (2014) population: dogs with b-cell lymphoma diagnosed by cytology and / or histopathology. sample size: 22 dogs with b-cell lymphoma. 14 control dogs with t-cell lymphoma. 14 control dogs with reactive lymph node hyperplasia. six control dogs with metastatic mast cell tumours. 25 healthy control dogs. intervention details: all dogs with lymphoma were staged according to the who staging system (owen, 1980). samples were taken from affected lymph nodes of study dogs. samples were assessed by flow cytometry for the cellular markers cd5, cd4, cd8, cd79b, cd21, cd34, class ii mhc, foxp3 and helios. cells were classified on the basis of the flow cytometric data. patients were then treated using various chemotherapeutic protocols. in the b-cell lymphoma group: 14 dogs underwent a chop protocol. three dogs underwent a cop protocol. one dog underwent a course of prednisolone. three dogs were classified as ‘other’ (included cytarabine, l-asparaginase and lomustine. one dog did not receive chemotherapy. time to remission, progression free survival and overall survival were calculated for each patient. study design: cohort study. outcome studied: the b-cell lymphoma group was compared to the other groups which were regarded as controls. the authors looked to correlate foxp3 and helios expression (thereby measuring helios-foxp3+ regulatory t-cells) and class ii mhc expression with time to remission, progression free survival and overall survival. main findings (relevant to pico question): patients with a total foxp3 expression less than or equal to the median value in the study (1.2%) survived longer than those with expression above the median value (322 days vs 169 days, p = 0.018). patients with lower foxp3 expression in the cd5+cd4+ t-cell population had a longer progression free survival than those with higher foxp3 expression (211 days vs 61 days, p = 0.012). patients with helios expression less than or equal to the median value (3.0%) had a longer progression free survival than those with expression above the median value (175 days vs 62 days, p = 0.014). class ii mhc expression was expressed as a ratio of mhc ii+:mhc iicells within the cd5subset. time to remission was longer in cases with expression ratios less than or equal to the median value (4.40) compared to cases with expression ratios greater than the median value (22 days vs 10 days). in the multivariable analysis, foxp3 expression was found to be associated with progression free survival and overall survival. class ii mhc expression was found to be associated with time to remission in the univariable analysis. limitations: various chemotherapeutic strategies used for dogs in the study. some dogs included in the study had been pretreated with corticosteroids or another cytotoxic chemotherapeutic drug prior to the study, however this was taken into account in the study and was not thought to impact the results. time to remission, progression free survival and overall survival were defined by owners and veterinarians observations of clinical signs and lymph node size. some dogs received rescue therapy while others did not. poggi et al. (2015) population: dogs with lymphoma diagnosed by clinical presentation, cytological examination and flow cytometric analysis. sample size: 90 dogs with lymphoma including 80 high-grade (62 b-cell and 18 t-cell) and 10 low-grade (3 b-cell and 7 t-cell). intervention details: fine needle aspirates were taken from lymph nodes of the patients and cells were assessed by flow cytometry for the presence of the following cell markers: cd3, cd5, cd4, cd8, cd21, cd79a and cd34 in order to classify the type of lymphoma. cells were also assessed using for the presence of ki67 using flow cytometry and proliferative activity was expressed as percentage of ki67+ cells. fine needle aspirates of enlarged lymph nodes were also used to produce smears for cytological examination. all cases were classified and allocated to the low-grade or high-grade group according to the updated kiel scheme (fournel-fleury et al., 1997; and ponce et al., 2010). study design: cohort study. outcome studied: the authors looked to evaluate the accuracy of percentage of ki67+ cells in discriminating high-grade and low-grade forms of lymphoma. main findings (relevant to pico question): a significantly higher percentage of ki67+ cells were found in the high-grade group (median 34.4%; range 7.8–85.0%) compared to the low-grade group (median 5.3%; range 1.3–11.4%) (p < 0.0001). roc curve analysis identified a high accuracy of percentage of ki67+ cells in discriminating between high-grade and low-grade lymphomas (area under the curve [auc] = 99.4%). a cut-off value of 12.2% was indicated to detect high-grade lymphomas with a sensitivity of 96.3% and a specificity of 100.0%. limitations: much smaller sample size of dogs with low-grade lymphoma compared to dogs with high-grade lymphoma – for the purposes of this review article, there were only three low-grade b-cell lymphoma cases included. not directly associated with prognosis but indicates a potential prognostic target. no survival data for the dogs so not really associated with prognosis directly. poggi et al. (2017) population: dogs with high-grade b-cell lymphoma diagnosed by clinical presentation, cytological examination of lymph nodes and flow cytometric analysis. sample size: 40 dogs from 21 different breeds. intervention details: fine needle aspirates were taken from lymph nodes of the patients and cells were immunophenotyped by flow cytometry. cells were assessed for the presence of the following cell markers: cd45, cd3, cd5, cd4, cd8, cd21, cd79b and cd34. cells were also assessed using for the presence of ki67 using flow cytometry and proliferative activity and was expressed as percentage of ki67+ cells (ki67%). patients were divided into ki67% groups: low if ki67 ≤0%, intermediate if ki67 between 20.1 and 40.0%, high if ki67 > 40.0%. fine needle aspirates of enlarged lymph nodes were also used to produce smears for cytological examination. all cases were classified and allocated to a specific grade of malignancy and cytological subtype according to the updated kiel scheme (fournel-fleury et al., 1997; and ponce et al., 2010). a uw-25 (chop based) chemotherapy protocol was initiated in all patients. information was collected following this including achievement of remission, occurrence of relapse, survival at the end of the first chemotherapy protocol, lymphoma specific survival (time in days between the start of treatment and death from lymphoma), relapse free interval (time in days from when a dog achieved complete remission until relapse), date and cause of death. responses were classified as complete remission, partial remission, stable disease or progressive disease. relapses were treated with a second uw-25 protocol or l-asparaginase and lomustine. study design: cohort study. outcome studied: the authors looked to assess if ki67% correlated with clinical outcome judged by achievement of remission, occurrence of relapse, survival at the end of the first chemotherapy protocol, lymphoma specific survival and relapse free interval. main findings (relevant to pico question): ki67% showed near significant association with survival (p = 0.063) and achievement of complete remission (p = 0.075) at the end of the chemotherapy protocol. percentages of both survival and complete remission were higher for dogs with intermediate ki67% (85.7% and 81.0% respectively) compared to dogs with low ki67% (50.0% and 33.0%) and high ki67% (50.0% and 60.0%) treated with uw-25 protocol. ki67% significantly influenced lymphoma specific survival (p=0.001) on univariable analysis and was confirmed to be an independent prognostic factor (p = 0.001) in the multivariable analysis. dogs with intermediate ki67% has significantly longer lymphoma specific survival (median = 866 days) than dogs with low (median = 42 days; p<0.001) and high (median = 173 days; p = 0.038) ki67%. intermediate ki67% was a significant predictor for 1 and 2 year survival (p = 0.001 and p = 0.004 vs low and high ki67%, respectively, at both time points). dogs with intermediate ki67% showed longer relapse free interval (median = 428 days) than dogs with low ki67% (median = 159 days; p = 0.014) and high ki67% (median = 100 days; p = 0.126), although the difference with the high ki67% group did not reach statistical significance. limitations: limited number of cases. multiple different classifications of b-cell lymphoma were included in this study. rescue chemotherapy protocol varied depending on when the relapse occurred and owner compliance. many breeds of dogs represented in the study population. rao et al. (2011) population: dogs with b-cell lymphoma diagnosed cytologically or histologically. sample size: 160 dogs. intervention details: fine needle aspirates of peripheral lymph nodes were taken from each patient and analysed by flow cytometry. patients were retrospectively assigned as class ii mhc low or class ii mhc high based on median fluorescence intensity. cells were classified as either medium or large lymphocytes based on median forward scatter of cd21 gated cells (large cells had a median forward scatter >720u, the remaining cases were categorised as medium cells). cases in which >5.0% of b-cells stained for cd34 above background isotype control were considered cd34+. treatment was initiated in all patients. patients received either prednisolone only, single agent doxorubicin (+prednisolone) or a chop based protocol. two outcomes were recorded: survival time (time interval from starting treatment to death) and first remission time (time from starting treatment to date of first confirmed recurrence of cancer). study design: cohort study. outcome studied: the authors looked to correlate expression of class ii mhc, cd34 and cell size with survival times and first remission times. main findings (relevant to pico question): level of cd34, cd5 and cd21 expression did not predict survival or remission. when taking into account other factors in the multivariable model, median survival time for dogs with low class ii mhc expression was 120 days, compared with 314 days for dogs with high class ii mhc expression. patients with low class ii mhc expression were found to be 2.9 times more likely to die (95.0% ci = 1.4–5.9) in any time period compared to those with high expression. patients with large tumour cells were 2.8 times more likely to die (95.0% ci = 1.0–7.5) in any time period compared to those with small tumour cells. a statistical model was produced by the authors which can be used to predict outcome of dogs with b-cell lymphoma based on significant prognostic factors (age, class ii mhc, cell size and treatment). limitations: the initial round of recruitment of patients did not have enough cd34+ cases, therefore a second round of recruitment was carried out. variation in chemotherapy protocols used for each patient. insufficient numbers of cases for breeds other than golden retrievers and labrador retrievers were recruited to be able to analyse separately. 28 patients had a histological diagnosis, but these were not subclassified. wide confidence intervals as low numbers some of the groupings. riondato et al. (2021) population: dogs with a diagnosis of nodal lymphoma with flow cytometric analysis of an enlarged peripheral lymph node. sample size: 128 dogs with lymphoma. 90 dogs had b-cell lymphoma. 38 dogs had t-cell lymphoma. intervention details: cases were categorised as highor low-grade bor t-cell lymphoma based on review of the cytological preparations. proliferation rate (ki67%) was measured as the percentage of ki67+ cells out of total nucleated cells. apoptotic rate (annv%) was measured as the percentage of cells staining positive for annexin v (used to detect apoptosis) but negative for propidium iodide. proliferation/apoptosis ratio (par) was calculated as ki67%/annv%. turnover index (ti) was calculated as ki67% + annv%. statistical analysis was then performed for each continuous variable within each lymphoma subgroup. study design: cohort study. outcome studied: the authors looked to correlate ki67%, annv%, ti and par to see if there was any difference between highand low-grade lymphoma cases. main findings (relevant to pico question): ki67% was significantly lower in low-grade b-cell lymphomas than in high-grade b-cell lymphomas (p < 0.001). annv% did not significantly vary between highand low-grade b-cell lymphomas. par was significantly lower in low-grade b-cell lymphomas than in high-grade b-cell lymphomas (p < 0.001). ti was significantly higher in high-grade b-cell lymphomas than in low-grade b-cell lymphomas (p < 0.001). limitations: this study looked at how ki67%, annv%, par and ti related to grade of b-cell lymphoma but not on the prognostic significance of this. classification was done by a single observer, increasing the chance of misclassification. breed and sex not known for all dogs, however compared to the sample size this likely had little impact. no samples were analysed from lymph nodes without lymphoma, limiting interpretation. tagawa et al. (2018) population: dogs with high-grade multicentric b-cell lymphoma confirmed cytologically or histologically. sample size: 18 dogs with lymphoma. nine healthy control dogs. intervention details: all dogs with lymphoma were staged according to the who staging system (owen, 1980). samples were taken from peripheral blood and fine needle aspirates were taken from palpable lymph nodes. cells were analysed by flow cytometry and were assessed for the following cell markers: cd4, cd8, programmed death-1 (pd-1) and cytotoxic t-lymphocyte-associated antigen-4 (ctla-4). rt-pcr amplification was also performed to measure the levels of pd-l1, pd-l2, cd80 and cd86 mrna. treatment was then started: 10 dogs were treated with a chop based protocol. five dogs were treated with prednisolone alone. three dogs were treated with l-asparaginase. survival time was then assessed for each dog, measured as the interval between the sampling day and death due to lymphoma. study design: cohort study. outcome studied: whether expression of pd-1 and ctla-4 on peripheral cd4+ and cd8+ lymphocytes was different between dogs with high-grade b-cell lymphoma and healthy control dogs. whether there is a correlation between expression of pd-1 and ctla-4 on peripheral cd4+ and cd8+ lymphocytes and survival time in dogs with high-grade b-cell lymphoma. main findings (relevant to pico question): the proportions of pd-1+ cells in cd4+ lymphocyte populations obtained from peripheral blood mononuclear cells and lymph node cells were significantly higher in the lymphoma group than in the control group (p<0.001). the proportion of ctla-4+ cells in cd4+ lymphocyte populations obtained from peripheral blood mononuclear cells was significantly higher in the lymphoma group than in the control group (p = 0.018). the proportion of pd-1+ and ctla-4+ cells in cd8+ lymphocyte populations obtained from peripheral blood mononuclear cells were not significantly higher in the lymphoma group than in the control group. optimal cut-off values for expression of pd-1 and ctla-4 on cd4+ and cd8+ lymphocytes were established. dogs with levels below the cutoff value for ctla-4 expression had a significantly longer survival time than dogs with values above the cutoff (multiple p values depending on sample and cd4+/cd8+). however, cd8+ ctla-4+ lymphocytes from lymph node cells did not meet a minimum auc of 0.7. dogs with levels below the cutoff value for cd4+ pd-1+ lymphocytes from lymph node cells had a significantly longer survival time than dogs with values above the cutoff (p = 0.023). however, this did not meet a minimum auc of 0.7. except for this, the expression of pd-1 on lymphocytes did not correlate with survival time. limitations: a small sample size was used for this study. two dogs were treated with prednisolone before sampling was carried out. there was variation in the chemotherapy protocol used to treat the dogs in the study. the authors highlighted a lack of protein quantification of the immune checkpoint ligands. cd4 expression is not exclusive to t-cells. wolf-ringwall et al. (2019) population: dogs diagnosed with multicentric b-cell lymphoma diagnosed by cytology, histology and confirmed by flow cytometry. sample size: 64 dogs. intervention details: all dogs were staged using the world health organization (who) system (owen, 1980) and the attending clinician was required to assign an approximate stage and substage. multiple fine needle aspirates from a representative lymph node and analysed by flow cytometry. cells were assessed for size and for the expression of the following cell markers: class ii mhc, cd21, cd22, cd5, cd45 and cd25 on the neoplastic b-cells, and percent cd4 infiltration. cases were assigned to cell size category large if cd21+ lymphocytes had a median forward scatter >720u. the remaining cases were assigned as medium. level of cd25 expression was measured as the percentage of b-cells expressing cd25. all patients had lymph node biopsies and blood collection prior to treatment and at disease progression which were histologically and immunohistologically analysed. all dogs were treated with a 19 week chop protocol. and response to therapy was determined using the veterinary cooperative oncology group v1.0 response evaluation criteria for lymphoma (vail et al., 2010). study design: cohort study. outcome studied: objective response rate was defined as the sum of patients with a complete response or a partial response. progression free survival time was defined as the time from initiation of the chemotherapeutic protocol to disease progression or death from any cause. overall survival time was defined as the time from initiation of the chemotherapeutic protocol to death from any cause. main findings (relevant to pico question): patients with diffuse large b-cell lymphoma with a high percent of cd25+ b-cells had a significantly decreased progression free survival (p = 0.04) and overall survival time (p = 0.03) compared to dogs with a lower percent of cd25+ b-cells. percentage of cd25 expression was found to be a prognostic factor for overall survival for dogs with diffuse large b-cell lymphoma on univariable analysis. cell size was not correlated with outcome in diffuse large b-cell lymphoma. class ii mhc expression was not correlated with outcome in diffuse large b-cell lymphoma. limitations: information is not given as to how sampled lymph nodes were chosen as representative. full staging was not performed in all dogs ― 23/64 dogs (35.9%) had thoracic radiographs, 22/64 (34.4%) had an abdominal ultrasound, none had their bone marrow sampled. overall survival time and progression free survival were used which assess death from any cause, not just death resulting from lymphoma. dogs lost to follow up were considered to have died of their disease if they were known to be out of remission at their last visit. only two patients fell into the large cell size category, which may explain the absence of correlation with survival. two dogs received a modified chop protocol with vinblastine instead of vincristine due to adverse effects. there was an inadequate sample size of the less common subtypes of b-cell lymphoma in order to investigate them fully. appraisal, application and reflection flow cytometry is now widely used in order to help classify lymphoma (regetti and bienzle, 2011) which can provide information relating to recommended treatment protocols and to help inform on prognosis from knowledge about different classes of lymphoma. with increasing availability of flow cytometers and antibodies against species specific cell markers in the veterinary sector, we are becoming aware of more markers whose expression becomes deranged in canine lymphoma. more studies are targeting cell markers or other cellular characteristics in lymphoma which may be useful as prognostic indicators or therapeutic targets. the twelve cohort studies evaluated in this knowledge summary provide evidence for the use of a range of cellular markers and characteristics in providing useful prognostic information in canine lymphoma. from the studies evaluated, eight correlated specific cellular markers measured by flow cytometry with prognosis (wolf-ringwall et al., 2019; tagawa et al., 2018; riondato et al., 2021; rao et al., 2011; pinheiro et al., 2014; poggi et al., 2015; poggi et al., 2017; and mizutani et al., 2016), two correlated cell size with prognosis (rao et al., 2011; and wolf-ringwall et al., 2019), one correlated peripheral lymphocyte/monocyte ratio with prognosis (marconato et al., 2015), one correlated bone marrow infiltration measured by flow cytometry with prognosis (marconato et al., 2013), one looked at evaluating extranodal infiltration by flow cytometry (joetzke et al., 2012) two correlated specific cellular markers with lymphoma grade (poggi et al., 2015; and riondato et al., 2021) and two correlated peripheral regulatory t-cells measured by flow cytometry with lymphoma severity (baek et al., 2017; and pinheiro et al., 2014). the significance of these will be assessed below. we must also take into account the various forms of lymphoma included in the study populations assessed in this review. four studies included dogs with any form of b-cell lymphoma in their study populations (rao et al., 2011; baek et al., 2017; poggi et al., 2017; and pinheiro et al., 2014). four studies only included dogs with multicentric b-cell lymphoma (wolf-ringwall et al., 2019; tagawa et al., 2018; marconato et al., 2013; and marconato et al., 2015). these studies are still very relevant to the pico however due to the high prevalence of multicentric b-cell lymphoma in veterinary practice. the remaining four studies included patients with both band t-cell lymphoma, however all had a study population predominantly containing dogs with b-cell lymphoma (poggi et al., 2015; mizutani et al., 2016; joetzke et al., 2012; and riondato et al., 2021).  additionally, four studies (mizutani et al., 2016; poggi et al., 2015; poggi et al., 2017; and rao et al., 2011) did not perform who classification on their cases, meaning that there is an unknown mix of b-cell lymphoma subtypes in these studies. we should consider these factors when interpreting the studies, however they likely still provide us with representative information. cellular markers eight of the studies identified an association between specific cellular markers and prognosis in b-cell lymphoma (wolf-ringwall et al., 2019; tagawa et al., 2018; riondato et al., 2021; rao et al., 2011; pinheiro et al., 2014; poggi et al., 2015; poggi et al., 2017; and mizutani et al., 2016). these markers may be useful in providing prognostic information in dogs with b-cell lymphoma by predicting survival, after treatment with cytotoxic drugs, usually based on their percentage expression in the relevant cellular population. mizutani et al. (2016) found that patients with lymphoma with a high percent of cd25+ b-cells in peripheral lymph nodes had a significantly decreased progression free survival and a subjectively decreased overall survival time compared to patients with a low percent of cd25+ b-cells. although this study included dogs with multiple lymphoid malignancies, it predominantly included dogs with high-grade b-cell lymphoma (17/26). this correlation was also found by wolf-ringwall et al (2019) who evaluated cd25 expression in dogs with multicentric b-cell lymphoma. cd25 binds the growth factor interleukin-2 which stimulates clonal expansion and maturation of activated t or b lymphocytes (lowenthal et al., 1985) which likely explains this relationship. these results suggest that cd25 could represent a useful prognostic marker for dogs with b-cell lymphoma. tagawa et al. (2018) assessed the expression of programmed death-1 (pd-1) and cytotoxic t-lymphocyte associated antigen-4 (ctla-4) in samples taken from the peripheral blood and palpable lymph nodes in dogs with high-grade multicentric b-cell lymphoma. pd-1 and ctla-4 are immune checkpoint molecules which are believed to be highly expressed on tumour infiltrating and peripheral lymphocytes and help evasion of the host immune system. dogs with high-grade b-cell lymphoma were found to have up-regulated expression of pd-1 on peripheral and tumour infiltrating lymphocytes and up-regulated expression of ctla-4 on peripheral cd4+ t-cells. dogs with ctla-4 expression below the cutoff value established by the study had significantly longer survival times compared to dogs with ctla-4 expression above the cutoff value (with the exception of cd8+ ctla-4+ cells from lymph nodes which did not meet the minimum auc required). although increased in dogs with b-cell lymphoma, the expression of pd-1 was not found to reliably correlate with survival times. although there were certain limitations with this study, such as a small sample size and varying chemotherapeutic protocols, the expression of ctla-4 on t-cells from peripheral blood and lymph node samples seems to be associated with a poorer prognosis in dogs with multicentric b-cell lymphoma, and further studies with larger populations could help to further refine the cutoff for its use as a prognostic indicator. class ii mhc is another cellular marker that is primarily expressed on ‘professional’ antigen presenting cells and has been assessed by three of the studies in this review (pinheiro et al., 2014; rao et al., 2011; and wolf-ringwall et al., 2019). rao et al. (2011) assessed for a correlation between class ii mhc expression and survival in dogs with b-cell lymphoma. they found that dogs with low class ii mhc expression had a lower median survival time than dogs with high class ii mhc expression. in their study, dogs with low class ii mhc expression were 2.9 times more likely to die in any time period compared to high expression. however, wolf-ringwall et al. (2019) did not find a correlation between class ii mhc expression and outcome in dogs with diffuse large b-cell lymphoma. one possible explanation for this put forward by wolf-ringwall et al. (2019) is that class ii mhc levels may not be important for survival in some histopathologic subtypes as rao et al. (2011) did not sub-classify the b-cell lymphomas in their study by histologic subtype. however, diffuse large b-cell lymphoma is the most common type of b-cell lymphoma in dogs, therefore it would be expected that diffuse large b-cell lymphoma would make up a large proportion of the population in the study by rao et al. (2011).  pinheiro et al. (2014) found that decreased class ii mhc expression was associated with increased time to remission in their study. this supports the findings by rao et al. (2011), suggesting that low expression of class ii mhc is associated with a poorer prognosis. the expression of class ii mhc could be a useful prognostic indicator, however further studies to clarify this would be required before implementing it as a prognostic tool. ki67 is a marker of cellular proliferation and is frequently used to assess the growth fraction of neoplastic populations (schlüter et al., 1993). poggi et al. (2015) and riondato et al. (2021) both investigated ki67 as a cellular marker. poggi et al. (2015) initially assessed the percentage of ki67+ cells in lymph nodes samples (ki67%) in dogs with lymphoma (including 65 with b-cell lymphoma) and confirmed that ki67% is increased in samples from dogs with high-grade lymphoma compared to low-grade. however, for the purposes of this review, only three dogs with low-grade b-cell lymphoma were included in the study population compared to 62 with high-grade b-cell lymphoma. the rest of the study population was made up of dogs with highand low-grade t-cell lymphoma. thus, when considering the significance of the study for this review, we need to be aware that this finding should be confirmed in a study with a greater population of dogs with low-grade b-cell lymphoma. riondato et al. (2021) lead a similar study with an increased sample size and found similar results. in the same study, poggi et al. (2015) also established a suggested cutoff value for ki67% of 12.2% to detect high-grade lymphoma which could be useful when classifying lymphoma and the prognostic implication that carries. for dogs with b-cell lymphoma, this should be confirmed before implementation by means of further investigation due to the lack of dogs with low-grade b-cell lymphoma included in the study as mentioned above. poggi et al. (2017) then looked to correlate ki67% with survival in dogs with high-grade b-cell lymphoma. ki67% was found to significantly influence lymphoma specific survival and dogs with an intermediate ki67% compared to a high or low ki67% had significantly longer relapse free interval and lymphoma specific survival. ki67% was also a significant predictor for 1 and 2 year survival. the authors suggest that this relationship is due to the fact that lymphomas with low proliferation rates (and therefore lower expression of ki67) exhibit resistance to cycle specific cytotoxic chemotherapy and lymphomas with high proliferation rates (and therefore higher expression of ki67) are more likely to regrow or acquire further mutations resulting in treatment failure. poggi et al. (2017) thus suggested that ki67 could be a useful prognostic indicator for addition to the routine panel of labelling for high-grade b-cell lymphoma with intermediate values of ki67% being associated with the best prognosis.  cellular size it has also been suggested that size of neoplastic cells in samples taken from dogs with b-cell lymphoma could represent a possible prognostic indicator. rao et al. (2011) classified cells taken from samples from peripheral lymph nodes of dogs with b-cell lymphoma on the basis of size evaluated by flow cytometry. in this study, the median forward scatter of cd21+ cells in the sample was assessed. large cells were categorised as having a median forward scatter of >720u. patients in the large cell group were found to be 2.8 times more likely to die in any time period compared to those in the small cell group. it is suggested that these large b lymphocytes correlate to more immature and aggressive neoplastic cells which are negatively associated with survival. wolf-ringwall et al. (2019) also characterised cd21+ cells taken from lymph nodes of dogs with multicentric b-cell lymphoma with flow cytometry. a cutoff value for median forward scatter of 720u was also used in this study, with median forward scatter of >720u being used to assign a sample to the large cell group. wolf-ringwall et al. (2019) did not find any correlation of cell size with survival, contrasting the findings of rao et al. (2011). however, the large cell group only comprised of 3.1% (2/64) patients in the study by wolf-ringwall et al. (2019), which may explain the lack of statistical correlation. in the study by rao et al. (2011), still only 6.9% (11/160) of the study population was assigned to the large cell group. as far fewer patients were assigned to the large cell group compared to patients in the small cell group in both studies, cell size measured by this basis may not provide a widely applicable prognostic test for dogs with b-cell lymphoma.  cell size can also be influenced by the time delay between sampling and flow cytometry, during which cells may swell and not be representative of their true size. additionally, the methods used for classifying cell size are not transferable between studies, making it difficult to compare between them. the significance of cell size on prognosis is still not clear, however further investigations are warranted for the use of flow cytometry for this purpose. bone marrow infiltration a novel use for flow cytometry was employed by marconato et al. (2013) who looked to correlate bone marrow infiltration by multicentric b-cell lymphoma with time to progression and lymphoma specific survival with a view to use it as a prognostic tool. bone marrow infiltration was reported as percentage of large cd21+ cells out of total cd45+ cells in the sample. they found that bone marrow infiltration significantly influenced time to progression and lymphoma specific survival, thus suggesting that level of bone marrow infiltration can be used as a prognostic tool in multicentric b-cell lymphoma. they suggested a cutoff of 3.0% bone marrow infiltration to identify dogs with an unfavourable prognosis. dogs with ≥3.0% bone marrow infiltration had a 3.3 times higher probability of progression and a 3.6 times higher probability of death when compared to dogs with < 3.0% bone marrow infiltration. analysis of bone marrow infiltration is commonly involved in the staging of canine lymphoma (marconato, 2011) and this study shows that flow cytometry can be used to assess bone marrow infiltration and give prognostic information relating to this. a cut-off value is also established which could be further refined and validated following further investigation and use. extranodal infiltration joetzke et al. (2012) used the ratio between t and b lymphocytes (log (t:b)) established by flow cytometry to differentiate between lymphoma infiltrated and healthy samples from blood, bone marrow, liver and spleen.  using this method they found that mean log (t:b) values in all samples were significantly lower in dogs with b-cell lymphoma compared to healthy control dogs. the authors suggest that the log (t:b) could be used as an indicator of the degree of lymphoma cell infiltration to predict prognosis, however this would need to be investigated in further studies as it has not been confirmed that log (t:b) correlates with prognosis, nor is it clear that that the b and t-cells are the neoplastic cells in question. however, the ability of log (t:b) to predict lymphoma infiltration would suggest that it may correlate with prognosis. although log (t:b) measured by flow cytometry has not yet been established as a prognostic measure in canine lymphoma, this study has shown that it may prove useful in the future and further studies should focus on establishing its use. peripheral lymphocyte/monocyte ratio marconato et al. (2015) suggested that peripheral lymphocyte/monocyte ratio (lmr) determined by flow cytometry may provide useful prognostic information in dogs with diffuse large b-cell lymphoma. this has previously been shown in humans (li et al., 2014). they found that the probability of lymphoma progression was 3.691 times higher in dogs with an lmr ≤1.2 compared with dogs with an lmr >1.2. as well as this, the probability of death due to lymphoma was 4.131 times higher in dogs with an lmr ≤1.2 compared with dogs with an lmr >1.2. this technique could be useful as it makes use of a peripheral blood sample rather than aspirates of lymph nodes which may be less stressful for the dog. however, this information could be obtained using a standard analyser rather than requiring flow cytometry a more complex technique. while lmr looks to be a promising addition to the range of prognostic indicators assessed by flow cytometry, it is not clear if there are advantages to calculating this using flow cytometry rather than a standard analyser.  while this study used a chemoimmunotherapy protocol to treat the patients, further investigations could assess the prognostic value of lmr in patients undergoing traditional chemotherapy. peripheral regulatory t-cell (treg) population it has been suggested that tregs are involved in host immunosuppression as a protective mechanism employed by tumours in order to escape the host protective immune system (yang et al., 2004). baek et al. (2017) thus investigated the percentage of tregs in total lymphocytes of the peripheral blood with flow cytometry in dogs with b-cell lymphoma of different stages. they found that the percentage of tregs in peripheral blood was increased in dogs with lymphoma compared to healthy control dogs. they also found that dogs with who stage v lymphoma had increased percentage of tregs in peripheral blood compared to dogs with who stage iv lymphoma. this suggests that percentage of tregs in peripheral blood could be used as a possible prognostic indicator due to its correlation with lymphoma grade. however, an association of treg percentage and survival was not assessed so we cannot make this assumption. as well as this, sample size was small and only dogs with who stage iv and v lymphoma were sampled, not giving a representative sample across different stages. pinheiro et al. (2014) assessed the expression of foxp3 and helios in samples from dogs with b-cell lymphoma.  in these dogs, foxp3 and helios expression is used as a surrogate for levels of regulatory t-cells in the affected lymph nodes. they found that increased foxp3 expression in patients was associated with poorer progression free survival and overall survival times. patients with higher helios expression also had a shorter progression free survival time. this study provides stronger evidence for the use of treg populations in lymph nodes as a prognostic indicator in dogs with b-cell lymphoma. peripheral treg percentage may have a role as a prognostic indicator, however its relationship with lymphoma grade and survival should be further characterised. conclusion there are several promising flow cytometric prognostic indicators and as our range of antibodies to cellular markers grows in dogs, it is likely that further targets will be revealed. from the studies evaluated, there is currently good evidence for the use of percentage expression of cd25 and ki67 cellular markers in providing prognostic information in canine b-cell lymphoma. this is due to the presence of more than one good quality study suggesting each of their prognostic values. however, this needs to be translated into clinical practice and their use should be evaluated on a wider scale, including the provision of cutoff values for estimates of survival or response to treatment. there is also evidence for the prognostic value of flow cytometric analysis of bone marrow infiltration, expression of class ii mhc and ctla-4, peripheral lymphocyte / monocyte ratio, nodal regulatory t-cell populations and the ratio between t and b lymphocytes in extranodal locations, however these need to be further investigated before introduction to clinical practice in order to confirm their value. this should involve more studies assessing these prognostic indicators with larger sample sizes. furthermore, the use of cellular size and peripheral regulatory t-cell populations as prognostic indicators cannot be confirmed from the studies evaluated due to the lack of good quality evidence on the subject including limitations with sampling. while they may still hold value in providing prognostic information, this needs to be assessed by further studies on this topic. flow cytometry offers the evaluation of numerous variables which can be used to help assess the prognosis of canine patients with b-cell lymphoma and its use will only grow as more canine antibodies against cellular targets become available. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform 1973–week 25 2021 pubmed 1973–2021 web of science 1973–2021 search strategy: cab abstracts: (dog or dogs or canine* or canis) or exp dogs/ or exp canis/ (((b-cell or b) and (lymphoma* or lymphosarcoma* or lymphoprolifer*)) or bcl) ((flow and cytomet*) or fc) 1 and 2 and 3   pubmed: ((dog or dogs or canine* or canis) and (((b-cell or b) and (lymphoma* or lymphosarcoma* or lymphoprolifer*)) or bcl) and ((flow and cytomet*) or fc))   web of science: ((dog or dogs or canine* or canis) and (((b-cell or b) and (lymphoma* or lymphosarcoma* or lymphoprolifer*)) or bcl) and ((flow and cytomet*) or fc)) dates searches performed: 27 oct 2021 exclusion / inclusion criteria exclusion: wrong species not b-cell lymphoma no full text available not relevant to pico non-english language publications published more than 25 years ago single case reports inclusion: correct species b-cell lymphoma english language papers relevant to pico full text available papers relevant to veterinary medicine search outcome database number of results excluded – not relevant to pico excluded – wrong species excluded – not b-cell lymphoma excluded – single case report total relevant papers cab abstracts 91 78 0 1 3 9 pubmed 137 123 0 5 1 8 web of science 132 116 2 5 2 7 total relevant papers when duplicates removed 12 conflict of interest the author declares no conflicts of interest. references baek, d. s., chung, t. h., kim, y. h., oh, s. k., so, k. m. & park, c. 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(2019). prospective evaluation of flow cytometric characteristics, histopathologic diagnosis and clinical outcome in dogs with naïve b‐cell lymphoma treated with a 19‐week chop protocol. veterinary and comparative oncology. 18(3), 342–352. doi: https://doi.org/10.1111/vco.12553 yang, s.-c., hillinger, s., riedl, k., zhang, l., zhu, l., huang, m., atianzar, k., kuo, b. y., gardner, b., batra, r. k., strieter, r. m., dubinett s. m. &sharma, s. (2004). intratumoral administration of dendritic cells overexpressing ccl21 generates systemic antitumor responses and confers tumor immunity. clinical cancer research. 10(8), 2891–2901. doi: https://doi.org/10.1158/1078-0432.ccr-03-0380 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. is there enough evidence to recommend surgical treatment as opposed to conservative treatment for dogs affected by bicipital tenosynovitis? a knowledge summary by alexandra penelas dvm1* 1university of zurich, vetsuisse faculty, rämistrasse 71, 8006 zürich, switzerland *corresponding author (apenelas@vetclinics.uzh.ch) vol 1, issue 2 (2016) published: 20 may 2016 reviewed by: bruce smith (bvsc ms fanzcvs dacvs) next review date: 30 may 2018 doi: 10.18849/ve.v1i2.29 clinical bottom line there is currently insufficient evidence to conclude that tenotomy or tenodesis has a better outcome compared to conservative treatment in cases of canine bicipital tenosynovitis. question is surgical treatment with tenotomy or tenodesis superior to conservative treatment for canine bicipital tenosynovitis? the evidence there is insufficient evidence for clinical decision-making regarding recommendation of surgical treatment versus conservative treatment. summary of the evidence bruce, w.j. et al. (2000) population: dogs with bicipital tendinitis, lame with pain localised to the biceps tendon, definitive diagnosis was established on the basis of clinical, sonographic and radiographic findings, synovial-fluid analysis. sample size: 15 dogs n=15 intervention details: 13 dogs initially underwent conservative treatment with rest (cage or small room and only short walks on a leash for six weeks and after improvement controlled walks on a leash for six weeks, followed by gradual return to normal exercise level) together with 2 to 4mg/kg daily carprofen for 2 or 3 weeks or a single peri-tendinous injection of 20 to 40mg of methylprednisolone acetate and rest. surgical treatment was done in 3 cases, 1 case that failed to improve after conservative treatment was treated by tenodesis and 2 additional cases were treated by either tenodesis or tenolysis. study design: non-comparative study (case series). outcome studied: subjective: re-examination by the authors at six weeks by lameness and shoulder assessment, sonography was done in 4 dogs, long-term follow-up was obtained by a telephone interview of the owners’ assessment and outcome was classified as excellent (never lame), good (only lame after heavy activity), fair (lame after moderate or normal activity) or poor (always lame, no improvement) according owners’ assessment. main findings (relevant to pico question): sonography was considered to be more sensitive by the authors than radiography or arthrography in characterising the lesion. conservative treatment resulted in good to excellent long-term results in 11 cases. in the 3 surgically treated cases the case which didn’t improve after conservative treatment also didn’t improve after surgery, another case improved and 1 case which didn’t improve had the diagnosis osteosarcoma in the follow-up time. 10 of 11 dogs treated conservatively showed improvement at a six-week follow-up. time to resolve the lameness ranged from 2 weeks up to seven months. limitations: a comparison between different treatments was not possible due to a lack of randomised treatment groups. only subjective assessment of treatment effect and therefore only a moderate rating about conservative versus surgical therapy can be made. wall, c.r. et al. (2002) population: diagnosis was based on clinical examination and diagnostic imaging, if conservative treatment (1 or 2 times intra-articular injection of long-acting corticosteroids) failed, surgery was performed. sample size: 5 dogs n=5 intervention details: initial treatment included intra-articular injection of 1.0mg triamcinolone acetonide and exercise restriction in 4 dogs and a tapering dose of carprofen with exercise restriction in 1 dog. if the dog didn’t respond to conservative treatment or after recurrence a bipolar radiofrequency electrosurgical system was used for arthroscopic transection of the bicipital tendon. study design: non-comparative study (case series) outcome studied: subjective revaluation 2 weeks after surgery which included a walk, follow-up 2 and 6 months following surgery which included gait at walk and trot, shoulder range of motion and pain assessment with palpation and shoulder movement. owner questioned regarding activity level and use of nsaids, results were placed into an objective rating scale and were assigned a rating of excellent, good, fair or poor. main findings (relevant to pico question): outcome after surgery of 4 dogs were rated as excellent and in 1 dog as good. limitations: subjective assessment of treatment outcome, no control group or different treatment groups for comparison, limited case number. stobie, d. et al. (1995) population: medical records from 1985 to 1992 of dogs with bicipital tenosynovitis, for medical treated cases where the diagnosis was based on clinical examination and radiographic features of bicipital tenovaginitis. for surgical cases the diagnosis has to be additionally confirmed by histology, owners had to be available for follow-up information in all cases, additional arthrogramm was done in 12 cases and arthrocentesis in 17 cases. sample size: 26 dogs (29 shoulders) n=26 intervention details: 21 of 29 shoulder joints were treated conservatively with methylprednisolone acetate injections (if no improvement was observed injection was repeated after 2 weeks, number of injection ranged from 1 to 3) and restricting exercise of 2 weeks (restriciting exercise was not precisely defined). if lameness didn’t improve injections were repeated at 2-week intervals (maximal 3 times). 14 cases underwent tenodesis of the biceps tendon and exercise restriction for 6 to 8 weeks (restricting exercise was not precisely defined) following surgery (6 of them had poor results after medical treatment and therefore underwent surgery). study design: retrospective case series outcome studied: efficacy of treatment was determined at the last physical examination and rated as excellent, good, fair or poor according to gait, limb function, range of motion and signs of pain. results were also assessed on follow-up information from the owners regarding activity level, degree of lameness, need of anti-inflammatory drugs and ability to work. results were considered to be excellent (never lame), good (only lame after heavy activity), fair (lame after moderate activity) and poor (always lame). 17 conservative treated cases and 12 of the surgically treated cases were available for clinical evaluation. main findings (relevant to pico question): of 17 conservative treated cases 3 were rated as excellent, 4 as good, 4 as fair and 6 as poor in the clinical revaluation. 8 of 12 clinical available surgically treated cases were rated as excellent and 4 as good. owners reported excellent results in 3, good results in 7, fair results for 5 and poor for 6 of 21 medically treated cases. of 14 surgically treated cases 11 were rated as excellent and 3 as good. time to achieve good or excellent clinical results after surgery ranged from 2 to 9 months. limitations: retrospective study and therefore not randomized control study, only subjective assessment. seventeen of 21 medically treated shoulders (16 dogs) and twelve of 14 surgical treated shoulders (11 dogs) were available for clinical reevaluation. owner assessment was available for all dogs. lost of follow-up in some cases, low number of cases. appraisal, application and reflection the purpose of this knowledge summary was to look for evidence regarding different outcomes of tenotomy or tenodesis of the biceps brachii compared to non-surgical treatments in canine bicipital tenosynovitis/tenovaginitis by reviewing veterinary literature. so far there are a few publications reporting different surgical techniques, but a real comparison between non-surgical and surgical treatments of canine bicipital tenosynovitis is lacking in veterinary literature. three non-comparative studies were found in the literature. all studies suffer, besides the weakness of being retrospective, in having an objective measurement of the therapy outcome. furthermore, the diagnostic challenge of shoulder pathologies was not considered in those studies. many shoulder diseases have similar clinical and radiographic appearances. diagnosis of bicipital tenosynovitis was based in all mentioned studies on clinical signs and radiographs only. therefore, other shoulder disorders cannot be definitively excluded. furthermore, it needs to be mentioned that non-surgical therapies can have a positive effect independent of treating bicipital tenosynovitis or another shoulder disorder, as they are non-specific treatments. in a descriptive study of 15 cases from bruce et al. (2000) good or excellent function at long-term follow-up was recorded for 11 of 13 conservative treated cases. on the basis of only 3 surgically treated dogs a comparison between conservative and surgical treatment of bicipital tenosynovitis in that study cannot be made. in addition the clinical follow-up was made without an objective measurement and the long-term follow-up was only done by the owners. this may have influenced the promising results of conservative treatment. the only possible implication for the practice from this study is that recovery time after conservative treatment can range from 2 weeks up to 7 months. this finding, even if it’s just from a case series, emphasises the importance of rest, as a considerable element of conservative treatment. the dogs were restricted to cage or small room for 6 weeks and another 6 weeks to the house of yard with controlled walks on a leash. another case series was published from wall et al. (2002). all dogs initially underwent conservative treatment but because lameness remained, arthroscopic tenotomy of the biceps brachii was done in all of them. the long-term outcome after arthroscopic tenotomy was good to excellent. there is not much information from this report to conclude whether conservative or surgical therapy of bicipital tenovaginitis is better, but all dogs improved post tenotomy compared to the presurgical condition. in a retrospective study of stobie et al. (1995) 29 cases of bicipital tenovaginitis were included. in the medical treated cases only 7 of 17 cases were clinically rated as good or excellent and owners reported good to excellent results in 10 of 21 cases. the moderate outcome of the conservative treatment in this study is opposed to the promising results of conservative treatment of bruce et al. (2000). these conflicting results may be due to the difference in the length of prescribed rest as part of conservative therapy. all dogs, which could be evaluated clinically after tenodesis, had an outcome of excellent to good. owners also rated the outcome of all surgically treated dogs as excellent to good. this result corresponds to the result of wall et al. (2000) and leads to the assumption that tenodesis may be promising and a good option if conservative treatment fails. in conclusion, there is insufficient evidence to support conservative therapy more than surgical treatment or vice versa. the only conclusion for clinical practice that can be made based on the literature is that if conservative treatment failed surgical therapy may be an option that may lead to improvement. methodology section search strategy databases searched and dates covered: the following search terms were applied to the pubmed database, accessed via the ncbi website (1910-2015) and the cab abstracts database (1973-2015) accessed on the ovid platform, scopus, web of science, vetmed resource search terms: dog or dogs or canine or bitch* or dogs/ or bitches or canis/ and biceps or bicipital* and tendonitis or tendinitis or tenosynovitis or “inflammation adj5 tendon*” and tenotom* or transect* or treat* or manag* or therap* or treatment/ or management/ or therapy/ dates searches performed: january 2016 exclusion / inclusion criteria exclusion: non-english language, reviews, case reports, conference papers inclusion: studies which investigated and compared the outcome of conservative and surgical therapy in bicipital tenosynovitis search outcome database number of results excluded – duplicates excluded – not english excluded – did not answer the pico question total relevant papers ncbi pubmed 16 0 0 13 3 scopus 26 2 3 25 1 web of science 49 1 1 47 2 cab abstracts 29 0 2 27 2 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflict of interest. references bruce, w. j. et al (2000) bicipital tendinitis and tenosynovitis in the dog: a study of 15 cases. new zealand veterinary journal, 48 (02), pp. 44-52. http://dx.doi.org/10.1080/00480169.2000.36157 stobie, d. et al (1995) chronic bicipital tenosynovitis in dogs: 29 cases (1985-1992). journal of american veterinary medical association, 207, pp. 201-7.  wall, c. r. and taylor, r. (2002) arthroscopic biceps brachii tenotomy as a treatment for canine bicipital tenosynovitis. journal of the american animal hospital association, 38 (2), pp. 169-75. http://dx.doi.org/10.5326/0380169 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. how to design a study in practice dr mark holmes ma, vetmb, phd, mrcvs1* 1cambridge university, the old schools, trinity lane, cambridge cb2 1tn *corresponding author (mah1@cam.ac.uk) vol 1, issue 2 (2016) published: 24 june 2016 doi: 10.18849/ve.v1i2.48 are dogs with hip dysplasia in less pain after total hip replacement than femoral head ostectomy? a knowledge summary by erica r. rehnblom dvm 1* wanda j. gordon-evans dvm phd dacvs dacvsmr 1 1university of minnesota college of veterinary medicine, 1365 gortner ave, st paul, mn 55108, usa *corresponding author (rehnb010@umn.edu) vol 7, issue 1 (2022) published: 07 jan 2022 reviewed by: andy morris (bsc[hons] bvsc certavp[gsas] mrcvs) and rob pettitt (bvsc pgcertlthe dsas[orth] sfhea frcvs) next review date: 08 oct 2023 doi: 10.18849/ve.v7i1.388 pico question in large breed juvenile dogs with hip dysplasia and radiographic bilateral osteoarthritis, is a total hip replacement superior/inferior/or equivalent to bilateral femoral head ostectomy at reducing the severity of long-term hip pain?   clinical bottom line category of research question treatment the number and type of study designs reviewed twelve papers were critically appraised. one paper was a systematic review. six papers were prospective case series. five papers were retrospective case series strength of evidence weak outcomes reported besides one systematic review, there are no other studies available that directly compare pain reduction with total hip replacement and femoral head ostectomy for the treatment of hip dysplasia in large breed juvenile dogs with radiographic evidence of secondary osteoarthritis. in one study, 12/12 (100%) of owners that responded to an owner outcome questionnaire reported no hip pain with femoral head and neck ostectomy. in this study, owners assessed pain based on activity level of the dog (running, playing, jumping, using stairs normally), gait abnormalities (only when running or after strenuous exercise), and duration of postoperative medications. in eight studies, 91–100% of cases had no hip pain with total hip replacement reported via clinical examination and/or owner outcome questionnaire conclusion there is evidence suggesting that both total hip replacement and femoral head ostectomy may be capable of reducing long-term pain as a result of osteoarthritis, secondary to hip dysplasia, however, based on the current literature, it is challenging to say whether total hip replacement is superior to femoral head and neck ostectomy at reducing long-term hip pain. it is important to recognise that other factors considered as outcomes (i.e. range of motion, ground reaction forces, force-plate analysis, etc.) may contribute to differing outcomes overall for total hip replacement vs femoral head ostectomy, but this paper focused specifically on pain. while there is a systematic review that provides evidence supporting that total hip replacement is superior at returning dogs to normal function, evaluating return to normal function was not the focus of this knowledge summary   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you diagnosed a 1 year old female golden retriever with bilateral hip dysplasia and persistent hip pain despite appropriate non-surgical management. she shifts her weight forward, bunny hops and has radiographic osteoarthritis. you recommend a total hip replacement or bilateral femoral head ostectomy. the owner wants to know if one option is better at reducing the severity of long-term hip pain. the evidence there is only one prospective case series that directly addresses the present clinical question, however the included population size is very small. of the literature that solely addresses total hip replacement outcome, five studies are prospective case series and five are retrospective case series. of the literature that solely addresses femoral head ostectomy outcome, one study is a retrospective case series. there is one systematic review that addresses both total hip replacement and femoral head ostectomy, however return to normal function was their main outcome measurement rather than pain. overall, because there is only one paper with a small population size directly addressing the present clinical question, the other included literature does not directly compare total hip replacement and femoral head ostectomy for long-term hip pain reduction, and because the current studies all use differing outcome measures and thus a direct comparison cannot be made, it is impossible to draw a meaningful conclusion as to which procedure is more efficacious at reducing long-term hip pain by comparing these studies. thr – total hip replacement fho – femoral head ostectomy load questionnaire – liverpool osteoarthritis in dogs questionnaire grf – ground reaction force summary of the evidence dueland et al. (1977) population: 17 dogs with degenerative joint disease secondary to hip dysplasia that underwent either thr and/or fho, and four unaffected dogs as controls. sample size: 21 dogs. intervention details: 17/29 dogs were selected for this study that were >25 kg, had radiographic evidence of dysplasia (except for the four unaffected dogs), had clinically successful thr and/or fho, and had an analysis done after a minimum of 1 year postoperatively group 1 (4/17): normal, unoperated dogs. group 2 (4/17): dogs with unoperated hip vs thr. group 3 (5/17): dogs with one thr and one fho. group 4 (4/17): dogs with bilateral thr. force-plate analysis was done to compare vertical and horizontal forces. speed of dog running was obtained by running them over a known distance and timing this. a linear relationship between velocity and force was established using least squares curve fitting technique. study design: prospective case series. outcome studied: objective: force-plate analysis. subjective: clinical evaluation of gait and lameness. main findings (relevant to pico question): when pain is reduced, the landing forces of the limb are increased. therefore, if a higher vertical force is apparent on one side in an individual, one should assume that this equals more weight bearing and better performance on that side. group 1: normal gait and comparable values between right and left hips in vertical forces. group 2: in 3/4 dogs, more vertical force was apparent on the normal, unoperated side. clinically, all four dogs walked and ran within normal limits. group 3: all five dogs showed normal gait, 3/5 showed higher vertical force on the fho side. group 4: all four dogs showed little clinical difference between the two hips, 3/4 dogs showed comparable vertical force between the two hips. successful thr may functionally approach a normal hip or improve a dysplastic hip. successful fho is still a valuable surgical treatment option which may equal or surpass thr clinically and biomechanically. limitations: small study population. case series. clinicians were unblinded during lameness evaluation. non-randomised study population. olmstead et al. (1983) population: dogs with hip disease (predominantly hip dysplasia) that underwent thr at the ohio state university veterinary teaching hospital (columbus, ohio, us) and berwyn veterinary associates hospital (berwyn, illinois, us). sample size: 190 dogs. intervention details: between august 1976 and july 1981, 221 thrs were performed in 190 dogs. disabling hip dysplasia was the indication for thr in 182/221 procedures. physicals, radiographic examination, and owner histories were used in preand yearly postoperative patient evaluation. dogs were evaluated before and yearly thereafter until the dog died, prosthesis was removed, or the owner could no longer be contacted. study design: prospective case series. outcome studied: subjective: clinical evaluation of lameness, owner questionnaire. main findings (relevant to pico question): 149 thrs were still being monitored by january 1982, and of these cases, 136/149 (91.2%) had satisfactory results when function could be evaluated. owners reported satisfactory results as an increase in muscle mass of the operated leg, and elimination of signs of pain. all 152 dogs with hip dysplasia included in the study were bilaterally affected, and unilateral replacement was adequate for 122 of the dogs. it is assumed that thr on one side allowed the dog to shift more of the weight bearing burden in that direction, relieving pressure on the dysplastic hip. only when a complication was encountered was there a risk that function would be unsatisfactory. 46/221 (20.8%) procedures had complications, and 27/46 (58.7%) ultimately achieved satisfactory function after revision. limitations: follow-up could not be completed on the entire population. case series. evaluation of function by examiner and owner is very subjective. parker et al. (1984) population: dogs with degenerative joint disease secondary to hip dysplasia underwent thr using a richards canine ii large size prosthesis. sample size: 20 dogs. intervention details: 17 dogs underwent unilateral thr only, and three dogs underwent bilateral thr (23 thrs) and were evaluated before and at 3 month intervals for 1 year postoperatively. all cases underwent preoperative evaluation which included a history, complete physical examination, neurological examination, complete blood count, chemistry panel, and radiographs. all cases had follow-up which consisted of direct observation or an owner telephone interview. the grading system for the affected leg(s) was adapted from gendreau & cawley (1977) and consisted of excellent (total weight bearing), good (slight lameness or gait abnormality), fair (noticeable lameness and may be non-weight bearing when running), and poor (severe lameness and may be non-weight bearing at all times. study design: prospective case series. outcome studied: subjective: clinical evaluation of lameness, owner telephone interview. main findings (relevant to pico question): 18/23 (78%) of cases were graded as good or excellent. one patient required revision surgery to achieve a good outcome. 5/23 (22%) of cases had poor or fair outcomes, and all developed permanent post-operative complications or had progression of undiagnosed pre-operative problems (degenerative myelopathy). limitations: small study population. case series. clinicians were unblinded during lameness evaluation. subjective owner telephone interviews used to determine outcome. study included some elderly dogs.   massat et al. (1994) population: dogs that underwent cemented thr. sample size: 84 dogs. intervention details: medical records were reviewed for all dogs that underwent thr from april 1986 to february 1992. dogs were included in the study if negative pressure had been applied to the medullary cavity of the ilium during cementing of the acetabular component. 96 cases were included. 88 cases were performed secondary to hip dysplasia. mean age 6.5 years (range: 10 months–13 years) 58 of the cases were evaluated by one of the authors or a referring veterinarian. mean follow-up time was 25.1 months (range: 6–70 months). the remaining 38 cases were evaluated via owner assessment outcome. mean follow-up time for these cases was 26.7 months (range: 3–75 months). study design: retrospective case series. outcome studied: objective: thigh circumference. subjective: clinical evaluation, owner assessment outcome. main findings (relevant to pico question): 42/58 cases clinically evaluated were graded as excellent, 15 were graded as good. limb function was graded as poor for one. 34 of the owner assessment outcome cases were graded as excellent, one as good, and three as fair. all four dogs with fair or poor results had complications which necessitated implant removal. six cases with excellent clinical outcome were selected for grf analysis. two dogs with contralateral degenerative joint disease had significantly greater vertical force in the thr limb than for the contralateral limb. the other four dogs had bilateral thr or unilateral thr with normal contralateral coxofemoral joint. no significant difference in peak vertical force in the hindlimbs of these four dogs was detected. 8/84 dogs had complications. four were corrected and hip function was eventually good or excellent. implant was removed in the other four dogs, and final hip function was fair in three dogs and poor in one. cemented thr is an effective treatment for disabling conditions of the coxofemoral joint in dogs. limitations: retrospective study design. case series. subjective owner assessment outcome. not all cases were clinically evaluated. two different thr systems were used. thigh circumference was only measured in good or excellent results. of the 6/84 dogs that underwent grf testing, two had bilateral thr, two had unilateral thr with normal contralateral coxofemoral joint, and two had unilateral thr and had contralateral degenerative joint disease. this variation in disease states can introduce significant bias when analysing grf.  budsberg et al. (1996) population: dogs with degenerative joint disease secondary to hip dysplasia underwent unilateral cemented thr. sample size: 16 dogs. intervention details: dogs underwent unilateral thr and were evaluated before and at 1, 3, 6, and 12 months post-operatively. of 16 cases, 14 had ≥12 months follow-up consisting of clinical evaluation and grf. study design: prospective case series. outcome studied: objective: grf. subjective: clinical evaluation of lameness. main findings (relevant to pico question): grf indicated significantly increased loading function of treated limb by 6 months postoperatively. vertical impulse decreased in untreated limb over course of study, indicating that dogs were beginning to compensate by shifting function to the treated limb. lameness scores for 14/16 dogs were available at 12 months and were 0.1 ± 0.3, and were available for 5/16 dogs at 24 months, which were all 0. a lameness score was graded from 0–4, with 0 being a normal gait and a 4 being non-weight bearing. limitations: small study population. case series. clinicians were unblinded during lameness evaluation. only five dogs had follow-up to 24 months. rawson et al. (2005) population: dogs referred to the veterinary specialists of south florida for evaluation of hip dysplasia and simultaneous bilateral fho. sample size: 15 dogs. intervention details: medical records were reviewed in all dogs from july 2000 to june 2003 that had radiographic evidence of bilateral osteoarthritis secondary to hip dysplasia and underwent simultaneous bilateral fho. 12/15 dogs were evaluated via owner between 6–48 months postoperatively via telephone survey. mean age at surgery 10.3 months (range: 6–25 months). study design: retrospective case series. outcome studied: subjective: owner outcome assessment (time to full recovery, evidence of pain, and overall satisfaction with the surgical procedure, concurrent orthopaedic problems). objective: duration and current medications. main findings (relevant to pico question): five owners graded results as excellent, seven graded the results as good. no dogs had hip pain at time of follow-up. seven dogs had slightly abnormal gait only when running or after strenuous exercise. limitations: retrospective study design. case series. wide range in follow-up time. subjective owner outcome assessment. all dogs were offered follow-up examination and radiographs. these were only performed in four dogs. only 12/15 (80%) of owners responded in a small study size. guerrero et al. (2009) population: dogs with degenerative joint disease secondary to hip dysplasia underwent 2nd generation zurich cementless thr. sample size: 60 dogs. intervention details: 59/65 thrs were completed between april 2001 and september 2003 on dogs with hip dysplasia and secondary coxoarthrosis. information obtained included breed, sex, body weight, date of surgery, indication for thr, operated side, surgical time, angles lateral opening (alo), inclination of cup (ai), longest clinical and radiographic follow-up, intraand postoperative complications, management of complications, and outcome. one surgeon performed all thrs. all dogs had postoperative evaluation which included clinical evaluation (pain on manipulation of hip joint, range of motion, muscle mass compared with contralateral leg, lameness) ≥6 months. clinical evaluation was scored based on a previously reported scale, of excellent, good, fair, poor, or failed function.   study design: prospective case series. outcome studied: subjective: clinical evaluation of lameness. main findings (relevant to pico question): 60/65 thrs were considered to have excellent clinical outcome, three had good outcome, and two as failed outcome. high complication rates, 11/65 (17%), consisted predominantly of thr luxations, 7/65 (11%). after revision, a successful outcome was achieved in 63/65 (97%) of thrs. limitations: small study population. case series. clinicians were unblinded during lameness evaluation. previously reported clinical evaluation scale was not disclosed. gemmill et al. (2011) population: dogs undergoing hybrid thr using a cementless acetabular component and a cemented femoral component. sample size: 71 dogs. intervention details: dogs were selected for the study from december 2005 to july 2009 if they had debilitating hip disease unresponsive to conservative management and absence of concurrent medical, orthopaedic, or neurologic disease that would preclude surgery. follow-up ≥ 6 months. of 78 procedures, hip dysplasia was indicated in 68. dogs were evaluated at 4 and 12 weeks, and 6–27 months by veterinarians. owner outcome assessment completed 6–40 months postoperatively. study design: prospective case series. outcome studied: subjective: owner outcome assessment, pain upon manipulation by veterinarian. main findings (relevant to pico question): pain, lameness, and disability were reported to be mild in 3/78 (3.8%) cases and absent in 75/78 (96.2%) cases. 73/78 (94%) of cases were reported to have normal quality of life at owner assessment outcome. of four cases that had postoperative complications, three were successfully revised. limitations: case series. veterinarian evaluation was done by the vet who performed the procedure, thus bias may be introduced by multiple examiners. subjective owner outcome assessment. bergh et al. (2014) population: dogs with naturally occurring canine hip dysplasia that were treated with various surgical procedures. sample size: 848 dogs. intervention details: of 477 manuscripts, 17 met inclusion criteria. these were grouped based on surgical procedure (thr, triple pelvic osteotomy, juvenile pubic symphysiodesis, chiari osteotomy/intertrochanteric osteotomy, and fho) and level of evidence (i–v) relative to the study question. there were seven total hip replacement studies and one femoral head ostectomy study. unilateral surgeries with >6 months follow-up were included. the outcome measurements included were orthopaedic exam, owner interview, visual gait observation, and force plate gait analysis depending on the study. study design: systematic literature review. outcome studied: subjective: orthopaedic examination, owner interview/questionnaire, and/or visual gait observation. objective: force plate gait analysis. main findings (relevant to pico question): thr consistently returned dogs to normal function. fho did not consistently return dogs to normal function.  limitations: the review was in depth but the studies measured mostly subjective outcomes. all thr and fho studies had low levels of evidence. comparison between procedures was difficult due to varying outcome measurements. the review assesses functional outcome instead of strictly pain outcome. three total hip replacement studies had level iii evidence, four had level iv evidence. the only fho study had level iv evidence. fitzpatrick et al. (2014) population: skeletally immature dogs with hip dysplasia undergoing thr using biomedtrix bfxtm biologic fixation implants after unsatisfactory outcome with medical management. sample size: 20 dogs. intervention details: medical records were reviewed from november 2007 to june 2010 and dogs that had unsatisfactory outcome with medical management due to coxofemoral pain resulting from canine hip dysplasia that underwent unilateral cementless thr using bfxtm implants were selected for the study. all dogs at time of surgery were 6–10 months of age. all dogs were available for follow-up immediately and 6 weeks postoperatively, 19 were available for long-term follow-up. study design: retrospective case series. outcome studied: subjective: owner outcome assessment via questionnaire at final follow-up (function, pain, and analgesia requirements), veterinary examination score (maximum possible score of 11, including lameness, musculature, pain, and range of motion) immediately, at 6 weeks, and at long-term follow-up (mean of 29.8 months, range: 12–48 months). main findings (relevant to pico question): mean veterinary examination score 0.8 (range: 0–4) at long-term follow-up. pain was not elicited in any and normal range of motion was achieved in all dogs at long-term follow-up. mean activity score (via owner questionnaire) 1.3 (from 0–5, 5 being the worst) for seven activities (walking, sitting, rising, running, climbing stairs, getting into the car, play or exercise). limitations: retrospective study design. case series. limited follow-up (mean of 29.8 months) despite young age of the population. small study population. lack of a control group. subjective outcome measurements. vezzoni et al. (2015) population: dogs that underwent zürich cementless thr at the clinica veterinaria vezzoni s.r.l, cremona, italy. sample size: 321 dogs. intervention details: records were reviewed from january 2002 to december 2007 and of 348 dogs and 479 z-thas, 321 dogs and 439 cases fit the inclusion criteria. this included 191 juvenile cases, 248 adult cases, and 118 bilateral cases treated for hip dysplasia. dogs with a follow-up ≥ 2 years were included. juvenile group ≤ 11 months old. adult group ≥ 11 months old. follow-up was done at 2, 6, and 12 months postoperatively, and yearly thereafter with physical examination. any outcome other than a normally functioning hip was classified as a complication. study design: retrospective case series. outcome studied: objective: weight change after surgery subjective: clinical examination including body condition score, muscle mass, range of motion, presence of any pain or discomfort during manipulation, and video recording of gait. main findings (relevant to pico question): adult group: 33/238 (14%) complications, 31 successfully revised, two explanted. 10 cases were not accounted for. juvenile group: 39/191 (20%) complications, 37 successfully revised, two explanted. difference in complication rate not statistically significant. limitations: retrospective study design. case series. subjective outcome measurements. two authors received honoraria and one received donated implants for biomechanical studies. bayer et al. (2019) population: dogs with hip dysplasia that underwent thr using a combined implant system consisting of innoplant screw cup, kyon taper head, and zürich cementless (z-thr) stem. sample size: 12 dogs. intervention details: records were reviewed from march 2010 to march 2015 and 16 hybrid thr procedures were performed in 12 dogs. follow-up examination was performed at 2, 6, and 12 months postoperatively. follow-up ≥2 years. mean age at surgery 31 months (range: 12–98 months). study design: retrospective case series. outcome studied: objective: owner-administered outcome load assessment. osteoarthritis was defined as mild for load scores 0–10, moderate for 11–20, severe for 21–30, and extreme from 31–52. subjective: clinical outcome examination including pain or discomfort upon manipulation of hip joint, range of motion, lameness grade (0–4), and thigh circumference compared to contralateral limb. main findings (relevant to pico question): 15 cases had full function and one had acceptable function at final follow-up. in dogs with full function, all had thigh circumference that was bilaterally symmetrical. median load score for procedures with full functional outcome was 5 (range: 3–11). three major complications occurred in three cases, all had complete revision and resolution. limitations: retrospective study design. case series. small study population. one surgeon performed all procedures, however they had limited experience (the surgeon had performed 28 tha procedures previously, compared to the proposed initial learning curve of a minimum of 44 tha procedures), which may introduce surgeon-related complications. subjective outcome measurements. appraisal, application and reflection after a thorough search of the literature, only one paper was found that specifically addresses the pico question, and twelve papers were found that partially address it. included in this knowledge summary is one systematic review, six prospective case series, and five retrospective case series. unfortunately, other than the systematic analysis and one prospective case series with force-plate analysis and very small population size, none of the other studies directly compare thr and fho, and differing outcome measures used throughout the studies make it difficult to draw a meaningful conclusion in regards to the clinical question. the strongest evidence available comes from the systematic review (bergh et al., 2014). included in the systematic review are seven manuscripts regarding thr and one manuscript regarding fho. in regards to the clinical question, thr consistently returned dogs to normal limb function while fho did not consistently return dogs to normal limb function. however, it is important to note that while the systematic review represents the highest level of evidence in this study, it is not without limitations. the systematic review focused on limb functionality, which only indirectly relates to the present clinical question in regards to reducing the severity of long-term pain. it is also important to point out that the manuscripts evaluated in the systematic review used differing outcome measurements and had low levels of evidence, which means that their conclusion must be interpreted with caution. one prospective case series (gemmill et al., 2011) analysed 71 dogs for a total of 78 hybrid thr replacement procedures with a cementless acetabular component and a cemented femoral component with follow-up of ≥ 6 months. at time of owner outcome assessment, 75/78 (96%) of dogs were reported to have no hip pain. this subjective outcome measure of owner outcome assessment and lack of a control group weakens the evidence of this study. a second prospective case series (budsberg et al., 1996) analysed 16 dogs for a total of 16 unilateral cemented total hip replacement procedures, 14 of which had follow-up ≥ 12 months. all dogs in this study had significantly increased grf for loading function of the treated limb by 6 months postoperatively. five dogs had follow-up at 24 months, and at this time all five dogs had lameness scores of 0. this study represents one of the few studies with objective outcome measurements in the form of grf, and thus strengthens the evidence for thr reducing the severity of long-term hip pain as a result of hip dysplasia. a third prospective case series (olmstead et al., 1983) analysed 221 thrs in 190 dogs performed predominantly as a result of hip dysplasia using physicals, radiographic examination, and owner histories in preand yearly post-operative patient evaluation. 136/149 (91.2%) of thrs had satisfactory function at time of follow-up suggesting that thr may reduce the severity of long-term hip pain as a result of hip dysplasia, however the subjective outcome of clinical evaluation and owner assessment weaken the evidence of this study. a fourth prospective case series (parker et al., 1984) analysed 20 dogs with 23 thrs using a richards canine ii large size prosthesis. outcome evaluation consisted of direct observation and owner telephone outcome assessment. through direct observation, thr outcome was graded using a grading system for the affected leg(s) that was adapted from gendreau & cawley (1977) and consisted of excellent (total weight bearing), good (slight lameness or gait abnormality), fair (noticeable lameness and may be non-weight bearing when running), and poor (severe lameness and may be non-weight bearing at all times. 18/23 (78%) of thrs had excellent or good outcome. subjective observation and owner telephone assessment weaken the evidence that thrs provide excellent to good outcome for decreasing pain in dogs with hip dysplasia, however using a standardised grading system minimises subjective grading bias. a fifth prospective case series (guerrero et al., 2009) anaylsed 60 dogs that underwent 65 thrs using 2nd generation zurich cementless thr. all dogs had post-operative evaluation which included clinical evaluation (pain on manipulation of hip joint, range of motion, muscle mass compared with contralateral leg, lameness) ≥ 6 months, and clinical evaluation was scored based on a previously reported scale, of excellent, good, fair, poor, or failed function. 60/65 (92.3%) of thrs were considered to have excellent clinical outcome. using a standardised scale for clinical evaluation minimises subjective clinical evaluation, however the scale used was not reported, weakening the evidence supporting that thrs decrease long-term pain associated with thr. finally, a sixth prospective case series (dueland et al., 1977) analysed 21 dogs, 17 of which had degenerative joint disease secondary to hip dysplasia that underwent either thr and/or fho, and four unaffected dogs as controls. dogs were divided into four groups, group 1 was normal, unoperated dogs, group 2 was dogs with one unoperated hip vs one thr, group 3 was dogs with one thr and one fho, and group 4 was dogs with bilateral thrs. force-plate analysis was done to compare vertical and horizontal forces, and clinical evaluation of gait and lameness was also reported. based on force-plate analysis, thr may functionally approach a normal hip or improve a dysplastic hip, and successful fho may equal or surpass thr clinically and biomechanically. this study provides strong objective analysis by using force-plate technology suggesting that thr and fho may improve gait, lameness, and force of operated limb. however, the sample size was incredibly low for each group (4–5 dogs) so a larger study should be performed before these results can be more widely accepted. there was one retrospective case series (bayer et al., 2019) that analysed 12 dogs for a total of 16 thr procedures using a combined implant system consisting of innoplant screw cup, kyon taper head, and zürich cementless (z-thr) stem. these cases were evaluated with clinical examination and load questionnaires performed by the owners. 15/16 cases had full function while 1/16 cases had acceptable function. median load score was 5 (range: 3–11). the load score is a standardised tool for collecting data from owners, and in this case supported the subjective clinical examination findings and outcome determined at the final follow-up visit that thr is efficacious at reducing the severity of long-term hip pain associated with hip dysplasia. although the retrospective and subjective outcome measures weaken the evidence of this study, this is the only retrospective case study out of five that used a standardised owner outcome questionnaire. of the three remaining retrospective case series regarding thr, one study (vezzoni et al., 2015) analysed 439 zürich cementless thr procedures and all dogs except for four had normal clinical outcome via clinical examination at their 12 month follow-up, and the remaining two studies (massat et al., 1994; and fitzpatrick et al., 2014) used both clinical examination and owner assessment outcome as outcome measurements, and found 84/88 cases had good or excellent outcomes, and 20/20 cases had no pain upon clinical examination respectively. there were only three studies for fho outcome that related to the present clinical question. the first (rawson et al., 2005) as discussed above, found that all dogs had no hip pain at time of follow-up according to owner questionnaire. the second study (ganesh et al., 2017) was unavailable and thus is not included in the answering of the present clinical question. the third study (dueland et al., 1977) used force-plate analysis to determine that successful fho may improve gait, lameness, and force of operated limb, which may be interpreted as decreased pain, however the study population was very small. unfortunately, fho studies are lacking, which contributes to the difficulty in answering the present clinical question. two studies (off & matis et al., 2010; and duff et al., 1977) discussing fho outcome were not included in this knowledge summary due to legg-calvé perthes disease being the predominant indication for surgery rather than hip dysplasia, presenting the possibility that femoral head necrosis may affect fho outcome differently than fho outcome due to hip dysplasia. from the available data, it is possible that both thr and fho may reduce the severity of long-term pain as a result of osteoarthritis secondary to hip dysplasia given the owner assessment outcomes and clinical evaluation outcomes in the aforementioned studies. however, given the differing outcome measurements between studies such as subjective non-standardised owner assessment outcomes, subjective clinical evaluation, grf, and force-plate analysis it is impossible to compare one study to another. it is also important to mention varying postoperative pain management and physical rehabilitation not only between different studies but between individual patients in a given study as an additional variable influencing outcome and ultimately long-term pain associated with fho and thr. it is also important to note that there are several more studies analysing thr than fho, which provides an unequal amount of evidence towards the success of thr at reducing long-term pain associated with hip dysplasia. from the evidence, it appears that thr provides a successful outcome in many cases, however it is not evident whether thr provides a superior/inferior/or equivalent outcome compared to fho given the lack of studies analysing fho. in order to definitively answer the present clinical question, a prospective, randomised clinical trial, with pre-determined standardised outcome measurements, comparing thr treated dogs to fho treated dogs with naturally occurring hip dysplasia would be necessary. two papers (vezzoni et al., 2015; and bayer et al., 2019) were not indexed by either database using the below search terms, however both papers were deemed applicable based on reference checking. this represents an inherent bias of the chosen databases, and represents a limitation of this knowledge summary. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform; 1973–aug 2021 pubmed on ncbi platform; 1972–aug 2021 search strategy: cab abstracts: (dog or dogs or canine or canines).mp. (hip and (dysplasia or subluxation)).mp. ((total hip and (replacement or arthroplasty)) or thr or tha).mp. ((femoral head and (excision or osteotomy or ostectomy)) or excision arthroplasty or fho).mp. 1 and 2 and (3 or 4)   pubmed: #1 dog or canine #2 hip and (dysplasia or subluxation) #3 ((total hip and (replacement or arthroplasty)) or thr or tha) #4 ((femoral head and (excision or osteotomy or ostectomy)) or excision arthroplasty or fho) #5 #1 and #2 and (#3 or #4)   the references of relevant articles were reviewed for further relevant articles missed in the initial search. dates searches performed: 08 oct 2021 exclusion / inclusion criteria exclusion: book chapters, conference proceedings, articles not available in english, clinical reviews, case studies, studies with fewer than 10 dogs at time of follow-up, studies using prototypic hip replacement models, biceps femoris muscle sling technique for fho. inclusion: articles written in english relevant to the pico question, studies with ≥ 6 months follow-up for all included cases, studies evaluating treatment primarily for hip dysplasia (hip dysplasia as the majority of cases included in the study), commercially available total hip replacement implants. search outcome database number of results excluded – reviews excluded – not available in english excluded – not relevant to pico question total relevant papers cab abstracts 139 26 30 76 6 pubmed 105 14 3 80 8 reference checking 6 0 0 4 2 total relevant papers when duplicates removed 12 conflict of interest the authors declare no conflicts of interest. references bayer, k., matiasovic, m., steger, h. & böttcher, p. (2019). complications and long-term outcome in 16 canine cementless hybrid hip arthroplasties. veterinary and comparative orthopaedics and traumatology.32(1), 73–78. doi: https://doi.org/1055/s-0038-1676072 bergh, m. s. & budsberg, s. c. (2014). a systematic review of the literature describing the efficacy of surgical treatments for canine hip dysplasia (1948–2012). veterinary surgery.43(5), 501–506. doi: https://doi.org/10.1111/j.1532-950x.2014.12208.x budsberg, s. c., chambers, j. n., lue, s. l. van, foutz, t. l. & reece, l. (1996). prospective evaluation of ground reaction forces in dogs undergoing unilateral total hip replacement. american journal of veterinary research. 57(12), 1781–1785. dueland, r., bartel, d. l. & antonson, e. (1977). force-plant technique for canine gait analysis of total hip and excision arthroplasty [proceedings]. journal of the american animal hospital association. 13(5), 547–552. duff, r. & campbell, j. r. (1977). long term results of excision arthroplasty of the canine hip. the veterinary record. 101(10), 181–184. fitzpatrick, n., law, a. y., bielecki, m. & girling, s. (2014). cementless total hip replacement in 20 juveniles using bfx™ arthroplasty. veterinary surgery.43(6), 715–725. doi: https://doi.org/10.1111/j.1532-950x.2014.12214.x ganesh, t. n., siobhan bridglalsingh & legall, c. (2017). femoral head and neck excision arthroplasty in 38 dogs: a two-year study with special reference to surgical indication and outcome. indian journal of veterinary surgery, 38(2), 77-80. [online] available from: http://ovidsp.ovid.com/ovidweb.cgi?t=js&page=reference&d=caba6&news=n&an=20193238298 [accessed 08 aug 2021] gemmill, t. j., pink, j., renwick, a., oxley, b., downes, c., roch, s. & mckee, w. m. (2011). hybrid cemented/cementless total hip replacement in dogs: seventy-eight consecutive joint replacements. veterinary surgery.40(5), 621–630. doi: https://doi.org/10.1111/j.1532-950x.2011.00827.x guerrero, t. g. & montavon, p. m. (2009). zurich cementless total hip replacement: retrospective evaluation of 2nd generation implants in 60 dogs. veterinary surgery.38(1), 70–80. doi: https://doi.org/10.1111/j.1532-950x.2008.00466.x massat, b. j. & vasseur, p. b. (1994). clinical and radiographic results of total hip arthroplasty in dogs: 96 cases (1986–1992). journal of the american veterinary medical association. 205(3), 448–454. off, w. & matis, u. (2010). excision arthroplasty of the hip joint in dogs and cats. clinical, radiographic, and gait analysis findings from the department of surgery, veterinary faculty of the ludwig-maximilians-university of munich, germany. 1997. veterinary and comparative orthopaedics and traumatology.23(5), 297–305. olmstead, m. l., hohn, r. b. & turner, t. m. (1983). a five-year study of 221 total hip replacements in the dog. journal of the american veterinary medical association. 183(2), 191–194. parker, r. b., spencer, c. p., bloomberg, m. s., bitetto, w. & rodkey, w. g. (1984). canine total hip arthroplasty: a radiographic correlation of clinical results in 20 cases. journal of the american animal hospital association. 20(1), 105–113. rawson, e. a., aronsohn, m. g. & burk, r. l. (2005). simultaneous bilateral femoral head and neck ostectomy for the treatment of canine hip dysplasia. journal of the american animal hospital association. 41(3), 166–170. doi: https://doi.org/10.5326/0410166 vezzoni, l., vezzoni, a. & boudrieau, r. j. (2015). long-term outcome of zürich cementless total hip arthroplasty in 439 cases. veterinary surgery. 44(8), 921–929. doi: https://doi.org/10.1111/vsu.12371 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. mortality rate comparison of enterotomy and resection and anastomosis (enterectomy) in dogs with foreign-body obstructions a knowledge summary by hillary mikulak dvm 1* wanda gordon-evans dvm dacvs-sa 2 1bluepearl veterinary hospital, 7717 flying cloud drive, eden prairie, mn 55344, usa 2university of minnesota college of veterinary medicine, 1365 gortner ave, st paul, mn 55108, usa *corresponding author (mikul073@umn.edu) vol 6, issue 4 (2021) published: 30 dec 2021 reviewed by: zofia lisowski (bvsc phd afhea mrcvs) and faye swinbourne (bvm&s mvetmed diplecvs mrcvs) next review date: 25 oct 2022 doi: 10.18849/ve.v6i4.390 pico question in dogs with gastrointestinal foreign-body obstruction undergoing surgical correction, is the mortality rate in the perioperative period for those receiving resection and anastomosis higher, lower, or equivalent to those receiving an enterotomy?   clinical bottom line category of research question outcome the number and type of study designs reviewed four retrospective studies were reviewed strength of evidence weak outcomes reported it would appear that the mortality rate for resection and anastomosis for the purpose of foreign-body removal is higher than that of enterotomies performed for the same reason conclusion there is insufficient evidence directly comparing enterotomies with resection and anastomoses in foreign-body obstructions to definitively state that the mortality rate is higher among resection and anastomosis procedures   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a foreign-body obstruction is diagnosed in a canine patient. an owner wishes to wait longer to decide to go to surgery risking additional intestinal damage. the owner wants to know if a resection and anastomosis became necessary instead of an enterotomy, would the risk of death increase. the evidence the available evidence is exclusively retrospective clinical studies. therefore, they suffer from inherent retrospective bias. there are no studies that aim to specifically compare mortality rates between enterotomies and resection and anastomoses in dogs whose indication for surgery is foreign-body obstruction. many studies found relevant to the subject of the pico question do not separate the reported data in a way that maintains direct relevance to the pico question. therefore, the studies all had small sample sizes relating specifically to mortality rates pertaining to foreign-body obstructions. studies directly comparing mortality rate between enterotomy and resection and anastomoses procedures for foreign-body removal in dogs would be valuable. summary of the evidence habenbacher et al. (2019) population: dogs and cats receiving enterotomies or intestinal resection and anastomosis over a 5 year period. sample size: 135 dogs; 85 cats. intervention details: medical records of dogs and cats undergoing enterotomies or resection and anastomosis over a 5 year period at a single institution were reviewed. pre-, peri-, and postoperative factors were documented to evaluate influence on clinical outcomes of animals undergoing enterotomies versus those undergoing resection and anastomosis procedures. study design: retrospective study. outcome studied: preoperative factors: signalment, duration of clinical signs before presentation, basic bloodwork values, presence of preoperative peritonitis, preoperative medical treatments administered. perioperative factors: intestinal region affected, number of surgical incisions, surgical procedure and additional procedures performed, surgeon experience, perioperative therapies administered, adverse anesthetic events, final cause for surgery, closure technique, feeding tube placement. postoperative factors: duration of hospitalisation, need of intensive care, type and duration of postoperative medication, basic bloodwork values, complications, requirement of revision surgery, follow-up, clinical outcome. comparison of pre, post and perioperative factors in patients receiving enterotomies and resection and anastomosis procedures to determine influence on clinical outcome. main findings (relevant to pico question): intestinal anastomosis is associated with a higher mean probability of death than enterotomy with a diagnosis of intestinal foreign body. limitations: retrospective study. rosenbaum et al. (2016) population: dogs that underwent intestinal resection and anastomosis using disposable skin staples from 2000–2014. sample size: 63 dogs. intervention details: medical records of all dogs that underwent intestinal resection and anastomosis using disposable staples at two separate specialty referral hospitals were reviewed. study design: retrospective study. outcome studied: mortality associated with certain variables in dogs undergoing intestinal resection and anastomosis performed with the use of disposable skin staples. variables evaluated; sex, body weight, breed, duration of hospital stay, indication for surgery, location of resection and anastomosis, number of surgical procedures performed, evidence of presence of peritonitis at the time of surgery, whether surgeon was residency trained, dehiscence, mortality. mortality was defined as those who died or were euthanised within a 10 day follow-up period. main findings (relevant to pico question): of the dogs whose indication for surgery was a diagnosis of foreign body, 18/19 survived and one dog died. limitations: retrospective study. strelchik et al. (2019) population: client-owned dogs with intestinal foreign bodies treated with enterotomy between november 2001–september 2017. sample size: 247 dogs. intervention details: medical records were searched for dogs that underwent enterotomy for removal of intestinal foreign bodies from november 2001–september 2017 at veterinary institution 1, and from june 2005–september 2017 at veterinary institution 2. study design: retrospective study. outcome studied: preoperative data evaluated for risk of dehiscence: signalment, body weight, body condition score, previous gastrointestinal surgery, pervious or current nsaid or corticosteroid treatment, presence of preoperative peritonitis, reported comorbidities, and preoperative bloodwork when available. intraoperative data evaluated for risk of dehiscence: date and duration of procedure, whether surgery was performed after hours, total duration of surgery and general anesthesia, frequency and duration of intraoperative hypotension, suture material and pattern, whether or not concurrent gastrotomy was performed, type of foreign body, other concurrent surgical procedures performed, any abnormal findings during exploratory surgery. postoperative data evaluated for risk of dehiscence: occurrence of intestinal dehiscence, survival to hospital discharge, duration of hospitalization, treatment with nsaids or corticosteroids, date of last follow-up, occurrence of any surgery related complications. main findings (relevant to pico question): 2/247 (0.8%) dogs did not survive to hospital discharge. limitations: retrospective study. ralphs et al. (2003) population: all dogs and cats that underwent intestinal resection and anastomosis from 1991–2000 at the university of minnesota teaching hospital. sample size: 90 and 25 cats. intervention details: medical records for all dogs and cats that underwent intestinal resection and anastomosis from 1991–2000 at the university of minnesota teaching hospital were reviewed. data on preoperative, intraoperative, and postoperative parameters were recorded. study design: retrospective study. outcome studied: preoperative factors evaluated as risk factors for dehiscence: species, breed, age, sex, body weight, initial compliant, duration of anorexia prior to surgery, steroid admission prior to surgery, whether there was evidence for peritonitis prior to surgery, white blood cell count (wbc) with or without left shift, platelet count, serum albumin, indication for surgery. intraoperative factors evaluated as risk factors for dehiscence: segment of bowel resected, surgeon experience, suture pattern, anesthesia and surgery time. postoperative factors evaluated as risk factors for dehiscence: duration of hospitalisation, whether patient ate the day after surgery, whether supplemental alimentation was provided, blood products administered, patient death as result of perioperative complications, confirmation of intestinal anastomotic leakage and how long leakage occurred after surgery if applicable. main findings (relevant to pico question): 38/90 (40%) underwent intestinal resection and anastomosis surgery because of a foreign body. anastomotic leakage occurred in 10/38 (26%) dogs that underwent intestinal resection and anastomosis due to a foreign body and 3/52 (6%) of dogs with resection and anastomosis for other reasons. development of anastomotic leakage significantly impacted outcome. 11/13 (85%) of the leakage group died, compared to 8/77 (10%) mortality in the non-leakage group. limitations: retrospective study. appraisal, application and reflection it has been presumed that resection and anastomosis procedures are associated with a higher mortality rate than enterotomy, which is regarded as a simpler procedure. time of obstruction prior to surgery is a possible factor that contributes to the damage done by obstruction and therefore the decision of which procedure is indicated. when discussing options with clients regarding intestinal foreign-body treatment, it is important to be able to communicate risks when offering treatment options. habenbacher et al. (2019) found that resection and anastomosis was associated with a higher probability of death than enterotomy when removing foreign bodies. rosenbaum et al. (2016) found that of the dogs whose indication for surgery was foreign-body obstruction, 1/19 died. strelchick et al. (2019) found that 2/247 (0.8%) of dogs with foreign bodies undergoing enterotomies died. ralphs et al. (2003) found that 10/38 (26%) of the dogs that underwent resection and anastomosis procedures for foreign bodies had an anastomotic leakage which was significantly higher than any other cause for intestinal surgery, and that anastomotic leakage significantly impacts outcome. based on these papers that are all retrospective, and only one with a direct comparison of enterotomy and resection and anastomosis, there is weak evidence that resection and anastomosis has a higher probability of death, but actual death rates cannot be compared. this search did not produce many papers that specifically and directly report mortality as an outcome, as well as clearly separating foreign-body obstruction as a cause for surgery, and make a clear distinction of which populations within their sample size received a resection and anastomosis versus an enterotomy. these specifics significantly narrowed the scope of studies included within the very specific pico question. however, the authors acknowledge that there are factors impacting mortality that are not within the scope of this pico question. dehiscence was identified as a risk factor for mortality. snowden et al. (2016) found that of dogs receiving a stapled functional end-to-end anastomosis, there was an overall mortality rate of 5/6 (83%), compared to a mortality rate of 10/47 (21%) for those who did not have dehiscence. this study, however, did not differentiate between dogs whose indication for surgery was foreign-body obstruction versus other causes, and so was excluded. duell et al. (2016) found that of dogs that experienced intestinal dehiscence, 22/29 (76%) did not survive a two-week postoperative period, compared to 3/17 (62%) in those whom did not experience post-operative dehiscence. there are other risk factors in addition to surgical procedure that have an impact on survival. gill et al. (2019) do not differentiate those which had a resection and anastomosis from those who received an enterotomy when reporting mortality rate, and so their paper was excluded. what they do report, however, was that preoperative and intraoperative bacterial peritonitis was more common among those dogs receiving a resection and anastomosis (18/81; 22%). bacterial peritonitis, in turn, was associated with a higher mean american society of anesthesiologists (asa) status (2.9, ± 1), versus those who were not found to have preoperative or intraoperative septic peritonitis (2.3, ± 1). this study also found that those that did not survive the two-week period following surgery had a higher asa status than those who survived. this study also found that dogs with postoperative dehiscence were more likely to have had a resection and anastomosis than other types of surgery, though no specific statistic is reported. grimes et al. (2011) also found that preoperative septic peritonitis had a significant correlation with failure to survive following surgery. similarly, the authors acknowledge that there are different techniques (stapling methods and hand suturing) when performing resection and anastomosis that may affect the dehiscence rate and therefore mortality rate, however the question being evaluated was specifically addressing all resection and anastomosis versus all enterotomies without specifying suture or staple methods. duell et al. (2016) did not report mortality rates; however, it is worth noting that they did not find a higher dehiscence rate for hand-sutured anastomoses when compared to stapled anastomoses. presence of a linear foreign body was found to have a negative impact on survival (hayes, 2009). intraoperative hypotension was found to be correlated with postoperative dehiscence of the anastomotic site by snowden et al. (2016). ideally, for the best evidence, a study randomizing dogs with foreign bodies to either enterotomy versus resection and anastomosis with a large enough sample size that the other risk factors would be balanced across groups would be performed. however, this type of study cannot be performed ethically as resection and anastomosis is sometimes necessary because of the amount of damage to the intestine and therefor the randomization could not be maintained. alternatively, a prospective observational study including all dogs undergoing either enterotomy or resection and anastomosis (enterectomy) for a gastrointestinal foreign body could be performed. data collected would include possible risk factors (presence of preoperative septic peritonitis, hydration status, bloodwork abnormalities, interoperative factors, post-operative factors, and co-morbidities), enterotomy versus resection and anastomosis, and the mortality rates. however, at this time, there were no studies directly comparing mortality rates between enterotomies and resection and anastomosis in dogs with gastrointestinal foreign bodies. risk can be extrapolated from many studies, but none set out with the specific aim of comparing mortality rates. evidence is lacking and studies aimed at this specific objective would be valuable. methodology section search strategy databases searched and dates covered: cab abstracts & pubmed; (1910 to 2020) search strategy: cab abstracts: (((((enterotomy or enterectomy or resection) and anastomosis) or resections) and anastomoses) or enterectomies or enterotomies or enteric or gastrointestinal surgery).af. (dogs or canine).af. 1 and 2 (foreign body or foreign bodies or foreign materials or gastrointestinal).af. 3 and 4 af 5 and 6   pubmed: ("enterotomies"[all fields] or "enterotomy"[all fields] or ("enterectomies"[all fields] or "enterectomy"[all fields]) or (("resect"[all fields] or "resectability"[all fields] or "resectable"[all fields] or "resectates"[all fields] or "resected"[all fields] or "resecting"[all fields] or "resection"[all fields] or "resectional"[all fields] or "resectioned"[all fields] or "resectioning"[all fields] or "resections"[all fields] or "resective"[all fields] or "resects"[all fields]) and ("anastomosis, surgical"[mesh terms] or ("anastomosis"[all fields] and "surgical"[all fields]) or "surgical anastomosis"[all fields] or "anastomosis"[all fields])) or (("resect"[all fields] or "resectability"[all fields] or "resectable"[all fields] or "resectates"[all fields] or "resected"[all fields] or "resecting"[all fields] or "resection"[all fields] or "resectional"[all fields] or "resectioned"[all fields] or "resectioning"[all fields] or "resections"[all fields] or "resective"[all fields] or "resects"[all fields]) and ("anastomose"[all fields] or "anastomosed"[all fields] or "anastomoses"[all fields] or "anastomosing"[all fields])) or ("enterectomies"[all fields] or "enterectomy"[all fields]) or ("enterotomies"[all fields] or "enterotomy"[all fields]) or ("digestive system surgical procedures"[mesh terms] or ("digestive"[all fields] and "system"[all fields] and "surgical"[all fields] and "procedures"[all fields]) or "digestive system surgical procedures"[all fields] or ("gastrointestinal"[all fields] and "surgery"[all fields]) or "gastrointestinal surgery"[all fields]) or (("enteric"[all fields] or "enterically"[all fields] or "enterics"[all fields] or "enteritis"[mesh terms] or "enteritis"[all fields] or "enteritides"[all fields]) and ("surgery"[mesh subheading] or "surgery"[all fields] or "surgical procedures, operative"[mesh terms] or ("surgical"[all fields] and "procedures"[all fields] and "operative"[all fields]) or "operative surgical procedures"[all fields] or "general surgery"[mesh terms] or ("general"[all fields] and "surgery"[all fields]) or "general surgery"[all fields] or "surgery s"[all fields] or "surgerys"[all fields] or "surgeries"[all fields])) or (("intestinalization"[all fields] or "intestinalized"[all fields] or "intestinally"[all fields] or "intestinals"[all fields] or "intestine s"[all fields] or "intestines"[mesh terms] or "intestines"[all fields] or "intestinal"[all fields] or "intestine"[all fields]) and ("surgery"[mesh subheading] or "surgery"[all fields] or "surgical procedures, operative"[mesh terms] or ("surgical"[all fields] and "procedures"[all fields] and "operative"[all fields]) or "operative surgical procedures"[all fields] or "general surgery"[mesh terms] or ("general"[all fields] and "surgery"[all fields]) or "general surgery"[all fields] or "surgery s"[all fields] or "surgerys"[all fields] or "surgeries"[all fields]))) and ("dogs"[mesh terms] or "dogs"[all fields] or ("canine s"[all fields] or "dogs"[mesh terms] or "dogs"[all fields] or "canine"[all fields] or "canines"[all fields]) or ("dogs"[mesh terms] or "dogs"[all fields] or "dog"[all fields]) or ("canine s"[all fields] or "dogs"[mesh terms] or "dogs"[all fields] or "canine"[all fields] or "canines"[all fields])) and ("foreign bodies"[mesh terms] or ("foreign"[all fields] and "bodies"[all fields]) or "foreign bodies"[all fields] or ("foreign"[all fields] and "body"[all fields]) or "foreign body"[all fields] or ("foreign bodies"[mesh terms] or ("foreign"[all fields] and "bodies"[all fields]) or "foreign bodies"[all fields] or ("foreign"[all fields] and "material"[all fields]) or "foreign material"[all fields]) or ("foreign bodies"[mesh terms] or ("foreign"[all fields] and "bodies"[all fields]) or "foreign bodies"[all fields])) and (("intestinalization"[all fields] or "intestinalized"[all fields] or "intestinally"[all fields] or "intestinals"[all fields] or "intestine s"[all fields] or "intestines"[mesh terms] or "intestines"[all fields] or "intestinal"[all fields] or "intestine"[all fields]) and ("surgery"[mesh subheading] or "surgery"[all fields] or "surgical procedures, operative"[mesh terms] or ("surgical"[all fields] and "procedures"[all fields] and "operative"[all fields]) or "operative surgical procedures"[all fields] or "general surgery"[mesh terms] or ("general"[all fields] and "surgery"[all fields]) or "general surgery"[all fields] or "surgery s"[all fields] or "surgerys"[all fields] or "surgeries"[all fields]))   hand search: habenbacher et al. is no longer available on cab abstracts as of the search on 25 october 2020. as it is relevant and has not been retracted, the authors have elected to include it in this knowledge summary. dates searches performed: 25 oct 2020 exclusion / inclusion criteria exclusion: full articles not available, not relevant to pico, not available in english. inclusion: full-text articles available in english relevant to pico. search outcome database number of results excluded – irrelevant to pico excluded – full-text article not available excluded – not available in english total relevant papers cab abstracts 17 17 0 0 0 pubmed 97 94 0 0 3 hand search 1 total relevant papers when duplicates removed 4 conflict of interest the authors declare no conflicts of interest. references duell, j.r., thieman mankin, k.m., rochat, m.c., regier, p.j., singh, a., luther, j.k., mison, m.b., leeman, j.j. & budke, c.m. (2016). frequency of dehiscence in hand-sutured and stapled intestinal anastomoses in dogs. veterinary surgery. 45(1), 100–103. doi: https://doi.org/10.1111/vsu.12428 gill, s.s., buote, n.j., peterson, n.w. & bergman, p.j. (2019). factors associated with dehiscence and mortality rates following gastrointestinal surgery in dogs. journal of the american veterinary medical association. 255(5), 569–573. doi: https://doi.org/10.2460/javma.255.5.569 grimes, j.a., schmiedt, c.w., cornell, k.k. & radlinksy, m.a.g. (2011). identification of risk factors for septic peritonitis and failure to survive following gastrointestinal surgery in dogs. journal of the american veterinary medical association. 238(4), 486–494. doi: https://doi.org/10.2460/javma.238.4.486 habenbacher, b., bockstahler, b., tichy, a. & dupre, g. (2019). enterotomy versus intestinal resection anastomosis: morbidity and mortality rates in 135 dogs and 85 cats. wiener tierarztliche monatsschrift. 106(5/6), 117–127. [onine] available from: http://ovidsp.ovid.com/ovidweb.cgi?t=js&page=reference&d=caba6&news=n&an=20193423203 [accessed 8 jul 2020] hayes, g. (2009). gastrointestinal foreign bodies in dogs and cats: a retrospective study of 208 cases. journal of small animal practice. 50(11), 576–583. doi: https://doi.org/10.1111/j.1748-5827.2009.00783.x ralphs, s.c., jessen, c.r. & lipowitz, a.j. (2003). risk factors for leakage following intestinal anastomosis in dogs and cats: 115 cases (1991–2000). journal of the american veterinary medical association. 223(1), 73–77. doi: https://doi.org/10.2460/javma.2003.223.73 rosenbaum, j.m., coolman, b.r., davidson, b.l., daly, m.l., rexing, j.f. & eatroff, a.e. (2016). the use of disposable skin staples for intestinal resection and anastomosis in 63 dogs: 2000 to 2014. the journal of small animal practice. 57(11), 631–636. doi: https://doi.org/10.1111/jsap.12584 snowdon,a., smeak, d.d. & chiang, s. (2015). risk factors for dehiscence of stapled functional end-to-end intestinal anastomoses in dogs: 53 cases (2001–2012). veterinary surgery. 45(1), 91–99. doi: https://doi.org/10.1111/vsu.12413 strelchik, a., coleman, m.c., scharf, v.f., stoneburner, r.m. & thieman mankin, k.m. (2019). intestinal incisional dehiscence rate following enterotomy for foreign body removal in 247 dogs. journal of the american veterinary medical association. 255(6), 695–699. doi: https://doi.org/10.2460/javma.255.6.695 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. evidence supporting intralesional stem cell therapy to improve equine flexor tendon healing a knowledge summary by sushmitha durgam bvsc, ms1 matthew stewart bvsc, phd1* 1university of illinois, veterinary clinical medicine, champaign, il 61801, usa *corresponding author (matt1@illinois.edu) vol 2, issue 1 (2017) published: 3 jan 2017 reviewed by: wanda gordon-evans (dvm, phd, dacvs-sa, dacvsmr) and peter clegg (ma vet mb phd certeo dipecvs mrcvs) next review date: 5 jan 2018 doi: 10.18849/ve.v2i1.50 clinical bottom line current experimental evidence suggests that intralesional stem cell administration improves the histological characteristics and matrix organisation of healing equine superficial digital flexor tendons (sdft); however, the clinical relevance of these findings are not clear. current case-based evidence suggests that cell-based therapies improve the quality of tendon healing and reduce the recurrence rates of sdft injuries but the lack of any randomised, controlled prospective studies with function-based outcomes is still concerning, give the widespread advocacy for and use of ‘stem cell’ therapies for the treatment of equine tendon injuries. question does intralesional stem cell therapy improve healing of equine superficial digital flexor tendons? the evidence to date, equine experimental and clinical case studies of tendon healing demonstrate improved histological and ultrasonographic features of matrix architecture, respectively with intralesional stem cell therapy. these findings encourage clinical use of stem cell-based therapies to enhance equine tendon healing. a few clinical studies indicate that re-injury rates are lower following stem cell treatment, than without. however, these studies do not provide any firm conclusions regarding the ideal cell source for therapy or optimal treatment protocol. collaborative research and long-term follow up among the veterinary community is needed to establish the optimal applications for cell-based therapies. summary of the evidence del bue (2008) population: clinical cases of superficial digital flexor tendon (sdft) tendinitis with a distinct core lesion diagnosed via ultrasonography. sample size: n = 16 intervention details: intralesional administration of allogeneic adipose-derived mesenchymal stem cells (ad-mscs) suspended in autologous platelet rich plasma (prp). study design: case series – (no controls, not blinded) outcome studied: serial ultrasonographic evaluations return to exercise/activity main findings (relevant to pico question): 14 out of 16 horses returned to activity limitations: small/limited case numbers no objective measurements of outcome no control groups inconsistent follow-up uncertainties regarding the relative contributions of ad-mscs and prp to outcome lacitignola (2008) experimental study component population: clinically healthy standardbred horses. pre-existing tendon injury was ruled out with baseline lameness and ultrasonographic evaluation. sample size: experimental study: n = 6 horses (24 sdfts) intervention details: collagenase-induced tendinitis was created in both forelimb and both hindlimb sdfts of four horses, and both forelimb and one hindlimb sdfts of two horses. at the time of collagenase injection, bone marrow aspirates were collected from tuber coxae to isolate bone marrow-derived mscs (bmmsc). bone marrow-derived mononuclear cells (bmmnc) were isolated from a second bone marrow aspirate just prior to treatments. three weeks after collagenase injections, the sdft lesions were treated with autologous bmmscs (5.5 x 106 cells) or bmmncs (1.22 x 108 cells) re-suspended in fibrin, fibrin alone or saline. the two injured hindlimb sdfts served as sham controls. study design: randomised, partially controlled, experimental study; not blinded outcome studied: semi-objective data: type lesion score (tls), fiber pattern score (fps) and percentage cross-sectional area of the lesion (% csa) at the maximal injury zone were derived from ultrasonographic evaluations every 2-3 weeks, up to 21 weeks after cell administration. collagen architecture was assessed in histological sections at 21 wks. collagen types i and iii, comp and cd34 distribution was assessed by immunohistochemistry main findings (relevant to pico question): at 8 weeks, cell-treated sdfts had a decreased lesion size (% csa) compared to controls; however, there was no difference between bmmscand bmmnc-treated tendons. at 16 weeks, % csa, fps, tls were significantly better in the cell-treated sdfts compared to control sdfts. both cell treatments improved collagen alignment compared to controls. limitations: small sample size and low power two of six hindlimb sdfts were used as the collagenase control uncertainties about ‘stem cell’ characteristics of primary culture-expanded bmmsc cell population quantitative data were not presented; only summary statements outcome measures were predominantly qualitative nominal outcome data were misrepresented and improperly analysed. significant outcomes were not designated biomechanical or other functional testing were not carried out lacitignola (2008) clinical study component population: standardbreds and showjumpers presented for evaluation and treatment of sdft or suspensory ligament injuries. sample size: 8 stbs, 12 showjumpers, 14 sdft lesions, 3 suspensory ligament (sl) body lesions, 3 sl branch lesions. intervention details: 1.23 x 108 bmmncs in fibrin were injected into the lesions under u-s guidance. horses were stall-rested for 8 weeks, followed by gradual return to exercise and competition over the following 20-30 weeks. study design: clinical case series; no control group, not blinded. outcome studied: ultrasonographic assessment 3 and 8 weeks after injections. changes in type lesion score (tls), fiber pattern score (fps) and percentage cross sectional area of the lesion (% csa) were recorded. time to return to training/racing, and re-injury rates main findings (relevant to pico question): 3 weeks after treatment (t3), the injury sites were pain-free. after 6 weeks, clinical lameness was resolved in all cases csa%, fps and tls improved in all patients by week 3, and this improvement continued throughout the study 12 of 20 patients (60%) had returned to work. the re-injury rate was assessed at 35%. limitations: small case numbers no control group variable lesion severities and locations variable follow-up intervals and functional outcome expectations no quantitative outcomes were presented; only summary statements. no statistical analyses nixon (2008) population: clinically healthy horses of various breeds. pre-existing tendon injury was ruled out with baseline lameness and ultrasonographic evaluation. sample size: n = 8 intervention details: collagenase-induced tendinitis was created in 1 randomly chosen forelimb sdft of all horses. five days after collagenase injection, adipose tissue was obtained from gluteal region for isolation of autologous adipose-derived nucleated cells (adncs). four randomly chosen horses received intralesional adncs in saline and remaining 4 horses received an equal volume of saline, 7 days after collagenase injection. all horses were euthanised 6 weeks after treatment. study design: randomised, controlled, experimental study; unclear whether analyses were blinded outcome studied: semi-objective data – serial ultrasonographic evaluations to determine the csa and fiber alignment; histological scores for fiber alignment, inflammatory cell infiltration and vascularity. objective data – biochemical (total dna, proteoglycan and collagen contents) and molecular characteristics (collagen type i and iii, comp gene expression) were measured in adncand saline-treated sdfts 6 weeks following treatment. main findings (relevant to pico question): adnc improved collagen organisation, in both ultrasonographic and histological analyses. adncs decreased inflammatory cell infiltration, suggesting immunomodulatory effects. the biochemical and molecular characteristics of adncand saline-treated sdfts were largely similar, except that comp mrna levels were higher in adnc-injected sdfts. limitations: small sample size (although satisfactory power in results were reported) short time frame, relative to clinical disease no biomechanical or other functional outcomes were performed. schnabel (2009) population: clinically healthy horses of various breeds. sample size: n = 12 intervention details: collagenase-induced tendinitis was created in both forelimb sdfts of all horses. five days after collagenase injection, 1 sdft from 6 randomly chosen horses received 1 x 107 autologous bmmscs and the other 6 horses received 1 x 107 autologous adenoviral igf-i infected bmmscs (adigf-bmmscs). the contralateral sdft in all 12 horses was injected with saline. all horses were euthanised 8 weeks after treatment. study design: randomised, controlled, experimental study outcome studied: semi-objective data – serial ultrasonographic evaluations; histological scores (evaluated by 2 blinded observers). objective data – biochemical and molecular characteristics, biomechanical properties (elastic modulus, stiffness) were measured in patient-matched cell-treated and saline-treated sdfts, 8 weeks following treatment. main findings (relevant to pico question): ultrasonographic evaluations did not demonstrate any difference between msc-treated and control sdfts. histologic scores of both cell treatments were significantly improved over saline control; however, bmmsc and adigf-bmmsc sdfts were not significantly different from each other. biochemical and molecular characteristics were statistically similar among the cell-treated and saline sdfts. biomechanical properties – stiffness of both cell-treated sdfts was higher than saline sdft; however, this was not significant. limitations: short time frame, relative to clinical disease improved healing demonstrated only in histological scores which was determined via semi-objective data. no functional outcomes (apart from biomechanical testing) were performed. watts (2011) population: clinically healthy horses of various breeds. sample size: n = 8 intervention details: collagenase-induced tendinitis was created in 1 randomly chosen forelimb sdft of all horses. seven days after collagenase injection, allogeneic fetal-derived embryonic stem cells (escs) were injected intralesionally. four randomly chosen horses received 3 x 106 escs suspended in culture medium and remaining 4 horses received an equal volume of culture medium. all horses were euthanised 8 weeks after treatment. study design: randomised, controlled, experimental study outcome studied: semi-objective data – serial ultrasonographic evaluations; magnetic resonance imaging (mri) immediately after euthanasia; histological scores (evaluated by 2 blinded observers). objective data – biochemical and molecular characteristics were measured in treated and control sdft samples, 8 weeks following treatment. main findings (relevant to pico question): ultrasonographic evaluations and histology demonstrated improved fiber pattern and decreased lesion size in esc-treated sdfts compared to control sdft lesions. mri did not demonstrate any difference in lesion size or signal intensity between the treated and control sdfts. biochemical and molecular characteristics of both groups were similar. limitations: improved healing demonstrated only in histological scores which was determined via semi-objective data. short time frame, relative to clinical disease no biomechanical or other functional outcome data. caniglia (2012) population: clinically healthy horses of various breeds. sample size: n = 6 intervention details: core lesions were created in both forelimb sdfts with a synovial resector. one randomly chosen sdft was treated with 1 x 107 autologous bmmscs suspended in bm supernatant, 4 weeks following injury. the contralateral sdft received an equal volume of bm supernatant only. horses were euthanised 12 weeks after treatment. study design: randomised, controlled, experimental study outcome studied: objective data – collagen fibril diameters were measured in transverse sections of sdfts by transmission electron microscopy. samples were obtained from healthy and injured regions of each sdft. main findings (relevant to pico question): intralesional administration of autologous bmmscs did not affect the collagen fibril diameters of the treated and control sdfts. limitations: single outcome measure (collagen fibril diameter) was evaluated which may not accurately reflect the healing response at 12 weeks post-treatment short time frame, relative to clinical disease no functional outcome assessments. godwin (2012) population: clinical cases of overstrain-induced sdf tendinitis in thoroughbred racehorses. sample size: n = 141 intervention details: intralesional injection of 1 x 107 autologous bmmscs in bm supernatant under ultrasonographic guidance. study design: case series – no controls, not blinded outcome studied: histological evaluation of bmmsc-treated sdft samples from 8 horses, 6-12 months after treatment; evaluators were not blinded. long-term follow-up of race records 2 years after treatment. re-injury rates were calculated from information retrieved from telephone conversations with owners/trainers. main findings (relevant to pico question): histological evaluation showed lesion repair and collagen crimp pattern restoration. high percentage of cases returned to racing (98.2%) with a lower re-injury rate (27.4%) than previously reported in other studies of conservatively managed cases (46%). limitations: no ‘in study’ controls. historical controls were used to determine the benefit of bmmsc therapy in reducing re-injury rates. unavoidable variations in severity of the lesions, intervals between injuries and therapy, and post-injection management/training practices marfe (2012) population: clinical cases of overstrain-induced sdf tendinitis diagnosed with a distinct core lesion by ultrasonography. sample size: n = 6 intervention details: intralesional administration of autologous blood-derived stem cells (bdscs) in 3 cases. conventional conservative treatment was followed in 3 control cases. study design: clinical case-control study; not blinded outcome studied: ultrasonographic evaluation of the injured tendons prior to and 4 months following bdsc injections. main findings (relevant to pico question): ultrasonographic evaluation of bdsc-treated cases showed complete in-fill of the injured site with linear collagen fiber alignment. control (conservatively treated) tendons showed disorganised fibrous tissue infill at the injured site. limitations: very small group sizes no objective/quantitative data of treatment outcomes or statistical analyses no long-term follow-up lange-consiglio (2013) population: clinical cases of sdf tendinitis, ddf tendinitis and suspensory desmitis, diagnosed via ultrasonography. sample size: n = 95 intervention details: group a – 51 clinical cases treated with 5 x 106 allogenic amniotic membrane-derived mesenchymal cells. group b – 44 clinical cases treated with 5 x 106 autologous bmmscs. study design: prospective randomised controlled study, not blinded. outcome studied: lameness and ultrasonographic evaluation at monthly intervals for 12-15 months. follow-up information on return to previous activity and re-injury, at 2 years after treatment. main findings (relevant to pico question): no major ultrasonographic differences between groups group a – returned to work 4-5 months after treatment. re-injury rate (4%) was lower than bmmsc group group b – returned to work after a recovery period that ranged between 4-12 months. mean re-injury rate was higher than group a (23.08%). limitations: no untreated control group wide ranges of ages, lesion sites and lesion severities, five performance disciplines that influence outcomes and re-injury rates smith (2013) population: clinical cases of career-ending sdft injury. sample size: n = 12 intervention details: six randomly selected horses were treated with intralesional injection of 1 x 107 autologous bmmscs in 2 ml of bm supernatant, under ultrasonographic guidance. remaining 6 ‘control’ horses received an equal volume of saline. horses were euthanised 6 months following treatment. study design: randomised, experimental study; not blinded. outcome studied: semi-objective data – ultrasonographic evaluation, histological scores objective data – biochemical and biomechanical characteristics, were measured in specimens from treated and control sdfts, 6 months following treatment main findings (relevant to pico question): reduced cross-sectional area of bmmsc-treated sdfts compared to saline controls at 6 months. no difference in total collagen content of sdfts dna and sulfated glycosaminoglycan contents of bmmsc-treated sdfts were significantly lower than saline controls and similar to the contralateral normal sdft. stiffness of bmmsc-treated sdft was similar to normal sdft; elastic modulus of bmmsc-treated sdft higher than saline control but not significantly different. overall, improved histological characteristics of bmmsc-treated sdft compared to saline control. limitations: small group sizes these cases had severe/end-stage lesions, which might not be reflective of responses in less severely injured cases. no functional assessment, apart from biomechanical tests   durgam (2016) population: clinically healthy american quarter horses sample size: n = 8 intervention details: collagenase-induced tendinitis was created in both forelimb sdfts of all horses. at the same time, a small segment of lateral digital extensor tendon was surgically collected to isolate tendon-derived progenitor cells (tdpcs). four weeks after collagenase injections, 1 randomly chosen sdft in each horse was injected with 1 x 107 autologous tdpcs in 2 mls of saline and the contralateral sdft received an equal volume of saline. all horses were euthanised 12 weeks after tdpc injections. study design: randomised, controlled, experimental study; no blinding. outcome studied: subjective data –collagen and proteoglycan distributions in longitudinal histological sections objective data – biochemical, biomechanical and molecular characteristics, measured in both forelimb sdfts and a normal hindlimb sdft, 12 weeks following treatment. fourier transform-second-harmonic generation (ft-s-hg) assessment of collagen alignment in longitudinal histological sections. main findings (relevant to pico question): biochemical and molecular characteristics of the tdpcand saline-treated sdfts were not significantly different. yield and maximal stresses of tdpc-treated tendons were statistically similar to normal sdft and higher than saline-treated tendons; however elastic modulus and stiffness of tdpc-treated sdft were significantly lower than normal sdft. subjectively, the collagen and proteoglycan distributions in histological sections of tdpc-treated sdfts were similar to normal sdft. these findings corroborated with quantitative ft-s-hg measurements of collagen alignment. limitations: hindlimb sdfts were used as controls small group sizes, although sufficient for statistical significance short time frame, relative to clinical disease biomechanical properties were determined in one-quarter longitudinal samples of the whole sdft which may have influenced the results. sdft lesion site specimens collected for biochemical and molecular analyses might not be reflective of the entire injury.  appraisal, application and reflection tendon injuries in horses range from acute tendon strains to chronic tendinopathy, and are both common and challenging problems in equine performance horse practice. the technique and feasibility of cell-based therapy (isolated from bone marrow) for treating equine sdft injuries was first reported by smith et al. (2003; 14). since then, intralesional stem cell therapy, using cells from multiple tissue sources, has become common and commercial services are now available to support cell-based therapies in horses. the purpose of this knowledge summary was to evaluate the available evidence from studies evaluating the efficacy of stem cell therapies for equine flexor tendon healing.   appraisal eleven studies were identified that addressed this issue (note that the outcomes from references 2 and 3 were replicated in reference 10. reference 10 was used to evaluate the collective outcomes from these manuscripts). these papers segregated into two distinct groups; six studies using experimental models of tendinopathy (references 1, 5, 10, 12, 13 and 17) and six case series of clinical tendinitis patients (references 4, 6, 9-11, and 15; reference 10 included data for both groups).  accepting the focused nature of the question under review, there was a remarkable degree of variability in the source of ‘stem cell’ used in these studies (bone marrow [7], blood [1], amnion [1], adipose tissue [2], embryonic [1], and tendon [1]), the protocols used to generate the therapeutic cell populations, donor-recipient matching (three allogeneic sources and 9 autologous sources), the diluents used for the cell injections (saline [5], bone marrow supernatant [4], plasma [1], prp [1], and fibrin/thrombin [1]) and, in the clinical studies, the specific disciplines the patients were engaged in. collectively, these sources of variation confounded any coherent meta-analysis. of the six experimental studies, five used intratendinous collagenase injections to generate sdft lesions (5, 10, 12, 13, 17) while caniglia et al 2012 (1) created a core lesion with a synovial resector. in only two of these studies, were at least some of the outcome assessments conducted in blinded fashion (13, 17). while acknowledging that there are no other accepted alternative models, the extent to which either induced lesion reflects the cumulative tensile strain injury of clinical tendinitis cases is debatable. self-evidently, neither model is generated by tensile overloading, and our own (5) and other’s (3, 16) experience with the collagenase model has shown that individual horse’s responses to collagenase vary considerably. accepting these concerns, in all six experimental studies, cell delivery improved the histological and ‘matrix organisation’ characteristics of the repair tissue, while the ultrasonographic findings were improved in three of the four studies that used ultrasonography for outcome assessment. in all but one experimental study (reference 5), histological outcomes were determined by a score derived from ‘cell and tissue characteristics’ grading schemes. there is clearly an element of subjectivity in these analyses, particularly given that only two were carried out in blinded fashion. of more general concern, although it makes intuitive sense that a ‘more histologically normal’ repair tissue corresponds to a better functional outcome, the relationship between these outcomes is very poorly defined, particularly since higher level matrix organisation has not been addressed in any study to date. with the possible exception of lacitignolo et al 2008 (10; 24 weeks), the experimental studies were conducted over time frames far less (7-16 weeks) than the ‘several months’ interval generally required for clinical tendinitis cases to resolve. it is possible, and even perhaps to be expected, that many of the significant differences between cell-treated and control samples detected at early time points in the experimental studies disappear over longer time frames, as healing in the ‘control’ groups catches up.    only two of the experimental studies (5,13) included biomechanical testing to provide some functional assessment of outcome. however, it is debatable how well single ‘tensile load to failure’ testing translates to the rapid, submaximal cyclic loading that flexor tendons are subjected to clinically. none of the experimental studies addressed the most clinically relevant issue; namely, do horses with tendinitis perform better after receiving cell-based therapies? the ultrasonographic, histological, biochemical, transcriptional and biomechanical analyses are, at best, indirect indices of ‘healing quality’ and functional return.  collectively, outcomes from the experimental studies should be considered as b2 evidence. of the six clinical case series, three had very small case numbers and/or no control group and/or marginal outcome assessments (4, 10, 11) and can be considered to be little more than anecdotal (grade e) in value. the study by godwin et al 2012 (6) is substantive by virtue of the large number of cases (141) enrolled in the analyses. there was no control/placebo group in this study; the authors used previously published outcomes from analogous patient groups for comparison. further, the great majority of godwin et al’s patients (105) were national hunt horses, and so their outcomes should be confined to this discipline. accepting this, 98% of treated horses returned to racing (albeit after an 8+ month layoff) and the re-injury rate (27%) was approximately half that reported in two studies from similar national hunt populations. although the evidentiary value of the godwin study should, at best, be classified as an uncontrolled prospective study (c), the clinical significance of the outcomes is high (grade 1 to 2). lange-consiglio et al 2013 (9) compared the responses of 95 performance horses with tendon or ligament injuries randomly assigned to be treated with allogeneic amnion-derived stem cells (amsc; 51 cases) or autologous bone marrow-derived stem cells (bmmsc; 44 cases) in a fibrin carrier. this study included show jumpers, dressage horses, eventers, trotters and thoroughbreds, with lesions in the superficial and deep digital flexor tendons and suspensory ligaments and a range of clinical signs and lesion severity, although these variables were distributed fairly evenly across both treatment groups. horses treated with amscs returned to training earlier than horses receiving bmmscs and the re-injury rates were considerably less in the amsc group (4%) than the bmmsc group (23%). the overall bmmsc group re-injury rate was reassuringly similar to the rate reported by godwin et al, above, although lange-consiglio’s thoroughbreds responded substantially better (12.5% recurrence) than godwin’s thoroughbreds (50%). the study by lange-consiglio et al 2013 should be considered b2.  in the final clinical study, by smith et al 2013 (15), was a prospective, randomised, controlled clinical trial involving 12 horses with end-stage tendinitis. further, the histological evaluations of the tendon samples were blinded. although the horses in the study were not exercised above trotting speeds, there were substantial improvements in ultrasonographic, histological and biomechanical characteristics of healing tissue six months after intralesional bmmsc treatment. from an experimental design perspective, this study provides the most compelling results supporting stem cell use for flexor tendinitis in horses and should be classified as b2.   application from an evidentiary perspective, the collective data supporting cell-based therapy for equine flexor tendinitis is not strong. in this review, we have raised concerns regarding the clinical applicability of the experimental tendinitis models, the relevance of indirect ‘healing quality’ outcomes to functional success, inadequate or nonexistent control groups and experimental design issues with published clinical trials. the clinical reality is that conventional approaches to managing flexor tendinitis/tendinopathy in performance horses require prolonged and intensive therapy and rehabilitation efforts yet carry a guarded prognosis. any novel therapeutic option, whether cell-based, biologic or pharmaceutical, will likely be embraced by the equine veterinary community if that option holds some promise of an improved outcome. this perspective makes any attempt to conduct a randomised, controlled, prospective clinical trial challenging, particularly given the funding constraints that veterinary researchers routinely work under. while acknowledging the questionable evidentiary value of some studies, there is a consistent collective body of evidence supporting the findings that cell-based therapies improve tendon matrix repair and reorganisation, both in experimental and clinical subjects, and significantly reduce recurrence rates following return to work. in light of these conclusions, and the lack of any more promising alternatives, cell-based therapies should be considered for treating equine flexor tendinitis cases and, by extension, for ligament injuries also. as the applications of these therapies evolve, there are many variables that need to be investigated and optimised. some of the major issues are as follow:  standardisation/optimisation of cell source(s), cell processing, and diluents optimisation of timing and dose(s) of cell delivery following injury agreement on effective post-therapeutic case management and rehabilitation protocols standardisation of meaningful outcome measures for specific equine disciplines conclusions and reflection cell-based therapy, in both the human and veterinary fields, is a highly dynamic, but poorly defined field of discovery. it is clear that clinical applications of cell-based therapies have far outstripped our understanding of the biological mechanisms by which stem cells influence healing. as noted above, there is little or no rationale for deciding on many of the variables that influence cell-based therapy efficacy. somewhat contentiously, the actual need for a ‘stem cell’ population, as opposed to any population of cells isolated from a tissue or fluid, has not been demonstrated through properly controlled experiments. further, data from recent cell-tracking studies (5,7,16) clearly show that exogenous stem cells are cleared from the injection site within a few weeks and do not contribute to the pool of tenocytes and/or progenitor cell engaged in tendon repair/regeneration beyond this time. it is probable that secreted stem cell cytokines and/or trophic factors contribute substantially to stem cells’ impact on tissue repair (8). identifying these factors could simplify and standardise ‘biologic therapy’ considerably. regardless of the specific biologic therapy in question, randomised, appropriately controlled studies using a consistent and translatable experimental model or clinical caseload, standardised treatment and rehabilitation protocols and credible outcome assessments, will be required to make meaningful headway on clarifying efficacy. given the costs and case numbers required for these clinical trials, multi-center/practice collaboration and significant financial support from private industry and foundations will be necessary. depending on regulatory developments in human medicine, the veterinary community might also stand to benefit from biomedical research efforts focused on validating cell-based therapies for people. methodology section search strategy databases searched and dates covered: search terms were applied in pubmed central accessed on ncbi website (1910-2016), cab abstracts database accessed on ovid platform (1973-2015) and scopus search terms: horse and tendonitis or tendinitis or stem cell or flexor tendon dates searches performed: august 2016 exclusion / inclusion criteria exclusion: non-english language, review articles, case reports, conference proceedings/abstracts inclusion: experimental studies and clinical case series evaluating the effect of intralesional stem cell therapy on equine superficial digital flexor tendon healing. search outcome database number of results excluded – did not answer pico question excluded – review articles excluded – not in english total relevant papers ncbi pubmed 24 11 2 0 11 scopus 18 8 0 1 9 cab direct 26 10 0 6 10 total relevant papers when duplicates removed 11 conflict of interest the authors declare no conflicts of interest. references caniglia, c.j. et al (2012) the effect of intralesional injection of bone marrow derived mesenchymal stem cells and bone marrow supernatant on collagen fibril size in a surgical model of equine superficial digital flexor tendonitis. equine veterinary journal, 44 (4), pp. 587-593. http://dx.doi.org/10.1111/j.2042-3306.2011.00514.x crovace, a. et al (2007) cell therapy for tendon repair in horses: an experimental study. veterinary research communications, 31 (s1), pp. 281-283. http://dx.doi.org/10.1007/s11259-007-0047-y crovace, a. et al (2010) histological and immunohistochemical evaluation of autologous cultured bone marrow mesenchymal stem cells and bone marrow mononucleated cells in collagenase-induced tendinitis of equine superficial digital flexor tendon. veterinary medicine international, 2010, article id 250978. http://dx.doi.org/10.4061/2010/250978 del bue, m. et al (2008) equine adipose-tissue derived mesenchymal stem cells and platelet concentrates: their association in vitro and in vivo. veterinary research communications, 32 (s2), pp. 51-55. http://dx.doi.org/10.1007/s11259-008-9093-3 durgam, s.s. et al (2016) tendon-derived progenitor cells improve healing of collagenase-induced flexor tendinitis. journal of orthopaedic research, doi: 10.1002/jor.23251, [epub ahead of print]. http://dx.doi.org/10.1002/jor.23251 godwin, e.e. et al (2012) implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstrain injury of the superficial digital flexor tendon. equine veterinary journal, 44 (1), pp. 25-32. http://dx.doi.org/10.1111/j.2042-3306.2011.00363.x guest, d. et al (2010) equine embryonic stem-like cells and mesenchymal stromal cells have different migration patterns following their injection into damaged superficial digital flexor tendon. equine veterinary journal, 42 (6), pp. 636-642. http://dx.doi.org/10.1111/j.2042-3306.2010.00112.x lange-consiglio, a. et al a (2013) conditioned medium from horse amniotic membrane-derived multipotent progenitor cells: immunomodulatory activity in vitro and first clinical application in tendon and ligament injuries in vivo. stem cells and development, 22 (22), pp. 3015-3024. http://dx.doi.org/10.1089/scd.2013.0214 lange-consiglio, a. et al b (2013) investigating the efficacy of amnion-derived compared with bone marrow-derived mesenchymal stromal cells in equine tendon and ligament injuries. cytotherapy, 15 (8), pp. 1011-1020. http://dx.doi.org/10.1016/j.jcyt.2013.03.002 lacitignola, l. et al (2008) cell therapy for tendinitis, experimental and clinical report. veterinary research communications, 32 (suppl 1), pp. s33-s38. http://dx.doi.org/10.1007/s11259-008-9085-3 marfe, g. et al. (2012) a new clinical approach: use of blood-derived stem cells (bdscs) for superficial digital flexor tendon injuries in horses. life sciences, 90, pp. 825-830. http://dx.doi.org/10.1016/j.lfs.2012.03.004 nixon, a.j. et al (2008) effect of adipose-derived nucleated cell fraction on tendon repair in horses with collagenase-induced tendinitis. american journal of veterinary research, 69 (7), pp.928-937. http://dx.doi.org/10.2460/ajvr.69.7.928 schnabel, l.v. et al (2009) mesenchymal stem cells and insulin-like growth factor-i gene enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons. journal of orthopaedic research, 27 (8), pp. 1392-1398. http://dx.doi.org/10.1002/jor.20887 smith, r.k. et al (2003) isolation and implantation of autologous equine mesenchymal stem cells from bone marrow into the superficial digital flexor tendon as a potential novel treatment. equine veterinary journal, 35 (1), pp. 99-102. http://dx.doi.org/10.2746/042516403775467388 smith, r.k.w. et al (2013) beneficial effects of autologous bone marrow-derived mesenchymal stem cells in naturally occurring tendinopathy. plosone, 8 (9), e75697. http://dx.doi.org/10.1371/journal.pone.0075697 sole, a. et al (2013) distribution and persistence of technetium-99 hexamethyl propylene amine oxime-labelled bone marrow-derived mesenchymal stem cells in experimentally induced tendon lesions after intratendinous injection and regional perfusion of the equine distal limb. equine veterinary journal, 45 (6), pp. 726-731. http://dx.doi.org/10.1111/evj.12063 watts, a.e. et al (2011) fetal derived embryonic-like stem cells improve healing in a large animal flexor tendonitis model. stem cell research and therapy, 2 (4), pp. 1-12. intellectual property rights knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. in pregnant bitches, is elective caesarean section more effective than vaginal delivery at improving puppy survival? a knowledge summary by mullika borisoot rvn 1* 1university of bristol, senate house, tyndall ave, bristol bs8 1th *corresponding author (mb15544@bristol.ac.uk) vol 5, issue 3 (2020) published: 13 aug 2020 reviewed by: soon hon cheong (dvm phd) and sebastian patrick arlt (dipl ecar) next review date: 27 sep 2021 doi: 10.18849/ve.v5i3.319 pico question in pregnant bitches due to whelp, is elective caesarean section more effective than vaginal delivery to improve puppy survival?   clinical bottom line category of research question the category of the research question is regarding the incidence of puppy mortalities as a result of vaginal delivery, emergency caesarean section and elective caesarean section. the number and type of study designs reviewed two retrospective articles were reviewed and critically appraised; one retrospective study with high single canine breed bias and one study on different canine breeds but limited support in directly answering the pico question. strength of evidence the studies selected both had strong uses of experimental designs but together provided weak evidence to determine a definitive answer to the pico question. outcomes reported the outcomes from both retrospective studies suggests that the mortality rates of newborn puppies can be reduced if pregnant bitches are scheduled ahead for elective caesareans, in comparison to undergoing an emergency caesarean section when complications develop, particularly in breeds with higher risks of dystocia. therefore, there is some evidence to support that it may be advantageous to consider the breed, age and overall health of the bitch during pregnancy to determine whether elective caesarean sections, for the safe delivery of puppies, should be considered. conclusion there are currently insufficient studies, literatures and evidence in veterinary medicine for caesarean sections to become a routine procedure in first opinion practices. future prospective studies should be conducted and include the optimum anaesthetic protocols with the lowest associated risks for the pregnant bitch and puppies.   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario following a radiographic examination of a french bulldog within a few days from her due date in a first opinion veterinary practice, the veterinary surgeon has concerns regarding the abnormally large sizes of the puppies’ heads in relation to the relatively narrow pelvic opening. with fear of dystocia due to foetopelvic disproportion, in addition to other complications associated with the nature of the brachycephalic breeds. if left without any intervention, the pregnant bitch may experience dystocia due to obstruction of the birth canal, endangering herself and her puppies. in this scenario, an emergency caesarean section may be necessary to resolve dystocia, which may increase surgical and anaesthetic risks, and possibly result in puppy loss. the veterinary surgeon discussed the advantages of an elective caesarean section with the owner, to reduce the likelihood of mortality of the puppies. however, the owner has strong beliefs in natural vaginal deliveries of newborns, with homeopathic or herbal remedies if necessary to facilitate labour and delivery. the veterinary surgeon researched for existing literature for evidence to support the recommendation to consider elective caesarean sections especially in situations and breeds with predispositions to dystocia, to maximise survival of the puppies. the evidence the literature research via various databases presented two articles that could be used in this knowledge summary (proctor-brownet al., 2019; and alonge & melandri, 2019), each with differing values of relevance to the pico question, which were reviewed and evaluated by the author of this knowledge summary. although the article written by alonge & melandri (2019) directly addresses the pico question, with the evidence producing a clear conclusion, the authors only discussed a single breed, the great danes. therefore, these results cannot be used to exclusively represent the entire canine species. the other article by proctor-brown et al. (2019) included multiple breeds but with more limitations with regards to the pico question. both articles have evidence which support that the mortality rates of puppies can be reduced with the pregnant bitch undergoing elective caesarean sections, in comparison to vaginal delivery and emergency caesarean sections. summary of the evidence proctor-brown et al. (2019) population: litters of puppies from 53 different breeds from one referral hospital sample size: 836 puppies intervention details: 150 bitches who underwent caesarean sections between june 2007 and march 2017 were divided into emergency (104) and elective (46) groups. 53 breeds were included in this study, most commonly the english/american bulldog and labrador retriever. 59/150 (40%) of the total number of participants were brachycephalic breeds and out of those, 23/59 (39%) underwent elective caesareans. study design: retrospective study outcome studied: variables included signalment of the pregnant bitch, information regarding whelping and timing, regarding anaesthesia and surgery. the dependent variable is perinatal death identified as a result of a caesarean section. main findings (relevant to pico question): the percentages of neonatal death from emergency compared to elective caesarean sections decreases from 45/104 (43%) to 7/46 (15%). only 6/16 (38%) of vaginal deliveries in emergency cases were successful. there is a 6.67 odds ratio of a minimum of one deceased puppy delivered via caesarean section should the anaesthetic time increase over 120 minutes. limitations: selection bias. inability to control variables. the study’s authors concluded that there is a correlation between duration of surgery and mortality rates but anaesthetic protocols were not evaluated as part of the study. alonge & melandri (2019) population: great dane litters from eight different kennels sample size: 46 different great dane litters, including a total of 303 puppies intervention details: three categories were evaluated; vaginal deliveries, elective caesarean sections and emergency caesarean sections. study design: retrospective study outcome studied: mortality risks were calculated, including early neonatal and perinatal forms. risks of stillbirths were calculated. data were analysed using the anova and chi-squared test with a significant value of less than 0.05. main findings (relevant to pico question): the number of stillbirth and neonatal mortalities were statistically significantly reduced in elective caesarean sections in comparison to vaginal deliveries and emergency caesarean sections, thus highlighting the effects of adverse obstetrical conditions on newborn litters. neonatal mortalities 2% in elective caesarean section 10% in emergency caesarean section 19% in vaginal delivery stillborn 4% in elective caesarean section 18% in emergency caesarean section 22% vaginal delivery the study’s authors suggested that some of the main factors resulting in neonatal death includes dystocia and prolonged labour. difficulty in parturition can affect the neonate’s intake of immunoglobin antibody through the bitch’s colostrum. natural delivery of puppies can lead to a 20% risk of perinatal mortality, which could be reduced down to 2% with elective caesarean section. accurate time of parturition estimation should be performed, along with appropriate choice of anaesthetic techniques, to avoid risk factors which could have adverse effects on the survival rates of puppies. limitations: the study was limited to one breed and therefore not representative of the canine species. selection bias. inability to control variables. appraisal, application and reflection although anaesthetic protocols for canine caesarean sections were not reflected as part of the pico question, it is important to acknowledge that the mortality or survival statistics of puppies in existing literatures alone should not solely determine if a patient should be scheduled for elective caesarean sections. anaesthetic protocols and other factors such as size of the litter, the breed and age of the pregnant bitch should also be considered (cornelius et al., 2019) and the risks should be compared to the benefits. there is also query regarding owner’s or breeder’s knowledge and experience with pregnancy and labour of canines. future investigations could explore the detection of labour, symptoms of dystocia and timing of decisions made regarding surgery. despite the article by proctor-brown et al. (2019) including 150 litters who underwent caesarean sections in the study, the article’s main objective was to investigate the impact of the decision to delivery interval on foetal death. no direct comparisons were investigated in the differences between vaginal delivery, elective and emergency caesarean sections. abdominal ultrasounds were performed in only 55% of all cases in order to assess foetal distress, making it unclear whether the puppies included in the data were already dead in utero and therefore these puppies would have not been in association with caesarean sections. furthermore, the ratio between the weight of the bitch and weight of the heaviest puppy may be a factor on the probability on the necessity of a caesarean section (dold et al., 2018). the article also explored the correlation between surgical time and rate of foetal death, another essential factor to take into consideration for conducting caesarean sections. the article uses evidence based medicine and relevant literatures to support their cases. the article by alonge & melandri (2019) included 303 puppies in total. there was only one breed and it is not specifically for breeds predisposed to dystocia evaluated. the article directly addresses the pico question, making clear and concise comparisons between vaginal delivery, elective and emergency caesarean sections. the results demonstrate a definitive outcome regarding the maximisation of successful neonatal delivery. alonge & melandri (2019) also made comparisons with human and cattle literature, which supports that dystocia has a negative effect on the offspring’s survival and their vitality. other considerations regarding a caesarean section were discussed within this article, including indications for the best time to perform surgery, anaesthetic protocol and diet of the pregnant bitch, making this article more relevant to the pico question than the article by proctor-brown et al. (2019). however, being retrospective studies, these articles are expected to be associated with limitations such as selection bias and the inability to control variables. despite the current evidence suggesting that an elective caesarean section reduces the rate of puppy mortalities, there is still resistance from breeders and first opinion veterinary practices to perform routine elective caesarean sections. however, it is also important to consider the possibility that an elective caesarean section should not be considered as a first line intervention as there are anaesthetic and surgical risks associated and the bitch may be able to whelp the puppies with only assistance and not surgical interventions. it can be argued that puppies may benefit from a vaginal delivery rather than a caesarean section due to greater vitality (oliva et al., 2018). equally, the ethics of elective caesarean sections should be recognised in future prospective studies; would the bitch experience more pain and complications associated with surgery than vaginal delivery, and should we, as veterinary practices, be supporting the breeding of canine breeds predisposed to dystocia and that do not have the capability to reproduce naturally without veterinary assistance? methodology section search strategy databases searched and dates covered: cab abstracts 1992 – 2019 medline 1966 – 2019 science direct 1986 – 2019 search strategy: cab abstracts: (dog or dogs or bitch or bitches or puppy or puppies).mp. [mp=abstract, title, original title, broad terms, heading words, identifier, cabicodes] (caesarean section or caesarean sections or cesarean section or cesarean sections).mp. [mp=abstract, title, original title, broad terms, heading words, identifier, cabicodes] (mortality or mortalities or mortality rate or mortality rates).mp. [mp=abstract, title, original title, broad terms, heading words, identifier, cabicodes] 1 and 2 and 3 medline: (dog or dogs or bitch or bitches or puppy or puppies) (caesarean section or caesarean sections or cesarean section or cesarean sections) (mortality or mortalities or mortality rate or mortality rates) 1 and 2 and 3 science direct: (dog or dogs or bitch or bitches or puppy or puppies) and (caesarean section or caesarean sections or cesarean section or cesarean sections) and (mortality or mortalities or mortality rate or mortality rates) dates searches performed: cab abstracts 27th september 2019 medline 10th october 2019 science direct 25th october 2019 exclusion / inclusion criteria exclusion: irrelevant to pico question, articles that do not discuss both emergency and elective caesarean sections, articles not written in the english language, conference abstract, duplicates, chapters or sections from a textbook, articles without full access, feline caesarean sections. inclusion: relevant to pico question, retrospective studies, review articles, observational studies, interventional studies, articles published in the english language. search outcome database number of results excluded – [did not answer pico question] excluded – [not written in the english language] excluded – [conference abstract only] excluded – [duplicates] total relevant papers cab abstracts 39 25 13 0 0 1 medline 21 18 2 0 1 0 science direct 56 49 0 5 1 1 total relevant papers 2 conflict of interest the author declares no conflicts of interest. references alonge, s. & melandri, m. (2019). effect of delivery management on first-week neonatal outcome: how to improve it in great danes. theriogenology, 125, pp.310–316. doi: https://doi.org/10.1016/j.theriogenology.2018.11.006 cornelius, a., moxon, r., russenberger, j., havlena, b. & cheong, s. (2019). identifying risk factors for canine dystocia and stillbirths. theriogenology, 128, pp.201–206. doi: https://doi.org/10.1016/j.theriogenology.2019.02.009 dolf, g., gaillard, c., russenberger, j., moseley, l. & schelling, c. (2018). factors contributing to the decision to perform a cesarean secton in labrador retrievers. bmc veterinary research, 14(1). doi: http://doi.org/10.1186/s12917-018-1381-8 oliva, v., queiroz, m., albuquerque, v., carreira, j., souza, t., ferreira, g., abimussi, c. & vides, j. (2018). vitality evaluation methods for newborn puppies after cesarean section performed under general inhalation anestesia. pesquisa veterinária brasileira, 38(6), pp.1172–1177. doi: http://dx.doi.org/10.1590/1678-5150-pvb-5350 proctor-brown, l., cheong, s. & diel de amorim, m. (2019). impact of decision to delivery time of fetal mortality in canine caesarean section in a referral population. veterinary medicine and science, 5(3), pp.336–344. doi: https://doi.org/10.1002/vms3.163 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. clinical effect of tibial plateau leveling osteotomy compared to lateral fabellar suture in dogs wanda j gordon-evans dvm, phd, dacvs, dacvsmr1 1wisconsin veterinary referral center, 360 bluemound road, waukesha, wi 53188 *corresponding author (wgordonevans@gmail.com) vol 1, issue 3 (2016) published: 27 july 2016 reviewed by: kristina kiefer dvm, phd doi: 10.18849/ve.v1i3.44 section index:    abstract | introduction | methods | results | discussion | conflict of interest | references | supplementary files abstract objective: this manuscript used evidence based statistical methods that estimate clinical treatment effect rather than whether groups were statistically different. background: the previously published blinded, randomised, controlled clinical trial comparing lateral fabellar suture (lfs) and tibial plateau leveling osteotomy (tplo) was reported with a traditional analysis comparing groups. although this was a well-designed study, evidence based statistical methods that estimate treatment effect would be helpful to the practitioner. methods: the effect size and number needed to treat (nnt) were calculated for the outcome measures with significant differences between groups using the data from a previously published randomised controlled clinical trial comparing tplo and lfs in dogs with cruciate rupture.   results: the effect size of the peak vertical force (pvf) at a trot, 1 year after tplo over lfs, was moderate to high (0.71) with a nnt of 6. the nnt for satisfaction was 7. conclusion/application: based on this study, the effect size and nnts are such that the clinical difference warrants recommending the tplo over the lfs in large and giant breed dogs. introduction the tplo has been advocated as a better treatment for cruciate rupture in the dog based largely on a randomised controlled clinical trial published in 2013 (gordon-evans et al., 2013; bergh et al., 2014). this paper describes a statistical difference in limb function between owner satisfaction and limb function (peak vertical force); however, the clinical difference between the groups using the effect size, nnt and number needed to harm (nnh) were not calculated (gordon-evans et al., 2013). the effect size is a statistical measure of the treatment impact. it is the quantification of the clinical difference between treatments. additionally, these statistics can be used to compare different studies if methodologies are similar. there are several ways to estimate effect size including cohen’s d and the numbers needed to treat or harm.  cohen’s d is the standardised mean difference of an outcome measure and directly describes the magnitude of the difference between the 2 groups (thallmeier and cook, 2015). conventionally, cohen’s d of 0.2 is small, 0.5 is medium, and 0.8 is high. the nnt is a statistic used in evidence based medicine to turn a numerical difference into a tool that can be used in clinical decision making. the nnt is the number of patients needed to treat with the new treatment to get 1 more response than the control group. this is helpful in determining the likelihood that the treatment will be successful. the nnh is a statistic that puts complications of a treatment into a clinically relevant number describing the number of patients added to the new treatment group before a complication would be expected. the number needed to treat should be low and the number needed to harm should be high. the purpose of this evaluation was to provide statistics that would be useful in clinical decision making based on the previously published randomised controlled clinical trial comparing tplo to lfs.  the hypothesis was that the tplo would have a moderate effect size with a low nnt compared to lfs. methods the randomised controlled clinical trial comparing tplo to lfs study by gordon-evans was reviewed (gordon-evans et al., 2013). although multiple outcome measures were used in the study, limb function as measured by pvf and owner satisfaction were the only measures with statistical difference. the limb function data was chosen to calculate the cohen’s d effect size at the 12 month time point (thalheimer and cook, 2015). the lfs was considered the control group for these calculations. to calculate the nnts success and failure must be defined and the dogs categorised. for pvf at the walk and trot, success was defined as pvf greater than 35% of bodyweight at a walk and 58% at a trot (evans et al., 2005; millis and levine, 2014).  the owner satisfaction score was on a scale of 1 to 10 with 10 being the best possible outcome. a 9 or 10 score was considered success and 8 and below to be failure. nnh was not calculated since there was no difference in complications between the 2 surgical interventions. results the results are presented in table 1: table 1: results of effect size and number needed to treat (nnt) calculations for peak vertical forces (pvf) at both a walk and trot. discussion for all 3 outcome measures, the treatment effect of tplo over lfs is moderate to high. an effect size of 0.51 is considered moderate and 0.71 would be considered moderate to high. for frame of reference, in a human metanalysis of surgical vs conservative treatment for decreasing the pain of osteoarthritis of the knee, showed an effect size of 0.35 at 3 months and 0.18 by six months. this was considered low at 3 months and negligible at 6 months (thorland et al., 2015). in contrast, diclofenac (a nonsteroidal anti-inflammatory) showed an effect size of 0.57 for decreasing pain over placebo in adults with knee ostoearthritis (dacosta et al., 2016). the authors used 0.37 as the cutoff for significant clinical effect (dacosta et al., 2016). the nnts calculated were also clinically significant. the nnt of topical ketoprofen (a nonsteroidal anti-inflammatory) for knee osteoparthritis pain relief is 7 over placebo in a recent chochran review (derry et al., 2016). this essentially means that 7 patients were treated in the ketoprofen group before 1 more person benefitted over placebo treatment. in contrast, in a study comparing 2 methods of preparation prior to total knee replacement the nnt was 145 for the experimental method. in other words 145 patients were prepped in the experimental treatment before 1 extra patient benefited over the standard (lamplot et al., 2015). this helps the clinician judge the clinical utility of a new procedure, drug, or implant. a treatment may work well but if it has a high complication rate and thus a low nnh, it may not be worth recommending. this is valuable to note from a clinical recommendation perspective. the nnh could not be calculated from this study because the complication rates between the groups were not different. based on this study, the effect size and nnt are such that the clinical difference warrants recommending the tplo over the lfs in large and giant breeds. conflict of interest acknowledgments: thank you to richard evans for guidance in calculating the effect size and numbers needed to treat. funding: funding for the original randomised controlled clinical trial was provided by morris animal foundation; however, no additional funding was used for this manuscript. competing interests: there are no competing interests. references bergh, m.s. et al. (2014) systematic review of surgical treatments for cranial cruciate ligament disease in dogs. journal of the american animal hospital association, 50 (5), pp. 315-21. http://dx.doi.org/10.5326/jaaha-ms-6356 da costa, b.r. et al. (2016) effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. the lancet, 387 (10033), p. 2093. http://dx.doi.org/10.1016/s0140-6736(16)30002-2 derry, s. et al. (2016) topical nsaids for chronic musculoskeletal pain in adults. cochrane database of systematic reviews, [epub ahead of print]. http://dx.doi.org/10.1002/14651858.cd007400.pub3 evans, r. horstman, c. and conzemius, m. (2005) accuracy and optimization of force platform gait analysis in labradors with cranial cruciate disease evaluated at a walking gait. veterinary surgery, 34 (5), pp. 445-9. http://dx.doi.org/10.1111/j.1532-950x.2005.00067.x gordon-evans, w.j. et al. (2013) comparison of lateral fabellar suture and tibial plateau leveling osteotomy techniques for treatment of dogs with cranial cruciate ligament disease. journal of the american veterinary medical association, 243 (5), pp. http://dx.doi.org/10.2460/javma.243.5.675 lamplot, j.d. et al. (2015) modified protocol decreases surgical site infections after total knee arthroplasty. journal of knee surgery, 28 (5), pp. 395-403. http://dx.doi.org/10.1055/s-0035-1544974 millis, d.l. and levine, d. (2014) canine rehabilitation and physical therapy. philadelphia, pa. saunders. thallheimer, w. and cook, s. (2002) how to calculate effect sizes from published research: a simplified methodology. [work-learning research] [online] available from: http://www.bwgriffin.com/gsu/courses/edur9131/content/effect_sizes_pdf5.pdf [accessed 25 april 2016] thorlund, j.b. et al. (2015) arthroscopic surgery for degenerative knee: systematic review and meta-analysis of benefits and harms. british journal of sports medicine, 49 (19), pp. 1229-35. http://dx.doi.org/10.1136/bjsports-2015-h2747rep supplementary files, images & tables all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. <p><span style="color: #7d0063; font-size: 20px;"><strong>thank you to our 2020 reviewers</strong></span></p> <!-authors --> <!-author 1 --><strong>dr kit sturgess </strong>ma vetmb phd certvr dsam certvc frcvs<sup>1*</sup><br /> <!-affiliations --> <p><span style="font-size: 12px;"> <sup>1</sup>vet freedom ltd brockenhurst, hampshire, so42 7qt<br> <sup>*</sup>corresponding author (<a href="mailto:kit.sturgess@btopenworld.com">kit.sturgess@btopenworld.com</a>) </span></p> <hr> <!-this is an anchor for "back to the top. do not delete" --><a name="index"></a> <!-dates and reviews --> <span style="font-size: 11px;"> <p><strong>vol 6, issue 1 (2021)</strong></p> <p><strong>published:</strong> 13 jan 2021</p> <p><strong>doi:</strong>&nbsp;<span style="color: #0000ff;"><a style="color: #0000ff;" href="https://doi.org/10.18849/ve.v6i1.464" target="_blank">10.18849/ve.v6i1.464</a></span></p> </span> </span> <hr> <p style="margin-top: 0cm; text-align: justify;"><span style="font-family: 'pt serif',serif; color: #222222;">2020 will be a year to remember! one of the standout features for me has been the speed with which &lsquo;science&rsquo; has responded to the crisis in terms of developing and disseminating new information to the community highlighting the importance of digital communication &ndash; a space that <em>veterinary evidence </em>comfortably occupies. the availability of pre peer-reviewed papers has become the norm but it has also emphasised the essential need and benefit of the peer-review process as a significant number of pre-review papers have not made it through to &lsquo;publication&rsquo; as issues were identified during the peer-review process.</span></p> <p style="margin-top: 0cm; text-align: justify;"><span style="font-family: 'pt serif',serif; color: #222222;">as editor-in-chief it makes me proud and thankful that <em>veterinary evidence </em>has a strong but agile peer-review process and i would like to thank all of our editors and reviewers for their continued support and their diligence in meeting demanding timelines during these challenging times allowing&nbsp;<em><span style="font-family: 'pt serif',serif;">veterinary evidence</span></em> to publish more content than ever before. without your highly valued knowledge, expertise and insights <em><span style="font-family: 'pt serif',serif;">veterinary evidence</span></em><span class="apple-converted-space">&nbsp;</span>would not be growing into the key knowledge source that it is today.</span></p> <p style="margin-top: 0cm; text-align: justify;"><span style="font-family: 'pt serif',serif; color: #222222;">the<span class="apple-converted-space">&nbsp;</span><em><span style="font-family: 'pt serif',serif;">veterinary evidence</span></em><span class="apple-converted-space">&nbsp;</span>editorial board meeting was held for the first time digitally on 7 december with the largest number of editorial board members able to attend. members from across the globe were able to take part in wide and varied discussions around the development of the journal, resulting in important strategic initiatives and some key action points to pursue. the availability of the board to attend digitally will facilitate more frequent meetings allowing the journal to be more inclusive, and responsive to the changing landscape, as well as providing a digital recording of the event available for those board members unable to attend.</span></p> <p style="margin-top: 0cm; text-align: justify;"><span style="font-family: 'pt serif',serif; color: #222222;">key areas discussed included development of the format of picos and further refining the process for approving them, strategies to encourage engagement and submissions from veterinary nurses, and the development of policies to encourage diversity and inclusion within the board and contributors to the journal, as well as ways to increase the reach of the journal. having only been editor-in-chief since september, i have been very impressed by how active and dedicated our reviewers and board members are and how dynamic and forward-looking <em>veterinary evidence </em>is as it matures into a key contributor to veterinary literature. none of this would be possible without your support for which i am very grateful.</span></p> <p>adewole adekola</p> <p>jane alexander</p> <p>fergus allerton</p> <p>isabel amores-fuster</p> <p>davina anderson</p> <p>debbie archer</p> <p>sarah baillie</p> <p>elizabeth baines</p> <p>kayleigh barker</p> <p>simon bate</p> <p>kieran borgeat</p> <p>jackie brearley</p> <p>jenny brown</p> <p>louise buckley</p> <p>valentina busin</p> <p>charles caraguel</p> <p>james carmalt</p> <p>tim charlesworth</p> <p>jacqueline cole</p> <p>eithne comerford</p> <p>francesca compostella</p> <p>rachel conwell</p> <p>matthieu cousty</p> <p>janet daly</p> <p>sean david langton</p> <p>janny de grauw</p> <p>luisa de risio</p> <p>michael de cozar</p> <p>laura dixon</p> <p>dr elizabeth mcinnes</p> <p>jacklyn ellis</p> <p>debbie emmerson</p> <p>virginia fajt</p> <p>erik fausak</p> <p>dr fiona margaret lovatt</p> <p>myra forster-van hijfte</p> <p>sam franklin</p> <p>david g thomas</p> <p>jennifer garcia</p> <p>barbara glanemann</p> <p>merran govendir</p> <p>dai grove-white</p> <p>matt gurney</p> <p>kelly hall</p> <p>martin hawes</p> <p>alastair hayton</p> <p>guy hinnigan</p> <p>john hird</p> <p>soon hon cheong</p> <p>jodie hughes</p> <p>karen humm</p> <p>jo ireland</p> <p>william john mcluskie mcfadzean</p> <p>stephen jones</p> <p>nicolette joosting</p> <p>alastair kay</p> <p>latifa khenissi</p> <p>christopher leighton norkus</p> <p>zofia lisowski</p> <p>kate loomes</p> <p>gwendoline louise covey-crump</p> <p>panayiotis loukopoulos</p> <p>cassie lux</p> <p>sohier m syame</p> <p>tim mair</p> <p>clare margaret knottenbelt</p> <p>michelle mcarthur</p> <p>anna meredith</p> <p>tristan merlin</p> <p>duncan michael barnes</p> <p>andy morris</p> <p>john munday</p> <p>malcolm ness</p> <p>constance neville white</p> <p>margaret nolan</p> <p>conor o'halloran</p> <p>kazuya oikawa</p> <p>joanne oultram</p> <p>james oxley</p> <p>catherine oxtoby</p> <p>nick parkinson</p> <p>james patrick crilly</p> <p>sebastian patrick arlt</p> <p>catrina pennington</p> <p>roberta perego</p> <p>robert pettitt</p> <p>kirstie pickles</p> <p>simon platt</p> <p>nina r kieves</p> <p>nicki reed</p> <p>david rendle</p> <p>jacqueline renee cole</p> <p>paul roger</p> <p>roger smith</p> <p>suzanne rogers</p> <p>silke salavati</p> <p>rebecca schofield</p> <p>michael schoonover</p> <p>gon&ccedil;alo serrano</p> <p>tom shaw</p> <p>virginia sherwin</p> <p>ellen singer</p> <p>eva spada</p> <p>bryden stanley</p> <p>mike steele</p> <p>frank steffen</p> <p>siddharth sudunagunta</p> <p>adam swallow</p> <p>elisabeth swann</p> <p>james swann</p> <p>faye swinbourne</p> <p>collette taylor</p> <p>sam taylor</p> <p>mary thompson</p> <p>chris thomson</p> <p>tom towers</p> <p>andrew van eps</p> <p>elke van der vekens</p> <p>nieky van veggel</p> <p>helene vandenberghe</p> <p>claire weeks</p> <p>richard white</p> <p>adele williams</p> <p>mikolaj wojciechowski</p> <p>maurice zandvliet</p> <hr> <br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="open access" /> full text template title | veterinary evidence skip to main content knowledge summary in rabbits with cheyletiellosis is topical selamectin or injectable ivermectin a more effective treatment? juliette mouëzy, bvmsci (hons) mrcvs 1 vsm building, university of surrey, daphne jackson rd, guildford gu2 7al * corresponding author email: jmouezy@yahoo.com vol 7, issue 4 (2022) submitted 19 aug 2021; published: 20 dec 2022; next review: 03 may 2024 doi: https://doi.org/10.18849/ve.v7i4.529 pico question in rabbits with cheyletiellosis is topical selamectin or injectable ivermectin a more effective treatment? clinical bottom line category of research treatment. number and type of study designs reviewed one paper directly answered the pico question, a retrospective clinical design study, and was critically reviewed. strength of evidence. strong. outcomes reported both topical selamectin and injectable ivermectin are safe and effective in treating cheyletiellosis. there is no significant difference in the effectiveness of both drugs in treating the infestation. conclusion in pet rabbits with cheyletiella parasitivorax infestations both topical selamectin and injectable ivermectin have been recognised to be a safe and effective treatment. there is currently insufficient evidence that one is more effective than the other and therefore veterinarians should consider their own clinical experience, client preference and use the licensed product first (in the uk, ivermectin (xeno, dechra) spot-on). however, this knowledge summary does not comment on the effectiveness of topical ivermectin in treating cheyletiellosis. if injectable ivermectin is not available, topical selamectin can be used under the cascade as an alternative treatment, as it is licensed for the same indication in dogs and cats. how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. the evidence one paper was reviewed in this knowledge summary, a retrospective clinical design study (mellgren & bergvall, 2008). two other papers were also found to be relevant to this knowledge summary as, although they do not address the pico question directly, they evidence the individual effectiveness of topical selamectin and injectable ivermectin in treating cheyletiellosis in rabbits (kim et al., 2008; and coşkunserçe et al., 2012). they are discussed in the appraisal section. these studies found both injectable invermectin and spot-on selamectin to be effective in treating the infestation.   weaknesses in the evidence were based around the lack of more comparative studies between the effectiveness of topical selamectin and injectable ivermectin in treating cheyletiellosis and a short follow-up period. overall, the strength of the evidence found was strong. summary of the evidence mellgren & bergvall (2008) population: across two practices (gästrike animal clinic, sandviken, sweden and animal clinic roslagstull, stockholm, sweden), medical records from 282 rabbits were reviewed. of these, 53 rabbits fulfilling prerequisites for selection were included in the study. sample size: 53 rabbits. intervention details: prerequisites for selection were: clinical signs compatible with cheyletiella infestation; diagnosis confirmation of cheyletiella mites through light microscopy examination of skin scrapings, material from flea combing or transparent tape preparations under 4 or 10 × 100 magnification; rabbits were treated with ivermectin or selamectin; a follow-up had to be possible with the owner via telephone or through a revisit at the clinic. the following information was collected from the two veterinary settings: age; sex; weight; clinical signs; diagnosis verification; treatment protocol (substance, dose, route of administration and interval); number of rabbits in the household; other treatments; evidence of concurrent diseases. the rabbits were divided into three treatment groups. for all groups, where rabbits were from multi-rabbit households, all in-contact rabbits were treated. group 1: ivermectin injections (ivomec®vet. injectable, 10 mg/ml, merial sas, lyon). 11 rabbits (females n = 3; males n = 8), all treated at the gästrike animal clinic, with a mean age of 4.4 years (range 9 months to 7 years) and bodyweights ranging from 1.4–4.6 kg. 9/11 were from single-rabbit households. the rabbits were treated with ivermectin injections subcutaneously (sc) at two (n = 5) or three (n = 6) occasions. the mean dose was 0.253 mg/kg(range 0.200–0.476 mg/kg) and the mean injection interval was 11 days (range 9–21 days). group 2: combination of injections and oral administration of ivermectin (ivomec®vet. injectable, 10 mg/ml, merial sas, lyon). 27 rabbits (females n = 4; intact males n = 20; castrated males n = 3), all treated at the animal clinic roslagstull, with mean age of 4 years (range 6 months to 9.5 years) and bodyweights from 1.6–6.5 kg. 24/27 lived in single rabbit households, and the rest in households with two or more rabbits. treatment consisted of three to six ivermectin administrations at 10 day intervals: the initial subcutaneous (mean dose of 1.044 mg/kg, range 0.618–2.185 mg/kg) were followed by two oral administrations of ivermectin by the owner, using the injectable formula (mean dose of 1.324 mg/kg, range 0.616–2.732 mg/kg). 23/27 rabbits were re-examined 30 days (range 28–35 days, one after 48 days) after the first visit. based on clinical signs, 2/27 were given no additional treatments, 21/27 had a second injection, (14/27 of which had two additional oral ivermectin treatments repeated, with the same doses and original intervals) after being considered to still have clinical signs (8/27) or to be mite positive after microscopic examination (4/27). group 3: topical selamectin (stronghold®/revolution, 60 mg/ml, pfizer inc., new york). 15 rabbits (females n = 5; intact males n = 8; castrated males n = 2), one treated at the gästrike animal clinic and 14 at the animal clinic roslagstull; with a mean age of 2.2 years (range 3 months to 7 years) and bodyweights ranging from 1–7.4 kg. 2/15 rabbits belonged to multi-rabbit households. treatment consisted of administration of selamectin spot on topically at one to three occasions. the mean dose of selamectin used was 12.5 mg/kg (range 6.2–20.0 mg/kg). treatment results were graded as in remission (free from clinical signs at re-examinations during the whole follow-up period), relapse (being free from clinical signs more than 3.5 months after treatment but showing signs again during the follow-up time) or treatment failure (cases that never cleared from clinical signs during the first 3.5 months or were recorded with relapse during this time) at the time of follow-up. adverse reactions of treatment were assessed by clinical examination during revisit and by questioning the owner. statistical analysis was made by using χ2 test. study design: retrospective clinical design study. outcome studied: determine the effectiveness of three different protocols using selamectin (stronghold®/revolution, 60 mg/ml, pfizer inc., new york) and ivermectin (ivomec®vet. injectable, 10 mg/ml, merial sas, lyon) in treating cheyletiellosis in rabbits. main findings (relevant to pico question): rabbits in remission were 9/11 (81,8%), 14/27 (51.9%) and 12/15 (80%) in groups 1, 2 and 3, respectively. one rabbit from group 1 did experience pain on injection. from group 1, one was classed as treatment failure and one was recorded as relapse. from group 2, five rabbits were graded as treatment failures, still showing clinical signs after treatment with three to six ivermectin doses, and seven were classed as relapses. from group 3, only one rabbit was recorded as a treatment failure and two relapsed. when comparing all treatment groups with each other no significant differences were found (p = 0.09, n = 53). rabbits with concurrent disease or that were overweight were seen in both treatment failure and remission groups, making concurrent health conditions not the main determinant of treatment effectiveness. results of this retrospective study suggest that both injectable ivermectin and topical selamectin are effective and safe for clearance of clinical signs of cheyletiellosis in rabbits. in the group including an oral administration of ivermectin (group 2) the treatment was shown to be less effective in comparison to groups 1 (ivermectin injections) and 3 (selamectin spot-on), although not statistically significant. limitations: bias of uncontrolled events and factors such as treated rabbits being asymptomatic carriers of cheyletiella mites as treatment response was in some cases assessed just by clinical cure and not parasitical cure. owner bias and the effect that poor compliance (difficulty to medicate the rabbit at home) or drug storage (e.g. ultraviolet (uv) protection) has on the cure rate of group 2. the environment not being a controlled factor of the study also affects sources of contamination / re-contamination. short follow-up time, not allowing for further visits to further validate the results of this study. decision to categorise a rabbit as ‘in remission’ after only a phone call or a clinical examination and not systematic parasitology. lack of information regarding the mean treatment time-span for rabbits enrolled in group 3.   appraisal, application and reflection although only one article was found to directly answer the pico question (mellgren & bergvall, 2008), two other articles were also found to be relevant to this knowledge summary (kim et al., 2008; and coşkunserçe et al., 2012), as they allowed the comparison to be drawn regarding the effectiveness of either selamectin or ivermectin in infested rabbits. whilst the heterogeneous nature of the study designs (one being a prospective case report and the other a clinical design study), rabbit populations and recorded data precludes direct comparison of their results with each other; these articles present clear evidence for the benefit of using either topical selamectin and injectable ivermectin to treat cheyletiellosis in rabbits. mellgren & bergvall’s (2008) retrospective case study, in addition to being the most relevant article available to treat our pico question, brings strong evidence in support of the efficacy of both drugs in treating cheyletiellosis in rabbits by comparing the effect of three different treatment programmes on a sample base from across two practices. the effectiveness of both topical selamectin (stronghold®/revolution, 60 mg/ml, pfizer inc., new york) and injectable ivermectin (ivomec®vet. injectable, 10 mg/ml, merial sas, lyon) was confirmed, whilst doubts about the success rate of oral ivermectin in treating cheyletiellosis were raised. despite variable treatment success rates between groups, this was not found to be statistically significant. the short length of follow-up time, and variables of the study (environment, client bias) were its biggest limitations. the variability of thoroughness of the post-treatment assessment also raised some risks of re-infection through shedding of mites by ‘in remission’ rabbits, re-infecting themselves, causing a relapse. a replication of this study with a larger cohort, more control over external parameters, a longer follow-up period with clinical examinations and strict microscopic examinations, would allow for a more thorough interpretation of the comparative effectiveness of both drugs. the prospective clinical design study led by kim et al., (2008) evaluated the effectiveness of a single application of spot-on selamectin (revolution®, pfizer; kalamazoo, mi, usa) in treating cheyletiellosis across a cohort of 23 pet rabbits. signs of improvement were evaluated at 3 and 5 weeks post-treatment through clinical and microscopic examination of epidermal debris for mites and eggs. complete cure was obtained after 5 weeks post-treatment for the whole group and no relapse was noted 12 weeks post-treatment, suggesting the effectiveness of a single spot-on application to treat the infestation. although successful, the lack of statistical analysis and control over external factors were the main limitations of the study. however, if the study was to be repeated with a large cohort size and addressed some of its limitations it would be a great advocate for the use via the cascade of spot-on selamectin. with no side effects resulting from its application it would be a more client and pet friendly (as no injection is required) alternative to injectable ivermectin when treating cheyletiellosis. finally, in the case study led by coşkunserçe et al. (2012), a single rabbit was treated for c.parasitivorax with subcuntaneous (sc) ivermectin (iverkol, etkin) injection to assess the effectiveness of high dose (1.2 mg/kg ) treatment in treating cheyletiellosis. the rabbit was then examined every 10 days for clinical sign improvements and every 7 days for skin scrapes to assess the presence of live mites. after day 14, no clinical signs nor microscopic signs of infestation were noted. however, as positive as the outcome of this case report is, and it describes the effectiveness of high doses of ivermectin in treating cheyletiellosis, it has many limitations: only one animal enrolled, descriptive approach but no statistical analysis of the relevance of the results, and the bias of interpretation as no grading system was used to assess the improvement of clinical signs. this study is relevant, as it demonstrates the effectiveness of ivermectin (iverkol, etkin) injections in the treatment of cheyletiellosis, however, it would need to address certain limitations if it was to be replicated to give more weight to its findings. despite numerous limitations within each study, evidence supports that both injectable ivermectin and topical selamectin are efficacious in treating cheyletiellosis in rabbits. effectiveness of avermectins in controlling rabbit mange has been reported in previous studies for moxidectin, selamectin, doramectin, and ivermectin (niaz & shoaib, 2015). altogether the effectiveness of the treatment, low rate of re-infestation and improvement of clinical signs, indicate that the use of both drugs can be warranted in treating cheyletiellosis. both drugs have their individual benefits, topical selamectin being client friendly and non-painful as it is delivered as a spot on (farmaki et al., 2009) and injectable ivermectin having proven efficacy and relying less on client compliance (mellgren & bergvall, 2008). currently, injectable ivermectin is not licensed for use in rabbits and therefore, unless prescriptible under the cascade, topical selamectin should be used for the treatment of cheyletiellosis in rabbits (robinson & brennan, 2016). although it has been seven years since their publication, there is no further evidence on this topic. however, with the risk of development of resistance, ivermectin should be used judiciously in treatment of rabbit mange (coşkunserçe et al., 2012). additional well-designed (prospective, controlled, randomised) studies comparing the effectiveness of topical selamectin and injectable ivermectin in larger groups are needed to further evaluate the benefit of both drugs. further research into the pharmacodynamics and bioavailability of each drug in rabbits post-treatment would also inform comparative results, assuming the literature is available, in helping a clinician choose between topical selamectin or injectable ivermectin (under the cascade). methodology search strategy databases searched and dates covered: cab abstracts on ovid platform 1973 surrey open search, university of surrey, 1990–2020 pubmed accessed via the ncbi website (1990-2020, filtered for veterinary science) science direct, elsevier, 1990–2020 search strategy: cab abstracts: “rabbit” and “treatment” and “cheyletiellosis” “rabbit” and “treatment” and “mange mites” (“comparative treatment” or “treatment efficacy”) and (“ivermectin” and “selamectin” or “avermectins”) and (‘’cheyletiella parasitivorax’’ or ‘’cheyletiellosis’’ or ‘’cheyletiella infection’’ or ‘’mites’’) and “rabbit” “comparative treatment” and (“ivermectin” and “selamectin”) and “mange mites” and “rabbit” surrey open search: “rabbit” and “treatment” and “cheyletiellosis” “rabbit” and “treatment” and “mange mites” “comparative treatment” and (“ivermectin” and “selamectin”) and “cheyletiellosis” and “rabbit” “comparative treatment” and (“ivermectin” and “selamectin”) and “mange mites” and “rabbit” pubmed: “rabbit” and “treatment” and “cheyletiellosis” “rabbit” and “treatment” and “mange mites” “comparative treatment” and (“ivermectin” and “selamectin”) and “cheyletiellosis” and “rabbit” “comparative treatment” and (“ivermectin” and “selamectin”) and “mange mites” and “rabbit” science direct: “rabbit” and “treatment” and “cheyletiellosis” “rabbit” and “treatment” and “mange mites” “comparative treatment” and (“ivermectin” and “selamectin”) and “cheyletiellosis” and “rabbit” “comparative treatment” and (“ivermectin” and “selamectin”) and “mange mites” and “rabbit” dates searches performed: 03 may 2022   exclusion / inclusion criteria exclusion: papers that do not answer the pico question. papers published prior to 1990. papers studying the use of ivermectin or selamectin in animals other than rabbits. papers that do not focus on treatment of cheyletiellosis but on identification; parasitology and other factors of the disease. papers that discuss the use of other drugs in the treatment of cheyletiellosis. inclusion: relevant papers, including papers comparing the effectiveness of selamectin and ivermectin in the treatment of cheyletiellosis in rabbits, with reproducible methods, a detailed approach and measurable results.   search outcome database number of results excluded – that do not answer the pico question excluded – study compared the use of other drugs excluded – study did not compare selamectin / ivermectin in rabbits excluded – study not discussing the treatment of cheyletiellosis total relevant papers cab abstracts 39 15 8 14 1 1 surrey open search 129 45 22 50 11 1 pubmed 123 112 5 0 5 1 science direct 1759 482 415 416 445 1 total relevant papers when duplicates removed 1   orcid juliette mouëzy: https://orcid.org/0000-0002-5838-9384 conflict of interest the author declares no conflicts of interest. references coşkunserçe, g., akdeşir, e., kaya, g. & coşkun, ş. (2012). severe sarcoptic mange and cheyletiellosis in a new zealand rabbit and its treatment with high dosage of ivermectin. veteriner fakültesi dergisi, uludağ üniversitesi. [online]. 31(2), 63–66. available at: https://acikerisim.uludag.edu.tr/handle/11452/14268 [accessed 18 aug 2021]. farmaki, r., koutinas, a. f., kasabalis, d., papazahariadou, m. g. & day, m. j. (2009). efficacy of a selamectin spot-on formulation in rabbits with sarcoptic mange. veterinary record. 164(14), 431–439. doi: https://doi.org/10.1136/vr.164.14.431 kim, s., lee, j., jun, h., song, k., park, b. & kim, d. (2008). efficacy of selamectin in the treatment of cheyletiellosis in pet rabbits. veterinary dermatology. 19(1), 26–27. doi: https://doi.org/10.1111/j.1365-3164.2007.00629.x niaz, k. & shoaib, m. (2015). comparative study of ivermectin and cypermethrin against sarcoptes scabiei in rabbit. international journal of innovative research and development. 4(5).  robinson n. & brennan, m. (2016). selamectin versus ivermectin for cheyletiellosis in pet rabbits. veterinary record. 178(14), 344-345. doi: https://doi.org/10.1136/vr.i1387 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use.   veterinary evidence is an rcvs knowledge initiative. issn: 2396-9776 first floor, 10 queen street place, london ec4r 1be resources student awards staff login policies privacy policy accessing information policy cookie declaration terms of use copyright notices stay connected podcasts twitter facebook instagram linkedin back to top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443. potential therapeutic effects of gs-441524 and gc376 in cats with feline infectious peritonitis a knowledge summary by omid nekouei dvm phd 1* sophie st-hilaire dvm msc phd 1 pak chun hui student 1 karen chan student 1 isabel sumyi chan student 1 sum yuet lorraine ngan student 1 yion chan student 1 ka po chung student 1 sunguk hong student 1 hiu man chan student 1 hoi lam iris or student 1 fong yuen chan student 1 hei tung yim student 1 vanessa r. barrs bvsc phd mvetclinstud gradcerted (higher ed) fanzcvs (feline medicine) 1 1jockey club of veterinary medicine and life sciences, city university of hong kong, kowloon, hong kong *corresponding author (omid.nekouei@cityu.edu.hk) vol 7, issue 1 (2022) published: 02 feb 2022 reviewed by: danielle gunn-moore (bsc[hon] bvm&s phd manzcvs fhea frsb frcvs) and severine tasker (bvsc bsc dsam phd dipecvim-ca fhea frcvs) next review date: 29 oct 2023 doi: 10.18849/ve.v7i1.522 pico question in cats with feline infectious peritonitis (fip), does treatment with the nucleoside analogue gs-441524 or the protease inhibitor gc376, compared to supportive measures alone, lead to longer survival times?   clinical bottom line category of research question treatment the number and type of study designs reviewed five studies, including four uncontrolled interventional studies and one case-series were critically reviewed strength of evidence moderate outcomes reported the reviewed studies collectively provide moderate evidence in support of the application of gs-441524 or gc376 to extend the survival time of cats suffering from feline infectious peritonitis conclusion while these antiviral drugs are considered the most likely options for fip treatment, more robust evidence should be obtained through well-designed randomised controlled trials to verify the observed positive effects in treating various forms of the disease and the potential long-term side effects. however, the ethical dilemmas of conducting double blinded placebo-controlled trials, which by necessity include untreated cats with an invariably fatal disease are recognised   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a 14 month old male domestic short-haired cat is presented to you with progressive signs of lethargy, inappetence, jaundice, fluctuating fever, and distended abdomen. your physical examination and complete blood work point to the possibility of feline infectious peritonitis (fip). abdominal effusion sample is a non-septic exudate with high protein and low cellularity. a molecular diagnostic test (reverse transcription quantative polymerase chain reaction [rt-qpcr]) detects high levels of feline coronavirus in the effusion sample and immunocytochemistry of the effusion confirms the diagnosis. a colleague suggests using gs-441524 or gc376 to treat the infected cat to increase his quality of life. however, you are not sure about the clinical efficacy and safety of these antiviral drugs due to the limited evidence available. the evidence following the eligibility criteria, five studies were deemed relevant to the pico question, including a case-series (dickinson et al., 2020) and four interventional studies (kim et al., 2016; murphy et al., 2018; pedersen et al., 2018; and pedersen et al., 2019). the case-series was limited to only four cases with neurological fip treated with different regimens of gs-441524, providing weak evidence for the treatment efficacy due to the nature of the study. although all of the four experimental studies showed a range of positive clinical effects from the treatment with either gs-441524 (murphy et al., 2018; and pedersen et al., 2019) or gc376 (kim et al., 2016; and pedersen et al., 2018), none of them included an independent control group. therefore, all four studies were prone to different types of bias. although there were similarities among the treatments in these studies, they were not directly comparable due to differences in the clinical presentation of cases and the details of interventions. it has been shown that nearly all cats with clinical fip die within a few weeks to a few months of diagnosis with supportive measures alone. overall, our assessment provides moderate support to these treatments to increase the survival times of affected cats. summary of the evidence dickinson et al. (2020) population: four cats, 7–18 months old, with naturally occurring neurological and ocular feline infectious peritonitis (fip). sample size: four cats. intervention details: fip diagnosis was presumed in the cats based on the combination of patient signalment and clinical findings as well as supportive laboratory findings including hyperglobulinameia, low albumin/globulin ratios, feline coronavirus antibody titres and response to the anti-viral treatment. all cats were treated with 5 mg/kg gs-441524, subcutaneously (sc), once daily as follows: two cats were treated for 14 weeks (cases 1 and 2). case 3 was first treated for 15 weeks. within 36 hours after cessation of the initial treatment, clinical signs recurred; therefore, the cat went under the second round of treatment for 12 weeks. case 4 with severe signs was treated for a total of 19 weeks in three courses: 1) initial 4 weeks with 5 mg/kg (along with prednisolone acetate 1% and dorzolamide 2% eye drops for the first 3 weeks); 2) with an increased dosage of 8 mg/kg for 10 more weeks; 3) with an increased dosage of 10 mg/kg for 5 additional weeks. study design: case report (case-series). outcome studied: resolution of clinical signs (through physical, behavioural neurological, and ophthalmic examinations). in case 4, normalisation of magnetic resonance imaging (mri) and cerebrospinal fluid (csf) findings and resolution of cranial and caudal ocular segment disease with ocular imaging. number of days the cases lived off the treatment. main findings (relevant to pico question): three cats (cases 1, 2, and 4) had long-term resolution of the clinical signs and remained normal until the publication of this study (at least 1 year). a dosage of 5 mg/kg, sc, once daily for 12–14 weeks was sufficient to treat the two less severe cases (cases 1 and 2). for case 3, limited efficacy associated with the 5 mg/kg dose was observed and repeated treatments at the same dosage only improved the clinical signs. injections of gs-441524 were associated with localised skin reactions and discomfort. once the treatment was stopped, there was a rapid clinical regression. this cat was euthanised. for case 4, increased dosage of the treatment was associated with improvements in the clinical and mri signs, biochemical abnormalities of csf, and weight gain. treating neurological fip may require a higher dosage of gs-441524 than those for non-neurological fip. limitations: case-series (being at the bottom of the pyramid of evidence). small sample size. the disease course and intensity was different among the cases. treatment course varied among the cases. the study was limited only to neurological fip cases. kim et al. (2016) population: eight laboratory-bred specific-pathogen-free (spf) cats (8–10 months old). sample size: eight cats. intervention details: two independent experiments were conducted: in the first experiment, four cats were intraperitoneally (ip) inoculated with a cat-passaged serotype i fipv. following infection, they developed lymphopenia and clinical signs, including inapparent or mild ascites, 14–20 days post in the second experiment, another four cats were infected in the exact same manner, but their ascites was allowed to progress to more profound, classical abdominal effusions resembling cats with naturally occurring feline infectious peritonitis (fip). fip diagnosis was made based on the develpment of supportive signs and laboratory abnormalities within 2–3 weeks of experimental inoculation, including high fever, weight loss, jaundice and absolute fever. ascites was also presented in 6/8 cats. both groups were treated with gc376 at 5–10 mg/kg, twice daily, subcutaneously, when they developed absolute lymphopenia and typical clinical signs. cats were treated for 14–20 days, except for two cats that were euthanised after 4 and 7 days following the antiviral treatment. study design: experimental study (uncontrolled). outcome studied: rectal. body weight. lymphocyte count over. viral load in the macrophages from ascites (in two cats). main findings (relevant to pico question): treatment with gc376 led to the reversal of the disease progression when initiated at the advanced clinical stages of fip in six cats (four from the first and two from the second experiment). 2/8 cats were euthanised due to the severity of their clinical signs. the six recovered cats remained healthy with no signs of relapse during 8 months of the follow-up period. limitations: small sample. lack of independent control group. limited generalisability due to using lab-bred cats and generating experimental infection (ip inoculation of a cat-passaged serotype i fipv) that could be different from the natural infection. murphy et al. (2018) population: 12 laboratory-bred specifc-pathogen-free (spf) cats (6–9 months old). sample size: 12 cats. intervention details: cats were intraperitoneally (ip) inoculated with the cat-passaged serotype i fipv. feline infectious peritonitis (fip) diagnosis was made based on the development of supportive signs and laboratory abnormalities within 2–3 weeks of experimental inoculation, including fever, inappetence, lethargy, weight loss, ascites, hyperbilirubinaemia, and absolute lymphopenia. 10/12 cats demonstrated clinical signs of wet fip within 10–18. two cats that did not develop disease signs served as controls (only) for   normal blood lymphocyte counts and rectal. infected cats with clear clinical signs of fip were divided into two groups of five, a & b, and treated with gs-441524, once daily, for 2 weeks, with 5 mg/kg and 2 mg/kg doses, respectively. cats with recurrent disease signs were treated with the same regimen for 2 additional. there were no ‘untreated’ control groups due to ethical reasons (published data on the fatal outcome of similar experiments). the post-treatment observation period was 8 months. study design: experimental study (uncontrolled). outcome studied: rectal temperature. blood lymphocyte counts. appetite. bilirubin levels. presence of ascites. main findings (relevant to pico question): 2 weeks of gs-441524 treatment at a dosage of 2 or 5 mg/kg subcutaneously q24h rapidly reversed the clinical signs and prevented fip-associated mortality in the study cats. 2/10 treated cats had recurrences of disease at 4 and 6 weeks post treatment. a second 2 week course of gs-441524 treatment resulted in rapid resolution of disease all 10 treated cats remained normal for, at least, the 8 months of follow-up. limitations: small sample. lack of independent control. limited generalisability due to using lab-bred cats and generating experimental infection (intraperitoneal inoculation of a cat-passaged serotype i fipv) that could be different from the natural infection. conflict of interest: three of the authors are employees of the manufacturer of the drug and hold stock interests in the company. pedersen et al. (2018) population: 20 client-owned cats, 3.3–82 months old, presented with various forms of naturally occurring feline infectious peritonitis (fip) to a clinic (at university of california, davis, usa). sample size: 20 cats. intervention details: fip diagnosis was presumed in the subjects upon entry based on signalment, clinical history, examination of prior laboratory test results, physical examination, and repeating basic blood and effusion analyses. the presence of fipv was further confirmed by quantitative reverse transcription polymerase chain reaction (qrt-pcr) either from abdominal or thoracic effusions taken at the time of admission (or at necropsy). gc376 was administered subcutaneously at 15 mg/kg q12h, initially for 2 weeks. the courses of treatment were progressively extended as long as the cats remained responsive to gc376. cats were discharged to their owners when a positive response to treatment was noted (usually within 5 days), and the owners continued the injections following appropriate instructions from veterinarians. the eventual duration and dosage of the treatment was variable among the subjects. study design: clinical trial (uncontrolled). outcome studied: remission of clinical signs (e.g., body temperature, appetite, the presence of neurological signs). weight gain. abdominal effusion and blood serum chemistry. the occurrence of relapse. main findings (relevant to pico question): 19/20 cats showed progressive improvement in health during the first 4 weeks of treatment. however, 13/20 cats ultimately succumbed due to the disease recurrence. failure to achieve sustained remission (or prevent relapse) was associated with either a high incidence of neurological disease or recurrence of abdominal lesions. attempt to treat neurological signs by increasing drug dose and treatment duration slowed the progression but did not reverse the signs. the other seven cats experienced long-term remission and were categorised as potential treatment successes (at least in 12 weeks of follow-up). sustained remissions were more likely to occur in cats <18 weeks of age, and less likely in cats >18 weeks of age presenting with dry, dry-to-wet, or ocular disease. the main adverse effects of treatment included transient stinging upon injection (with dermal reaction) and retarded juvenile dentition development. limitations: no independent control group (due to ethical concerns). inconsistent duration of treatment for some studied cats. injections of the drug were partially conducted by the cat owners. cats with neurological signs were not included in the study. pedersen et al. (2019) population: 31 client-owned cats, 3.4–73 months old, presented with naturally occurring feline infectious peritonitis (fip) to a clinic (at university of california, davis). sample size: 31 cats. intervention details: fip diagnosis was presumed in the subjects upon entry based on signalment, clinical history, examination of prior laboratory test results, physical examination, and repeating blood and effusion analyses. thoracic or abdominal effusions from wet fip cases were confirmed positive for feline coronavirus by quantitative reverse transcription polymerase chain reaction (qrt-pcr). cats with signs of non-effusive fip were further tested by abdominal and thoracic ultrasonography for primary lesions such as low-volume effusions, organomegaly and lymphadenopathy. gs-441524 was administered at 2 mg/kg, subcutaneously, q24h for at least 12 weeks. the initial treatment was extended for one or more weeks in cats that still had abnormal serum protein values. the dosage was increased during later stages of the trial from 2–4 mg/kg in cases with extended treatment or disease relapse. study design: clinical trial (uncontrolled). outcome studied: remission of clinical signs (e.g., body temperature, appetite, the presence of neurological signs). weight gain. resolution of abdominal effusion and blood serum chemistry abnormalities. the occurrence of relapse. main findings (relevant to pico question): 4/31 cats died or euthanised within the first 2–5 days of treatment due to severe disease and other complications and another cat was euthanised after 26 days due to no treatment 26/31 cats completed the planned course of treatment (12 weeks or longer). from these 26, only eight suffered relapses over the follow-up period and were retreated with the original or higher dosage (4 mg/kg) for a second or third round of treatment. among the eight cats, only one with neurological signs failed to respond to the second round of treatment and was euthanised. overall, 25/26 cats achieved sustained remission of fip (i.e., long-term survivors > 9 months). limitations: no independent control group (due to ethical concerns). inconsistent courses of treatment for eight study cats. injections of the drug were partially conducted by the cat owners. cats with obvious neurological and ocular fip were not included in the study (limited generalisability). appraisal, application and reflection although gs-441524 (nucleoside analogue) and gc376 (protease inhibitor) are the most recommended antiviral drugs for treating and increasing the longevity of cats with feline infectious peritonitis (fip) they are not commercially available (kennedy, 2020). this knowledge summary was prepared to address a critical question posed by many small animal practitioners regarding the efficacy of these drugs in a clinical setting. following the specified eligibility criteria, five studies were found relevant to our pico question, including a case-series (dickinson et al., 2020) and four interventional studies (kim et al., 2016; murphy et al., 2018; pedersen et al., 2018; and pedersen et al., 2019). these studies provided different levels of support to the efficacy of gs-441524 or gc376 in resolving the clinical signs and extending the survival time of cats with fip, especially when the treatment was administered in an earlier stage of the disease and/or continued for an extended period. three studies investigated the application of gs-441524 (murphy et al., 2018; pedersen et al., 2019; and dickinson et al., 2020;), and two studies involved gc376 (kim et al., 2016; and pedersen et al., 2018). these studies generally showed the safety and positive effects of gc376 or gs-441524 as evidenced by rapid remission of clinical signs and survival times extending to the duration of study in most cases. importantly, several limitations were notable in the design and conduct of these studies. there were a variety of fip forms and stages of infection among the study cats. in the clinical studies of cats with naturally occurring disease (pedersen et al., 2018; and pedersen et al., 2019), cats had different levels of disease progression and associated complications. as a result, the course of treatment and protocols were not uniform among the studies. in addition, the duration of treatment and drug doses were not uniform. some cats, such as those that relapsed following the original treatment regimen, received extended periods of treatment and/or a higher drug dose. cats that developed neurological signs of fip, before or after the initial treatment, were either treated for extended periods or euthanised. limitations associated with the experimental model of infection (intraperitoneal inoculation of fipv as carried out by kim et al., 2016; and murphy et al., 2018) include that it could be substantially different from spontaneously occurring natural disease, which typically occurs after faecal-oral exposure of young cats to feline coronavirus. in naturally infected cats, fip only develops in a minority of cases, subsequent to virus mutations that occur within the host and favour macrophage tropism and systemic spread. the experimental infection causes wet fip in nearly all subjects and natural extraneous factors cannot affect the progression and presentation of the disease, as well as responses to the treatment (pedersen et al., 2018). furthermore, naturally occurring fip is mostly subclinical for several weeks or months prior to the detection of apparent signs, whereas experimental signs often appear within 2–4 weeks and progress rapidly (pedersen et al., 2018). the most critical issue with the design of all four interventional studies was the lack of an independent control group (e.g., placebo-based). all four experiments adopted a before-after approach and assumed the disease would have continuously progressed and eventually led to the death of infected cats if the interventions of interest had not been administered. as in many interventional studies, this assumption might not be consistent with reality, and many confounding factors related to animals and their environment may influence the course of the disease and the potential outcomes of treatment. pedersen et al. (2018 and 2019), who studied client-owned cats, explain that they did not include separate control groups because of ethical considerations relating to the suggested efficacy of these drugs in previous in vitro studies. in addition, it has been shown that nearly all cats with clinical fip will eventually die within a few weeks to a few months of diagnosis with supportive measures alone (izes et al., 2020; and kennedy, 2020). while valid, it is sadly true that none of these explanations can lend extra support to the presented level of evidence generated by these studies. a limitation of the two laboratory-based experiments (kim et al., 2016; and murphy et al., 2018) was the small number of cats enrolled in the studies, which could not represent the broad spectrum of fip presentations and background variables of affected cats in natural circumstances. there were no explanations regarding the chosen sample size in these studies. as a result of the small sample size and variability in the treatments, no analytical statistics were attempted. the recommended regimen for gs-441524 was 4 mg/kg, subcutaneously (sc), once daily, for at least 12 weeks, excluding neurological forms of fip (pedersen et al., 2019). as for neurological fip, adequate evidence was not available to support the higher dosage and duration of treatment (compared to non-neurological cases) suggested by dickinson et al. (2020) in their small case report. the two gc376-based trials also demonstrated the safety and efficacy of the drug in reversing the clinical signs and extending survival times of the majority of fip subjects (excluding the neurological cases) using a maximum of 15 mg/kg, twice daily, sc for at least 12 weeks (pedersen et al., 2018). the collective evidence suggests that the potential side-effects of these treatments are mainly limited to transient pain upon injection (with dermal reaction), localised hair loss and/or ulceration of the injection site due to repeated injections. however, retarded juvenile dentition development was reported in four kittens (3–5 months old) associated with long-term treatment with gc376 (pedersen et al., 2018).  in conclusion, although all of the reviewed studies suggest that the administration of gc376 or gs-441524 can extend the survival times of cats with fip, even though relapses and adverse outcomes were reported, the presented evidence is assessed to have moderate strength due to the outlined limitations. well-designed randomised controlled trials are still required to increase the level of evidence in favor of using these antiviral drugs for clinical cases in the future. however, the ethical dilemmas of conducting double blinded placebo-controlled trials, which by necessity include untreated cats with an invariably fatal disease are recognised. methodology section search strategy databases searched and dates covered: cab abstracts on ebsco host: from 1973 to week 43, 2021 pubmed via ncbi: from 1910 to week 43, 2021 search strategy: cab abstracts: ("feline infectious peritonitis") and ((nucleoside analog*) or (gs-441524) or (protease inhibitor*) or (gc376))   pubmed: ("feline infectious peritonitis") and ((nucleoside analog*) or (gs-441524) or (protease inhibitor*) or (gc376)) dates searches performed: 29 oct 2021 exclusion / inclusion criteria eligibility criteria were defined based on the relevance of studies to the pico question in a clinical setting, where adequate details on the treatment protocols were provided to enable reproducibility. exclusion: unrelated to pico in vitro studies studies on non-feline species single case reports inclusion: studies related to pico in english in vivo studies peer-reviewed original articles presented adequate details on the intervention included more than one cat search outcome database number of results excluded – in vitro studies excluded – studies on non-feline species excluded – intervention details excluded – unrelated to pico question excluded – single case report total relevant papers cab abstracts 17 2 1 3 5 1 5 pubmed 37 9 2 8 12 1 5 total relevant papers when duplicates removed 5 conflict of interest the author declares no conflicts of interest. references dickinson, p. j., bannasch, m., thomasy, s. m., murthy, v. d., vernau, k. m., liepnieks, m., montgomery, e., knickelbein, k. e., murphy, b. & pedersen, n. c. (2020). antiviral treatment using the adenosine nucleoside analogue gs-441524 in cats with clinically diagnosed neurological feline infectious peritonitis. journal of veterinary internal medicine. 34(4), 1587–1593. doi: https://doi.org/10.1111/jvim.15780 izes, a. m., yu j., norris, j. m. & govendir, m. (2020). current status on treatment options for feline infectious peritonitis and sars-cov-2 positive cats. veterinary quarterly. 40(1), 322–330. doi: https://doi.org/10.1080/01652176.2020.1845917 kennedy, m. a. (2020). feline infectious peritonitis: update on pathogenesis, diagnostics, and treatment. veterinary clinics of north america: small animal practice. 50(5), 1001–1011. doi: https://doi.org/10.1016/j.cvsm.2020.05.002 kim, y., liu, h., galasiti kankanamalage, a. c., weerasekara, s., hua, d. h., groutas, w. c., chang, k-o. & pedersen, n. c. (2016). reversal of the progression of fatal coronavirus infection in cats by a broad-spectrum coronavirus protease inhibitor. plos pathogens. 12(5), e1005531. doi: https://doi.org/10.1371/journal.ppat.1005531 murphy, b. g., perron, m., murakami, e., bauer, k., park, y., eckstrand, c., liepnieks, m. & pedersen, n. c. (2018). the nucleoside analog gs-441524 strongly inhibits feline infectious peritonitis (fip) virus in tissue culture and experimental cat infection studies. veterinary microbiology. 219, 226–233. doi: https://doi.org/10.1016/j.vetmic.2018.04.026 pedersen, n. c., kim, y., liu, h., galasiti kankanamalage, a. c., eckstrand, c., groutas, w. c., bannasch, m., meadows, j. m., & chang, k-o. (2018). efficacy of a 3c-like protease inhibitor in treating various forms of acquired feline infectious peritonitis. journal of feline medicine and surgery. 20(4), 378–392. doi: https://doi.org/10.1177%2f1098612x17729626 pedersen, n. c., perron, m., bannasch, m., montgomery, e., murakami, e., liepnieks, m. & liu, h. (2019). efficacy and safety of the nucleoside analog gs-441524 for treatment of cats with naturally occurring feline infectious peritonitis. journal of feline medicine and surgery. 21(4), 271–281. doi: https://doi.org/10.1177%2f1098612x19825701 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. evaluation of accelerometer inter-device variability and collar placement in dogs anastasia m. olsen dvm1* richard b. evans phd2 felix m. duerr dvm, ms, diplomate acvs-sa, diplomate ecvs, diplomate acvsmr1 1department of clinical sciences, veterinary teaching hospital, colorado state university, fort collins, co 80525 2rcvs knowledge, belgravia house, 62-64 horseferry road, london, sw1p 2af *corresponding author (amolsen@purdue.edu) vol 1, issue 2 (2016) published: 05 may 2016 reviewed by: wanda gordon-evans (dvm, phd, dacvs dacvsmr) doi: 10.18849/ve.v1i2.40 section index:    abstract | introduction | methods | results | discussion | footnotes | conflict of interest | references | supplementary files abstract objective: to compare accelerometer inter-device variability and evaluate the effect of canine collar tightness on activity counts. evidentiary value: this is a prospective study of six dogs each wearing actical accelerometers over 24 hours with variable placement to evaluate accelerometer inter-device variability and collar tightness. methods: six skeletally mature medium to large breed client-owned dogs were enrolled in the study. twelve identical accelerometer devices were used, with the same two devices used for each dog. all accelerometers were placed on the ventral cervical region. a total of four placement patterns (p1: two accelerometers on the same collar; p2: two separate collars with same tightness with one accelerometer on each collar; p3 & p4: one collar loose/one collar tight and one accelerometer on each collar) were evaluated. pearson’s correlation, paired t-tests, and percent of variation between total activity counts for each placement period were calculated. results: for p1-p4, pearson’s correlation was 0.92, 0.95, 0.93, and 0.86 (p<0.0001 for all comparisons). for p1-p4, t-ratio was -20.59 (p<0.0001), 9.78 (p<0.0001), -8.95 (p<0.0001), and -2.15 (p<0.0313), respectively. when evaluating inter-device variability, the percent differences between total activity counts of device pairs ranged from 2.5 to 56.8%. conclusion: while the correlations between devices for all placements were high, the high inter-device variability shows that further investigation is necessary. from this study, the results suggest that changing devices throughout a study should be avoided. we recommend that attachment of the accelerometers to the collar, including collar tightness, should be kept consistent until further studies are available. application: when accelerometer data are used for objective outcomes, accelerometer inter-device variability and collar tightness should be taken into account. introduction accelerometers have been studied for the objective measurement of activity in animals (brown et al., 2010; dow et al., 2009; hansen et al., 2007; moreau et al., 2009; preston et al., 2012; yam et al., 2011). previous validation studies have focused on the evaluation of overall functionality of accelerometers as well as device placement on the animal’s body (brown et al., 2010; moreau et al., 2009; preston et al., 2012). for example, accelerometer placement on the ventral portion of the cervical region in dogs has been suggested to be the most convenient and well tolerated while also providing reliable results (brown et al., 2010; dow et al., 2009; hansen et al., 2007; yashari et al. 2015). in humans, translation equations (paul et al., 2007; straker et al., 2012) have been designed to compare data from different models of accelerometers. in the veterinary literature, multiple authors have identified some lack of correlation between currently accepted outcome measures such as validated owner questionnaires, ground reaction forces, and accelerometry (jones et al., 2014; malek et al., 2012; rialland et al. 2012; walton et al., 2013; wernham et al., 2011). while it has been suggested that accelerometers are measuring a different outcome that may not be related to established outcomes (rialland et al., 2012), weak correlations may also be caused by variability in data collection. specifically, inter-device variability and collar tightness may affect activity counts. if significant inter-device variability were present, using different accelerometers (regardless of whether the devices are the same model) throughout a study period may influence the collected data. similarly, if collar tightness is not controlled during a study, a loosely placed collar may be associated with greater activity counts as the collar may be moving more. to the authors’ knowledge, neither collar tightness nor whether the same accelerometer was used throughout the study period has been described in previous studies using accelerometry. these factors have not been investigated as possible sources of variability. as such, the purpose of this study was: (1) to compare the inter-device variability of a commonly used accelerometer and (2) to evaluate the effect of collar tightness on activity counts. we hypothesized that there would be low inter-device variability and that a loose collar would result in greater activity counts compared to a tight collar. methods dogs – the study protocol was approved by the institutional animal care and use committee (iacuc) at colorado state university. six medium-large breed dogs were enrolled in the study and owner consent was obtained for each dog. to be eligible for inclusion, dogs must have been skeletally mature and used to the placement of cervical collars. in addition, all dogs must have been able to ambulate unassisted in their home environment. study protocol – all dogs remained in their home environment throughout the study period and the level of exercise performed was at the discretion of the owner. a daily activity log was recorded by the owner for each dog enrolled. in total, 12 acticala devices were utilized, and activity in each dog was recorded by the same two actical accelerometers for each placement pattern. the actical epoch length was set to 15 seconds, which allowed for a total of 240 data points collected per hour. data was recorded for a minimum of 24 hours per placement for each dog. all accelerometers were placed ventrally on the same size and brand dog collarb for all placement patterns. the devices were attached by sliding the collar through the metal loop of the accelerometer to ensure a secure fit. a total of four placement patterns (p1-p4) were evaluated over the course of the study. all dogs underwent four different data recording sessions with the activity monitors placed (one session for each placement). all dogs progressed through each placement pattern in the same order, starting with p1. for p1, both accelerometers were placed on one collar (see figure 4) with a tight fit (defined as a comfortable form fit to the dog’s neck). for p2, two identical collars were placed with the same tightness and one device was placed per collar in identical fashion. for both p3 and p4, the cranial collar was placed loosely (defined as increasing the collar width by four buckle holes [see figure 5] as compared to the tight fit) and the caudal collar was placed tightly (using the same tightness as for p1 and p2). for p3, one monitor was placed on the cranial collar and one on the caudal collar. for p4, the monitors were switched to the opposite collar (i.e. the monitor on the cranial collar was switched to the caudal collar). the holes in the collars were labeled to ensure placement in the desired tight versus loose placement (see figure 5). activity counts – to further evaluate inter-device variability, the percentage difference between total activity counts for each placement period was calculated for each device pair (1-[device 1/device 2]*100). regardless of device placement on the collar, the same device was labeled as device 1 and device 2 for each dog. for p2, device 1 was defined as the device placed on the cranial collar. for p3, device 1 was the device that was placed on the cranial (loose) collar. for p4, device 1 was the device that was placed on the caudal (tight) collar. to evaluate inter-device differences for each 15 second epoch, an assessment of which device recorded a greater reading was calculated. individual activity counts for each epoch were subtracted (total activity from device 1 – total activity from device 2) and the number of positive (i.e. device 1 recorded a larger activity count than device 2) and negative (i.e. device 2 recorded a larger activity count than device 1) ‘subtracted activity counts’ was then divided by the total number of counts during a placement period. all epochs where both devices recorded zero activity were excluded from this calculation. statistical analysis – two analyses were used to measure the agreement between the devices for each placement using commercially available softwarec. pearson’s correlation measured the linear relationship (with visual inspections of the scatterplots confirming the linearity), and paired t-tests assessed any shift of the data between devices by a constant (i.e., translation). statistical significance was set at p≤0.05. results pearson’s correlation and paired t-tests for p1-p4, pearson’s correlation for activity monitor counts for each monitor was 0.92, 0.95, 0.93, and 0.86, respectively. pearson’s correlation results were statistically significant (p<0.0001). scatterplot matrix activity count data are represented in figure 1. for p1-p4, t-ratio was -20.59 (p<0.0001), 9.78 (p<0.0001), -8.95 (p<0.0001), and -2.15 (p<0.0313), respectively. figure 1. scatterplot matrix of activity count data for p1-p4. the x-axis is activity count for device 1 and the y-axis is activity count for device 2. each point on the graph is the activity level for one placement at one epoch for all six dogs. the graphs were visually inspected for linearity. activity counts when evaluating inter-device differences, the percentage difference between total activity counts of device pairs ranged from 2.5% to 56.8% (mean 28.3%, 14.3%, 14.6%, and 13.1% for p1-p4, respectively) for all placements with the largest difference during p1 and the smallest during p3 (see figures 2 and 3 for graphical depiction of these results). figure 2. graphical depiction of the percentage difference between total activity counts for each placement period for each device pair. percentage difference was calculated using the formula: 1-[total activity device 1/total activity device 2]*100. therefore, negative values indicate a greater activity count of device 1. for example, pair 1 device 1 had a 15% greater total activity count during p2 but a 7.8% lower total activity count during p3. p1 is depicted in blue, p2 in red, p3 in green, and p4 in purple. figure 3. graphical depiction of the percentages of positive values when activity counts of both devices were subtracted for each epoch for p1-p4. for this calculation, each individual activity count for each epoch was subtracted (total activity device 1 – total activity device 2) and the number of positive ‘subtracted activity counts’ was then divided by the total number of counts during a placement period. as such, a number above 50% indicates a larger recording of device 1 compared to device 2. for example, during p2 (for pair 1), device 1 showed a greater individual activity count 20.2% of the time but only 4.9% of the time during p3. p1 is depicted in blue, p2 in red, p3 in green, and p4 in purple. discussion we identified good correlations between devices; however there also appears to be a large difference between activity counts measured by the devices. this is not necessarily surprising since a high correlation does not require that devices measure the same exact number of activity counts. however, this inter-device variability does not appear to be consistent. when evaluating patterns of activity counts we did not identify that one device consistently overor underestimates activity counts. furthermore, we did not identify a clear pattern when evaluating the different placements and collar tightness. when comparing collar tightness, it was expected that a loose device would show higher recordings. as such, the number of positive values for ‘subtracted activity counts’ should fall above and below baseline for p3 and p4. however, regardless of which placement may serve as the more accurate ‘baseline’ for comparison of collar tightness, this was not observed consistently either. the reason for our findings may be that collar tightness does not affect activity counts or that other factors may have a greater influence on activity counts. since we did not use the same device pairs on multiple dogs, it is not possible to evaluate whether these findings may be associated with the study subjects (individual dogs) or the actual devices. figure 4. demonstration of actical accelerometer placement. for p1, both actical devices were placed side by side on the same collar with a tight fit. there are several activity monitoring devices currently available for use in veterinary patients. one such device is the actical activity monitor, which is used to measure total activity counts over a period of time. the actical accelerometer weighs 16 grams, can be attached to a dog collar, and operates using a lithium coin cell battery. the actical device uses an accelerometer, which integrates the amplitude and frequency of motion and produces an electrical current that varies in magnitude. the device has a tri-axial range (vertical, horizontal, and diagonal) and the plane is selected based on which has the highest amplitude and frequency of motion (mitter, 2008). an increased intensity of motion produces an increase in voltage. this information is reported in activity counts over a period of time. the actical devices are calibrated at a factory prior to purchase to ensure accuracy, however it is unknown whether this calibration may lose accuracy over time. further studies evaluating the age of the device in relation to activity counts over time should be pursued. the actical devices in this study ranged in age from three months to 1 year, which may contribute to variable data. in addition, a calibration test may be required throughout the life of the accelerometer to ensure accuracy in data collection. figure 5. demonstration of actical accelerometer placement and determination of collar tightness. for p2, p3, and p4, one actical accelerometer is placed per collar. for p2, both collars were placed with the same tightness. the buckle holes are numbered such that the collar can be loosened by four holes for p3 and p4, based on the buckle hole number used for tight fit for each dog. for example, if a dog had a tight fit of buckle hole 16, the loose fit was 20. although previous studies have reported on the validity and use of accelerometers in dogs, consistent device and collar placement have not been reported. for this reason, it is unknown how our results may impact interpretation of previous results. furthermore, while consistent device and collar placement were employed throughout the study herein, the data was collected on dogs in their normal home environment which includes additional factors such as dog to dog variability in activity, environment, and the types of activities performed in a 24 hour period. as such, it would be ideal to test the accelerometers in a consistent setting such as a ‘robotic dog’ to allow for controlled movements in a repeatable fashion and reliably test inter-device variability, while also replicating similar movements to that of a living dog to ensure applicability of the results. while we were unable to confirm our hypothesis, the results from this study should not be interpreted to suggest that collar tightness does not affect activity counts. rather, our results show that accelerometry can be variable and is likely affected by many factors that are currently not accounted for. while the correlation between devices for all placements was high, the inter-device variability shows that further investigation into the reasons for these findings is necessary. it has previously been shown that dogs with osteoarthritis treated with carprofen showed a 20% increase in activity counts (brown et al., 2010). given our findings that inter-device variability may be as high as 57%, controlling for any variables that may affect activity data is indicated. the results from our study suggest that changing devices throughout a study should be avoided. furthermore, until further studies are available, we suggest that attachment of the accelerometers to the collar (including collar tightness) should be kept consistent. footnotes actical, respironics mini mitter division, bend, or. 3/4” collar strap, sportdog, knoxville, tn. jmp software, version 11.2.0, sas institute, cary nc. conflict of interest acknowledgments: none. funding: partial funding for this study was provided by the eldred foundation. competing interests: there are no conflicts of interest to report. references brown, d.c. boston r.c., farrar j.t. (2010) use of an activity monitor to detect response to treatment in dogs with osteoarthritis. journal of the american veterinary medical association, 237 (1) pp. 66-70 http://dx.doi.org/10.2460/javma.237.1.66 dow, c. et al. (2009) evaluation of optimal sampling interval for activity monitoring in companion dogs. american journal of veterinary research, 70 (4) pp. 444-448 http://dx.doi.org/10.2460/ajvr.70.4.444 hansen, b.d. et al. (2007) evaluation of an accelerometer for at-home monitoring of spontaneous activity in dogs. american journal of veterinary research, 68 (5) pp. 468-475 http://dx.doi.org/10.2460/ajvr.68.5.468 jones, s. et al. (2014) use of accelerometers to measure stress levels in shelter dogs. journal of applied animal welfare science, 17 (1) pp. 18-28 http://dx.doi.org/10.1080/10888705.2014.856241 malek, s. et al. (2012) effect of analgesic therapy on clinical outcome measures in a randomized controlled trial using client-owned dogs with hip osteoarthritis. bmc veterinary research, 8 (1) pp. 185 http://dx.doi.org/10.1186/1746-6148-8-185 mini mitter, (2008) actical instruction manual version 2.12. pp. 1-6. moreau, m. et al. (2009) use of a tri-axial accelerometer for automated recording and classification of goats’ grazing behaviour. applied animal behaviour science, 119 (3-4) pp. 158-170 http://dx.doi.org/10.1016/j.applanim.2009.04.008 paul, d.r. et al. (2007) comparison of two different physical activity monitors. bmc medical research methodology, 7 (1) pp. 26 http://dx.doi.org/10.1186/1471-2288-7-26 preston, t. baltzer, w. and trost, s. (2012) accelerometer validity and placement for detection of changes in physical activity in dogs under controlled conditions on a treadmill. research in veterinary science, 93 (1) pp. 412-416 http://dx.doi.org/10.1016/j.rvsc.2011.08.005 rialland, p. et al. (2012) clinical validity of outcome pain measures in naturally occurring canine osteoarthritis. bmc veterinary research, 8 (1) pp. 162 http://dx.doi.org/10.1186/1746-6148-8-162 straker, l. and campbell, a. (2012) translation equations to compare actigraph gt3x and actical accelerometers activity counts. bmc medical research methodology, 12 (1) pp. 54 http://dx.doi.org/10.1186/1471-2288-12-54 walton, m.b. et al. (2013) evaluation of construct and criterion validity for the 'liverpool osteoarthritis in dogs' (load) clinical metrology instrument and comparison to two other instruments. plos one, 8 (3) pp. e58125 http://dx.doi.org/10.1371/journal.pone.0058125 wernham, b. et al. (2011) dose reduction of meloxicam in dogs with osteoarthritis‐associated pain and impaired mobility. journal of veterinary internal medicine, 25 (6) pp. 1298-1305 http://dx.doi.org/10.1111/j.1939-1676.2011.00825.x yam, p.s. et al. (2011) validity, practical utility and reliability of actigraph accelerometry for the measurement of habitual physical activity in dogs. journal of small animal practice, 52 (2) pp. 86-91 http://dx.doi.org/10.1111/j.1748-5827.2010.01025.x yashari, j.m. duncan, c.g. and duerr, f.m. (2015) evaluation of a novel canine activity monitor for at-home physical activity analysis. bmc veterinary research, 11 (1) pp. 46 http://dx.doi.org/10.1186/s12917-015-0457-y supplementary files, images & tables all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form,and will in return retain certain rights as detailed on the form. in dogs with osteoarthritis, is intra-articular allogenic mesenchymal stem cell therapy more effective than placebo effect? a knowledge summary by megan moloney bvmsci 1* 1vsm building, university of surrey, daphne jackson rd, guildford gu2 7al *corresponding author (moloneymegan@hotmail.co.uk) vol 7, issue 3 (2022) published: 10 aug 2022 reviewed by: andy morris (bsc[hons] bvsc certavp[gsas] mrcvs) and lesca monica sofyan (baavbs[honsii] mvs dvm) next review date: 06 jan 2024 doi: 10.18849/ve.v7i3.473 pico question in dogs diagnosed with osteoarthritis in the hip, elbow, stifle or shoulder joint, is treatment with intra-articular allogenic mesenchymal stem cell therapy, in comparison with a placebo effect, more effective at reducing lameness and pain?   clinical bottom line category of research question treatment the number and type of study designs reviewed all three papers were randomised controlled trials strength of evidence weak outcomes reported intra-articular allogenic stem cell therapy is effective at reducing pain and lameness in dogs with osteoarthritis when compared to a placebo effect. two studies indicated a statistically significant improvement in both client and veterinary outcome measurements. client outcome measurements utilised included: the canine brief pain inventory; a measure of any changes in pain and lameness based on owners perception, and the client-specific outcome measure; and an evaluation of the impact of osteoarthritis on three client selected activities and how this changed with treatment. veterinary outcome measurements included veterinary pain score based on manipulation of the limb, veterinary assessment of clinical outcomes and veterinary pre and post lameness examinations, all of which were subjective measures. the final study identified a statistically significant improvement in both pain and lameness based on owner assessments utilising the canine brief pain inventory and the hudson visual analogue scale for lameness scoring. no statistically significant improvement was identified when considering subjective and objective veterinary measurements including force plate gait analysis and veterinary orthopaedic examination conclusion there is moderate evidence from owner observation and veterinary assessment to suggest that intra-articular allogenic (adipose and umbilical derived) stem cell therapy has some efficacy for reducing pain and lameness compared to a placebo effect. however, it must be noted that these studies did not compare the use of intra-articular allogenic stem cells with conventional treatments such as intra-articular corticosteroid injections. therefore, comparison trials are required. whilst all three papers showed significant improvements in the subjective measurements, objective data outcomes and assessment by board certified veterinary surgeons failed to find a significant improvement in peak vertebral force or lameness with the use of intra-articular stem cell therapy in comparison to a placebo effect. furthermore, whilst no significant adverse reactions to intra-articular stem cell therapy were recorded, information regarding the safety for multiple dosing is lacking and ambiguity remains as to the most appropriate lineage and quantity of allogenic stem cells for the best clinical effect   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. the evidence two of the three papers (harman et al., 2016; and maki et al., 2020) investigated the use of allogenic adipose derived mesenchymal stem cells whilst the last paper (kim et al., 2019) investigated the use of allogenic umbilical derived mesenchymal stem cells. summary of the evidence harman et al. (2016) population: 93 client owned dogs from nine different clinical study sites across the us. 52 female and 41 male dogs varying from large to small breeds. inclusion criteria: age: 9 months + (average age was 8.1 years). weight: 2.5 kg + (average weight was 29.63 kg). signs and diagnosis: physical exam and radiographic conformation of osteoarthritis (oa) in one or two of the following joints: hips, elbows, stifles or shoulders. owner confirmed pain / lameness for at least 3 months prior and a subjective veterinary assessed pain on manipulation score of ≥ 3 based on a scoring system of 1–5 (where 1 indicated no response to palpation and 5 indicated the dog did not allow manipulation/palpation) for each arthritic joint. exclusion criteria: participants could not be pregnant, lactating or in oestrus. no known malignant or benign interfering neoplasia. sample size: 93 dogs. intervention details: adipose derived mesenchymal stem cells (mscs) from a healthy donor dog were manufactured in accordance with standard operating procedures. each study site was expected to enrol 10 participants, five for group a and five for group b. overall 47 dogs were enrolled into group a and 46 into group b. physical examination and radiographs were used to confirm the presence of oa. participants were separated into two groups according to a blinded randomisation chart – group a treated with stem cells and group b treated with placebo. dogs were sedated and given an intra-articular injection of either 0.7 ml of saline or 0.7 ml of stem cell solution that contained a target dose of 12 x 106 viable adipose stem cells. owners were instructed to restrict exercise post injection. dogs were assessed at day 0 and day 60. study design: prospective, double-blinded, placebo controlled, randomised trial. outcome studied: subjective: client-specific outcome measurement (csom). pain on manipulation – veterinary subjective pain on manipulation score based on patient response to manipulation of the limb. veterinary assessment of clinical outcomes – veterinary global score. owner assessment of clinical outcomes – owner global score. safety – monitoring for adverse events. main findings (relevant to pico question): owner csom showed a statistically significant improvement in the treated versus the placebo group (p = 0.02). veterinary pain score on manipulation showed a statistically significant improvement in the treated versus the placebo group (p = 0.01). veterinary global outcome score showed a statistically significant improvement in the treated versus the placebo group (p = 0.0085). owner global outcome showed an improvement in the treated versus the placebo group however this improvement was not statistically significant. 15 adverse events were reported throughout this trial: six in the treated group and nine in the control group. in each group, two of these events were deemed to be serious however all were assessed to be not related nor caused by the administered cell product. in total 74 of the original 93 enrolled dogs completed the study, 38 in group a (the stem cell treated group) and 36 in group b (the placebo group). limitations: uncontrolled environmental conditions – dogs were taken home with discharge instructions however owner compliance is uncontrollable. loss of 19 participants to follow-up due to non-compliance with the protocol (11) and low enrollment at sites (eight). difference in severity of oa between dogs – dogs were allowed to have one or two joints affected. subjective outcomes. measure of pain on manipulation of the limb by a veterinarian was subjective. quantity of viable adipose stem cells unmeasured – potential for discrepancies between the amount of viable stem cells injected into each patient. conflict of interest – not a truly independent study. the lead author is an employee and shareholder of the funding company, vetstem biopharma. kim et al. (2019) population: 51 client owned dogs (28 male and 23 female) at the university of florida small animal hospital. inclusion criteria: age: 12 months to 11 years. weight: 11.5 kg to 60 kg. signs and diagnosis; visible unilateral forelimb lameness for more than 6 months attributable to elbow osteoarthritis (oa). osteoarthritic changes to the elbow confirmed on computerised tomography (ct) imaging. owner assessment of canine brief pain inventory score (cbpi) (hudson et al., 2004) greater than 2 for baseline pain severity and pain interference scores. general health; otherwise healthy. any medication must have been at a stable dose 4 weeks prior to and throughout the trial. exclusion criteria: lameness for any reason other than forelimb elbow oa. sample size: 51 dogs. intervention details: 51 dogs were randomly assigned to umbilical cord derived mesenchymal stem cell (umsc) therapy or placebo groups via the method of minimisation. stem cells were obtained and cell banks generated from canine umbilical cords. all dogs were sedated and underwent arthrocentesis to confirm the presence of osteoarthritis in the joint via cytological evaluation of the joint fluid. 28 dogs were injected with intra-articular umsc (0.5 ml containing approximately 7 x 106 cells) and 23 with intra-articular saline (0.5 ml) via the preplaced needle used for arthrocentesis. owners were advised to restrict their dog’s activity for 2–3 days post injection. all dogs were assessed at baseline, 1, 3 and 6 months post treatment using force plate gait analysis, owner assessed hudson visual analog scale (hvas) and cbpi and veterinary orthopaedic exams. study design: prospective, double-blinded, placebo-controlled randomised trial. outcome studied: objective: force plate gait analysis. subjective: owner assessed cbpi level of pain – primary outcome measure. owner assessed degree of lameness using hvas. veterinary orthopaedic exam. safety – monitoring for adverse events. main findings (relevant to pico question): no significant difference in age, body weight, proportion of dogs using non-steroidal anti-inflammatory drugs (nsaids) and symmetry index between the treatment and placebo groups. owner assessed cbpi scores – statistically significantly higher treatment success rate in the umsc treated group compared with the control group at 1 and 6 months after treatment. no significant difference (p = 0.056) observed at 3 months. mean hvas mood and sum indexed hvas scores both significantly improved following treatment in the umsc group. no significant differences were observed for the placebo group. plate vertical force (pvf) – no differences were seen in either the treatment or control group. veterinary orthopaedic exam – no differences seen in either group. seven serious adverse events occurred – five in the umsc group, and two in the placebo group. all were classified as unlikely to be related to treatment. limitations: lack of representation of the wider clinical population – the paper assessed the efficacy of umsc treatment on unilateral osteoarthritis cases. the majority of osteoarthritis cases seen in dogs are bilateral. under-powered study – the group sizes for the umsc and placebo intervention were different and the total number of subjects completing the study was below the original target set by the pre-study power analysis. subjective primary outcome variable cbpi prone to bias. bias was limited by blinding and subjecting both groups to the same confounding variables. less stringent definition of success based on cbpi – a reduction of pain interference score (pis) >2 is usually used as a measure of success whereas this study utilised a reduction of pis >1 to indicate success. uncontrolled environmental conditions – dogs were taken home with discharge instructions however owner compliance was uncontrollable. no indication as to whether the same veterinarian conducted the orthopaedic exam on the dogs at each time point. only the subjective outcomes studied in this paper improved with the umsc treatment, objective outcomes measured did not. short time period – in total the study only ran for 6 months. conflict of interest – several authors were employed by the animal cell therapies company, though it is declared that the research was conducted in the absence of commercial relationships. maki et al. (2020) population: 20 client owned dogs, 12 female and 8 male, from two private veterinary clinics in hong kong. inclusion criteria: age: 1 year + (median age 11.25 years). weight: 9 kg + (median weight 25.5 kg) and body condition score of 7/9 or less. signs and diagnosis: clinical signs of osteoarthritis (oa) for at least 1 month in one or both hip joints with radiographic evidence of arthritic changes. noticeable lameness, limited range of motion, and evident pain on palpation / manipulation at the time of evaluation. patient must have undergone at least 1 month of medical and / or physical therapy / cage rest management with little or no improvement and all treatments had to be stopped at least a week prior to start of trial. exclusion criteria: patients could have no additional significant illnesses nor have had any surgery in the affected area within the previous year. sample size: 20 dogs. intervention details: stem cells were obtained from fat tissue of a healthy 5 month old female donor dog during an ovariohysterectomy. all patients were put under general anaesthesia for treatment. 16 dogs were injected intra-articularly with mesenchymal stem cells (mscs) at different concentrations – five received 5x106 cells per joint, six received 25x106 cells per joint, and five received 50x106 cells per joint. the other four dogs were injected intra-articularly with saline. blood was taken and pain and lameness scores were recorded before treatment, at day 0 (day of treatment), day 5, day 30 and day 90 after the injection. study design: prospective, double blinded, placebo controlled, randomised control trial. outcome studied: objective: blood – anti / pro inflammatory and immunomodulatory biomarkers. subjective: lameness score – owner canine brief pain inventory (cbpi) score and veterinary pre and post assessment forms. pain score – owner cbpi. main findings (relevant to pico question): lameness scores – 6/7 (86%) of the dogs with low to moderate lameness scores showed improved lameness scores following msc administration however, only 3/4 (75%) of dogs with severe lameness scores showed improved lameness scores (p <0.05). dogs injected with msc had a statistically significant improvement of lameness within the first 30 days (p <0.05). overall compared with the placebo group, improvement in lameness with mscs was extremely statistically significant (p <0.0001). interleukin receptor antagonist protein (irap) levels – all dogs that were seen to have improvement in lameness also had increased irap levels indicating that increased irap levels could be a good indicator for lameness improvement. (no power factor was given so to be taken with caution). cbpi owner assessed pain scores – results mirrored the veterinary assessed lameness scores of the participants. all animals receiving mscs were seen to have improved pain scores. no statistical significance between age of dog and lameness response to msc treatment or sex of the dog and lameness response to msc treatment. limitations: small sample size and small placebo group containing only four participants – very underpowered study. variable group sizes. volume of stem cell injection and saline injection not stated ­– unknown whether they were the same or not. varying degrees of oa in all participants. subjective primary outcomes. injection site ambiguity – entry into the joint was not always confirmed by aspiration and was sometimes only judged on ‘surgeon feel of a slight pop’. increased chance for human error. uncontrolled environmental conditions – owner instructions for at home care were broad and not monitored. ambiguity in the numbers of enrolled dogs at each stage with attrition not clearly described. conflict of interest – the study was funded by vetcell therapeutics (vct) usa and vct asia who are both stem cell manufacturers. two dogs were lost to follow-up due to receiving other medications / treatment during the study period. appraisal, application and reflection the aim of osteoarthritis treatment is to decrease pain and increase limb function – enhancing the quality of life of the patient. the current treatment of choice for canine osteoarthritis (oa) is non-steroidal anti-inflammatory drugs (nsaids) alongside other conventional therapies including the use of polysulphated glycosaminoglycans, nutritional modifications, physical therapy and weight management (pettitt & german, 2015). although proven to be effective at combatting pain and lameness in dogs suffering with oa, owner compliance to daily administration of nsaids can be poor (harman et al., 2016). new interventions such as platelet rich plasma (prp) and mesenchymal stem cell injections are becoming increasingly popular for their reduced side effects and safety as long-term treatment (singh, 2012). there are two forms of stem cell therapy available, allogenic and autologous. most commercially available stem cell therapies for use in dogs are autologous. this knowledge summary looked into the efficacy of the use of allogenic stem cells for treatment of oa when compared to a placebo effect. the papers reviewed provided some moderate subjective evidence. no objective evidence was observed. one of the papers (kim et al., 2019) showed no improvement in lameness based on both subjective and objective veterinary measurements thus indicating that allogenic stem cell treatment alone may have a limited effect on improvement of lameness. comparisons between the use of autologous and allogenic stem cells for oa in dogs are yet to be investigated. both forms of stem cell therapy offer benefits and limitations. allogenic stem cells offer the benefit of being available ‘off the shelf’ and appear to have a relatively long duration of action (kim et al., 2019) however questions as to the safety of multiple dosages of allogenic stem cells should be considered. studies of allogenic stem cell use in animals for other disease processes have identified complications due to graft-versus-host disease (michálek et al., 2003; and wi et al., 2021). all three papers reviewed only assessed single dose interventions and the longest time period studied in any of these papers was 6 months (kim et al., 2019), meaning that long-term adverse effects and the total duration of improvement of a single intra-articular injection of stem cells is unknown. there is also consideration to be made as to the ethics of collecting allogenic stem cells. in two of the studies (kim et al., 2019; and maki et al., 2020) the stem cells were collected as a by-product from donor dogs that were already undergoing surgery for other procedures, however in the final study (harman et al., 2016) it is not stated as to whether the donor dog was undergoing a general anaesthetic for any reason other than stem cell collection. collection of allogenic stem cells carries all the risks of a general anaesthetic and does not benefit the donor in any way thus it poses a major ethical issue. autologous stem cells pose less of a risk when considering the patients’ immune system (khaddour et al., 2020) however they require harvesting from the patient themselves which poses a risk through the need for surgical collection. autologous stem cells also pose an ethical issue as their production warrants the need for at least two general anaesthetics for the patient (rvc canine stem cell treatments owners' frequently asked questions, 2021). further safety data is required for both forms of stem cell therapy to determine the risk, benefit ratio. mesenchymal stem cells can be obtained from a number of different tissues in the body (hass et al., 2011). both adipose and umbilical derived stem cells were used in these studies. one study (kim et al., 2019) suggested that umbilical derived stem cells may be better than adipose derived as they are a population of younger stem cells with a greater ability to differentiate and proliferate. as well as stem cell lineage, the number of viable stem cells in the solution injected into the osteoarthritic joints differed amongst all three papers. one paper (maki et al., 2020) compared intra-articular injection of different quantities of stem cells and did not identify any significant difference between lower and higher dosages in any of the measured outcomes. increased volumes of stem cell did appear to have an increased level of il-10 biomarker in the patients’ serum however, due to sample sizes this correlation was not significant. age, lineage and quantity of the stem cells may well impact their efficacy and therefore it may be beneficial for future studies to compare these. the sample size across all three studies was small. only one of the papers (kim et al., 2019) had done a pilot study to calculate a power analysis and even in this study the clinical trial sample size was smaller than that calculated therefore indicating a lack of power in the study. not having a large enough study group could mean that the results were not true of the wider population and statistical analysis done on the results would have been invalid (suresh & chandrashekara, 2012). all studies were blinded.  the necessity for blinding was obvious in all three studies as there was a significant placebo effect noted in each. however, the effects of the stem cells went beyond that of the placebo. the papers reviewed all used subjective primary measure outcomes which have a high potential for bias. this bias was mitigated through use of two well regarded subjective measures – canine brief pain inventory and hudson visual analog scale scores, both of which have been evaluated in multiple studies and are well accepted (hudson et al., 2004; and brown et al., 2008). force plate gait analysis used in one paper (kim et al., 2019) is an objective measure however it is very difficult to take accurately and has lots of room for error (mclaughlin, 2001). in all of the papers the animals were client owned and taken home throughout the duration of the study and therefore there was a lack of environmental control. however, this provided a perspective on how the animal coped within their usual environment. there was a potential limitation in the conflict of interest in two of the papers (harman et al., 2016; and kim et al., 2019). both papers had input from employees of major stem cell research companies. this limitation was mitigated through the declaration of the remaining authors expressing that the research was conducted in the absence of any commercial or financial relationship however further funding is required for true independent studies to take place. overall, there is weak evidence to suggest that allogenic stem cell use in dogs with osteoarthritis is more efficacious than a placebo effect. however, consideration must also be taken when providing allogenic stem cell use as a treatment to owners such as donor, recipient, dosing, cell therapy formulation, route of administration and veterinary surgeon experience (maki et al., 2020). whilst these studies have suggested that allogenic stem cell use is effective as treatment for canine oa when compared to a placebo effect, it would be more useful to compare and recognise its uses to the current known treatments for canine oa, such as nsaids or intra-articular corticosteroids. methodology section search strategy databases searched and dates covered: cab abstracts via cab direct (2007–2021) scopus via scopus.com (2005–2021) pubmed via the ncbi interface (2005–2022) search strategy: cab abstracts: ((“stem cell*”) and (oa or osteoarthritis) and (shoulder or stifle or hip or elbow) and (dog or canine) and (placebo or control)) ((“stem cell*” or mesenchymal or msc or stem) and (osteoarthritis or oa or djd or “degenerative joint disease”) and (shoulder or stifle or hip or elbow) and (canine or dog) and (placebo or control)) scopus: ((“stem cell*”) and (oa or osteoarthritis) and (shoulder or stifle or hip or elbow) and (dog or canine) and (placebo or control)) ((“stem cell*” or mesenchymal or msc or stem) and (osteoarthritis or oa or djd or “degenerative joint disease”) and (shoulder or stifle or hip or elbow) and (canine or dog) and (placebo or control)) pubmed: ((“stem cell*”) and (oa or osteoarthritis) and (shoulder or stifle or hip or elbow) and (dog or canine) and (placebo or control)) ((“stem cell*” or mesenchymal or msc or stem) and (osteoarthritis or oa or djd or “degenerative joint disease”) and (shoulder or stifle or hip or elbow) and (canine or dog) and (placebo or control)) dates searches performed: 06 jan 2022 exclusion / inclusion criteria exclusion: treatment group received additional therapies beyond allogenic stem cell therapy. stem cells were obtained from a different species. stem cells were not allogenic. stem cells were autologous. no placebo / control group used in the study. paper did not answer the pico. lameness levels not measured. review papers. inclusion: allogenic stem cells compared to a placebo / control group. any allogenic stem cell type. clinical signs of osteoarthritis visible for 1 month or greater. answered the pico. measured lameness levels. paper written in the english language. search outcome database number of results excluded – paper did not answer the pico excluded – study group did not compare to placebo / control excluded – did not use purely allogenic canine stem cells excluded – did not measure lameness as an outcome total relevant papers cab abstracts 26 18 4 1 0 3 scopus 33 24 2 3 1 3 pubmed 28 21 3 1 0 3 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflicts of interest. references brown, d., boston, r.c., coyne, j.c. & farrar, j.t. (2008). ability of the canine brief pain inventory to detect response to treatment in dogs with osteoarthritis. [online]. available at: https://www.caninebpi.com [accessed 6 jan 2022]. harman, r., carlson, k., gaynor, j., gustafson, s., dhupa, s., clement, k., hoelzler, m., mccarthy, t., schwartz, p. & adams, c. (2016). a prospective, randomized, masked, and placebo-controlled efficacy study of intraarticular allogeneic adipose stem cells for the treatment of osteoarthritis in dogs. frontiers in veterinary science. 3, 16. doi: https://doi.org/10.3389/fvets.2016.00081 hass, r., kasper, c., böhm, s. & jacobs, r. (2011). different populations and sources of human mesenchymal stem cells (msc): a comparison of adult and neonatal tissue-derived msc. cell communication and signalling biomed central. 9(12). doi: https://doi.org/10.1186/1478-811x-9-1 hudson, j.t., slater, m.r., taylor, l., scott, h.m. & kerwin, s.c. (2004). assessing repeatability and validity of a visual analogue scale questionnaire for use in assessing pain and lameness in dogs. american journal of veterinary research. 65(12), 1634–1643. doi: https://doi.org/10.2460/ajvr.2004.65.1634 khaddour, k., hana, c.k. & mewawalla, p. (2020). hematopoietic stem cell transplantation statpearls ncbi bookshelf. statpearls.[online]. available at: https://www.ncbi.nlm.nih.gov/books/nbk536951/ [accessed 10 jan 22]. kim, s.e., pozzi, a., yeh, j.c., lopez-velazquez, m., au yong, j.a., townsend, s., dunlap, a.e., christopher, s.a., lewis, d.d., johnson, m.d. & petrucci, k. (2019). intra-articular umbilical cord derived mesenchymal stem cell therapy for chronic elbow osteoarthritis in dogs: a double-blinded, placebo-controlled clinical trial. frontiers in veterinary science. 6(december), 1–10. doi: https://doi.org/10.3389/fvets.2019.00474 maki, c.b., spaas, j.h., camiel alice samoy, y., fahie, m., c-bcc, w., beck, a., cheuk chi wallis, c.-b., choo, j., ramos, t., tong, r., borjesson, d.l. & izadyar, f. (2020). intra-articular administration of allogeneic adipose derived mscs reduces pain and lameness in dogs with hip osteoarthritis: a double blinded, randomized, placebo controlled pilot study. frontiers in veterinary science. 1, 570. doi: https://doi.org/10.3389/fvets.2020.00570 mclaughlin, r.m. (2001). kinetic and kinematic gait analysis in dogs. the veterinary clinics of north america : small animal practice. 31(1), 193–201. doi: https://doi.org/10.1016/s0195-5616(01)50045-5 michálek, j., collins, r.h., hill, b.j., brenchley, j.m., douek, d.c. (2003). identification and monitoring of graft-versus-host specific t-cell clone in stem cell transplantation. the lancet. 361 (9364), 1183–1185. doi: https://doi.org/10.1016/s0140-6736(03)12917-0 pettitt, r.a. & german, a.j. (2015). investigation and management of canine osteoarthritis. in practice. doi: https://doi.org/10.1136/inp.h5763 (2021). rvc canine stem cell treatments owners' frequently asked questions. [online]. available at: https://www.rvc.ac.uk/small-animal-vet/specialist-referrals/advanced-techniques/stem-cell-clinic/information-for-dog-owners#panel-will-my-dog-be-treated-with-stem-cells-from-other-dogs [accessed 24 jan 2022]. singh, j.a. (2012). stem cells and other innovative intra-articular therapies for osteoarthritis: what does the future hold? bmc medicine. 44. doi: https://doi.org/10.1186/1741-7015-10-44 suresh, k., chandrashekara, s. (2012). sample size estimation and power analysis for clinical research studies. journal of human reproductive sciences. 5(1), 7-13. doi: https://doi.org/10.4103/0974-1208.97779 wi, h., lee, s., kim, y., no, j.g., lee, p., lee, b.r., oh, k.b., hur, t.y. & ock, s.a. (2021). immunosuppression-enhancing effect of the administration of allogeneic canine adipose-derived mesenchymal stem cells(ca-mscs) compared with autologous ca-mscs in vitro. journal of veterinary science.  22(5), 1–14. doi: https://doi.org/10.4142/jvs.2021.22.e63 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. does ranitidine administration improve gastrointestinal hypomotility in dogs? a knowledge summary by lara brunori dvm certavp(ecc) mrcvs 1* 1vetsnow 24/7 pet emergency hospital, 123–145 north street, glasgow, g3 7da *corresponding author (lara.brunori@gmail.com) vol 6, issue 1 (2021) published: 11 feb 2021 reviewed by: gonçalo serrano (dvm msc) and james swann (ma vetmb dacvim decvim mrcv) next review date: 14 may 2022 doi: 10.18849/ve.v6i1.357 pico question in dogs presenting with gastrointestinal (gi) hypomotility is ranitidine administration (any route) beneficial in improving gi motility?   clinical bottom line category of research question treatment the number and type of study designs reviewed one prospective controlled clinical trial and five experimental crossover studies strength of evidence weak outcomes reported the vast majority of the evidence investigating ranitidine as a prokinetic has been carried out in experimental settings both in vivo with healthy conscious and anaesthetised dogs and in vitro. under these circumstances ranitidine has shown some prokinetic properties. however, it is difficult to translate these results into reliable clinical recommendations, as the doses mentioned in these studies are often higher than the ones clinically recommended and healthy canine patients might respond differently to clinically affected ones conclusion although in experimental settings ranitidine has shown some prokinetic activities, no reliable clinical recommendations can be drawn from the appraised studies. there is a need of prospective clinical trials evaluating the administration of ranitidine to dogs presenting with gi hypomotility. until further relevant studies become available, the efficacy of ranitidine administration as a prokinetic agent in dogs with gi hypomotility remains uncertain   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are presented with a 3-year-old mixed breed female neutered dog diagnosed with postsurgical gi hypomotility on ultrasound. you wonder if the administration of ranitidine will be helpful in improving your patient’s gi motility. the evidence the evidence currently available on the use of ranitidine as a prokinetic agent pertains, for the vast majority, to experimental settings. five single centred experimental non-randomised non-blinded crossover studies (fioramonti et al., 1984; bertaccini et al., 1985; mizumoto et al., 1990; kishibayashi et al., 1994; and lidbury et al., 2012) investigated potential prokinetic properties of ranitidine both in vitro (bertaccini et al., 1985; and mizumoto et al., 1990) and/or in vivo on healthy conscious or anaesthetised dogs (fioramonti et al., 1984; bertaccini et al., 1985; mizumoto et al., 1990; kishibayashi et al., 1994; and lidbury et al., 2012). although four out of five studies (fioramonti et al., 1984; bertaccini et al., 1985; mizumoto et al., 1990; and kishibayashi et al., 1994) found some degree of gastrointestinal motility stimulation post-ranitidine administration, these results are difficult to compare and generalise due to the limited number of animals included in each study, different patient populations evaluated (conscious vs anaesthetised, starved vs non-starved), a variety of techniques employed to estimate gi motility and discordant dosing regimes or route of administration. one single centred randomised non-blinded prospective controlled clinical trial (favarato et al., 2012) investigated the effect of ranitidine on the incidence of post-anaesthetic regurgitation in dogs undergoing elective surgical procedures, however the results of this paper are hindered by a type ii error due to a too small sample size and a low incidence of regurgitation episodes in this population. summary of the evidence lidbury et al. (2012) population: privately owned healthy adult dogs sample size: eight dogs (one excluded due to self-limiting diarrhoea prior to any intervention) intervention details: measurement of gastric emptying time, small and large bowel transit time, and total transit time via wireless motility capsules (wmc) before and after administration of ranitidine at 2 mg/kg adminsistered orally (po) twice daily (bid) in dogs hosted in their home environment study design: single centred experimental non-blinded crossover study outcome studied: assess the effect of oral ranitidine (2 mg/kg bid) on gi transit times using the wmc system main findings (relevant to pico question): no statistically significant effects of oral ranitidine on gi transit times were found in this group of dogs gastric emptying median time before ranitidine 719 (622–1320) min vs after ranitidine 757 (628–1128) min (p.6149) small intestinal median transit time before ranitidine 183 (92–290) min vs after ranitidine 162 (86–215) min (p5007) large intestinal median transit time before ranitidine 1398 (644–2588) min vs after ranitidine 1227 (490–2634) min (p6215) small and large intestinal median transit time before ranitidine 1636 (746–2588) min vs after ranitidine 1227 (490–2634) min (p6215) total median gastrointestinal transit time before ranitidine 2735 (1898–3296) min vs after ranitidine 2083 (1248–3262) min (p0.2759) limitations: only healthy dogs enrolled small sample size (potential type ii error) authors cannot rule out that a higher dose of ranitidine could have caused a detectable decrease in gi transit times favarato et al. (2012) population: healthy female dogs admitted for elective ovariosalpingohysterectomy at the veterinary hospital of the universidade federal de viçosa (minas gerais, brazil) from 2007 to 2009 sample size: 90 dogs intervention details: population randomised into three groups: control group (n=30): no drugs received before and during surgical procedure, other than the ones included in the standard anaesthetic protocol* metoclopramide group (n=30): metoclopramide 1 mg/kg intravenous (iv) 5 minutes before anaesthetic induction, followed by 1 mg/kg/h continuous rate infusion (cri) immediately after anaesthetic induction and the infusion maintained throughout the general anaesthetic ranitidine group (n=30): ranitidine 2 mg/kg iv 6 hours before anaesthetic induction * anaesthetic protocol consisting of: acepromazine, propofol and isofluorane study design: single centred prospective randomised non-blinded controlled clinical trial outcome studied: determine whether administration of metoclopramide during the preand transanaesthetic periods could prevent episodes of gastroesophageal reflux determine whether administration of ranitidine during the preanaesthetic period could prevent episodes of gastroesophageal reflux main findings (relevant to pico question): overall, only 7.8% of dogs (7/90) presented with gastroesophageal reflux episodes: 13.3% (4/30) in the control group, 6.66% (2/30) in the ranitidine group and 3.33% (1/30) in the metoclopramide group. no statistically significant difference (p<0.05) was found between different treatment group. therefore, no beneficial effects could be demonstrated for the administration of 2 mg/kg iv ranitidine 6 hours preanaesthetic on the rate of gastroesophageal reflux during general anaesthesia limitations: low incidence of gastroesophageal reflux in the population leading to potential type ii error only healthy dogs enrolled kishibayashi et al. (1994) population: healthy mongrel mixed sex dogs and healthy male beagle dogs sample size: 17 anaesthetised mongrel dogs 19 conscious beagle dogs intervention details: anaesthetised dogs (n=17): rubber balloons inserted into the gastric antrum and colon respiration rate and pattern measured with glass tube inserted in trachea blood pressure measured via femoral artery catheter slow (10s) iv injections of: kw-5092 0.03 mg/kg; 0.1 mg/kg; 0.3 mg/kg; 1 mg/kg neostigmine 0.03 mg/kg; 0.1 mg/kg ranitidine 1 mg/kg; 3 mg/kg;10 mg/kg conscious dogs (n=19): 2 weeks prior to the beginning of the study ‘strain gauge force transducers’ were surgically implanted onto the seromuscular layer of the gi tract in the gastric antrum, duodenum, ileum and colon to measure circular muscle contractions slow (10s) iv injections of: kw-5092 0.03 mg/kg; 0.1 mg/kg; 0.3 mg/kg; 1 mg/kg neostigmine 0.01 mg/kg; 0.03 mg/kg; 0.1 mg/kg ranitidine 1 mg/kg; 3 mg/kg oral administration of: kw-5092 1 mg/kg; 3 mg/kg; 10 mg/kg neostigmine 1 mg/kg; 3 mg/kg ranitidine 10 mg/kg; 30 mg/kg study design: single centred experimental non-blinded non-randomised crossover study outcome studied: effects of kw-5092 (synthetic ranitidine derivative with negligible h2-receptor blocking activity) on gi motor activity in anaesthetised dogs and in conscious dogs in the digestive state, compared with those of neostigmine and ranitidine main findings (relevant to pico question): anaesthetised dogs (average results):   ranitidine at 1 mg/kg iv significantly enhanced the gastric antral motor activity (gastric antral motor index increased by 200% within 10 minutes post injection) ranitidine at 3 mg/kg significantly enhanced gastric antral and colonic motor activity (gastric antral and colonic motor index both increased by 250% within 10 minutes post injection) ranitidine at 10 mg/kg iv significantly enhanced gastric antral and colonic motor activity (gastric antral motor index increased by 400% and colonic motor index increased by 1000% within 10 minutes post injection) ranitidine at doses higher than 3 mg/kg iv decreased blood pressure, frequency and amplitude of respiration conscious dogs (average results): ranitidine at 1 mg/kg iv significantly enhanced the gastric antral motor activity (gastric antral motor index increased by 120% at 30 minutes post injection) ranitidine at 3 mg/kg iv significantly enhanced gastric antral (motor activity increased by 200% at 30 minutes post injection) and colonic motor activity (increased by 280% at 10 min post-injection). however at this dose, ranitidine also induced severe side effects like temporal suppression of gastric antral motor activity (66%), collapse (66%) and akinesia (33%) ranitidine po at 10 mg/kg and 30 mg/kg significantly enhanced the gastric antral (motor index increased by 150% and 250% respectively at 1 hour post administration) and ileal motor activities (motor index increased by 150% and 200% respectively at 1 hour post administration) without inducing behavioural side effects limitations: statistics were not discussed at all within the paper (i.e. number of animals excluded) material and methods lack details especially in terms of route of administration, dosages and respective timings high doses of ranitidine administered only healthy dogs enrolled mizumoto et al. (1990) population: in vivo part of the study conducted on healthy mixed breed adult dogs sample size: four conscious dogs five anaesthetised dogs intervention details: in vivo: extraluminal force transducers implanted in the serosal surface from the gastric body to the duodenum measurements of gastric motility index in conscious dogs receiving two 5 minutes infusions of acetylcholine (ach) at 0.05 mg/kg/min intercalated with 0.3, 1.0 and 3.0 mg/kg/h iv infusions of ranitidine measurements of gastric motility index in conscious dogs receiving slow iv boluses of ranitidine at 0.3, 1.0 and 3.0 mg/kg measurement of blood pressure in anaesthetised dogs receiving iv boluses of 0.3, 1.0 and 3.0 mg/kg ranitidine iv all measurements were repeated during saline infusion as a control in vitro: measurement of ach esterase activity at increasing concentration of ranitidine study design: single centred experimental in vivo and in vitro non-blinded non-randomised crossover study outcome studied: in vivo: effect of ranitidine infusions (0.3, 1.0 and 3.0 mg/kg/h) on ach-induced contractions in conscious dogs effect of ranitidine boluses (0.3, 1.0 and 3.0 mg/kg) on gastric motor activity in conscious dogs effect of ranitidine boluses (0.3, 1.0 and 3.0 mg/kg) on blood pressure in anaesthetised dogs in vitro: median concentration of ranitidine to achieve acetylcholinesterase inhibition main findings (relevant to pico question): in vivo: iv infusion of ranitidine at a dose of 1.0 and 3.0 mg/kg/h markedly enhanced ach-induced contractions (motor index ratio of 2.04 ±46 and 2.89 ± 0.57 respectively vs 0.77 ± 0.06 of saline control) in conscious dogs a bolus of 3mg/kg of ranitidine iv significantly increased gastric motor activity (motor index ratio of 1.87 ±27 vs 1.02 ± 0.04 of saline control) in conscious dogs a bolus of 3 mg/kg of ranitidine iv significantly decreased blood pressure (decrease of 106 ± 10/74 ± 11 vs 19 ± 10/27 ± 5 of saline control) in anesthetised dogs in vitro: inhibition of acetylcholinesterase activity was noted at a median ranitidine molar concentration of 3.5 x 10-6m limitations: only healthy dogs enrolled small sample size (potential type ii error) materials and method section is lacking details especially regarding the saline control for the in vivo part bertaccini et al. (1985) population: in vivo part of the study conducted on experimental mixed breed adult healthy dogs sample size: 30 anaesthetised dogs intervention details: in vivo (n=30 dogs): gut motility was measured by means of a surgically inserted small rubber balloon filled with water and connected with an external manometer iv boluses of ranitidine at 0.25, 0.5, 1.0 and 2.0 mg/kg followed by injections of stimulatory substances: ceruletide, acetylcholine, angiotensin and physalaemin in vitro: small strips of ileum were surgically removed and suspended in an organ bath changes in isometric tension were measured by a transducer connected with a microdynamometer stimulatory compounds and ranitidine were sequentially added to the bath study design: single centred experimental in vivo and in vitro non-blinded non-randomised crossover study outcome studied: in vivo: observe ileal motility after ranitidine injections at 0.25, 0.5. 1.0 and 2.0 mg/kg observe the effect of ranitidine on ceruletide-, acetylcholine-, angiotensinand physelaemininduced motility in vitro: observe the effects on ileal tissue preserved in an organ bath with increasing concentration of 1) ranitidine; 2) ranitidine + ceruletide; 3) acetylcholine; 4) angiotensin; and 5) physelaemin main findings (relevant to pico question): in vivo (average results): ranitidine boluses at all doses (0.5–0 mg/kg) had a slight and erratic stimulatory effect on basal motility, causing an increase of both tone and amplitude of phasic contractions ranitidine (doses not specified) consistently potentiated contractions induced by acetylcholine and angiotensin ranitidine boluses at0 mg/kg also caused a constant potentiation of contraction (more than 200%) induced by ceruletide (5 ng/kg). this effect was prevented by administration of small doses of atropine (5–10 µg/kg) in vitro (average results): ranitidine by itself starting at 10-4m was able to increase basal ileal tissue motility as well as potentiating acetylcholine induced contractions limitations: no details regarding statistical analysis within the paper only healthy dogs enrolled materials and method section is lacking details especially regarding the saline control for the in vivo part and the number of tissue strips for the in vitro part fioramonti et al. (1984) population: female mongrel dogs (12–16 kg) chronically fitted with intraparietal electrodes in the gastric antrum, duodenum and jejunum sample size: four dogs intervention details: record of physiological gi motility via chronically fitted intraparietal electrodes in the antrum, duodenum and jejunum iv injections of: ranitidine 1 mg/kg and 3 mg/kg oxmetidine 1 mg/kg and 3 mg/kg study design: single centred experimental non-blinded non-randomised crossover study outcome studied: comparison between the effects on gi motility of oxmetidine and ranitidine in dogs record of gi motility post ranitidine and oxmetidine injections via the above mentioned intraparietal electrodes main findings (relevant to pico question): in all four dogs ranitidine at both doses induced a stimulatory effect on gi motility, while oxmetidine did not limitations: small sized sample administered doses and respective timings are not clearly stated only healthy dogs enrolled appraisal, application and reflection this summary stems from the need to look for further guidance in the treatment of a frequently encountered disorder in clinical practice. dysmotility of the gastrointestinal (gi) tract, characterised by the inhibition of forward movement of ingesta, is a common cause of upper gi signs in dogs (hall, 2008). the physiological regulation of coordinated gi movements requires a complex interaction between multiple neurohumoral factors and the enteric nervous system (whitehead et al., 2016). any disruption to this finely tuned mechanism can result in oesophageal motility disturbances, delayed gastric emptying and functional ileus (whitehead et al., 2016). a number of pathologies have been associated with gi hypomotility: infectious diseases (i.e. parvovirosis and ascarid infestation), inflammation of the gi tract (i.e. gastritis, enteritis, ulcers, and post-surgical gastroparesis), neoplasia with severe infiltrative processes (i.e. alimentary lymphoma), metabolic disturbances (i.e. hypokalaemia, hypoadrenocorticism, diabetes mellitus, uraemia), drug administration (i.e. opioids, adrenergic agonists and cholinergic antagonists) and acute stress with significant sympathetic stimulation (hall, 2008). motor neurones located within the gi wall are usually excited by substances like acetylcholine, serotonin and substance p, while other signalling compounds like somatostatin, nitric oxide, catecholamines and gamma-ammino butyric acid tend to inhibit neuromuscular transmission (whitehead et al., 2016). the cornerstone of gi hypomotility treatment consists in the administration of agents promoting an excitatory response within the gi nervous system, these drugs are usually referred to as ‘prokinetics’. the veterinary literature offers few reviews suggesting the use of a number of prokinetic drugs based on their mechanism of action (hall & washabau, 1999; and whitehead et al., 2016). ranitidine is frequently mentioned in these reviews and it is often considered in practice for the treatment of dogs with gi hypomotility due to its acetylcholinesterase inhibitor effect (hall & washabau, 1999). a thorough search has been performed using both cab abstract and pubmed databases and applying multiple search word combinations. the current available literature concerning ranitidine in dogs with upper gi disturbances is mainly focused on its h2-antagonist properties and gastroprotectant activity (marks et al., 2018). the few studies centred on its role as an acetylcholinesterase inhibitor and prokinetic have mainly been carried out in experimental settings and on healthy canine patients (fioramonti et al., 1984; bertaccini et al., 1985; mizumoto et al., 1990; kishibayashi et al., 1994; and lidbury et al., 2012). two studies included in vitro experiments (bertaccini et al., 1995; and mizumoto et al., 1990) and they both proved ranitidine to have consistent anticholinesterase properties. the same papers also showed a pro-kinetic effect in vivo at clinically relevant doses.   two in vivo only studies found ranitidine administered both orally and intravenously to have stimulatory effect on gi motility (fioramonti et al., 1984; and kishibayashi et al., 1994) however the doses administered in these papers were generally higher than the one currently indicated in clinical practice. two more recent studies (favarato et al., 2012; and lidbury et al., 2012) investigating ranitidine administered at 2 mg/kg either orally or intravenously to healthy dogs who failed to show gi motility enhancement. overall, interpretation of the available evidence to draw clinical practice recommendations is significantly hindered by the fact that only healthy patients have so far been included. furthermore, the populations considered are difficult to compare as some studies evaluated conscious patients and others anaesthetised patients as well as starved animals vs non-starved animals. these are all variables that in humans have been proven to modify gi motility (luckey et al., 2003) as well as the gi tract response to prokinetic administration (smout et al., 1985). on top of this there is also a significant variability, amongst the available literature, in the techniques employed to estimate gi motility, as well as discordant dosing regimes and route of administration. in light of all the above, it is fair to conclude that ranitidine has shown effective prokinetic activity in vitro and in vivo when healthy experimental dogs have been evaluated, although often at dosages higher than the ones commonly recommended in clinical practice. its efficacy in clinical scenarios with dogs presenting for hypomotility disorders, has yet to be evaluated. further studies will be needed to try and support its rational use in canine patients with gi hypomotility. methodology section search strategy databases searched and dates covered: cab abstracts on the ovid interface – 1973 to 2020 week 18 pubmed on ncbi interface – 1920 to may 2020 search strategy: cab abstracts: (dog or dogs or canine or canines or canis).mp. or exp dogs/ or exp canis/ (vomit* or emesis or anorexi* or inappetence or hyporexia or gastri* or gastroent* or gastrointestinal disorders or enteropat*).mp. or exp vomiting/ or exp anorexia/ or exp gastroenteritis/ or exp gastritis/ (ranitidine or h2-antagonist* or h2 antagonist* or h2 blocker or histaminergic antagonist* or acetylcholinesterase inhibitor or parasympathetic agent*).mp. 1 and 2 and 3 pubmed: (dog or dogs or canine or canines) (vomit or emesis or anorexia or inappetence or hyporexia or gastritis or gastroenteritis or gastrointestinal disorders or enteropathy) (ranitidine or h2-antagonist or h2 antagonist or h2 blocker or histaminergic antagonist or acetylcholinesterase inhibitor or parasympathetic agent) 4. 1 and 2 and 3 dates searches performed: 14 may 2020 exclusion / inclusion criteria exclusion: book chapters, clinical review articles, single case reports, articles not relevant to pico, articles not available in english inclusion: articles available in english which were relevant to pico search outcome database number of results excluded – book chapters excluded – review articles excluded – single case reports excluded – not relevant to pico excluded – full article not available excluded – not available in english total relevant papers cab abstracts 57 3 2 1 48 1 1 1 pubmed 202 0 1 0 199 0 0 2 additional papers* 3 total relevant papers when duplicates removed 6 *referenced by relevant papers or suggested by reviewers conflict of interest the author declares no conflicts of interest. acknowledgement: clare boulton, head of library and knowledge services references bertaccini, g., coruzzi, g. & poli, e. (1985). ‘histamine h2 receptor antagonists may modify intestinal motility independently of their primary action on the h2 receptors’. pharmacological research communications. 17(3), 241–254. doi: https://doi.org/10.1016/0031-6989(85)90099-2 favarato, e.s., souza, m.v., costa, p.r.s., favarato, l.s.c., nehme, r.c., monteiro, b.s. & bonfá, l.p. (2012). ‘evaluation of metoclopramide and ranitidine on the prevention of gastroesophageal reflux episodes in anesthetized dogs’. research in veterinary science. 93(1), 466–467. doi: https://doi.org/10.1016/j.rvsc.2011.07.027 fioramonti, j., soldani, g., honde, c. & bueno, l. (1984). ‘effects of ranitidine and oxmetidine on gastrointestinal motility in conscious dog’. agents and actions. 15(3–4):260–263. doi: https://doi.org/10.1007/bf01972359 hall, j.a. (2008). ‘gastric motility disorders & prokinetic therapies in small animals’. proceedings acvim forum, san antonio, texas, usa, 4–7 june, 2008. veterinary proceedings. 670–672. hall, j.a. & washabau, r.j. (1999). ’diagnosis and treatment of gastric motility disorders.’ veterinary clinics of north america: small animal practice. 29(2), 377–395. doi: https://doi.org/10.1016/s0195-5616(99)50027-2 kishibayashi, n., tomaru, a., ichikawa, s., kitazawa, t. & shuto, k. (1994). ‘enhancement by kw-5092, a novel gastroprokinetic agent, of the gastrointestinal motor activity in dogs.’ japanese journal of pharmacology. 65(2), 131–142. doi: https://doi.org/10.1016/s0021-5198(19)35772-5 lidbury, j.a., suchodolski, j.s., ivanek, r. & steiner, j.m. (2012). ‘assessment of the variation associated with repeated measurement of gastrointestinal transit times and assessment of the effect of oral ranitidine on gastrointestinal transit times using a wireless motility capsule system in dogs’. veterinary medicine international. 2012:article id 938417. doi: https://doi.org/10.1155/2012/938417 luckey, a., livingston, e. & taché, y. (2003). ‘mechanisms and treatment of postoperative ileus’. arch surg. 138(2):206–14. doi: https://doi.org/10.1001/archsurg.138.2.206 marks, s.l., kook, p.h., papich, m.g., tolbert, m.k. & willard, m.d. (2018). ‘acvim consensus statement: support for rational administration of gastrointestinal protectants to dogs and cats.’ journal of veterinary internal medicine. 32(6), 1823–1840. doi: https://doi.org/10.1111/jvim.15337 mizumoto, a., fujimura, m., iwanaga, y., miyashita, n., yoshida, n., kondo, y. & itoh, z. (1990). ‘anticholinesterase activity of histamine h2-receptor antagonists in the dog; their possible role in gastric motor activity’. neurogastroenterology and motility. 2(4), 273–280. doi: https://doi.org/10.1111/j.1365-2982.1990.tb00035.x smout, a.j., bogaard, j.w., grade, a.c., ten thije, o.j., akkermans, l.m. & wittebol, p. (1985). ‘effects of cisapride, a new gastrointestinal prokinetic substance, on interdigestive and postprandial motor activity of the distal oesophagus in man’. gut. 26(3), 246–51. doi: https://doi.org/10.1136/gut.26.3.246 whitehead, k., cortes, y. & eirmann, l. (2016). ’gastrointestinal dysmotility disorders in critically ill dogs and cats’. journal of veterinary emergency and critical care. 26(2), 234–253. doi: https://doi.org/10.1111/vec.12449 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. current evidence supporting simultaneous prophylactic gastropexy in canine patients undergoing complete splenectomy a knowledge summary by olivia harris bs 1* wanda j gordon-evans dvm phd dacvs dacvsmr 1 1university of minnesota college of veterinary medicine, 1365 gortner ave, st paul, mn 55108, usa *corresponding author (olivia.harris@westvet.net) vol 6, issue 4 (2021) published: 24 dec 2021 reviewed by: zofia lisowski (phd fhea bvsc) and april l paul (dvm dacvecc) next review date: 15 jun 2021 doi: 10.18849/ve.v6i4.443 pico question in dogs that have undergone a complete splenectomy, does performing a concurrent gastropexy decrease the risk of future gastric dilatation-volvulus (gdv) development when compared to not performing a concurrent gastropexy?   clinical bottom line category of research question risk the number and type of study designs reviewed five papers were critically reviewed which included one retrospective case series, one retrospective case-control study, and three combined retrospective cohort and cross-sectional survey studies strength of evidence weak outcomes reported in dogs that have had a complete splenectomy, there is no conclusive evidence that prophylactic gastropexy decreases the risk of lifetime gdv development conclusion based on the limited information available, it is difficult to conclude if prophylactic gastropexy should be recommended routinely at the time of complete splenectomy   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. the evidence the evidence available consists of all retrospective studies. retrospective studies are low on the hierarchy of evidence due to the difficulty in avoiding sources of bias and confounding. inconsistent findings were found between the critically reviewed studies and could be due to a variety of reasons including study design, disease processes that led to complete splenectomy, inclusion and exclusion criteria, and inconsistent follow-up times, among other reasons. based on the weak level of evidence and inconsistent findings, it is difficult to make a conclusion regarding the benefit of performing concurrent gastropexy in dogs receiving splenectomy. summary of the evidence degroot et al. (2016) population: dogs that underwent exploratory laparotomy with suspected primary splenic torsion (pst) between august 1992 and may 2014 at seven referral hospitals. sample size: 102 dogs with pst. intervention details: medical records of dogs were reviewed for patient history and follow-up information. in 101 dogs a complete splenectomy was performed. the surgical technique was recorded for 93 dogs which included suture ligation (n = 36), suture ligation in combination with a ligate-divide-staple device (n = 28), suture ligation in combination with a vessel-sealing device (n = 15), or use of a vessel-sealing device alone (n = 14). in one dog the splenic pedicle was derotated and the spleen was repositioned and left in situ. study design: retrospective multi-centre case series. outcome studied: the percentage of dogs surviving to hospital discharge. factors associated with death prior to hospital discharge. the proportion of dogs undergoing splenectomy for pst that develop gdv in later life. main findings (relevant to pico question): of the 64 dogs that follow-up information was available, 49 (77%) had a concurrent gastropexy at the time of splenectomy. in the dogs that had a concurrent gastropexy (49 dogs), one dog (2%) developed gdv 3 years after surgery. in the dogs that did not have a concurrent gastropexy (15 dogs), one dog (2%) developed gdv 4 months after surgery. the percentages of dogs with and without gastropexy that developed gdv were not significantly different. the authors could not draw meaningful conclusions regarding the importance of gastropexy or the risk of gdv in dogs following splenectomy for pst. limitations: retrospective nature of this study. only cases of pst were included. uniform follow-up information was not available for all dogs. underpowered study due to small sample size. goldhammer et al. (2010) population: retrospective study #1: dogs that had undergone splenectomy were compared with records of dogs that had undergone other abdominal surgery at a referral hospital between 1999 and 2007. retrospective study #2: dogs that had presented for a non-elective gastropexy at a referral hospital between 1999 and 2007. no dogs in either the non-elective gastropexy group or the control group had a history of previous splenectomy. sample size: retrospective study #1: 37 case group dogs presenting for splenectomy compared to 43 bodyweight matched control group dogs presenting for other abdominal surgery. retrospective study #2: 33 case group dogs presenting for non-elective gastropexy due to recent or current gdv compared to 39 bodyweight matched control group dogs presenting for unrelated reasons. intervention details: retrospective study #1: medical records of dogs which had splenectomy performed at a veterinary referral hospital were reviewed. the incidence of gdv in the 12 months following splenectomy was established by follow-up survey of referring veterinary surgeons. the results were compared to a control group of dogs presenting for abdominal surgeries that did not include splenectomy. retrospective study #2: medical records of dogs which presented for non-elective gastropexy at a veterinary referral hospital were reviewed. the occurrence of previous splenectomy in dogs that presented with gdv was compared to that of a control group. study design: retrospective single-centre cohort study and cross-sectional survey. outcome studied: retrospective study #1: the prevalence of gdv in dogs with splenectomy compared to other abdominal surgeries. retrospective study #2: the prevalence of splenectomy performed in the past in dogs presenting with gdv. main findings (relevant to pico question): retrospective study #1: in the case group, 1/37 dogs (3%) developed gdv 48 hours following splenectomy. no other dogs in the case group developed gdv within the 12 month follow-up period. no dogs in the control group developed gdv within the 12 month follow-up period. there was no evidence that splenectomy was associated with an increased incidence of subsequent gdv. retrospective study #2: no association between a current episode of gdv and previous splenectomy was found. limitations: retrospective nature of this study. study included patients from only one veterinary referral hospital. follow-up time of 12 months may have falsely lowered true incidence of gdv development. retrospective questionnaire may have resulted in inaccurate data. underpowered study due to small sample size. grange et al. (2012) population: dogs that underwent splenectomy between january 2002 and february 2010 at angell animal medical center. sample size: 172 dogs that underwent splenectomy were compared to 47 sex-matched dogs that underwent enterotomy. intervention details: medical records were reviewed for patient information. follow-up information was obtained via medical records review and a written client questionnaire. study design: retrospective single-centre cohort study and cross-sectional survey. outcome studied: whether dogs undergoing splenectomy had an increased risk of gdv, especially in breeds considered to be at high risk for gdv, compared with a control group of dogs undergoing enterotomy. main findings (relevant to pico question): gdv developed after surgery in 14/172 dogs (8.1%) in the splenectomy group and in 3/47 dogs (6.4%) in the control (enterotomy) group with a median follow-up time of 65.5 and 1,577 days for medical records and owner questionnaires in the splenectomy group respectively, and 14 and 740 days for medical records and owner questionnaires in the control (enterotomy) group respectively. there was no significant difference in incidence of gdv between the splenectomy and control groups. limitations: retrospective nature of this study. study included patients from only one veterinary referral hospital. dogs in the splenectomy group were significantly older and heavier than in the control group. all dogs that underwent splenectomy for splenic torsion received a prophylactic gastropexy and were excluded from the study results. retrospective questionnaire may have resulted in inaccurate data. maki et al. (2017) population: mediumto large-breed dogs that had undergone surgery with a vessel sealing or a stapling device at ocean state veterinary specialists from 2008 to 2015. sample size: 238 dogs that underwent splenectomy and 209 dogs that underwent emergency laparotomy. dogs that had a gastropexy at any point prior to or during the study were excluded. intervention details: medical records were reviewed for patient history. case follow-up was completed by reviewing medical records and conducting either an email or telephone interview with the owner and/or the primary care veterinarian. study design: retrospective single-centre cohort study and cross-sectional survey. outcome studied: to determine the rate of occurrence of gdv following splenectomy in mediumto large-breed dogs. to define the time from surgery to occurrence of gdv in affected dogs. to determine if there was an association of age, weight, sex, or presence of a haemoabdomen at time of surgery with occurrence of gdv. main findings (relevant to pico question): 10/238 dogs (4%) in the splenectomy group and 3/209 dogs (1%) in the control group were considered to have had a gdv following surgery. there was no significant difference in incidence of gdv between the case and control groups. median time from surgery to subsequent gdv was 124 days (range 15–1,273 days) in the splenectomy group and 1029 days (range 570–1,663 days) in the control group. this difference was significant. limitations: retrospective nature of this study. dogs were excluded from the study if the spleen was not submitted for histopathology, which could have lowered incidence of gdv. dogs were excluded from the study if the primary surgical technique utilised was suture ligation, but, the authors did not note how many dogs, if any, were actually excluded from the study due to this technique. this study included dogs that died of suspected gdv but not confirmed. dogs in the splenectomy group were significantly older at the time of surgery. retrospective follow-up with owners and primary care veterinarians may have resulted in inaccurate data with median follow-up in the splenectomy group being 471 days (range 19–1,688 days) and in the control group being 1,184 days (range 214–2,776 days). sartor et al. (2013) population: dogs that underwent exploratory laparotomy or abdominal ultrasonography at either the matthew j. ryan veterinary hospital of the university of pennsylvania from august 2004 to august 2009 or the veterinary medical and surgical group in ventura, california from january 2006 to august 2009. sample size: 151 dogs treated surgically for gdv and 302 control dogs with no history of gdv. controls were matched within 3 years of age and 5 kg to case dogs and related as closely as possible in regard to sex, neuter status, and breed. intervention details: medical records were searched for dogs that underwent exploratory laparotomy or abdominal ultrasonography. study design: retrospective multi-centre case-control study. outcome studied: determine whether there is a significant association between previous splenectomy and the development of gdv. for patients without a spleen, the time elapsed between splenectomy and the development of gdv was recorded for the case animals, and the time elapsed between splenectomy and either laparotomy or abdominal ultrasonography was recorded for the control animals. main findings (relevant to pico question): 6/151 dogs (4%) in the gdv group and 3/302 dogs (1%) in the control group had a history of previous splenectomy. in the case group (dogs with gdv development), the odds of having a history of previous splenectomy was 5.3 times those of dogs without a history of previous splenectomy. time elapsed between splenectomy and gdv ranged from 1.5 to 12 months, with a median time of 2.5 months. limitations: retrospective nature of this study. aetiology of splenectomy was only discussed for dogs that eventually developed gdv. did not discuss if previous gastropexy was performed in any patients. wide confidence interval (95% ci, 1.1 to 26.8) for the odds of dogs with gdv (case group) having a previous splenectomy compared to not having a previous splenectomy. appraisal, application and reflection gastric dilatation-volvulus (gdv) is a life-threatening condition in which the stomach dilates and rotates on its mesenteric axis. while this disease process is more commonly recognised in largeto giant-breed dogs, a study performed by maki et al. (2017) revealed that gdv development is a documented post-surgical complication in some patients that have undergone a splenectomy. it has been suggested in the veterinary literature that a prophylactic gastropexy should be considered in dogs that have undergone complete splenectomy to decrease the lifetime risk of gdv development, but the basis for this recommendation has been anecdotal. while there may be a perceived benefit to performing a gastropexy in any largeor giant-breed dogs undergoing a splenectomy, the current literature does not provide a true consensus. it may be that breeds predisposed to splenic torsion are also predisposed to development of gdv instead of a causative relationship between complete splenectomy and gdv development. grange et al. (2012) discussed that a gastropexy is a relatively routine procedure that may help prevent gdv development, which is a life-threatening and quickly progressive disease, but could not find causation to perform a gastropexy in patients undergoing a previous complete splenectomy. goldhammer et al. (2010) evaluated 33 dogs presenting for a non-elective gastropexy procedure due to gdv and noted that no study patients had a history of a previous splenectomy being performed. degroot et al. (2016) also found no statistical significance between gdv development in post-splenectomy patients (1/49 dogs) compared to patients that had not undergone a previous splenectomy (1/15 dogs). hypotheses as to why there anecdotally may be an increased risk of gdv development secondary to complete splenectomy include increased laxity of gastric ligaments secondary to transection and increased intra-abdominal dead space, both of which allow for increased gastric mobility in the abdominal cavity. degroot et al. (2016), a retrospective case series, could not draw meaningful conclusions regarding the importance of prophylactic gastropexy after complete splenectomy secondary to pst as there was no significant difference in the percentage of dogs with and without gastropexy that developed gdv. goldhammer et al. (2010), grange et al. (2012), and maki et al. (2017), all of which were retrospective cohort studies with a cross-sectional survey component, drew similar conclusions to degroot et al. (2016) in that it was difficult to draw clinical conclusions based on results of their respective studies and further research was needed. sartor et al. (2013), a retrospective case-control study, found results that conflicted with the previously mentioned studies. to the author’s knowledge, this is the only study truly documenting an increased odds of previous splenectomy having been performed in gdv patients, but it is difficult to draw meaningful clinical conclusions regarding the pico question from these results as cases were compared to a general population of dogs that were presented to the veterinary hospital for a wide variety of ailments. in sartor et al. (2013), they found that the odds of gdv in dogs with a history of previous splenectomy were significantly increased compared to those of dogs without a history of previous splenectomy, but the authors did not discuss whether any cases or controls had a gastropexy procedure previously and also did not discuss the aetiology of why a complete splenectomy was performed in the patients. grange et al. (2012) made an important point that while performing a prophylactic gastropexy is a relatively routine procedure, it is crucial to remember that the procedure is not without risk. possible complications of prophylactic gastropexy, while rare, include anaesthetic complications, surgical failure with need for possible repair, changes in gastric motility, leakage of caustic stomach contents into the abdominal cavity secondary to full-thickness tissue penetration, and other complications related to increased surgery and anaesthesia time. it is essential to take into consideration individual patient factors when deciding if the benefit of an extra surgical procedure outweighs the risks. the documented complication rates for a gastropexy depends on the specific technique utilised with a recent shift towards a more minimally invasive procedure. loy son et al. (2016) evaluated complications following laparoscopic-assisted gastropexy in dogs. this study noted an intraoperative complication rate of 4-10% which included organ laceration, unsatisfactory suture location, and surgical access issues. a postoperative complication rate of 34% was found secondary to surgical site abnormalities (swelling, bruising, erythema, seroma formation, surgical site infection) with a majority of complications being minor and self-limiting. further research is needed in order to answer this pico question. more ideal study designs include prospective cohort or case-control studies with follow-up information taken over the course of each dog’s lifetime, but ethical dilemmas may preclude these studies from progressing. currently, there is no strong evidence that shows causation between complete splenectomy and gdv development, so it is difficult to draw clinical conclusions as to if a concurrent prophylactic gastropexy during and / or soon after complete splenectomy is of benefit to the general population of canine patients. methodology section search strategy databases searched and dates covered: pubmed on ncbi platform; 1984–2020 cab abstracts on ovid platform; 1973–2020 search strategy: pubmed and cab abstracts: (dog or canine) and (gdv or gastric dilatation or gastric dilatation volvulus or gastropexy or bloat) and (splenectomy or spleen) dates searches performed: 15 jun 2021 exclusion / inclusion criteria exclusion: book chapters. clinical review articles. articles not available in english. inclusion: articles available in english which were relevant to the pico and involved more than one animal. search outcome database number of results excluded – review excluded – not relevant excluded – full article not available excluded – one animal study total relevant papers pubmed 23 2 15 0 1 5 cab abstracts 36 2 29 0 3 2 total relevant papers when duplicates removed 5 conflict of interest the authors declare no conflicts of interest. references degroot, w., giuffrida, m.a., rubin, j., runge, j.j., zide, a., mayhew, p.d., culp, w.t.n., mankin, k.t., amsellem, p.m., petrukovich, b., ringwood, p.b., case, j.b. & singh, a. (2016). primary splenic torsion in dogs: 102 cases (1992–2014). journal of the american veterinary medical association. 248(6), 661–668. doi: https://doi.org/10.2460/javma.248.6.661 goldhammer, m.a., haining, h., milne, e.m., shaw, d.j. & yool, d.a. (2010). assessment of the incidence of gdv following splenectomy in dogs. journal of small animal practice. 51(1), 23–28. doi: https://doi.org/10.1111/j.1748-5827.2009.00844.x grange, a.m., clough, w. & casale, s.a. (2012). evaluation of splenectomy as a risk factor for gastric dilatation-volvulus. journal of the american veterinary medical association. 241(4), 461–466. doi: https://doi.org/10.2460/javma.241.4.461 maki, l.c., males, k.n., byrnes, m.j., el-saad, a.a. & coronado, g.s. (2017). incidence of gastric dilatation-volvulus following a splenectomy in 238 dogs. the canadian veterinary journal. 58(12): 1275–1280. sartor, a.j., bentley, a.m. & brown, d.c. (2013). association between previous splenectomy and gastric dilatation-volvulus in dogs: 453 cases (2004–2009). journal of the american veterinary medical association. 242(10), 1381–1384. doi: https://doi.org/10.2460/javma.242.10.1381 loy son, n.k., singh, a., amsellem, p., kilkenny, j., brisson, b.a., oblak, m.l. & ogilvie, a.t. (2016). long-term outcome and complications following prophylactic laparoscopic-assisted gastropexy in dogs. veterinary surgery. 45(s1), 77–83. doi: https://doi.org/10.1111/vsu.12568 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. should doses exceeding 0.2 mg/kg of oral meloxicam be given to reduce surgical recovery time in rabbits and should twice daily administration be considered? a knowledge summary by eleanor best bvsc msc mrcvs 1* 1university of bristol veterinary school, langford house, langford, bristol, bs40 5du *corresponding author (elliebest1001@gmail.com) vol 6, issue 3 (2021) published: 22 jul 2021 reviewed by: laura dixon (bsc(hons) phd) and rebecca schofield (rvn bsc hons) next review date: 29 mar 2023 doi: 10.18849/ve.v6i3.372 pico question in reducing surgical recovery time in rabbits (oryctolagus cuniculus), should doses exceeding 0.2 mg/kg of oral meloxicam be given and is twice daily administration more effective than a single daily dose?   clinical bottom line category of research question treatment the number and type of study designs reviewed nine papers were critically reviewed, yet no studies were found to directly investigate the effects of twice daily dosing with meloxicam postoperatively in rabbits. there were five descriptive, non-comparative case series; two nonblinded parallel group randomised control trials; one blinded, placebo-controlled parallel group randomised trial and one prospective, randomised crossover trial strength of evidence weak outcomes reported the current recommended oral dose of meloxicam in rabbits of 0.2–0.3 mg/kg once a day was consistently described as inadequate for postoperative analgesia following surgery (delk et al., 2014). instead, higher doses of 1–1.5 mg/kg were required to reach a similar peak plasma concentration as found to be clinically effective in other species, such as canines, and provide a better degree of analgesia in rabbits (montoya et al., 2004; and delk et al., 2014). although no studies were found evaluating twice daily administration of meloxicam, the available evidence suggests a dose exceeding 0.2–0.3 mg/kg daily is required for adequate postoperative analgesia in rabbits. whether this increased dose could be given twice daily should be investigated, providing scope for future research conclusion further studies are required to directly assess the benefits of twice daily oral meloxicam. however, it is possible that a dose exceeding 0.2–0.3 mg/kg is required and therefore higher doses should be considered in these studies   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are a veterinarian working in a first opinion small animal practice and have scheduled a routine ovariohysterectomy on a rabbit. you perform the surgery, which went well, and the patient is now ready to be discharged. you know that you will need to send the rabbit home with some pain medication to aid their recovery after surgery, so plan to prescribe meloxicam, as the only clinically licensed drug for pain relief in rabbits. however, you are unsure whether the recommended dosage should be increased to provide adequate pain relief, and whether medication should be given once or twice daily to reduce postoperative pain as much as possible, as the current indication is considered low by some sources (turner et al., 2006; carpenter et al., 2009; and delk et al., 2014). the evidence nine papers were critically reviewed. these included five descriptive, non-comparative case series; two nonblinded parallel group randomised control trials; one blinded, placebo-controlled parallel group randomised trial and one prospective, randomised crossover trial. as none of the papers directly studied the effects of twice daily dosing with meloxicam and there was only one blinded randomised control trial, the strength of the evidence relating to the pico question is weak. further studies are required to provide stronger evidence answering the query. summary of the evidence eshar & weese (2014) population: 3 month old, entire female new zealand white rabbits. all weighed between 2.52–2.71 kg and were free from specified pasteurella spp. sample size: six rabbits intervention details: all rabbits were housed individually at a temperature of 21°c, with 16 hours of light and 8 hours of dark provided each day. rabbits were fed ad libitum water and a free choice of timothy hay and pelleted diet. they were left to acclimate to the research facility for 5 days and were ‘habituated’ to handling before the study began. each rabbit was clinically assessed through a physical exam, complete blood count, serum biochemistry and urinalysis prior to the study. they were shown to demonstrate normal behaviour. this was assessed subjectively following a thorough physical exam. each rabbit was given 1 mg/kg meloxicam once daily, orally for 29 days. the rabbits’ behaviour including activity, eating, drinking and defecation, was assessed daily by the researchers. 10 fresh faecal samples were collected from each rabbit. at 08:00 on days 0 (prior to treatment beginning), 6, 14 and 21. therefore, a total of four faecal samples were collected from each rabbit throughout the study. dna was extracted from the faeces via polymerase chain reaction (pcr) for detection of pathogens. the microbiome of the hard faeces was assessed using the mothur algorithm (schloss et al., 2009) package. the relative abundancies of microorganisms were compared between rabbits. study design: descriptive, non-comparative case series outcome studied: the faecal bacterial microbiota was objectively assessed to determine the impact of long-term administration of meloxicam on the gut microbiome of rabbits. the rabbits’ behaviour was assessed subjectively by the researchers. it was not specified how this was determined or whether an ethogram was used. main findings (relevant to pico question): there were no apparent behavioural changes reported between rabbits. there was minimal difference in the faecal microbiota population structures identified between timepoints. no significant difference detected with the yue & clayton measure of dissimilarity using an analysis of molecular variance (amova), (p = 0.082). significant differences were found with the jaccard index (a measure of community membership) using an amova, (p = 0.011) between days 0–21 (p = 0.002) and days 14–21 (p = 0.030). study suggests that 1 mg/kg of oral meloxicam administered once daily is safe for use clinically in rabbits with minimal gastrointestinal side effects. limitations: the behaviour of the rabbits was subjectively assessed by the researchers and so the potential for bias or variation in behavioural interpretations remains strong. behavioural changes in rabbits cannot be relied upon as the sole indicator of pain. pain levels were not assessed in the rabbits using an accepted scale such as the rabbit grimace scale (rbtgs). the study does not consider rabbits that were recovering from surgery. this study was carried out on healthy laboratory rabbits rather than pet rabbits and it does not consider a veterinary context. only faecal samples were analysed and therefore this may not be a true reliable representation of the overall gut health of the rabbits. a small sample size was used and there was no control group. only hard faeces were analysed and soft faeces were not considered. breed and sex differences were not considered. the behaviour of the animals was not filmed – as rabbits are prey animals, the presence of the observer may have altered their behaviour. delk et al. (2014) population: 3 month old, entire female new zealand white rabbits. all weighed between 2.52–2.71 kg and were free from specified pasteurella spp. sample size: six rabbits intervention details: all rabbits were housed individually at a temperature of 21°c, with 16 hours of light and 8 hours of dark provided each day. rabbits were fed ad libitum water and a free choice of timothy hay and pelleted diet. they were left to acclimate to the research facility for 5 days and were ‘habituated’ to handling before the study began. each rabbit was clinically assessed through a physical exam, complete blood count, serum biochemistry and urinalysis prior to the study. they were determined to be behaviorally normal, although the criteria for determining this was not specified by the authors. each rabbit was given 1 mg/kg meloxicam orally every 24 hours for 29 days. the rabbits’ behaviour including activity, eating, drinking and defecation was assessed daily. blood samples were collected from either the lateral saphenous vein or auricular artery of each rabbit at 0 (prior to meloxicam administration), 2, 4, 6, 8 and 24 hours after meloxicam administration on days 1, 8, 15, 22 and 29 during the treatment. at each 0 timepoint and at an additional timepoint 36 hours after the final meloxicam dose on day 29, 1.5 ml of blood was collected for packed cell volume (pcv) and pharmacokinetic analysis. at all the other timepoints, 0.5 ml of blood was collected for pharmacokinetic analysis. a total of 31 blood samples were taken from each rabbit throughout the duration of the study. each rabbits’ behaviour was monitored subjectively by a single investigator throughout the study and they were weighed weekly. the study does not specify how the behaviour was monitored or whether an ethogram was used. after the study, the rabbits were humanely euthanised and a post-mortem necroscopy was carried out for any gross abnormalities. study design: descriptive, non-comparative case series outcome studied: pharmacokinetic parameters. auc0-24 – area under the curve for plasma concentration vs time. from administration of dose to 24 hours afterwards. aucinf – area under the curve for plasma concentration vs time. curve extrapolated to infinity following administration of a single dose. cmax – maximum plasma concentration of meloxicam. time to maximum plasma concentration. terminal half life. behaviour of the rabbits. weight of the rabbits each week. blood sample analysis including biochemistry. post-mortem gross abnormalities. main findings (relevant to pico question): there were no apparent adverse reactions to meloxicam administered at this dose throughout the study, suggesting it is well tolerated orally. there were no changes in behaviour, food or water consumption, activity or faecal production. there were no post-mortem findings which could be attributed to meloxicam toxicity. there was no significant difference detected for any pharmacological parameter assessed between days 8, 15, 22 and 29. the mean time to reach peak plasma concentration of meloxicam was 6.3 ± 0.8 hours, 5.3 ± 1.0 hours, 4.7 ± 1.0 hours, 5.0 ± 1.1 hours, and 4.3 ± 0.8 hours on days 8, 15, 22 and 29 respectively. the peak plasma concentration of meloxicam achieved in this study was proportionally higher than the peak plasma concentration reached following administration of the currently recommended meloxicam dose (0.2 mg/kg). the peak plasma concentration of meloxicam in this study was said to be similar to the peak plasma concentration achieved in clinically effective doses of meloxicam in other species (montoya et al., 2004). the authors state that rabbits therefore need a much higher dose of meloxicam than 0.2 mg/kg to reach the same plasma concentration effective in other species. further research is required to determine whether the effective plasma concentration in other species correlates to the effective plasma concentration in rabbits. limitations: only studied the pharmacological parameter changes after 1 mg/kg meloxicam, rather than looking at the clinical impact this might have on surgical recovery time. although rabbits were determined to be behaviourally normal prior to the beginning of the study, the criteria used to decide this was not specified by the authors. a small sample size was used and there was no control group. multiple doses of meloxicam in a 24 hour period was not considered. did not relate to surgical recovery time. breed and sex differences were not considered. only examined the pharmacokinetics of meloxicam in healthy animals, as clearance may have been affected in an unhealthy rabbit. subjective behavioural assessments by the investigator allows room for bias. the behaviour of the animals was not filmed – as rabbits are prey animals, the presence of the observer may have altered their behaviour. goldschlager et al. (2013) population: male new zealand white rabbits aged between 2–3 months. each weighed approximately 3 kg. free from specified pathogens bordetella bronchiseptica, salmonella spp., cilia-associated respiratory bacillus, helicobacter, encephalitozoon cuniculi, pasteurella multocida, pasteurella pneumotropica, pseudomonas spp., and hepatic and intestinal coccidiosis. the rabbits were purchased from charles river laboratories inc. (wilmington, ma) to be part of an additional study on the induction and treatment of atherosclerosis. sample size: 39 rabbits intervention details: each rabbit was individually housed at between 20–23°c with 12 hours of daylight and 12 hours of darkness provided each day. they were left to acclimate to their environment for 7 days. the rabbits had access to ad libitum water and were fed a commercial rabbit diet. each rabbit was randomly allocated into one of four groups following a vascular cut down procedure of the femoral artery. group 1 (n=10) – given 0.03 mg/kg buprenorphine subcutaneously (sc) every 12 hours for 3 days. group 2 (n=10) – given 0.2 mg/kg meloxicam sc every 24 hours for 3 days. group 3 (n=10) – given 0.01 mg/kg buprenorphine and 1 mg/kg meloxicam sc every 24 hours for 3 days. group 4 (n=9) – given 0.5 ml of 0.5% bupivacaine locally immediately after surgery. the rabbits’ were weighed weekly. baseline serum biochemistry analysis was carried out prior to the study and at 7 days after the surgery. rectal swabs were taken on day 7 to assess the gut microflora. faecal samples were collected on days 0, 3, 7, 14, 21 and 28. each sample collected was a pooled sample from the last 24 hours for each rabbit. the faecal samples were analysed for faecal corticosteroid metabolites. rabbits which displayed signs of no appetite or absent faecal production were withdrawn from the study. none of the rabbits exhibited these signs and so none were removed from the study. study design: nonblinded, parallel-group, randomised control trial outcome studied: faecal corticosteroid metabolite (fcm) levels measured on days 0, 3, 7, 14, 21 and 28 after surgery. body weight was measured weekly. serum biochemistry was recorded on days 0 and 7. data was analysed using an analysis of variance (anova) on statistical package for the social sciences (spss) software, with huynh-feldt corrected p values to report statistical significance. one rabbit was excluded from analysis incorporating the fcm levels in the buprenorphine group on day 14, as data was missing. main findings (relevant to pico question): groups 1, 2 and 4 all showed elevated corticosteroid metabolites in the faeces until 7 days, before then decreasing to baseline level as detected prior to the beginning of the study. group 3 showed unchanged faecal corticosteroid metabolite levels until treatment ceased at 3 days, at which point it began to rise. all rabbits showed decreased food intake at day 1 postoperatively and began to return to normal baseline levels from days 7–14. however, it was not specified as to whether the food was weighed or whether this was assessed subjectively. all groups showed a decrease in body weight, however group 3 decreased the least. there were no notable changes in gut microflora or haematological parameters for any of the rabbits. group 3 given multimodal analgesia seemed to ‘mitigate postsurgical stress in rabbits’ and showed the highest weight gain over the study duration, however the rise in fcm after treatment ceased suggests the duration of analgesia should be prolonged to provide adequate pain relief postoperatively. all groups showed decreased active behaviours postoperatively. the frequency of inactivity began to decrease over the 7 day postoperative period, suggesting a decrease in pain over this time. meloxicam administered as the sole analgesic at a dose of 0.2 mg/kg did not provide adequate pain relief compared with multimodal analgesia combining meloxicam and buprenorphine. limitations: the study only considered subcutaneous administration of meloxicam rather than oral administration. the study used laboratory rabbits rather than pet rabbits and so this may not be fully applicable to a veterinary context. study assumes that increased faecal corticosteroid metabolites equates to postoperative pain in rabbits. behavioural assessments were made subjectively and could not have been filmed to reduce any alterations due to the presence of an observer. some of the observed effects of the surgery on the rabbit’s behaviour, haematological parameters and body weight, may have been a result of the surgical procedure and not necessarily linked directly to postoperative pain. fredholm et al. (2013) population: 8 month old, clinically normal, new zealand white rabbits weighing between 2.41–2.89 kgs sample size: six rabbits intervention details: each rabbit was individually housed at a temperature of 21°c with 16 hours of light and 8 hours of darkness per day. they were fed alfalfa pelleted food and timothy hay with access to ad libitum water. they were left to acclimate for 5 days and habituated to handling before the study. 0.5 ml of blood was taken from either the lateral saphenous vein, cephalic vein, or auricular artery to determine baseline blood values (haematocrit, plasma total protein, biochemistry) before meloxicam administration. a physical exam was conducted and faecal samples were taken. 1 mg/kg meloxicam was administered orally to each rabbit. 5 ml of blood was collected at 0 (before meloxicam administration) 0.25, 0.5, 1, 2, 3, 4, 6, 8,12, 24 and 36 hours following administration. a 10 day wash out period followed in which the rabbits were not given any further drugs. after the 10 day washout period, 1 mg/kg meloxicam was administered every 24 hours for 5 days. 5 ml of blood was collected at 0 and 4 hours post administration for the first 4 days. on day 5, 0.5 ml of blood was collected at 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 26 hours post administration. an additional 0.5 ml of blood was collected at the final timepoint for serum biochemistry parameter analysis. study design: descriptive, non-comparative case series outcome studied: pharmacokinetic parameters measured: aucinf. auc 12–24. terminal half life. cmax. tmax. λz. area under the first moment curve extrapolated to infinity. mean residence time extrapolated to infinity. baseline plasma biochemical analysis and plasma biochemistry following 5 days meloxicam administration. main findings (relevant to pico question): there were no adverse reactions to meloxicam and no changes in the rabbit’s behaviour. there were no significant differences between the serum biochemistry of the rabbits before and after treatment which fell outside the ‘normal’ reference ranges for a rabbit. 1 mg/kg of meloxicam administered orally once every 24 hours to rabbits caused higher plasma concentrations of meloxicam than the maximum plasma concentration achieved when administering meloxicam at the currently recommended oral dose (0.2 mg/kg). cmax achieved here – 0.83 µg/ml. the cmax in this study is similar to the cmax achieved in dogs (0.82 µg/ml) given the clinically effective dose of meloxicam (0.2 mg/kg). study suggests that therefore a higher dose of meloxicam is needed to achieve the same clinically effective plasma meloxicam concentrations as found in other species. meloxicam was found to accumulate after 5 days of receiving 1 mg/kg orally every 24 hours, so the study suggests that the dose may need to be reduced if administering for a period of time longer than 5 days. the time to reaching maximum plasma concentration in this study was 6.5 hours after administration of oral meloxicam. limitations: a small sample size was used and there was no control group included. behaviour was used as the sole indicator of pain in the rabbits and this did not take into account potential external stressors, for example, handling stress. the study was performed in healthy rabbits and not those undergoing surgery, which could affect drug clearance and impact adverse effects. sexes of the rabbits not stated. did not explore clinical efficacy of the given dose. did not explore multiple doses given in a 24 hour period. carpenter et al. (2009) population: 8 month old, clinically normal, female new zealand white rabbits weighing between 3.75–3.98 kg. free from pasteurella spp. sample size: eight rabbits intervention details: rabbits were housed in indoor runs, however it was not specified whether they were housed individually or in groups or pairs. each run contained two pet carriers to be used as ‘hide’ boxes. they were provided with 16 hours of light and 8 hours of darkness every 24 hours. they were fed a pelleted diet and timothy hay free choice, with access to ad libitum water. the rabbits’ behaviour was subjectively assessed three times a day (mentation, attitude, food consumption, activity level, faecal production). the rabbits’ were observed and it was not specified as to whether an ethogram was used. before the study, each rabbit was given a physical examination, including blood samples taken to assess pcv, total protein (tp) and a urinalysis was performed. 2 mg/kg of meloxicam was administered orally every 24 hours to each rabbit for 10 days. 5 ml of blood was sampled from either the lateral saphenous and cephalic vein or central ear artery at 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours on days 1 and 10 after drug administration. additional samples were collected prior to meloxicam administration and 3 hours afterwards on days 3, 5 and 7 during the study. study design: descriptive, non-comparative case series outcome studied: pharmacokinetic parameters measured. area under the plasma vs time curve for the treatment period of 24 hours. area under the first moment curve for the treatment period of 24 hours. terminal half life. cmax. tmax. λz. changes in behaviour were assessed three times a day. main findings (relevant to pico question): there were no changes in mentation, activity level, faecal production or food consumption that the authors could attribute to an adverse reaction in any of the rabbits. drug accumulation was found to occur from day 3. the study suggests that 0.2 mg/kg every 24 hours is a suitable dose of meloxicam to be used in rabbits. the peak plasma concentration was reached at 6 hours post meloxicam administration. the mean cmax concentration reached with 0.2 mg/kg administration of meloxicam on day 10 in this study (0.24 ± 0.066 µg/ml). limitations: a small sample size was used and there was no control group. the authors assumed that any behavioural changes were indicative of adverse drug reactions, and that the lack of behavioural change in these rabbits implied that there were no adverse reactions. breed, age and sex differences were not explored. subjective behavioural assessment by the investigators may have impacted the rabbit’s behaviour as prey animals. the rabbits could have been filmed to reduce this. it was not specified whether the same investigator assessed all the rabbits in the study – if there were different assessors, this could result in bias. the study did not assess clinical efficacy of the given dose. the study was performed in healthy laboratory animals and is therefore not directly related to surgical recovery time in rabbits, or reflective of a veterinary setting. cooper et al. (2009) population: female dutch belted rabbits all weighing between 2–3 kg were used. all rabbits were free from specified pathogens bordetella bronchiseptica, salmonella spp., coccidia spp., cilia-associated respiratory bacillus, encephalitozoon cuniculi, pasteurella multicoda, and treponema cuniculi. they were purchased from myrtle’s rabbitry (thompsons station, tn). sample size: 30 rabbits (however one died from anaesthetic complications during surgery) intervention details: each rabbit was housed individually at a temperature of 21–23°c with 12 hours of light and 12 hours of darkness each day. they were fed 250 g of commercial rabbit feed daily with access to ad libitum water via an automatic watering system. they were allowed 5–7 days to acclimate to their surroundings. baseline parameters were collected from each rabbit. these included food intake, faecal production, urine output, body weight, physical examination, complete blood count and biochemistry, rectal culture and behavioural assessment (attitude, posture, grooming, activity levels on a scale of 1–5). an ovariohysterectomy was performed on each rabbit under general anaesthesia. each rabbit was randomly assigned to one of three treatment groups postoperatively. group 1 (n=10) – 0.03 mg/kg buprenorphine administered via intramuscular injection every 12 hours for 48 hours. group 2 (n=10) – 0.2 mg/kg meloxicam via subcutaneous injection every 24 hours for 48 hours. group 3 (n=9) – 0.5 ml of 0.5% bupivacaine locally infused to the incision site after surgery. any rabbit showing signs of anorexia or lack of faecal production was supplemented with 0.5 mg/kg of metoclopramide once daily for 2 days, and one handful of timothy hay. each rabbit was observed and monitored for 7 days following the procedure by a non-blinded observer. pain assessment, food intake, faecal output, urine output, abdominal palpation and physical examination including the incision site was assessed. a complete blood count and biochemistry, weight, rectal temperature and cultures were also performed on days 2 and 5 postoperatively.  study design: nonblinded, parallel group, randomised control trial outcome studied: behavioural assessments of each rabbit postoperatively, including a pain assessment. blood sample analysis of each rabbit. main findings (relevant to pico question): according to this study, meloxicam appeared to be a more appropriate analgesic for use following soft tissue surgery than an opiate. group 2 showed the fastest return to the baseline food intake level by day 5 following surgery. faecal output was statistically greater in group 2 compared with group 3 on day 1 postsurgery (p = 0.0256), however there was no significant difference in faecal output between any of the groups after this period. groups 1 and 2 both showed a gradual return to baseline faecal output and food consumption by day 7. all groups showed weight loss and reduced faecal output immediately after surgery. rectal culture, physical examination, blood parameters and body temperature remained similar to baseline levels throughout the study for all three groups. four rabbits in group 3 showed signs of gut stasis immediately after surgery and so were treated with metoclopramide, fluids and timothy hay. limitations: behavioural assessments were subjective and nonblinded which could have led to some bias. again they could have been filmed to assess more natural rabbit behaviour. breed, sex and age differences were not considered. the age of the rabbits was not stated. the reduction in faecal output and gut stasis was assumed to be a direct result of pain, rather than the result of stress from the procedure, change in environment and being housed alone. the rabbits were not fed any form of roughage and instead were only fed commercial rabbit feed. this is not reflective of an appropriate rabbit diet and therefore could have been an extra source of stress within the study. the study administered meloxicam via subcutaneous injection rather than orally, which may be better suited to manage postoperative pain in rabbits being sent home with medications. leach et al. (2009) population: 12 week old female new zealand white rabbits weighing between 1.8–2.3 kg purchased from harlan uk limited (bicester, uk). sample size: 28 rabbits intervention details: each rabbit was individually housed at a temperature of 22°c with 12 hours of light and 12 hours of darkness each day. they were free from the common pathogens as identified by the felasa health monitoring recommendations (mähler convenor et al., 2014). rabbits were fed pellets, hay and ad libitum water. cardboard tubes and a chew block were provided in each enclosure for enrichment. the rabbits were allowed 14 days to acclimate to the surroundings prior to the study. each rabbit was randomly allocated into one of four groups to be given either meloxicam or a placebo orally. group 1 (n=7) – placebo of 2 ml/kg saline on the day of surgery and for 2 days following. group 2 (n=7) – 0.2 mg/kg meloxicam on the day of the surgery and 0.1 mg/kg on the following 2 days. group 3 (n=7) – 0.6 mg/kg meloxicam on the day of the surgery and 0.3 mg/kg on the following 2 days. group 4 (n=7) – 1 mg/kg meloxicam on the day of the surgery and 0.5mg/kg on the following 2 days. each group received their placebo or drug dose orally one hour before the surgery, followed by doses at 09:00 for the following 2 days. the rabbits all underwent a routine ovariohysterectomy under general anaesthesia. they were left to recover for one hour after surgery in an incubator before being returned to their individual enclosures. following surgery, the rabbits were monitored regularly by a veterinarian. the rabbits were filmed at 3, 7, 27, 31, 51, 55, 75 and 79 hours postoperatively, for 20 minutes at each timepoint to monitor their behaviours. the data was recorded by a blinded observer, and an ethogram detailing the frequency and duration of each behaviour observed. rescue analgesia consisting of 0.01 mg/kg intravenous (iv) buprenorphine was given to any animal exhibiting two of the following behaviours in 5 minutes – abdominal writhing, belly pressing, back arching or contraction of the abdominal muscles. study design: blinded, placebo-controlled, parallel-group randomised trial outcome studied: frequency and duration of specified behaviours displayed postoperatively by the rabbits. main findings (relevant to pico question): inactivity levels associated with pain increased significantly postoperatively at all timepoints (p<0.0001, ± 2 standard error (se)) compared to the preoperative period with no significant difference between any of the groups. group 4 showed a significant difference in searching behaviour during the morning observation periods in comparison to the placebo group (p<0.05, ± 2 se), being significantly higher in the high dose meloxicam group. groups 3 and 4 showed a significant difference in the duration of consuming behaviours (p<0.05 and p<0.05 respectively, ± 2 se), and group 3 showed a significant difference in the duration of interaction behaviours compared with the placebo group. all groups showed a significant decrease in food consumption following surgery compared to before surgery (p<0.0001), however there was no difference between the groups. the frequency of inactivity was significantly higher postoperatively compared to preoperatively, however did not decrease to baseline levels throughout the duration of the study (2 days postoperatively). no group provided complete analgesia following ovariohysterectomy. limitations: 20 minute filming periods may not have been long enough to accurately assess the rabbit’s behaviour. the study assumed that inactivity levels were associated with pain rather than stress. no sex, age or breed differences were considered. turner et al. (2006) population: 3 month old, female, new zealand white rabbits, all weighed approximately 3 kg. all rabbits were free from specified diseases encephalitozoon cuniculi, cilia-associated respiratory bacillus, clostridium piliforme, reovirus, rotavirus, pasteurella multocida, salmonella spp, bordetella bronchiseptica, pseudomonas aeruginosa, clostridium perfringens, and hepatic and intestinal coccidiosis. they were obtained from charles river canada. sample size: 10 rabbits intervention details: the rabbits were housed in a group in floor pens with 12 hours light and 12 hours of darkness a day, at a temperature of 20°c. rabbits were fed twice a day with a commercial diet and provided with timothy hay and water ad libitum. the rabbits were given 7 days to acclimate to the conditions and were habituated to handling prior to the study taking place. each rabbit was randomly allocated to one of two initial treatment groups to be given a single dose of oral meloxicam. group 1 (n=5) – 0.3 mg/kg meloxicam orally at 08:00. group 2 (n=5) – 1.5 mg/kg meloxicam orally at 08:00. a 1 ml blood sample was collected from each rabbit at 0, 0.5, 1, 2, 4, 6, 8, 24, 48, 72 and 96 hours following administration of the single meloxicam dose. there was a wash-out period of 14 days following. after the wash out period, the rabbits were then allocated to one of two repeat dose groups. group 1 from the single dose study (receiving 0.3 mg/kg meloxicam) was now given 1.5 mg/kg oral meloxicam each day for 5 days. group 2 from the single dose study (receiving 1.5 mg/kg meloxicam) was given 0.3 mg/kg oral meloxicam for 5 days. a 1 ml blood sample was collected from each rabbit at 0, 4, 24, 28, 48, 96, 100, 120 and 144 hours after dosing. the body weight of each rabbit was measured each week. baseline blood biochemistry parameters were measured before the study, and at 5 days following both the single and repeat dose experiments. study design: randomised crossover trial outcome studied: plasma meloxicam levels and time to reaching peak plasma concentration were measured. body weight was recorded weekly. biochemical parameters were established at baseline and 5 days post administration of both the single and multiple dose studies. pharmacokinetic parameters were calculated. elimination constant. plasma concentration-time curve. auc. oral clearance. main findings (relevant to pico question): there was no significant change in body weight or biochemical parameters for either group in either study. the maximum plasma concentration of meloxicam for 0.3 mg/kg and 1.5 mg/kg single daily dosing was reached between 6–8 hours and decreased to untraceable levels by 24 hours (0.025 ± 0.06 µg/ml and 0.069 ± 0.021 µg/ml for group 1 and 2 respectively). the elimination half-life was 8 hours for both doses, implying no saturation as the dose was increased to 1.5 mg/kg. the repeated dose experiments showed little evidence of accumulation at either dose given for 5 consecutive days, with meloxicam eliminated quickly after dosing ceased. the plasma meloxicam levels after 4 hours on days 1, 2 and 4 following meloxicam administration were similar for both doses in the repeated and single dose studies. there was some individual variation between the maximum plasma concentration in each rabbit. the peak plasma concentration of meloxicam reached in this study (0.14 ± 0.02 µg/ml and 0.30 ± 0.09 µg/ml for the low and high dose groups respectively) was much lower than the maximum plasma concentration reached in other species, using the same dose of meloxicam (e.g. 0.0464 µg/ml in beagle dogs after a dose of 0.2 mg/kg) – this was hypothesised to be as a result of poor drug absorption rather than over-saturation. the study hypothesises that feeding food and roughage prior to meloxicam administration can slow the absorption of oral meloxicam. 3 mg/kg and 1.5 mg/kg were both determined to be clinically safe doses in rabbits. the oral clearance and volume of distribution increased from the low to high dose groups, again hypothesised here to be a result of poor absorption. this study suggests that meloxicam is metabolised faster in rabbits than in other species e.g. humans, rats and dogs and further studies are needed to assess the effective plasma concentration of meloxicam in rabbits. limitations: breed, gender and age differences were not considered. the clinical efficacy of either dose was not considered. the study was conducted in healthy rabbits and so it is possible the metabolism and clinical efficacy of meloxicam could be different in a sick animal. no behavioural effects of the drug were monitored or measured throughout either study. raillard et al. (2019) population: 17 week old, male new zealand white rabbits obtained from charles river laboratories, france sample size: 14 rabbits intervention details: each rabbit was individually housed with 12 hours of light and 12 hours of darkness each day, at a temperature of between 19–21°c. the rabbits maintained visual contact with each other as the space between two enclosures was left open. if there was any aggression, a transparent partition was placed between enclosures. a wooden block, chew ball and elevated level was provided in each enclosure for enrichment. the rabbits were left to acclimate for 3 weeks prior to the study. they were fed 200 g of commercial rabbit food with ad libitum water each day. the rabbits were anesthetised, and calvarial bone surgery was performed on each rabbit. postoperative pain was monitored and assessed using the composite behavioural scale and rbtgs (keating et al., 2012). baseline pain scores were assessed 3 days before surgery. postoperative pain was assessed before drug administration by one of three trained persons at 06:00, 10:00, 14:00, 18:00 and 22:00 on the day of surgery and for 3 days following. 3 mg/kg meloxicam was given via subcutaneous injection once daily for 4 days, and 20–30 mcg/kg buprenorphine was given three times daily (06:00, 14:00 and 22:00) via subcutaneous injection for 3 days after surgery. rescue analgesia consisting of 20–30 mcg/kg buprenorphine sc was given at 10:00 and 18:00 if a score higher than 3 on the composite pain scales, or higher than 4 on the rbtgs was reached. study design: nonblinded, descriptive non-comparative case series outcome studied: postoperative pain assessments were obtained. main findings (relevant to pico question): postoperative pain was observed in every rabbit despite the administration of multimodal analgesia. the peak pain levels were reached at 12 hours following surgery and on the first day after surgery. every rabbit required analgesia every 4–8 hours on the day of the surgery and for 1 day following surgery. the study suggests that rigorous pain monitoring is required postoperatively in rabbits and that analgesia should be administered for at least 48 hours after any surgical procedure. limitations: breed, age and sex differences were not considered. the study did not account for the stress that might have been associated with the change in environment for the rabbits and did not consider whether they were used to living alone or in pairs. this could have increased stress levels and been mistaken for increased pain levels postsurgery. the rabbits were not fed any form of roughage which is not representative of an appropriate rabbit diet and therefore could have acted as an extra cause of stress during the study. increasing the dose of meloxicam was not considered. the study did not consider directly comparing the efficacy of different postoperative analgesic protocols. the observers were not blinded, leaving room for some bias. there was no control group to compare against. the presence of the observers could have affected the display of pain behaviour and the behaviour of the rabbits could have been filmed to eliminate bias. appraisal, application and reflection much of the literature reviewed here agrees that a dose exceeding the currently recommended 0.2–0.3 mg/kg/day is required to provide adequate analgesia for rabbits postoperatively. these papers consisted of one nonblinded, randomised control trial (cooper et al., 2009); two descriptive case series’ (delk et al., 2014; and fredholm et al., 2013); one blinded, placebo-controlled, parallel-group, randomised trial (leach et al., 2009) and one randomised crossover trial (turner et al., 2006). despite their concordance, the strength of the evidence remains weak pertaining to the pico question asked in this knowledge summary. none of the papers consider dosing with meloxicam twice daily, and not all the studies assess postoperative pain behaviours directly. leach et al. (2009) conducted a blinded randomised control trial assessing postoperative behaviour of rabbits following ovariohysterectomy. this is perhaps the most directly relevant paper to the pico in this sense, especially as it considers increasing the daily doses of meloxicam in a surgical context, yet it again fails to consider dosing twice a day. the study found that inactivity behaviours increased following surgery, and only the higher dose group showed an increase in searching and consuming after surgery. despite this, the increased searching and consuming behaviours were only significant in the morning observation periods and none of the meloxicam groups provided adequate analgesia postoperatively, even up to a dose of 0.6 mg/kg/day, again suggesting an increased dose is necessary. it is important to note, however, that each study used different, subjective criteria to assess pain and so there is scope for variation amongst what was deemed to be ‘painful’ in each study. fredholm et al. (2013) and delk et al. (2014) examined the pharmacokinetics of meloxicam in rabbits. both concluded that the peak plasma concentration of meloxicam in rabbits given 1 mg/kg orally was much higher than that reached when 0.2 mg/kg was administered (carpenter et al., 2009). as the rabbit metabolism is very fast, this could mean that higher doses are required to maintain a higher plasma concentration of the drug and provide adequate pain relief, although the study did not examine the significance of the relationship between plasma concentration and clinical efficacy. again, the plasma concentration reached with 1 mg/kg of meloxicam was much closer to the plasma concentration reached with the clinically effective doses of meloxicam in other species (delk et al., 2014), implying that a higher concentration is required to be clinically effective in rabbits. however, this was not directly assessed in this paper and instead assumes that a higher plasma concentration equals clinical effectiveness, leaving scope for future research to be undertaken here. carpenter et al. (2009) and cooper et al. (2009) both imply that 0.2 mg/mg of meloxicam is an adequate dose for rabbits in their studies, contradicting the previous findings. however, cooper et al. (2009) conducted a randomised control trial and found that whilst 0.2 mg/kg meloxicam allowed a faster return to baseline levels following ovariohysterectomy, all rabbits still showed decreased activity and faecal output levels immediately after surgery. this may suggest that either a higher daily dose, or a lower dose given more frequently, may be necessary to provide adequate analgesia postoperatively. again, the strength of the evidence provided by cooper et al. (2009) in their nonblinded, parallel group control trial is much greater than carpenter et al. (2009) in their descriptive case series, perhaps giving more credibility to their conclusions. some sources concluded that there are no adverse side effects associated with an increased dose of meloxicam (turner et al., 2006; delk et al., 2014; and eshar & weese, 2014). these studies assessed meloxicam concentrations between 1–1.5 mg/kg/day, each finding that there were no behavioural changes or alterations in the gut microbiome following administration of this increased dose. as two descriptive case series’ and one randomised crossover trial, they provide moderate evidence suggesting that there are minimal associated side effects with increased meloxicam concentrations in rabbits. however, these studies were conducted on healthy animals, rather than those recovering from surgery, therefore are not directly relevant to the pico contrary to this, carpenter et al. (2009) and fredholm et al. (2013) both found some level of drug accumulation following meloxicam administration for 3 and 5 days respectively. drug accumulation occurs when the repeated administration of a drug results in gradually higher plasma concentrations than the first time a drug is administered, often leading to toxic side effects (wagner, 1967). in meloxicam in dogs, these toxic side effects include renal, hepatic and gastrointestinal toxicity (boehringer ingelheim, 2014). therefore, further investigation of this is needed to determine a safe clinical dose with minimal risk of drug accumulation. carpenter et al. (2009) only considered meloxicam administration at 0.2 mg/kg/day and instead suggests that this is a suitable dose for rabbits, despite the evidence of accumulation at days 3 and 5. fredholm et al. (2013) instead found accumulation after 5 days of 1 mg/kg administration of meloxicam and suggested that a decrease in drug concentration may be necessary. the suspected accumulation of meloxicam at this higher dose of 1 mg/kg suggests that this pico question warrants further investigation into whether lower doses of meloxicam administered more frequently, such as twice daily, are needed to provide adequate pain relief and minimise the risk of drug accumulation. carpenter et al. (2009) also assumed that a lack of behavioural changes indicated that there were no adverse reactions to this dose of meloxicam. whilst a loss of appetite could indicate an adverse reaction, other factors, such as diarrhoea, were not considered, therefore limiting the value of this study further. both studies were descriptive case series’ with no comparative control group and therefore cannot provide strong enough evidence to draw reliable conclusions. each paper studied only one age and breed of rabbit, using heavily controlled environments and the results, therefore, are less applicable to a real-life veterinary scenario involving pet rabbits. however, each of these papers provide a useful starting point for future research into this topic. as previously discussed, there were no directly relevant papers comparing the effects of twice daily meloxicam administration with single daily dosing. instead, it is only possible to extrapolate data from the existing available literature. again, each of the studies examined in this knowledge summary used only laboratory rabbits, rather than pet rabbits. most of these animals were housed individually, rather than in groups, which is unacceptable according to the animal welfare act, 2006 (legislation.gov.uk, 2006). these conditions are not fully reflective of a veterinary context and could have provided an extra source of stress to the rabbits, further influencing their behaviour and the interpretation of study results. whilst these studies do not provide enough basis on which to build any solid conclusions, they point in the direction of future research which is most certainly required to ascertain a reliable answer to the clinical query asked here, and to allow veterinarians to provide the best possible postoperative care to their patients. it is therefore vital that additional research is conducted that accounts for other external stressors such as poor diets, housing and the threat of predation if kept outside, to allow for appropriate assessment of pain relief in domestic rabbits. methodology section search strategy databases searched and dates covered: cab abstracts via ovid 1973 – 2021 pubmed via ncbi 1948 – 2021 search strategy: cab abstracts: rabbit* or leporid* or lagomorph* or lapine or oryctolagus* and meloxicam or metacam or mlx or loxicom or meloxidyl or nonsteroidal or non-steroidal or “non steroidal” or nsaid or analgesi* and dose* or dosing or dosage* or inject* or administ* filters applied: english   pubmed: (((rabbit or lapine or lagomorph or rabbits or oryctolagus)) and (meloxicam or metacam or mlx or nonsteroidal or non-steroidal or "non steroidal" or nsaid or analgesia))) and ((dose or doses or dosing or dosage or inject or administer or administration)) filters applied: english, other animals, veterinary dates searches performed: 29 mar 2021 exclusion / inclusion criteria exclusion: review articles, not in english, book or book chapters, not relevant to pico, dose charts, opinion articles, inability to access full paper inclusion: articles relevant to pico search outcome database number of results excluded – irrelevant to pico excluded – review paper/book chapters/inability to access etc. total relevant papers cab abstracts 222 189 24 9 pubmed 698 679 10 9 total relevant papers when duplicates removed 9 conflict of interest the author declares no conflicts of interest. references boehringer ingelheim. 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[online] 48(3), 279–285. available at: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2696831/ [accessed: 5 may 2020]. delk, k. w., carpenter, j. w,, kukanich, b., nietfeld, j. c. and kohles, m. (2014). pharmacokinetics of meloxicam administered orally to rabbits (oryctolagus cuniculus) for 29 days. american journal of veterinary research. 75(2), 195–199. doi: https://doi.org/10.2460/ajvr.75.2.195 eshar, d. & weese, j. s. (2014). molecular analysis of the microbiota in hard feces from healthy rabbits (oryctolagus cuniculus) medicated with long term oral meloxicam. bmc veterinary research. 10, 62. doi: https://doi.org/10.1186/1746-6148-10-62 fredholm, d. v., carpenter, j. w., kukanich, b. and kohles, m. (2013). pharmacokinetics of meloxicam in rabbits after oral administration of single and multiple doses. american journal of veterinary research. 74(4), pp. 636–641. doi: https://doi.org/10.2460/ajvr.74.4.636 goldschlager, g. b., gillespie, v. l., palme, r. and baxter, m. g. 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(1967). drug accumulation. the journal of clinical pharmacology and the journal of new drugs. 7(2), 84–88. doi: https://doi.org/10.1002/j.1552-4604.1967.tb00290.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. full text template title | veterinary evidence skip to main content knowledge summary heatstroke and brachycephalic dogs – is there an increased risk? anna ewers clark, bvetmed bsc certavp mrcvs 1 blue cross, house 1, sheppard, 5 hugh st, london, sw1v 1qq * corresponding author email: aewers@alumni.rvc.ac.uk vol 7, issue 4 (2022) submitted 02 sep 2021; published: 22 dec 2022; next review: 21 feb 2024 doi: https://doi.org/10.18849/ve.v7i4.534 pico question do dogs that are brachycephalic have an increased risk for developing heat-related illness compared to dogs that are not brachycephalics? clinical bottom line category of research risk. number and type of study designs reviewed four studies were critically appraised. three of these were cohort studies, one was a case-control study. strength of evidence moderate. outcomes reported brachycephalic dogs are at increased risk of developing heat-related illness and brachycephalic breeds are over-represented in presentations for heatstroke. other factors named, such as body weight, also contributed to the risk of developing heat-related illness. conclusion dogs that are brachycephalic are likely to have an increased risk for developing heat-related illness compared to non-brachycephalic dogs. how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are presented with a 3 year old male, neutered pug with severe dyspnoea and tachypnoea. the day is sunny and 23oc, and the patient moderately exercised at midday. after stabilising and treating the patient, the owner wishes to discuss why their brachycephalic dog has needed emergency treatment when their labrador was unaffected by exercise at the same time. you need evidence to explain that brachycephalic breeds can be more at risk of developing heatstroke. the evidence the literature search revealed four papers relevant to the pico. one study aimed to investigate risk factors for development of heat-related illness, another aimed to investigate the effect of brachycephaly on response to heat stress and the final two recorded brachycephaly of dogs as part of their aims to investigate heatstroke. the four papers provide evidence to support that brachycephalic dogs are at high risk or increased risk of heatstroke compared to non-brachycephalic dogs. summary of the evidence hall et al. (2020) population: client owned dogs with a record of presentation for heat-related illness (hri) to uk vetcompass registered primary care veterinary practices from 2016–2018. sample size: 905,543 dogs, of which 1222 dogs experienced hri (1259 hri events). intervention details: database search carried out from submitted electronic patient records of primary care practices. cases identified using final diagnosis, insurance claims, and / or clinical signs related to hot conditions (search parameters and inclusion criteria are clearly stated). sample subdivided for separate analysis into ‘triggers for dogs with first hri events’ and ‘fatality in hri events between 2016–2018’. risk factors for fatality and triggers analysed by multivariable logistic regression. study design: retrospective cohort study. outcome studied: objective assessment of seasonality and event fatality for hri and risk factor analysis for exertional, environmental, and vehicular hri, (including breed type, skull shape, adult bodyweight, sex / neuter, and age). main findings (relevant to pico question): skull shape significant risk factor for hri, with brachycephalic dogs having 1.32 times odds (95% ci 1.10–1.60, p = 0.004) of exertional hri, 2.36 times odds (95% ci 1.50–3.72, p = <0.001) of environmental hri and 3.07 times odds (95% ci 1.60–5.87, p = 001) of vehicular hri compared to mesocephalic dogs. as individual breeds, bulldogs and french bulldogs have significantly higher odds ratio of environmental, exertional and vehicular hri compared to labrador retrievers (bulldog: environmental 7.52 or, 95% ci 2.76-20.47, p = <0.01, exertional 3.73 or, 95% ci 2.34-5.93, p = <0.01, vehicular 16.63 or, 95% ci 3.02–91.53, p = 0.001; french bulldog: environmental 3.16 or, 95% ci 1.03–9.73, p =0.045, exertional 2.96 or, 95% ci 1.96-4.47, p = <0.001, vehicular 6.70 or, 95% ci 1.11–40.65, p = 0.039). other brachycephalic breeds also significantly increased odds for some types of hri. majority of events presented due to exertional heatstroke (74.2%). limitations: unknown reliability of reporting from primary care veterinary practices may be subject to recall or observer bias. potential for recording bias as some breeds more likely to be classified with hri on presentation / with mild signs. potential for bias due to missing data during data collection as retrospective study looking at clinical records. no record of prevalence of brachycephaly in population. evaluated all presentations for hri, using a wider definition of clinical signs. no standardised veterinary definition for heat-related illness or heatstroke. brachycephaly classified according to breed type not individual patient skull morphology.   segev et al. (2015a) population: client owned dogs presented to the emergency and critical care unit of the hebrew university veterinary teaching hospital between 1999 and 2008. sample size: 126 dogs presented with heat-related illness (hri). intervention details: clinical records searched for diagnosis of heatstroke which was based on clinical signs following exposure to heat stress. clinical progression (from clinical records) and diagnostic test results evaluated. variables analysed and weighted to create a predictive model for heatstroke with outcome. model evaluated by logistic regression. study design: retrospective cohort study. outcome studied: objective assessment of signalment, vital signs on presentation, history of exertional / environmental heatstroke, mortality, and results from diagnostic testing. main findings (relevant to pico question): brachycephalic breeds represented 36/126 (29%) of dogs in the study, which was higher than the general population presented to the hospital (16%). brachycephalic breeds included boxer, english bulldog, french bulldog, dogue de bordeaux, chinese shar-pei, american staffordshire terrier, and pekingese. no significant difference detected in mortality between brachycephalic and non-brachycephalic dogs. majority of dogs had exertional heatstroke (64%). limitations: no sample size calculation provided. only recorded from one referral population, limiting generalisability. dogs euthanised on financial grounds or where owner declined treatment were excluded, which may bias the included cases, for example those with less severe presentations perceived to have a better prognosis. dogs with concurrent conditions excluded which may affect representation of some breeds (for example, some breeds are more likely to have breed-related health conditions). unknown reliability of reporting from veterinary practice may be subject to recall or observer bias. limited data available for classification of breeds. full signalment data not available which means unable to compare brachycephalic breeds to other breeds presenting. no record of how brachycephaly of breeds was classified.   segev et al. (2015b) population: client owned dogs presented to the emergency and critical care unit of the hebrew university veterinary teaching hospital between 2011 and 2013. sample size: 30 individual dogs presented with heat-related illness (hri) and 13 healthy staff owned dogs. intervention details: patients enrolled on diagnosis of heatstroke, inclusion criteria based on clinical signs and history. blood samples analysed for markers of acute kidney injury at specified time points. samples compared to healthy controls. clinical outcomes of cases recorded and compared. study design: prospective cohort study. outcome studied: objective assessment of signalment, clinical signs, renal biomarkers, and fatalities. main findings (relevant to pico question): 10/30 (33%) of enrolled dogs affected by hri classified as brachycephalic. of these dogs, most common breeds were boxer and french bulldog. majority of dogs affected by environmental hri; 10/30 (33%) affected by exertional hri. limitations: client consent needed for enrolment so high likelihood of selection bias. small sample size (and no sample size calculation provided). method contains limited details so unable to tell if all patients received the same treatment or if laboratory sample analysis was blinded. only recorded from one referral population, limiting generalisability. dogs euthanised on financial grounds or where owner declined treatment were excluded, which may bias the included cases, for example those with less severe presentations perceived to have a better prognosis. dogs with concurrent conditions excluded which may affect representation of some breeds (for example is some breeds are more likely to have breed-related health conditions). unknown reliability of reporting as from veterinary practicemay be subject to recall or observer bias. no record of prevalence of brachycephaly in population for comparison. limited data available for classification of breeds. full signalment data not available which means unable to compare brachycephalic breeds to other breeds presenting. no record of how brachycephaly of breeds was classified.   davis et al. (2017) population: client owned dogs enrolled at oklahoma state university. sample size: 105 dogs (52 brachycephalic). intervention details: dogs exposed to two environmental conditions using laboratory climate control system. dogs were placed in a cool environment (to assess tolerance for measurements); followed by a hot environment (to assess response for heat stress). a room temperature maintenance phase was used between tests. measures of heat stress were compared between brachycephalic and non-brachycephalic breeds (assigned based on breed type) and between hot and cold treatments. study design: case control study. outcome studied: objective measures of respiratory pattern, body temperature, tidal volume, breathing cycle duration at different environmental condition. main findings (relevant to pico question): 5/52 (10.4%) brachycephalic dogs unable to complete hot environment trial due to respiratory distress. respiratory rate increased significantly (p = 0.012) more in brachycephalic breeds than non-brachycephalic breeds when exposed to the hot environment. brachycephalic dogs had a significantly (p = 0.004) greater increase in body temperature when exposed to the hot environment. however, this effect was only present when an interaction between breed type and body condition score was removed from the model. when this interaction was included, neither the interaction nor breed type was significant. limitations: no sample size calculation provided. evaluated response to laboratory controlled environment so may not be generalisable to naturally occurring hri or heatstroke. all dogs exposed to cool temperature first and no consistent interval stated for testing meaning stress or other factors may have affected results. although significance stated, no values for increase in body temperature or respiratory rate reported in results to determine if these are meaningful increases. no dogs with boas included. brachycephaly assigned according to breed type not morphology.   appraisal, application and reflection heat-related illness (hri) and heatstroke are serious and potentially fatal conditions in dogs (bruchim et al., 2017).  the influence of breed and skull morphology are often discussed as risk factors for the development of hri (hall et al., 2020) and dogs with brachycephaly are often thought to be less able to cope with heat stress (davis et al., 2017). this is supported by evidence appraised in this summary, which suggests that brachycephalic dogs are at increased risk of hri compared to non-brachycephalic dogs. the evidence provided by the summarised papers is moderate. although there are no systemic reviews currently available for analysis, four studies were identified of relevance to the question: two retrospective cohort studies, one prospective cohort study, and one case-control study. hall et al. (2020) has a large sample size and is likely to be representative for veterinary professionals in the uk as the study utilised clinical records from primary care practice. the study focused specifically on risk factors and development of hri and identified skull shape as a significant factor for increased odds of exertional, environmental, and vehicular hri, reporting that this was more significant than breed classification. however, other factors were also found to influence risk, including age and body weight. this was in line with the findings of davis et al. (2017) which reported body condition score had a greater influence on response to heat stress than breed. it is important for this to be noted when making any recommendations with regards to breed risk for hri, as the condition is often multifactorial (hall et al., 2021). segev et al. (2015a) and segev et al. (2015b) used alternative outcome measures, but they had smaller sample sizes and are less generalisable, recording findings from one referral population, and their findings include high numbers of brachycephalic dogs affected by hri (36/126 [29%] of dogs in segev et al. 2015a and 10/30 [33%] in segev et al. 2015b). while segev et al. (2015b) does not provide a comparison of prevalence of brachycephalic breeds within the wider population, the high percentage of dogs that were classified as brachycephalic in the study does suggest that they were commonly presented with hri, and this is strengthened when contextualised alongside the findings of segev et al. (2015a) and hall et al. (2020) which contain comparisons showing an increased risk. segev et al. (2015a) has stronger evidence for the increased risk in brachycephalic dogs as it provides a comparison of the percentage of brachycephalic dogs presenting with hri, compared to the percentage presenting for other conditions at the hospital, making these results more generalisable to the wider population and reducing the chance of potential bias due to breed popularity. in addition, segev et al. (2015a) and segev et al. (2015b) selected patients that presented with more severe hri. the data has been collected from an emergency referral hospital which will be less likely to see mild cases of hri compared to primary care practice, and the inclusion criteria selected for patients with severe clinical signs of hri. the fact that brachycephlic dogs made up a high percentage of cases, and were shown to be over-represented compared to the general population in segev et al. (2015a), points to brachycephalic dogs being at higher risk of clinically significant or severe hri, although further evidence for direct comparison of severity of hri in brachycephalic vs non-brachycephalic breeds would be needed to confirm this impact. the findings from davis et al. (2017) indicated that brachycephalic dogs were more sensitive to heat stress and experience a more profound thermoregulatory response, such as higher respiratory rates or development of respiratory distress, compared to non-brachycephalic dogs. however, there are some limitations to interpretation of these studies.  it should be commented that there is a lack of standardised definitions for the condition and clinical signs of hri, both between the papers and within the veterinary field. many terms, including heatstroke, hri and heat stress are used to describe the condition and the clinical signs of hri can be non-specific, especially in the early stages. while scoring systems have been proposed (segev et al., 2015a; and hall et al., 2021) these have yet to be more widely utilised or validated. this weakens the strength of evidence and may lead to selection bias; especially as certain breeds may show more overt clinical signs related to hri without the underlying pathology of significant non-pyrogenic hyperthermia. further study and a validated scoring system for hri events would enable stronger evidence for risk factors (including brachycephaly) for hri to be generated. the impact of the lack of a universal clinical definition or scoring for hri is further compounded when looking at brachycephaly. brachycephalic breeds may more frequently demonstrate the early clinical signs of hri, such as panting, especially those that are suffering from brachycephalic obstructive airway syndrome (boas) (packer et al., 2015), as they may be less tolerant of exercise (lilja-maula et al., 2017). this may increase the likelihood of a hri diagnosis, based on their clinical signs alone without a meaningful increase in body temperature. although davis et al. (2017) attempted to address this with their ‘cool’ environment and found that in this environment there was no significant difference in the resting respiratory rates of brachycephalic and non-brachycephalic dogs, this study did not account for dogs that had been diagnosed with boas. moreover, none of the other studies included boas as an independent factor for development of hri, and several studies excluded dogs with concurrent conditions which may have included boas, so it is impossible to determine whether the effects of boas may have led to selection or interpretation bias. further study to investigate the relationship of boas as a specific risk factor for hri, including looking at the relationship between boas classification and severity of hri, would help to determine if brachycephaly alone is a risk factor for hri or whether boas is more relevant. some of the impact from the lack of definition for hri can be mitigated when considering the inclusion and exclusion criteria in the studies. hall et al. (2020) used a broad definition of heatstroke and included all recorded presentations classified as hri, from mild to severe clinical signs. this means it is likely that the breadth of the different definitions for hri were likely captured within these broad inclusion criteria. in addition, although the large number of observers (resulting from the use of primary care veterinary practice records) may have led to inconsistency, this does limit the chance of individual observer bias affecting the classification of hri and means it is likely a more representative sample of the general uk dog population as primary care cases with hri were included. although this makes the study more generalisable, it is possible that these inclusion criteria may have selected for cases where hri was not the true cause of clinical signs. however, the findings of increased brachycephalic risk for heatstroke were similar in segev et al. (2015a) and segev et al. (2015b) which had more specific inclusion criteria for dogs with more severe clinical signs of heatstroke.  moreover, davis et al. (2017) found that brachycephalic dogs developed hyperthermia more rapidly when exposed to heat stress, with significantly increased attempts at thermoregulation, compared to non-brachycephalic dogs. although this study had methodology which used unnatural conditions compared to dogs presenting with hri in veterinary practices, it does provide a standardisation of environment to ensure there is direct comparison between the different breeds and reducing the chance of differing environmental or exercise patterns being responsible for the increased risk. a further limitation for consideration was that all the studies relied on breed classification to determine whether a dog was brachycephalic. although hall et al. (2020) identified skull shape as a risk factor to increase odds for hri, the classification was based on recorded breeds and average skull morphology of the breed. the rest of the studies (segev et al., 2015a; segev et al., 2015b; and davies et al., 2017) did not state their criteria for classification of breeds. no studies evaluated skull shape or degree of brachycephaly of the individual dogs studied as an independent variable to breed classification. there will be a wide variation of skull morphology present in dogs classified as a brachycephalic breed (packer et al., 2015) especially as there will be variation in breed recording according to the observer, and not all animals classified as a particular breed will meet the breed standard for skull and muzzle conformation. this will especially impact the studies using clinical records to determine signalment. further studies where skull to muzzle ratios are recorded would strengthen the evidence and reduce the risk of bias due to breed classification. however, some of this impact will be mitigated as it is thought that breed classifications tend to represent a minimum extreme for the breed (knowler et al., 2019; and packer et al., 2015), so it is likely that the evidence is still strong for brachycephalic dogs experiencing a higher risk of hri. it should also be noted that the studies analysed are from several different countries and include widely differing sample sizes, populations, and study designs. although this means the results are not directly comparable, and therefore an overall prediction of odds or degree of increased risk is not possible, the population from the collective samples in these studies is felt to be generalisable to the population seen in veterinary practice, so provides meaningful evidence for a wide population of dogs. the findings from these studies are felt to be highly relevant for dog welfare, especially given the current popularity of certain brachycephalic breeds such as french bulldogs (o’neill et al., 2018). alongside this, there are concerns that skull and muzzle conformation are becoming more extreme in brachycephalic dogs (knowler et al., 2019, brachycephalic working group, 2020), which may further compound their risk of hri. raising awareness of the risk of hri in brachycephalic dogs is important to help protect dogs from this potentially life-threatening condition. efforts should be made to educate owners about the impacts exertional hri (segev et al., 2015a; and hall et al., 2020) as well as the risk of environmental hri, especially given the impacts of climate change which may lead to increased temperatures and extreme weather events in the uk and across the world (ipcc, 2022). overall, the studies provide moderate evidence to support brachycephaly as a risk factor in the development of hri. across all the cohort studies (hall et al., 2020; segev et al., 2015a; and segev et al., 2015b), brachycephalic dogs were over-represented in presentations of hri and in davis et al. (2017), they were found to be more affected by exposure to heat stress. to provide stronger evidence, further study including systematic reviews with meta-analysis, impact of boas and specific investigations of skull morphology instead of breed classification would be beneficial. additionally, it is also important to consider that hri is a multifactorial condition and that other factors, such as body condition score and age, are also likely to be significant factors in the development of hri in addition to skull morphology. methodology search strategy databases searched and dates covered: cab abstracts on cab direct platform (1914–week 7 of 2022) pubmed on the ncbi platform (1946–week 7 of 2022) search strategy: cab abstracts: heatstroke or "heat stroke" or "heat related illness" or "nonpyrogenic hyperthermia" or "heat stress" or "heat strain" or "heat induced illness" dog or canine or canid or canis 1 and 2 pubmed: ((dog or cani* or canine) and ("heatstroke" or "heat related illness" or "heat induced illness" or "heat stroke" or "non pyrogenic hyperthermia" or "heat stress")) dates searches performed: 21 feb 2022   exclusion / inclusion criteria exclusion: articles irrelevant to pico question. textbook, case report or expert opinion. studies not including brachycephalic breeds. studies with study populations overlapping included study (most relevant study included). studies investigating subgroups of heated related illness (hri) presentations. studies not recording proportional representation of brachycephalic breeds. inclusion: original research articles investigating hri in dogs and including proportional representation of brachycephalic breeds.   search outcome database number of results excluded – articles not relevant to pico question excluded – textbook, case report or expert opinion excluded – studies not available in english excluded – studies not including brachycephalic breeds excluded – studies with study populations overlapping included study excluded – studies investigating subgroups of hri presentations excluded – studies not recording proportional representation of brachycephalic breeds total relevant papers cab abstracts 186 75 81 2 14 3 3 4 4 pubmed 183 139 25 1 2 6 3 3 4 total relevant papers when duplicates removed 4   orcid anna ewers clark: https://orcid.org/0000-0001-6091-3109 conflict of interest article prepared with assistance from university of liverpool veterinary postgraduate unit. references brachycephalic working group. (2020). setting a limit for conformational exaggerations in dog breeds to halt the slide towards even more extreme conformations (full version). [online]. available at: http://www.ukbwg.org.uk/wp-content/uploads/2020/12/201030-full-version-bwg-position-on-setting-a-limit-for-conformational-exaggerations-in-dog-breeds-.pdf [accessed may 2022]. bruchim, y., horowitz, m. & aroch, i. (2017). pathophysiology of heatstroke in dogs – revisited. temperature. 4(4), 356–370. doi: https://doi.org/10.1080/23328940.2017.1367457 davis, m., cummings, s. & payton, m. (2017). effect of brachycephaly and body condition score on respiratory thermoregulation of healthy dogs. journal of the american veterinary medical association. 251(10), 1160–1165. doi: https://doi.org/10.2460/javma.251.10.1160 hall, e., carter, a. & o’neill, d. 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(2017). comparison of submaximal exercise test results and severity of brachycephalic obstructive airway syndrome in english bulldogs. the veterinary journal. 219, 22–26. doi: https://doi.org/10.1016/j.tvjl.2016.11.019 o’neill, d., baral, l., church, d., brodbelt, d. & packer, r. (2018). demography and disorders of the french bulldog population under primary veterinary care in the uk in 2013. canine genetics and epidemiology. 5(3). doi: https://doi.org/10.1186/s40575-018-0057-9 packer, r., hendricks, a., tivers, m. & burn, c. (2015). impact of facial conformation on canine health: brachycephalic obstructive airway syndrome. plos one. 10(10), e0137496. doi: https://doi.org/10.1371/journal.pone.0137496 segev, g., aroch, i., savoray, m., kass, p. h. & bruchim, y. (2015a). a novel severity scoring system for dogs with heatstroke. journal of veterinary emergency and critical care. 25(2), 240–247. doi: https://doi.org/10.1111/vec.12284 segev, g., daminet, s., meyer, e., loor, j. de, cohen, a., aroch, i. & bruchim, y. (2015b). characterization of kidney damage using several renal biomarkers in dogs with naturally occurring heatstroke. the veterinary journal. 206, 231–235. doi: https://doi.org/10.1016/j.tvjl.2015.07.004 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use.   veterinary evidence is an rcvs knowledge initiative. issn: 2396-9776 first floor, 10 queen street place, london ec4r 1be resources student awards staff login policies privacy policy accessing information policy cookie declaration terms of use copyright notices stay connected podcasts twitter facebook instagram linkedin back to top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443. can idexx angio detect™ accurately detect canine angiostrongylosis? a knowledge summary by natashia weir bvetmed pgcert vet anaesthesia & analgesia certavp mrcvs 1* jo ireland bvms phd certavp(em) fhea frcvs 1 1institute of infection, veterinary and ecological sciences, university of liverpool, leahurst campus, chester high road, neston, wirral, uk, ch64 7te *corresponding author (natashiaweir@btinternet.com) vol 6, issue 4 (2021) published: 10 dec 2021 reviewed by: anji jonas (bsc [hons] rvn certsan dipavn [small animal]) and adam swallow (bvsc mrcvs) next review date: 22 apr 2023 doi: 10.18849/ve.v6i4.515 pico question in dogs, is idexx angio detect™ as accurate as baermann coprology when diagnosing angiostrongylus vasorum infection?   clinical bottom line category of research question diagnosis the number and type of study designs reviewed eight papers were critically reviewed: three diagnostic accuracy studies, two cross-sectional studies (one of which also included a retrospective case series), one cohort study, one case-control study, and one case series strength of evidence weak outcomes reported angio detect™ (idexx) was shown to have low-moderate sensitivity and high specificity in comparison to baermann coprology. occasionally, false-negative results occurred with angio detect™ when compared to baermann coprology. this was thought to be due to antigen-antibody complex formation. positive angio detect™ assays were obtained in both symptomatic and asymptomatic canine patients. in an experimental setting, angio detect™ was shown to obtain a positive result five weeks post-inoculation conclusion there is weak evidence supporting angio detect™ as a highly specific and moderately sensitive diagnostic test when compared to baermann coprology   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a coughing dog with epistaxis presents to your clinic. the patient has thrombocytopenia and prolonged coagulation parameters on in-house blood analysis. the clinical presentation along with the haematological and coagulopathic deficits makes you suspect angiostrongylus vasorum (a. vasorum) infection as a potential differential diagnosis. it is possible to post a faecal sample to an external laboratory for baermann coprology (conboy, 2009), but the results will take at least 2 days to obtain. the patient’s condition is deteriorating. you wonder if the rapid in-house immunochromatography assay (angio detect™; idexx) could provide you with an accurate diagnosis within a quicker time frame compared to baermann coprology conducted at an external laboratory. the evidence three cross-sectional diagnostic test accuracy studies were found, of which two used case-control selection (schnyder et al., 2014; and canonne et al., 2018). the other study used cohort selection for the majority of the study population, but also included a group of known a. vasorum-positive cases and a control group of animals with other confirmed nematode infections (liu et al., 2017). these studies were considered to represent the most appropriate study designs; however, they are subject to biases and limitations that limit the strength of evidence provided. two cross-sectional studies included some information regarding the accuracy of angio detect™ (olivieri et al., 2017; and lempereur et al., 2020), one of which also included a retrospective case series (olivieri et al., 2017). a small cohort study at a single kennel tested dogs with angio detect™ and baermann coprology on three occasions in a 6 week period (di cesare et al., 2014). a case-control study evaluated angio detect™ and baermann coprology in dogs presenting with clinical signs suggestive of a. vasorum infection and a control group of dogs presented to participating practices for routine preventive health care or unrelated conditions (lempereur et al., 2016). one case series utilised angio detect™ and baermann coprology in addition to thoracic ultrasonography and radiography in dogs presenting with respiratory distress to participating practices (venco et al., 2021). when not included within the publication, the sensitivity and specificity (with 95% confidence intervals [ci]) of angio detect™ in comparison to baermann coprology were calculated (sergeant, 2018), where possible, and are presented in italic font within the summary of evidence tables. summary of the evidence canonne et al. (2018) population: client-owned dogs presented to the university veterinary small animal teaching hospital of liège, belgium, between march 2013–april 2017 were retrospectively selected. dogs were of various breeds, aged from 9 months–10 years. inclusion criteria were respiratory clinical signs (cough, respiratory distress or exercise intolerance) and recorded diagnostic results for natural a. vasorum infection (baermann coprology, angio detect™, and enzyme linked immunosorbent assays [elisa] both for antigens and specific antibodies). a. vasorum infection was suspected based on compatible respiratory signs (as above), radiographic findings, bronchoscopy, and bronchoalveolar lavage (bal) cytology examination. owner-reported duration of respiratory clinical signs varied from 2 weeks–2 months. angiostrongylosis was confirmed in all seven dogs by: positive quantitative (q) pcr from bal samples and clinical recovery after administration of either 50 mg/kg q24h fenbendazole po for 3 week treatment duration or 2.5 mg/kg moxidectin repeated after 2–4 weeks. sample size: seven dogs (two male, five female). intervention details: at the time of diagnosis one or two serum samples were obtained and frozen prior to analysis. one sample per dog was thawed for angio detect™ diagnostic testing. the second serum sample underwent a. vasorum antigen and antibody sandwich-elisas; both analysed at the institute of parasitology, vetsuisse faculty, university of zurich, switzerland. faecal samples were obtained from each dog over 3 consecutive days for baermann coprology. all coprology was undertaken in the laboratory of parasitology of the faculty of veterinary medicine, university of liège, belgium. study design: cross-sectional diagnostic accuracy study. outcome studied: objective assessment: positive or negative results from angio detect™, a. vasorum antigen sandwich-elisa, a. vasorum antibody sandwich-elisa and baermann coprology. positive baermann coprology result was determined by identifying l1 larvae of a. vasorum in the faeces. a. vasorum l1 larvae distinguished from crenosoma vulpis (c. vulpis) l1 larvae due to their characteristic tail notch. main findings (relevant to pico question): of the seven angiostrongylosis cases, two were positive on angio detect™ and three were positive on baermann coprology. in one dog, positive on a. vasorum antigen sandwich-elisa, the angio detect™ assay was repeated twice as invalid results were obtained (the control line was not visible). compared to baermann coprology, angio detect™ had a specificity of 100% (95% ci 39.8–100%; n = 4/4) and sensitivity of 66.7% (95% ci 9.4–99.2%; n = 2/3). not all diagnostic test results were available for each dog; however, all pico relevant data were available. limitations: small sample size. the title is suggestive of angiostrongylosis infection with negative in-house diagnostic results, which was not reflective of all seven cases. results of all diagnostic tests available for each dog were not reported. the spectrum of clinical signs and severity of the target disease (angiostrongylosis) found within the university hospital setting may introduce referral bias. the population used may not be representative of all clinical contexts. it was unclear whether the indeterminate index result (the invalid angio detect™ reading obtained twice for dog 3) was classified as a negative or positive result and therefore could introduce information and interpretive bias to the results. no postulated reason for indeterminate angio detect™ results was provided, which could aid evaluation of the usefulness of this diagnostic test within a clinical setting. no measure of diagnostic accuracy was reported. evaluation of measures of diagnostic accuracy may have aided the analysis of superiority or non-inferiority among the index diagnostic tests used. di cesare et al. (2014) population: jack russell terrier dogs that resided in a privately owned kennels with a history of a. vasorum infection, in gallicano municipality, tuscany, italy. sample size: 15 dogs. intervention details: day -15 faecal samples were obtained from all dogs for baermann coprology. blood samples were taken from all dogs and placed into ethylenediaminetetraacetic acid (edta) sample pots. plasma from each blood sample underwent angio detect™ diagnostic testing. day 0 dogs that had positive test results on day -15 testing (n = 3) were treated with topical advocate®; bayer (10% imidacloprid and 2.5% moxidectin). days 14 and 28 the three treated dogs had faecal samples collected for baermann coprology and phlebotomy for angio detect™ (methodology as above for both diagnostic tests). study design: cohort study. outcome studied: objective assessment: positive or negative results from angio detect™ and baermann coprology: positive baermann coprology result was determined by identifying l1 larvae of a. vasorum. the dog was considered negative if a. vasorum larvae were not identified. main findings (relevant to pico question): no dogs showed clinical signs suggestive of a. vasorum infection. however: dog 4 tested positive with baermann coprology but negative with angio detect™. dogs 13 and 14 tested positive with both baermann coprology and angio detect™. all three of these dogs were negative with both diagnostic tests on days 14 and 28. compared to baermann coprology, angio detect™ had a specificity of 100% (95% ci 73.5–100%; n = 12/12) and sensitivity of 66.7% (95% ci 9.4–99.2%; n = 2/3). limitations: small sample size. it was assumed eligibly was limited only to residing in the kennel as eligibility criteria were not reported. the population was asymptomatic leading to challenges in comparing data obtained to patients exhibiting clinical signs. the prophylactic anthelmintic treatment history of each individual dog prior to enrolling in the study was not reported, which could potentially introduce bias in the results. it was unclear if the population for this study had been infected with a. vasorum before during the kennel’s previous history of a. vasorum infection and if this would impact on the results. it was not clear if a veterinarian(s) conducted the clinical examinations of the dogs and what aspects of physical examination were being assessed by the individual(s). single, rather than three consecutive day, faecal samples were obtained for baermann coprology; potentially reducing baermann sensitivity and introducing measurement bias. lempereur et al. (2016) population: client-owned dogs were enrolled from one of 17 volunteer small animal practices based in wallonia, belgium from november 2014–february 2016. the study population included case dogs showing clinical signs suggestive of a. vasorum and control dogs presented to their registered clinic for conditions unrelated to a. vasorum. the clinical signs group contained dogs that presented with clinical signs suggestive of a. vasorum, including; dyspnoea, cough, exercise intolerance, bleeding abnormalities and neurological disorders. the control group contained dogs that presented to the practices for routine healthcare or unrelated conditions. eligibility for enrolment was not restricted by age, breed or sex. dogs were excluded if travel outside belgium had occurred within 3 months prior to entering the study. sample size: 979 dogs were enrolled: 757 dogs in a control group; 222 dogs in a clinical signs group. intervention details: angio detect™ test results were performed following manufacturer’s instructions with all tests undertaken within a strictly adhered 15-minute time frame. all staff undertaking the angio detect™ test were trained and observed by the first author with positive results recorded by intensity (+, ++, or +++). faecal samples were obtained for baermann coprology from 41 seropositive dogs (24 controls and 17 symptomatic dogs) and six seronegative dogs with strong suspicion of angiostrongylosis (one control and five symptomatic dogs). recently passed faeces were collected on 3 consecutive days, or one or two samples per dog where this was not possible. owners completed a questionnaire detailing the patient’s location, breed, sex, age, recent antiparasitic prophylactic protocol, and lifestyle. study design: case-control study. outcome studied: objective assessment: positive or negative results from angio detect™ and baermann coprology: positive baermann coprology result was determined by identifying l1 larvae of a. vasorum (using their characteristic tail notch to identify them compared to other parasitic larvae). the dog was considered negative if a. vasorum larvae were not identified. prevalence of a. vasorum infection in both dogs displaying consistent clinical signs and controls. main findings (relevant to pico question): control group prevalence of angio detect™ positive cases was 3.6% (n = 27/757). 3/27 angio detect™ positive cases did not have baermann coprology performed. 17/24 (70.8%) angio detect™ positive dogs had negative baermann coprology. clinical signs group prevalence of angio detect™ positive cases was 8.6% (n = 19/222). 2/19 angio detect™ positive cases did not have baermann coprology performed. 8/17 (47.1%) angio detect™ positive dogs had negative baermann coprology. 1/17 positive angio detect™ dogs had only c. vulpis larvae found on baermann coprology. 1/5 angio detect™ negative dog was positive on baermann coprology (mixed parasite burden found). of the 19 angio detect™ positive dogs: 6 were coughing 3 were dyspnoeic 3 had exercise intolerance 5 had coughing with exercise intolerance 1 had a bleeding disorder 1 had a neurological disorder limitations: volunteer bias could have been introduced due to the selection process of small animal practices. there was variability in faecal sample collection and the frequency with <3 consecutive daily samples collected was not reported. both of these factors introduce measurement bias to baermann coprology. it is unclear what time period was considered recent for faecal collection. the method of faecal storage prior to baermann coprology was also not explained. there may have been inconsistencies and variation, introducing baermann coprology measurement bias. angio detect™ positive readings were recorded as +, ++, or +++, however the relevance and results of this classification system were not explained. unable to calculate diagnostic accuracy for angio detect™ compared to baermann coprology, as only seropositive dogs were sampled. lempereur et al. (2020) population: client-owned dogs were enrolled from one of 26 volunteer small animal practices based throughout belgium and the netherlands from february–june 2017. the dogs had non-parasitic conditions (examples provided include neutering, trauma, and vaccination). dogs were > 6 months, of either sex and any breed. dogs were excluded if travel outside belgium or the netherlands occurred within 3 months or if anthelmintic treatment had been administered within 2 months of entering the study. sample size: 239 dogs. intervention details: pico relevant: faeces, collected by the owner, underwent baermann coprology. dogs underwent phlebotomy at the veterinary clinic. blood was collected in heparinised or plain tubes, centrifuged and angio detect™ conducted using manufacturer’s instructions. study design: cross-sectional study. outcome studied: objective assessment: positive or negative results from angio detect™ and baermann coprology: positive baermann coprology was determined by identifying l1 larvae of a. vasorum. the dog was considered negative if a. vasorum larvae were not identified. prevalence of a. vasorum in dogs not presenting for parasitic conditions. main findings (relevant to pico question): 3/216 (1.4%) faecal samples were positive for a. vasorum on baermann coprology. 1/237 (0.4%) serum samples were positive for a. vasorum on angio detect™. this dog was also one of the 3 baermann-positive dogs. compared to baermann coprology, angio detect™ had a specificity of 100% (95% ci 98.3–100%; n = 213/213) and sensitivity of 33.3% (95% ci 0.84–90.6%; n = 1/3). none of the dogs that tested positive by either test method had signs of gastrointestinal parasitism. limitations: volunteer bias could have been introduced due to the selection process of small animal practices. recall bias is possible regarding the owner’s recollection of whether and/or when anthelmintics had been administered, which could have affected sample selection since this was an exclusion criterion. it is unclear what time period was considered recent for faecal collection. the method of faecal storage prior to baermann coprology was also not explained. there may have been inconsistencies and variation, introducing measurement bias. no explanation for missing diagnostic test results is provided (baermann 23 dogs and angio detect™ two dogs). a. vasorum-positive dogs were reported not to have clinical signs of gastrointestinal parasitism, but information regarding other clinical signs was not reported. liu et al. (2017) population: client-owned dogs that were suspected of clinical a. vasorum infection were selected by their registered veterinarian (based within the united kingdom [uk]) during june 2012–april 2013. inclusion criteria for suspected clinical a. vasorum infection were at the discretion of the patient’s veterinarian. dogs that had been historically diagnosed (via baermann coprology performed by two authors based in either zurich, switzerland or copenhagen, denmark) were also included in the study. a control group contained samples from dogs that were a. vasorum negative but positive for other parasite infections. sample size: 214 dogs: 195 dogs suspected of being infected with a. vasorum volunteered from the uk. 19 dogs diagnosed with a. vasorum by baermann coprology via archive. an additional 89 negative control samples were obtained: 79 dogs negative for a. vasorum based on antigen elisa and positive for dirofilaria immitis (via post-mortem). three dogs negative for a. vasorum and positive for crenosoma vulpis based on baermann coprology. four dogs experimentally infected with dirofilaria repens. three dogs experimentally infected with whipworms, hookworms, and ascarids. intervention details: faecal samples obtained from the suspected a. vasorum uk cases underwent baermann coprology at idexx reference commercial laboratories. serum or plasma obtained from the suspected a. vasorum uk cases were frozen at -20°c (due to time delay between collection and angio detect™ testing). serum samples were obtained (from archive) for the historically a. vasorum diagnosed dogs. all serum samples (from uk dogs, archive and controlled) underwent randomized blind labelling prior to angio detect™ diagnostic testing undertaken by blinded personnel. in cases where baermann coprology results did not match angio detect™ results the patient’s sample underwent a. vasorum antigen elisa testing. study design: cross-sectional diagnostic accuracy study. outcome studied: objective assessment: positive or negative results from angio detect™ and baermann coprology, and a. vasorum antigen elisa (where applicable): positive baermann coprology was determined by identifying l1 larvae of a. vasorum (using their characteristic tail notch to identify them compared to other parasitic larvae). the dog was considered negative if a. vasorum larvae were not identified. main findings (relevant to pico question): dogs with suspected clinical a. vasorum infection from the uk: 16/195 of dogs (8.2%) had a. vasorum positive baermann coprology results. 15/16 dogs had a positive angio detect™ test result. the remaining dog of these 16 (i.e. with a positive baermann coprology result and a negative angio detect™ test result) tested negative with a. vasorum antigen elisa. 2/179 dogs with negative a. vasorum larvae baermann coprology result tested positive with angio detect™. these two samples also tested positive with a. vasorum antigen elisa. archive dog samples: all 19 samples were positive on angio detect™ testing. to be eligible for this group all 19 had previously tested positive for  a. vasorum larvae on baermann coprology. compared to baermann coprology, angio detect™ had a reported specificity of 98.9% (95% ci 96.0–99.9%) and sensitivity of 97.1% (95% ci 85.1–99.9%). limitations: the process of archive sample selection was not described. this could influence the eligibility of this population group, may introduce selection bias and therefore reduce the strength of the evidence obtained. the eligibility criteria for clinical a. vasorum signs were not described and were left to the submitting veterinarian’s opinion, with veterinarians possibly differing in the methods used to identify eligible cases. this could introduce misclassification bias and result in this group not being a true representation of dogs with clinical a. vasorum. it could also affect the accuracy of diagnostic data obtained. the clinical settings (e.g. first opinion, referral) of uk practices where faecal and serum samples were obtained were not noted in the methods section. this could introduce spectrum and/or referral bias as the spectrum of clinical signs and disease severity could vary in different clinical settings. the method(s) used for faecal sample transport was not described and it is unclear if they were consistent. if faecal storage was not adequate it could have resulted in false-negative results obtained by baermann coprology. the process of thawing the serum/plasma samples and duration of sample freezing was not described and it is therefore uncertain if these could have altered angio detect™ testing and introduced measurement bias. it is unknown how many faecal samples were obtained over multiple days for a single patient compared to single faecal samples submitted, which could introduce measurement bias for baermann coprology. olivieri et al. (2017) population: kennel a. vasorum cross-sectional study: dogs that resided at a kennel in italy. two breeds were present – belgian shepherds (n = 3, all males) and cavalier king charles spaniels ((ckcs) n = 17; 13 females and four males). retrospective a. vasorum case series: these were dogs that had been diagnosed with a. vasorum infection (by post-mortem, angio detect™, bal, and/or baermann coprology) and were recorded on archive at the veterinary pathology laboratories, veterinary school of milan university, italy, between 1998–2016. breeds included jack russell terrier (n = 1), cao de agua portuguese (n = 1), maltese (n = 1), springer spaniel (n = 1), italian hound (n=1), lurcher (n = 1), rhodesian ridgeback (n = 1) and mixed-breed (n = 4). ages ranged from 8 months to 144 months (but not all age records were complete). both male (n = 5) and female (n = 6) dogs were represented. sample size: cross-sectional study: 20 dogs: two clinical angiostrongylosis cases (both ckcs). 18 dogs resident at same kennels. retrospective case series: 11 dogs. intervention details: cross-sectional study: faecal samples were obtained from each dog for baermann coprology. each dog was tested with angio detect™. all of the above tests were not performed on the dog that was the second clinical case. retrospective case series: data recorded on cases within the veterinary pathology laboratories archives were examined for positive a. vasorum results. study design: cross-sectional study and retrospective case series. outcome studied: cross-sectional study: positive or negative results from angio detect™ and baermann coprology: positive baermann coprology was determined by identifying l1 larvae of a. vasorum. the dog was considered negative if a. vasorum larvae were not identified. retrospective case series: clinical signs, angio detect™ results, results obtained for a. vasorum larvae identification, post-mortem findings and clinical outcome of all cases that were recorded positive for a. vasorum in the archive records. main findings (relevant to pico question): cross-sectional study: 1 dog had positive baermann coprology and was also angio detect™ positive. compared to baermann coprology, angio detect™ had a specificity of 100% (95% ci 81.5-100%; n = 18/18) and sensitivity of 100% (95% ci 2.5-100%; n = 1/1). retrospective case series: four dogs had both baermann coprology and angio detect™ performed. of these, all four were positive on angio detect™ and only one was positive on baermann coprology. limitations: small sample size. in the cross-sectional study, the origin of each dog was recorded but the relevance of this information was not explained. additional information such as how long the dog had been in the kennel along with history of when and where any additional boarding may have occurred could have made this information more relevant. the search strategy of the retrospective case series was not included and bias may have occurred in retrieving the data due to record keeping potentially not being standardised. it is unknown how many different clinicians treated the archive cases and they may not have had standardisation of record keeping. this could introduce selection bias or could have resulted in lower numbers within this study than were truly eligible. single, rather than three consecutive day, faecal samples were obtained for baermann coprology for the cross-sectional study. similarly, frequency of faecal collection was not clear in the retrospective case series. inconsistencies potentially reduced baermann sensitivity and introduced measurement bias. schnyder et al. (2014) population: naturally infected a. vasorum-positive dogs which included: a. vasorum baermann positive dogs from switzerland. a. vasorum-positive dogs (confirmed by larval analysis) from germany that had been enrolled on previous lungworm studies. the population also included experimentally infected a. vasorum-positive dogs, some of which were treated with imidacloprid/moxidectin topical medication. there was also a control group consisting of dogs both experimentally and naturally infected with parasitic infections other than a. vasorum as well as negative baermann coprology. these dogs came from germany, switzerland, czech republic and italy. sample size: 210 dogs: the group with natural a. vasorum infection included 39 dogs the group of 38 dogs with experimental a. vasorum infection included: 10 dogs who received imidacloprid/moxidectin topical treatment. the control group contained 133 dogs. intervention details: natural a. vasorum infection group: serum was obtained from all dogs. experimental a. vasorum infected group: for 28 of these dogs that were experimentally infected with a known a. vasorum worm burden, serum samples were obtained before inoculation and also: at days 21, 35, 49, and 62 (±1) after inoculation for all 28 dogs. at days 21, 35, 49, 62, and 76 (±1) after inoculation for 20 of these 28 dogs. at days 21, 35, 49, 62, 76, and 91 (±1) after inoculation for 15 of these 28 dogs. at days 21, 35, 49, 62, 76, 91, and 97 (±1) after inoculation for four of these 28 dogs. two of these 28 dogs received serum samples up until 286 days after inoculation. baermann coprology results were available for these 28 dogs. an additional 10 dogs had serum samples obtained before and after experimental inoculation of a. vasorum. they had advocate® (10 mg/kg imidacloprid / 2.5 mg/kg moxidectin. this is the equivalent of 0.1 ml/kg advocate® product application) topically administered between days 81–110 after inoculation. baermann coprology results were available for these 10 dogs. control group: this group was enrolled for cross-reactivity testing. experienced laboratory personnel analysed all serum samples with angio detect™ (following instructions from manufacturer). serum samples were positive or negative for angio detect™ with positive bar readings being subclassified into: + meaning a visible but slight colour intensity positive; ++ meaning a good visible colour intensity positive; +++ meaning an intensely coloured positive. the serum samples also underwent a. vasorum antigen elisa testing. serum samples were either positive or negative for a. vasorum antigen elisa testing with optical density (od) readings being subclassified into: negative being od < 0.159; + being od 0.159–0.350; ++ being od 0.351–0.800; +++ being od > 0.800. study design: cross-sectional diagnostic accuracy study. outcome studied: objective assessment: positive or negative results from angio detect™ and baermann coprology: positive baermann coprology was determined by identifying l1 larvae of a. vasorum. the dog was considered negative if a. vasorum larvae were not identified. a. vasorum antigen elisa was also used to compare/confirm a positive or negative a. vasorum infection. main findings (relevant to pico question): natural a. vasorum infected group: all 39 dogs had positive baermann coprology. 33/39 dogs tested positive with angio detect™. compared to baermann coprology, angio detect™ had a reported sensitivity of 84.6% (95% cl 69.5–94.1%). experimental a. vasorum infected group: the 28 a. vasorum inoculated dogs: within 47–55 days post inoculation patency was achieved in all 28 dogs with baermann coprology. the 10 dogs treated with advocate®: one dog (which had a worm burden on post-mortem examination) was positive for angio detect™ but produced a negative result on baermann coprology. baermann coprology was negative 9–20 days after treatment, at 3 weeks after treatment three dogs had negative angio detect™ results. control group: positive angio detect™ results were obtained for both dogs that had a. vasorum and c. vulpis combined infections. compared to baermann coprology, angio detect™ had a reported specificity of 100% (95% ci 74.1–100%). limitations: the method of selecting the eligible population is not reported and there is the potential for selection bias. sensitivity reportedly based on 39 serum samples from naturally infected dogs; however methods state these comprised samples from 28 dogs from switzerland and 13 serum samples from germany from previous lungworm studies, with no explanation provided for this discrepancy. the severity and spectrum of clinical signs of the population are not reported. this makes extrapolation of the tests’ diagnostic accuracy to a clinical setting difficult. there was no explanation why not all 28 dogs within the experimentally inoculated group were tested for the same duration with both angio detect™ and antigen elisa tests. flow of experimentally inoculated participants throughout the study was also not clear. as a result, interpretation of the results should be cautious. venco et al. (2021) population: client-owned dogs presenting with respiratory distress to one of three italian clinics from november 2016–january 2020. eligible ages were 4 months–2 years (median age 10 months). sample size: 26 (11 females, 15 males). intervention details: all dogs underwent conscious thoracic ultrasonography (b-mode and m-mode) in standing position. faecal samples were obtained from all dogs (except one) for baermann coprology. faecal sample from thermometer underwent microscopic faecal smear. all dogs were tested with angio detect™. study design: case series. outcome studied: positive or negative results from angio detect™ and baermann coprology: positive baermann coprology was determined by identifying l1 larvae of a. vasorum. the dog was considered negative if a. vasorum larvae were not identified. main findings (relevant to pico question): a. vasorum-positive baermann coprology in 12 of 25 cases. angio detect™ positive in 11 of 26 cases (9 were also baermann positive). compared to baermann coprology, angio detect™ had a specificity of 92.3% (95% ci 64.0–99.8%; n = 12/13) and sensitivity of 75.0% (95% ci 42.8–94.5%; n = 9/12). limitations: small sample size. high risk of spectrum bias, since the study population comprised solely of young dogs presented for respiratory distress, and as such is not representative of the population of dogs undergoing diagnostic testing for a. vasorum infection. 25/26 dogs were reported by their owners to be receiving monthly ivermectin-based chemoprophylaxis at the time of presentation, but time since last administration was not reported. single, rather than three consecutive day, faecal samples were obtained for baermann coprology, potentially reducing baermann sensitivity and introducing measurement bias. appraisal, application and reflection canine angiostrongylosis varies from acute presentation of cardiovascular signs, neurological deficits, haematological abnormalities to subclinical infection, making diagnosis challenging to the clinician (di cesare et al., 2015). baermann coprology is the academic reference standard (mcgarry & morgan, 2009) with faecal samples collected over three consecutive days advised due to intermittent shedding of diagnostic l1 larvae (koch & willesen, 2009), which can make baermann coprology sometimes impractical in a clinical setting. baermann coprology could be considered as a suboptimal reference standard for angiostrongylosis diagnosis. variations in the pre-patent period of a. vasorum have been reported in experimentally inoculated populations (33–76 days) (oliveira-júnior et al., 2006). this poses challenges in a clinical setting, since the duration of inoculation will be unknown and during the pre-patent period larvae will not be found on baermann coprology (elsheikha et al., 2014). reduced, inconsistent larval shedding during low-severity a. vasorum infections has also been reported to reduce baermann coprology sensitivity (verzberger-epshtein et al., 2008). as baermann coprology is inexact, it is debatable whether bias could be introduced when obtaining sensitivity and specificity results for angio detect™ when considering it as reference standard (naeger et al., 2013). however, it was selected as the comparator for this knowledge summary due to the absence of a true gold standard test and because baermann coprology is commonly considered the reference standard test utilised for angiostrongylosis diagnosis (conboy, 2009; traversa et al., 2010; di cesare et al., 2014; schnyder et al., 2014; liu et al., 2017; canonne et al., 2018; and venco et al., 2021). further alternative diagnostic tests have also been suggested in the literature, such as a faecal smear (humm and adamantos, 2010), a. vasorum antigen sandwich-elisa (schnyder et al., 2011), or thoracic ultrasonography (venco et al., 2021). use of qpcr on bal could also potentially aid early diagnosis as one a. vasorum-positive dog was diagnosed 16 days prior to baermann coprology in an experimental study (barçante et al., 2008). angio detect™ may be chosen as a substitute diagnostic test due to its convenience of being a cage-side kit easily stored at room temperature. the versatility of being able to use serum or plasma, and ease of use with a result obtained within 15 minutes with minimal user training required, may also appeal to practitioners. literature comparing angio detect™ results with baermann coprology in a canine population was confined to eight papers; all containing limitations. within the pico relevant literature, only two publications calculated sensitivity and specificity values with 95% confidence intervals (schnyder et al., 2014; and liu et al., 2017). a pre-determined minimum population size is advised in diagnostic accuracy studies to reduce type-1 error affecting the sensitivity and specificity results obtained (bujang & adnan, 2016). small study populations often result in imprecise measures of diagnostic accuracy (cohen et al., 2016), and inadequate sample sizes may result in misleading estimates of test accuracy. post-test probabilities and/or likelihoods ratios were not provided, which could influence diagnostic decision making in suspected a. vasorum cases. although not reported, using the information provided, the sensitivity and specificity of angio detect™ compared to baermann could also be calculated in five included studies (di cesare et al., 2014; olivieri et al., 2017; cannonne et al., 2018; lempereur et al., 2020; and venco et al., 2021). across all seven papers (di cesare et al., 2014; schnyder et al., 2014; liu et al., 2017; olivieri et al., 2017; canonne et al., 2018; lempereur et al., 2020; and venco et al., 2021), the sensitivity of angio detect™ ranged from 33.3–100%. however, the range of specificity of angio detect™ was more consistent between these seven publications; 92.3–100%. the available evidence indicates that angio detect™ has high specificity; therefore suggesting a high probability of a negative result indicative of the patient not having angiostrongylosis (swift et al., 2020). it must also be noted, due to the small sample size in these studies, the confidence intervals for calculated sensitivity results were wide. unanimous results were not obtained using both diagnostic methods with conflicting results occurring within the literature. antigen detection inhibited by antigen-antibody complexes were considered the reason for negative results obtained with angio detect™ where baermann coprology was positive (schnyder et al., 2014; and canonne et al., 2018). collection of a single faecal sample, reading angio detect™ beyond the 15-minute timeframe and owner recall bias regarding anthelmintic treatment administration were postulated as reasons for obtaining negative baermann coprology with a positive angio detect™ result (lemperuer et al., 2016). parasites other than a. vasorum cross-reacting on angio detect™ serology did not occur in two studies (schnyder et al., 2014; and liu et al., 2017) but happened on one occasion in the case-control study (lempereur et al., 2016). further research is required on ascertaining angio detect™ sensitivity in mixed worm burdens as an angio detect™ negative result was obtained yet baermann confirmed the presence of a. vasorum with c. vulpis (lempereur et al., 2016). the three diagnostic test accuracy studies represented the best available design for determining diagnostic accuracy (schnyder et al., 2014; liu et al., 2017; and canonne et al., 2018). two of these used case-control selection (schnyder et al., 2014; and canonne et al., 2018), while the other used a cohort selection for part of the study population (liu et al., 2017). the retrospective analysis of canonne et al. (2018) could introduce selection bias; resulting in a weaker evidence strength compared to that of prospective studies. none of these diagnostic accuracy studies provided a priori hypothesis (thus data-dredging bias could not be excluded), no sample size calculations were reported and all lacked a clearly defined intended clinical role for index tests. all of the naturally infected population in schnyder et al. (2014) received both baermann coprology and angio detect™, as did all dogs in both lui et al. (2017) and canonne et al. (2018). cross-sectional studies are better suited to estimate prevalence rather than evaluating diagnostic test accuracy, therefore the evidence obtained is of low strength, but still contributes to the pico question (olivieri et al., 2017; and lempereur et al., 2020). the population size in oliveri et al. (2017) was small. although origin of the individual was recorded the relevance of this information in relation to interpretation was not explained. the sample size of the other cross-sectional study was larger overall; however, the prevalence of a. vasorum within the study population was low (lempereur et al., 2020). details on eligibility criteria were minimal and further information on why the dog presented to the clinic along with any clinical signs would have been useful due to the broad spectrum of clinical presentations a. vasorum-positive dogs can present with. it was uncertain if and when reported administration of anthelmintic treatment was based on owner declaration (which may be subject to recall bias) or clinical records (misclassification bias is possible if notes are inaccurate or if the anthelmintic was obtained from another source). due to the practices entering the study voluntarily this could introduce volunteer bias. the reason that baermann coprology and angio detect™ tests were not done on all dogs was not explained and could introduce measurement bias. the retrospective case series is low in the hierarchy of evidence for evaluation of diagnostic accuracy (olivieri et al., 2017). naturally infected case inclusion criteria were limited. the description of methods for archival retrieval was not particularly detailed, which may introduce misclassification bias if author-led selection occurred. missing data could potentially rule additional a. vasorum cases out of inclusion. it is unknown how many clinicians treated these cases with potentially no standardisation in clinical record keeping. presumably differing clinician opinion caused inconsistency in the diagnostic approach to each patient. the case-control study (lempereur et al., 2016) addressed a clear objective. descriptions of control and clinical group criteria and size were detailed. volunteer bias could have existed within population selection. efforts were made to reduce measurement bias and maintain interruptive consistency with author monitored angio detect™ interpretation and externally conducted baermann coprology. selection bias existed in determining the eligibility of dogs undergoing baermann coprology when obtaining a negative angio detect™ result due to subjectively determined allocation. not all dogs received coprology and the frequency of multiple faecal collections not occurring were not recorded. the population size was small for the cohort study (di cesare et al., 2014). population demographic information was not recorded, and the publication also lacked any statistical analysis of obtained results. the aim of the study was not clearly defined nor was the process of kennel selection, with only a single kennel purposively selected. detailed information of the kennel’s previous a. vasorum history was undisclosed. the population included in the case series was restricted to dogs under 2 years of age presenting to one of three institutions (venco et al., 2021). insufficient information was provided to ascertain if referral bias existed as the level(s) of veterinary care provided by these institutions (i.e. first opinion or referral) was not reported. there was inconsistency of faecal collection duration in the pico-relevant literature. only one study reported desiccation of faecal samples as a complication (lempereur et al., 2016), with the other studies not mentioning if this also happened. two studies did not describe methods for transporting faecal samples for submission (liu et al., 2017; and lempereur et al., 2020). the baermann technique relies on active parasite larvae to obtain results therefore fresh faeces are preferable. if delay in testing is unavoidable, faecal samples should be stored at 2–8°c and transported on ice within a 24-hour period (broussard, 2003). delaying baermann testing and/or the use of inappropriate transport media could result in false-negative results. all publications, with the exception of one (schnyder et al., 2014), were on naturally infected populations. this is more reflective of the population encountered clinically. however, details on clinical signs were missing from two studies (liu et al., 2017; and lempereur et al., 2020), which makes direct comparison of the sample populations with clinical practice difficult. additionally, misclassification bias could have occurred, but risk of this bias could not be assessed where defined eligibility criteria were not reported (liu et al., 2017). details on disease severity were also lacking in all publications, making extrapolation to the clinical scenario presented difficult. it is unknown if the experimental population in schnyder et al. (2014) displayed clinical signs. the available evidence has shown angio detect™ can obtain positive a. vasorum results in dogs displaying respiratory, haematological, and neurological signs as well as asymptomatic cases (lempereur et al., 2016). one study obtained positive angio detect™ and baermann coprology in asymptomatic dogs (di cesare et al., 2014). asymptomatic patients will not be presenting in the suggested clinical scenario. however, veterinarians should consider the possibility of encountering an asymptomatic patient; pre-surgical screening with angio detect™ was debated in a recent roundtable discussion (bourne et al., 2020). schnyder et al. (2014) highlights the earliest positive a. vasorum result could be obtained at 9 weeks post inoculation for angio detect™ in an experimental population. further research in this area is required due to patient drop-out resulting in interpretive bias in this study; however, a larger population size could be an ethical dilemma. analysing the available evidence, there is weak evidence indicating that angio detect™ is a highly specific and moderately sensitive test for diagnosing angiostrongylosis, in comparison to baermann coprology. therefore, in the clinical scenario, the application of the quick, in-house angio detect™ test will be an aid for the clinician to rule out angiostrongylosis as a differential diagnosis for the canine patient. however, it should be appreciated that the sample sizes of the studies are small and the comparator test (baermann coprology) is a debatable reference standard with questionable sensitivity due to intermittent shedding and pre-patent period. as angio detect™ has moderate sensitivity, if a negative result were obtained in the clinical scenario (i.e. a patient with high clinical suspicion of angiostrongylosis) additional diagnostic procedures, such as bal, would be advised. methodology section search strategy databases searched and dates covered: pubmed on ncbi interface (1920–april 2021) cab abstracts on the ovid interface (1973–2021 week 15) search strategy: cab abstracts: (dog* or cani* or bitch* or pup*) (angiostrongyl* or 'french heartworm' or lungworm) (baermann* or baermann-wetzel or angio detect or (angiostrongyl* and coprol*)) 1 and 2 and 3   pubmed: (dog or canine or bitch or puppy) and (angiostrongylosis or 'french heartworm' or lungworm) and (baermann or baermann-wetzel or coprology or angio detect) dates searches performed: 22 apr 2021 exclusion / inclusion criteria exclusion: literature that investigated any species (including human) other than dogs. literature that discussed any parasite other than angiostrongylus vasorum. exclusion included different species of parasite belonging to the genus angiostrongylus. published review and opinion articles. published research that focused on treatment and did not contain diagnostic results of a. vasorum in dogs. published case reports presenting four or less cases. studies on a. vasorum prevalence that yielded only one positive case with baermann and/or angio detect™. published research that did not utilise angio detect™ as a diagnostic tool. published research that only used angio detect™. published research that used diagnostic tests other than angio detect™ and baermann coprology. inclusion: peer reviewed published literature that focused on angiostrongylus vasorum in dogs (either naturally or experimentally infected) and recorded diagnostic results. diagnosis was using angio detect™ in combination with baermann(-wetzel) coprology on the same dog. the literature had to be fully accessible and could be in any language as long as it could be translated into english. search outcome database number of results excluded – population not canine and/or the parasite not a. vasorum excluded – did not use both angio detect™ and baermann; or used angio detect™ and baermann but had only one positive result excluded – publication had a treatment focus or was a review paper excluded – case study of ≤4 cases total relevant papers cab abstracts 123 40 38 11 27 7 pubmed 69 15 23 8 17 6 total relevant papers when duplicates removed 8 conflict of interest the authors declare no conflict of interest. this knowledge summary was originally prepared, by the first author, as a graded assessment for the evidence based veterinary medicine module as part of the university of liverpool’s rcvs accredited certavp postgraduate qualification. the first author wishes to thank the assessor for their feedback which has been extremely beneficial while preparing the revised knowledge summary for publication. thanks also to clare boulton, head of library and knowledge services at rcvs knowledge for assistance with the literature search during knowledge summary preparation. references barçante, j.m.p., barçante, t.a., ribeiro, v.m., oliveira-junior, s.d., dias, s.r.c., negrão-corrêa, d. & lima, w.s. 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(2021). utility of thoracic ultrasonography in a rapid diagnosis of angiostrongylosis in young dogs presenting with respiratory distress. the veterinary journal. 271(105649), 1–6. doi: https://doi.org/10.1016/j.tvjl.2021.105649 verzberger-epshtein, i., markham, r.j.f., sheppard, j.a., stryhn, h., whitney, h. & conboy, g.a. (2008). serologic detection of angiostrongylus vasorum infection in dogs. veterinary parasitology. 151(1), 53–60. doi: https://doi.org/10.1016/j.vetpar.2007.09.028 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. veterinary telemedicine: a literature review lori massin teller dvm dabvp (canine/feline) cvj1 heather k. moberly msls ahip fhea pgcert (vet ed)1, 2* 1college of veterinary medicine and biosciences, texas a&m university, college station tx 77843-4461 usa 2university libraries, texas a&m university, college station, tx 77843-4462 usa *corresponding author (hmoberly@library.tamu.edu) vol 5, issue 4 (2020) published: 30 oct 2020 reviewed by: adam swallow (bvsc mrcvs) and collette taylor (bvsc mrcvs) doi: 10.18849/ve.v5i4.349 section index:    summary | introduction | methods | results | discussion | conflict of interest | references summary as telemedicine becomes more mainstream in the veterinary profession, it is important to understand when and how to utilise it successfully, and its potential downsides. this literature review supports the use of veterinary telemedicine for teleconsultations, and using wearable and mobile health (mhealth) devices for monitoring animal health. data supporting the provision of virtual care directly to a client within an established veterinarian-client-patient relationship (vcpr) is more limited, and some of what we know comes from paediatric medicine on the human side. as we have learned from human health care providers, we must be aware there could be a tendency to overprescribe antimicrobials in a virtual visit compared to an in-person visit. data have also shown telemedicine can be just as effective in diagnosing respiratory disease when compared to traditional visits to a doctor’s office or hospital. telemedicine is especially effective in areas where access to care is limited, whether because of geography, finances, or lack of resources. overall, veterinary telemedicine and telehealth can provide positive results.   introduction telemedicine, telehealth, and virtual care are recent buzzwords in veterinary medicine, despite veterinarians practicing it for years. the animal medical center and dr. tilley (dvm) are credited with introducing telemedicine through telecardiology in 1980 by transmitting electrocardiograms over telephone lines for interpretation by a cardiologist or internist thus allowing primary care providers to benefit from advice from experts thousands of miles away (robertson, 1999). virtual care is an extension of veterinary practice that includes any interaction among clients, patients, and their circle of care that occurs remotely, using any form of technology, with the goal of delivering quality and effective patient care (american veterinary medical association & american animal hospital association, 2018). it encompasses telehealth, telemedicine, and mobile health (mhealth). this narrative review explores the literature of veterinary virtual care through four lenses: the overarching context of telemedicine in human health, teleconsulting (veterinarian-to-veterinarian), telemedicine (veterinarian-to-client), and mhealth/wearables/smartphone applications (apps). telemedicine is not a single or standardised method and as such, a review about it must begin with an overview of the scopes and definitions. this paper focuses on practice in the united states, united kingdom, and western europe and employs definitions of the topic from leading organisations in these locales. the american veterinary medical association (avma) defines telehealth as ‘the overarching term that encompasses all uses of technology geared to remotely deliver health information or education’. it defines telemedicine as ‘the use of medical information exchanged from one site to another via electronic communications to improve a patient’s clinical health status’. it also defines mobile health or mhealth as ‘a subcategory of telehealth that employs mobile devices,’ including wearables and mobile applications (avma practice advisory panel, 2017). the royal college of veterinary surgeons (rcvs) (2018) states ‘telemedicine is the use of electronic communication and information technologies to provide clinical healthcare remotely’. it further states ‘telemedicine extends to the provision of veterinary services by video link, text, instant messaging or telephone, or by any other remote means,’ (rcvs, 2018). another definition to understand is the veterinarian-client-patient relationship (vcpr). the avma (2019) defines it as: the veterinarian-client-patient relationship is the basis for veterinary care. to establish such a relationship the following conditions must be satisfied: the licensed veterinarian has assumed the responsibility for making medical judgments regarding the health of the patient(s) and the need for medical therapy and has instructed the client on a course of therapy appropriate to the circumstance; there is sufficient knowledge of the patient(s) by the veterinarian to initiate at least a general or preliminary diagnosis of the medical condition(s) of the patient(s); the client has agreed to follow the licensed veterinarian's recommendations; the licensed veterinarian is readily available for follow-up evaluation or has arranged for: emergency or urgent care coverage, or; continuing care and treatment has been designated by the veterinarian with the prior relationship to a licensed veterinarian who has access to the patient's medical records and/or who can provide reasonable and appropriate medical care. the veterinarian provides oversight of treatment; such a relationship can exist only when the veterinarian has performed a timely physical examination of the patient(s) or is personally acquainted with the keeping and care of the patient(s) by virtue of medically appropriate and timely visits to the operation where the patient(s) is(are) kept, or both; patient records are maintained.   the rcvs does not have a written definition of vcpr, however they provide information in their code of professional conduct (rcvs, n.d. [accessed 6 october 2020]): 2.29 specific advice provided remotely, for example via phone or video-link with or without additional physiological data (commonly referred to as telemedicine or telehealth), should only be given to the extent appropriate without a physical examination of the animal. the more specific the advice, the more likely it is that the animal's owner should be advised to consult a veterinary surgeon in person for a physical examination. in this scenario, the animal owner should be asked to provide the veterinary surgeon carrying out the physical examination with a copy of any advice given remotely. 2.30 veterinary surgeons should ensure as far as possible that the provision of specific advice provided remotely does not compromise welfare, since the animal has not been examined and there is no ability to monitor the animal.   the federation of veterinarians of europe (fve) does not have a specific definition of telemedicine or of the vcpr. they do recommend in the european veterinary code of conduct with regards to the utilisation of digital technology (federation of veterinarians of europe, 2019): ‘veterinarians should utilise digital and emerging technologies to enhance their provision of services as long as they can use these technologies competently, and hold up-to-date knowledge of the animal(s), of the owner and/or of the farm(s)/farmer(s).’   the fve further believes that an examination is necessary to make a diagnosis and issue a prescription. however, they state that a diagnosis can be made with a physical exam or an investigative examination of samples: ‘fve strongly believes that examination, diagnosis, recommendations for subsequent action, and the prescription of medicines or surgery are all strongly linked and must be the exclusive preserve of the veterinarian. a diagnosis cannot be made without examination, either physical examination of the animal or investigative examination of samples. a treatment cannot be recommended or a surgical intervention performed without an examination and a diagnosis. neither can a veterinary prescription be issued without a diagnosis.’ (federation of veterinarians of europe, 2019)   despite the recent surge in popularity of veterinary telemedicine, few narrative reviews were identified (devi et al., 2015; and mars & auer, 2006). veterinary telemedicine is not a new topic, commentaries, opinions, and case reports have been published since the 1980s (araújo et al., 1999; robertson, 1999; and tilley et al., 1986). in 2001, papageorges et al. wrote several articles about telemedicine ranging from an overview of ‘what it is’ to ‘how to make it work’ and ‘how to choose a system to use,’ (papageorges, 2001; papageorges et al., 2001; and papageorges & hebert, 2001a). these were part of a 2001 theme issue in clinical techniques in small animal medicine about veterinary telemedicine (papageorges, 2001). in 2007, the italian society of veterinary science (sisvet) [sic] recognised the potential impact telemedicine could have on the veterinary profession and created the first veterinary telemedicine study group. they brought together veterinarians, medical researchers, engineers, physicians, and lawyers with the goal of contributing to the development of veterinary telemedicine in italy and the european union (forlani et al., 2010). more recently some evidence-based articles documented the role of telemedicine in the veterinary profession. this is discussed later in the paper.   methods the objective of this narrative review is to survey the literature of veterinary telehealth. the search report models the prisma-s draft reporting guidelines to the best ability of the researchers (rethlefsen et al., 2019). a veterinary information specialist/librarian (moberly) in consultation with a veterinary telemedicine expert (teller) constructed and executed all searches.   information sources and methods a comprehensive literature search was conducted using three databases, citation searching, hand searching, and alerts. the search strategy was peer-reviewed. initial searches were conducted on 10 may 2019. they were peer-reviewed, updated several times during the project, and conducted for the final time on 21 january 2020. searches were conducted in pubmed using the legacy algorithm, cab abstracts using the ovid search platform, and proquest dissertations & theses global abstracts using the proquest search platform (cab abstracts, n.d.; national library of medicine et al., n.d.; and palmer, n.d.). citation searching consisted of browsing reference lists and following citing references to both keystone articles and those presenting underrepresented data. citing references were followed using web of science and google scholar. no searches were conducted simultaneously on a single platform and no study registries were searched. no additional studies or data were sought; however, one author was contacted and asked for clarification of an article. online browsing of four publications (clinician’s brief, veterinary team brief, dvm 360, and today’s veterinary business) was conducted at each publication website using the native search interface (today’s veterinary business | an official journal of the navc, n.d.). these publications were tallied in the hand searching count.   search strategies the final search strategies are presented below in a format designed to be copied and pasted for replication. screenshots of the searches within the database and search platform are available from the authors upon request.   pubmed search via legacy platform and algorithm: (((((((telecommunication or telecommunications or telecommunicat* or teleconsult or teleconsultation or teleconsultations or teleconsult* or "virtual visit" or "virtual visits" or "virtual care" or telehealth or telehealth* or telemedicine or telemedicin* or videoconference or videoconferences or videoconferencing or videoconfer* or "mobile phone" or "mobile phones" or smartphone or smartphones or telephone[mesh] or "cell phone" or "cell phones" or "remote consult" or "remote consultation" or "remote consultations" or teleradiology or telepathology or telepatholog* or telediagnosis or telediagnos* or telepet or petfax or telemetry))))))) and (((("practice management, veterinary"[mesh]) or (((office management[mesh] and veterinary medicine[mesh]))))) or (((((veterinary medicine[mesh terms]) or veterinary[title/abstract])))))   cab abstracts via ovid: ((telecommunication or telecommunications or telecommunicat* or teleconsult or teleconsultation or teleconsultations or teleconsult* or "virtual visit" or "virtual visits" or "virtual care" or telehealth or telehealth* or telemedicine or telemedicin* or videoconference or videoconferences or videoconferencing or videoconfer* or "mobile phone" or "mobile phones" or smartphone or smartphones or "cell phone" or "cell phones" or "remote consult" or "remote consultation" or "remote consultations" or teleradiology or telepathology or telepatholog* or telediagnosis or telediagnos* or telepet or petfax or telemetry).mp. or (mobile telephones/ or telecommunications/ or telemedicine/)) and ((veterinarian or veterinarians or veterinary).mp. or (veterinary medicine/ or veterinary science/ or veterinary services/ or veterinarians/))   proquest dissertations & theses global via proquest platform: noft(veterinar*) and noft(telecommunication or telecommunications or telecommunicat* or teleconsult or teleconsultation or teleconsultations or teleconsult* or "virtual visit" or "virtual visits" or "virtual care" or telehealth or telehealth* or telemedicine or telemedicin* or videoconference or videoconferences or videoconferencing or videoconfer* or "mobile phone" or "mobile phones" or smartphone or smartphones or "remote consult" or "remote consultation" or "remote consultations" or teleradiology or telepathology or telepatholog* or telediagnosis or telediagnos* or telepet or petfax or telemetry)   searches were conducted with no limits. no limits were applied to results. no published search filters were used and no search strategies from previously published literature reviews were adapted or reused. searches in pubmed, cab abstracts and proquest dissertations & theses global were updated by rerunning searches on several occasions. a comprehensive literature search was conducted using three databases, citation searching, hand searching, and email alerts of new results from database searches. final searches were conducted in pubmed, cab abstracts, and proquest dissertations & theses global on 21 january 2020. online browsing of four publications dvm 306, clinician’s brief, veterinary team brief, and today’s veterinary business was conducted at each publication website. these search interfaces were relatively unsophisticated. they each allowed truncation and returned results in a relevancy ranking. terms searched were teleconsult*, telemed*, telecommun*, telepath*, telediagn*, telerad*, telepet, and petfax. clinician’s brief and veterinary team brief use the same platform, however, they need to be searched separately. the site allowed truncation and content selection. for each publication, the articles section was searched. results were presented in a ranked order and up to the first 50 for each term were evaluated. today’s veterinary business uses a custom google search for the website which allowed truncation. the dvm 360 site simultaneously searched two other publications, vetted magazine and firstline magazine, and results from there were disregarded. dvm 360 site allowed searching of 2018 and 2019 when searched in 2019. it allowed only 2019 and 2020 when searched in 2020. searches of these publications were last updated 21 january 2020.   peer-review initial search strategies were peer-reviewed by clare boulton, head of library and knowledge services, royal college of veterinary surgeons knowledge. search strategies were edited and finalised based on peer-review input.   managing records a total of 191 records were identified in pubmed, 249 records in cab abstracts, and 17 in proquest dissertations & theses global. additionally, 42 records were identified through hand searching. this resulted in 306 records after deduplication. database results were exported from the databases into zotero, a cloud-based citation management system, (corporation for digital scholarship, n.d.). an effort was made to locate each record identified through hand searching in a database and exporting to add to zotero in order to keep the information collected about each record consistent. duplicates were identified using the zotero duplicate items function and individually verified before removal. five articles (10 items) were duplicates and treated as such; however, they did legitimately have different citations because they were identical articles each included in two tracks of the same conference (a veterinarian track and a veterinary technician/nurse track).   inclusion criteria inclusion criteria included an english language version of the article being available. there were no date or geographical limits. the topic is veterinary telemedicine, defined broadly, including remote monitoring of health characteristics and evaluation of client acceptance where it related to telemedicine.   exclusion criteria exclusion criteria included articles where no english language version of the article could be located. topical exclusions included aquaculture, telephone technology from the 1970s, remote monitoring of the physical location of animals, technology related to education, teaching distance education, client experience, telecommunication skills, marketing, conservation, infrastructure disparities (e.g. broadband), information technology, telecommunications, veterinary smartphone applications not related to telemedicine (e.g. drug dose calculations).   results telehealth in human health telehealth is a topic of significant discussion in human health care, generating a large literature that includes review articles; specialised guidelines and applications; and summaries about utilisation, reliability, and prescribing of antimicrobials (burke et al., 2015; kane & gillis, 2018; mcswain et al., 2017; ray et al., 2019; shigekawa et al., 2018; and siew et al., 2016). kane and gillis (2018) analysed physician use of telemedicine and found in 2016 that 15% used telemedicine for patient interactions and 11% used it to interact with other physicians. this was especially true of physicians in non-metropolitan areas. physicians in larger practices were also more likely to use telemedicine than those in smaller practices. this is most likely due to the financial burden of implementation (kane & gillis, 2018). shigekawa et al. (2018) published a rapid review of systematic reviews and meta-analyses on patients’ use of telemedicine. they set out to answer two questions. first, does the research evidence indicate if telehealth services are equivalent to in-person services? second, does it indicate whether the use of telehealth services affects the use of other services? the research indicated that in most cases, telehealth was equivalent to in-person care, and in some areas, like telerehabilitation and telenutrition, it was better. results varied for teledermatology, which revealed live video visits were equivalent, but store-and-forward, or asynchronous, care was not. few reviews covered the effects of telehealth’s impacts on other healthcare services, so the authors could not reach a conclusion in that regard. they did conclude telehealth has the potential to improve access to care for people in rural communities, those with transportation barriers, and those facing provider shortages (shigekawa et al., 2018). when veterinary telehealth discussions arise, frequent comparisons are made to paediatrics, especially to the care of infants and toddlers because neither they nor animals can reliably communicate their feelings or complaint. in 2017, the american telemedicine association (ata), founded in 1993, created a set of guidelines and operating procedures for the use of telehealth in paediatric medicine. these have been endorsed by the american academy of pediatrics (aap) (mcswain et al., 2017). this endorsement ‘automatically expire(s) 5 years after publication unless reaffirmed, revised, or retired at or before that time,’ (american academy of pediatrics, 2017). burke & hall (2015) state: teleconsultation works well for both acute and chronic disease. advantages of such consultations include increased access for the medically underserved, improved access for the rural and inner-city child, enhanced care through faster and more accurate assessment than can be provided by telephone consultation, and decreased cost to the health care system and the patient’s family. telepractice involves establishing links between doctors and their patients who may be located in a child care centre, preschool, school, or juvenile detention facility. telepractice does not replace the in-person visit but rather adds to it. the advantages of such links include an enhanced medical home in which personal physicians care for children; reduced health care system costs, as well as fewer school absences for the children; less money spent by parents on travel; less time away from employment for parents; and less crowding in emergency departments.   interestingly, veterinarians often quote a statement in the paediatric telehealth guidelines: telehealth services should not be provided to children under two years of age in their home or other non-clinical setting except when the provider or their surrogate primary care medical home (pcmh*) has referred them for subspecialty consultation (mcswain et al., 2017). *pcmh – patient-centered medical home   some interpret this to mean that using telehealth is not an acceptable modality of care for infants and toddlers, so it must not be acceptable for animals either. when mcswain was contacted by this author and avma staff for clarification on that statement, he provided a written letter to disabuse that notion. his letter (mcswain, personal communication, 2019) states: the above language was provided out of the recognition that children below the age of 2 years represent a high-risk population with significantly different care management best practices for common conditions than for older children. as an example, a urinary tract infection requires significantly more diagnostic work up for a child in this age group than for an older child due to the risk of an underlying causative anatomic abnormality. as such, continuity of care with a medical home was considered important by the authors as often the management cannot be completed in one encounter. additionally, examination via telemedicine may be complicated by the lack of tools that are appropriately sized or validated in this age range. the ability of the patient to communicate with the provider was not a significant consideration in the development of this provision. in most cases of pediatric telehealth, there is a guardian present during the encounter. conversely, telehealth is a valuable tool in many situations and populations in which the patient is non-communicative for a variety of reasons, including behavioral, developmental, and other medical conditions. access to care afforded by telehealth is particularly important for high risk populations. the ability to intervene early and leverage the continuum of care afforded by telehealth are benefits which we would encourage all healthcare fields to consider.   siew et al. (2016) assessed the reliability of telemedicine in seriously ill children. they examined 132 febrile children between the ages of 2 and 36 months and 145 children between the ages of 2 months and 18 years with respiratory distress. for all cases, they found good to excellent agreement between the telemedicine and bedside exams, and they concluded telemedicine is reliable in the assessment of febrile children and those with respiratory distress (siew et al., 2016). a lesson veterinarians can learn from paediatric virtual care visits is to be cautious about prescribing antibiotics. ray et al. (2019) published a study comparing prescribing antibiotics for acute respiratory infections in children 0–17 years of age. they looked at the number of prescriptions written for direct-to-consumer (dtc) telemedicine visits as compared to urgent care visits and with visits to the primary care provider. children who had co-morbidities were excluded in this study. the study indicated antibiotic prescribing was highest in dtc telemedicine visits with 52% of patients receiving a prescription, compared to 42% of urgent care visits and 31% of primary care visits (ray et al., 2019).   teleconsulting (veterinarian-to-veterinarian) teleradiology, a subset of teleconsulting that began in the mid-1980s, allows an attending veterinarian to take images, such as radiographs, cts, or mris and send them to a radiologist for interpretation. the radiologist provides a report with their findings, interpretation, potential differential diagnoses, other tests to consider, and/or possible treatment options (poteet, 2008; and tilley et al., 1986). veterinarians paid a fee for these services and passed them to the client as an accepted part of patient care. in 2001, nearly two decades ago, papageorges & tilley (2001) asked, ‘why telemedicine?’ one example was a veterinarian outside of houston, texas, who started to send all his radiographs, sonograms, and cytology to specialists via a telemedicine connection. telemedicine allowed him to elevate his practice from vaccines and a “shotgun” approach to complicated problems and provided the ability to practice higher quality medicine in a more efficient and accurate manner. his practice became more profitable as a result (papageorges & tilley, 2001). martinelli (2001) also noted that the large ratio of general practitioners to specialists provided ‘ample impetus for a telemedicine system’ and telemedicine had advantages compared to a telephone consult, including the ability to review pertinent documents and images. the job analysis of the american college of veterinary radiology regularly surveys radiologists asking about the procedures they perform, species they see, and how they spend their time to better tailor the objectives of radiology residency training (fischetti et al., 2017). in the most recent analysis, 37% of the diplomates engage in teleradiology and there is a significant trend of radiologists moving from academia to private practice. to help ensure there are enough radiologists to meet the needs of the profession, hybrid residencies bridge private practice and the academe. these private practices contribute partial funding and the academic institutions provide core educational objectives not available in a private practice, like large animal imaging or nuclear medicine. there is no obligation for the resident to remain with the private practice or academic institution at the completion of the residency. this contrasts with corporate residency sponsorship with an obligation for the resident to immediately work for the corporate sponsor and practice teleradiology preventing the newly boarded radiologist from the opportunity to develop and mature in a veterinary hospital setting where there is the opportunity to work with colleagues and continue to build experience (fischetti et al., 2017). noel et al. (2016) compared the accuracy of off-site use of smartphones and a standard computer workstation to diagnose mechanical obstructions in the small intestine of dogs and cats. there were no statistical differences in accuracy based on the device used. the only accuracy differences appeared to come from the years of experience the radiologist had, with the more experienced radiologist obtaining a higher degree of accuracy (noel et al., 2016). papageorges et al. (1998) wrote a letter to the editor of javma stating that telemedicine could alleviate the shortage of veterinarians qualified to interpret sonograms. they pointed out that there are two parts to a diagnostic scan; the skill of the sonographer that collects the images and the abilities of the person reading the scan. at the time that letter was written, there were not enough qualified individuals to interpret sonograms, so one of the solutions to the undersupply was the recommendation to utilise telemedicine (papageorges et al., 1998). marr (2001) suggested that telemedicine could be used to improve the sensitivity and specificity of equine ultrasonography techniques. navas de solis et al. (2019) documented that real time telehealth using ultrasonography is feasible and can have positive results in equine practices. there were two different phases to this study. in phase 1, an equine veterinarian in private practice performed an ultrasound exam while connected virtually with a veterinary sonographer at a veterinary college. the sonographer could visualise the ultrasound in real time and provide guidance to the private practitioner. in phase 2, horses in a teaching hospital had two ultrasound scans. the first exam was done by an inexperienced sonographer (usually a resident) with virtual guidance by a remote expert. this was immediately followed by a scan performed by an expert sonographer who was on-site. in phase 1, 100% of the remote interactions were considered useful, for the following reasons: improved case management, increased reassurance to the practitioner and/or owner about the clinical plan, educational value, and rapid input from a specialist without the need to travel. in phase 2 the residents felt that the remote assistance had both clinical and educational value. in both phases of the study, a drawback was variable internet quality, however, only one consultation had to be discontinued due to poor internet connectivity. the other negative finding, which had been expected, was that the sonograms take longer when performed by inexperienced veterinarians (navas de solis et al., 2019). other forms of teleconsulting are becoming more common. digital pathology, also known as virtual microscopy, is increasing with the development of rapid and dependable slide scanners. whole-slide images can be viewed and manipulated in all directions, and the quality of the image has nearly the equivalent optical resolution and visual magnification of a light microscope (bertram & klopfleisch, 2017). recommendations for the use of telecytology, especially for both consultations between colleagues and client education, date back to 2001 (hebert et al., 2001; and papageorges & hebert, 2001b). maiolino et al. (2006) documented 100% agreement between a pathologist’s telediagnosis and conventional glass slide diagnosis. as digital pathology becomes more common, pathologists can share images with colleagues to obtain a second opinion on a cytology or tissue sample. in this era of big data, automated image analysis is also being studied. some uses are validated for human pathology, such as certain breast cancers, but work is still needed on the veterinary side (bertram & klopfleisch, 2017). there are only 86 board-certified veterinary behaviourists in the world (american college of veterinary behaviorists, n.d.). because of the limited numbers, it can be impossible for some owners to obtain an in-person consultation to get help for their animal. the cummings school of veterinary medicine at tufts university began offering behavioural consults via fax almost 20 years ago. studies were performed to determine if there was a difference in remote vs. in-person consultations for the treatment of canine aggression toward owners and for the treatment of canine separation anxiety (cottam et al., 2008; and dodman et al., 2005). the studies revealed significant improvement in the treatment of both owner-directed aggression and separation anxiety and further showed there was no significant difference in the results whether the consult was handled remotely or in-person. more recently the university of pennsylvania school of veterinary medicine is piloting a web-based app to provide behavioural consultations to veterinarians with behaviourists (carrozza, 2018). while radiology, pathology, and behaviour may seem like obvious choices for teleconsulting, specialty fields are also utilising virtual care. papageorges & hebert (2001b) suggested many other applications for telemedicine, including cardiology, endoscopy, dermatology, and ophthalmology. oncologists are teleconsulting support to primary care practitioners because it can be difficult for non-oncologists to keep up with the various treatment modalities for cancer in multiple species. additionally, clients may not have the resources to travel to a specialist for regular chemotherapy appointments, but a veterinary oncologist can provide support and guidance to an interested general practitioner to appropriately manage the case. penzo & pietersma (2012) outline potential benefits of oncology teleconsultations including: improved access to specialist oncology care, specific case-oriented advice, elevated level of care in a primary care practice, increased profitability from more advanced diagnostics and therapies, and increased range of services offered by the practice. further benefits include assistance with interpretation of lab work and staging of the cancer, possible prognosis depending on treatment plan that is chosen, palliative care, appropriate drug handling and administration, and educational information for staff and clients. potential drawbacks may be the inability of the specialist to perform a complete work-up, including physical exam, the skillset of the general practitioner, a perceived threat to the role of the specialist, and concerns about medical liability and malpractice (penzo & pietersma, 2012). lanevschi-pietersma et al. (2011) consider telemedicine both a time management and educational tool for veterinarians and their clients. virtual consults with a specialist can provide the primary care practitioner a patient-specific written report with recommendations for diagnostics and therapeutics. these can be added to the patient’s medical record and a copy provided to the client. there is a difference between a request for a structured consult and an informal consultation that may take place on an electronic forum. virtual consults also tend to be more efficient than telephone or email exchanges where the appropriate information may not be provided at the time of the request, resulting in much back-and-forth communication. when a primary care practitioner works with a specialist via a virtual visit, clients seem to appreciate the team approach to the patient’s care, especially when referral is not an option (lanevschi-pietersma et al., 2011). niessen & forcada (2019) note primary care practitioners appreciate the ability to informally request help from a local specialist or an academician, but the time demands and the sheer increase in demand for these services is leading to the need for scheduled virtual consults occurring in real time. virtual consults can also provide a support system for veterinarians in primary care practices, especially solo practitioners or those presented with complicated or unusual cases. often, a specialist or more seasoned practitioner can guide an attending veterinarian in remote ultrasound, ophthalmologic exam, or in the identification of abnormal heart sounds. digital stethoscopes, otoscopes, ophthalmoscopes, and other technology make some aspects of a virtual exam easier to perform. veterinarian-to-veterinarian teleconsulting also provides the possibility for mentorship, especially for veterinarians in rural practice or in the case where a younger veterinarian is also a new business owner and is feeling the dual stresses of practice and owning a new business (niessen & forcada, 2019). in an interview in beef magazine, dr. arn anderson (dvm) praises the ability of telemedicine, ‘between dvms, this technology allows us to mentor younger veterinarians in rural environments and allows us to share cases and get second opinions easier and faster. it is better medicine,’ (ishmael, 2015). dr. anderson goes on to state rural veterinarians can increase the ‘scope and sophistication‘ of their practice and clients do not have a problem paying for telemedicine services (ishmael, 2015).   telemedicine and its role in global health telemedicine is seen as part of the future of animal health care in developing countries where there may be neither enough veterinarians to meet workforce needs nor an adequate veterinary infrastructure. the national research council (2013) states the veterinary profession needs to expand its capacity to address complex global problems. in india, there is enough work to support 67,000 veterinarians, but there are only 34,500 veterinarians available to meet their needs for both animal and public health (devi et al., 2015). animal health care workers in india see the potential for consulting with specialists, including dermatologists, radiologists, pathologists, surgeons, and cardiologists to receive assistance with diagnostic, prognostic, and therapeutic planning. they also appreciate the role remote monitoring can play to improve herd health management and disease prevention. the major barriers to implementing telemedicine in developing countries are interstate licensing issues, confidentiality concerns, broadband and internet connectivity, and potential ethical issues and cost effectiveness (devi et al., 2015). in developing countries in africa, telemedicine conducted with smartphone-based technology has been used to increase referrals from paraprofessionals to veterinarians in countries like kenya and uganda (ilukor et al., 2014). many countries rely on paraprofessionals, defined by the world organisation for animal health (oie) (2019) as: a person who, for the purposes of the terrestrial code, is authorised by the veterinary statutory body to carry out certain designated tasks (dependent upon the category of veterinary paraprofessional) in a territory, and delegated to them under the responsibility and direction of a veterinarian. the tasks for each category of veterinary paraprofessional should be defined by the veterinary statutory body depending on qualifications and training, and in accordance with need.   because of potentially detrimental impacts on animal disease, public health, and the overuse of antimicrobials by paraprofessionals operating without veterinary oversight, the oie recommends strengthening the bond between paraprofessionals and veterinarians (ilukor et al., 2014; and oie, 2019). with this improved bond, expectations include more appropriate pharmaceutical prescriptions, improved diagnoses, more accurate disease surveillance, and better adherence to veterinary care standards. ilukor et al. (2014) noted paraprofessionals with smartphone devices were much more likely to refer to a veterinarian because these devices increased access and allowed better communication. veterinarians also saw clientele growth when they improved the bond with paraprofessionals and encouraged referrals. increased referrals are expected to lead to decreases in the prevalence of infectious and zoonotic diseases, like brucellosis, tuberculosis, and rift valley fever, leading to public health improvements. some potential impediments are lack of broadband connectivity and the difficulty of farmers to differentiate between the quality of care provided by paraprofessionals vs veterinarians, both of whom are called animal doctors (ilukor et al., 2014). global health has become increasingly more important to ensure a healthy food supply and in the identification of potentially zoonotic emerging diseases. in addition to the benefits telemedicine can provide to address these issues in developing countries, it can also be used as an educational tool for students to better understand these problems and the role developed countries can play in helping to resolve them (mazan et al., 2015). in many developing countries, the population remains dependent on small-scale agriculture for income. working equids, like donkeys, mules, and horses are the mainstay of the agriculture industry. though people depend on working equids, particularly donkeys, the farmers frequently do not have the financial resources to provide veterinary care. the cummings school of veterinary medicine at tufts university partnered with the veterinarians at the american fondouk in fez, morocco, and the equitarian initiative (minnesota, u.s.) to provide speciality veterinary care via teleconsulting to the farmers and their equids. in addition, students participated in these virtual visits and learned about problems faced in developing countries. calling their programme “patients without borders” the two institutions and initiative utilised both synchronous video visits and asynchronous exchanges of information. the donkeys benefitted from expert care that the farmers did not otherwise have access to, and the students benefitted from new educational experiences. the biggest obstacles were unstable internet connections and time zone differences. imaging – whether radiographs, sonograms, or endoscopic exams – were provided ahead of video visits to limit the use of bandwidth during virtual visits and to allow the faculty and students time to review the information. students saw medical conditions they would not see in the u.s. or conditions they might have been familiar with but required different treatment options because of limited resources available in morocco (mazan et al., 2015).   telemedicine (veterinarian-to-client) this review identified less peer-reviewed research about assessing virtual care between a veterinarian and the animal-owning client. many opinions and editorials discuss both the benefits and concerns around providing telemedicine visits to the animal owner, whether a veterinarian-client-patient relationship (vcpr) exists or not. gyles (2019) noted the value of a telemedicine service is it can guide clients to the ‘appropriate level of intervention’ and clients are willing to pay for this convenience. the consistent message across many of these opinion pieces and editorials describes the benefits of telemedicine: improved access to care, client convenience, enhanced veterinary-to-client bond, reducing the workload on front office staff, and a better choice than the client consulting the internet (freiman, 2019; and lacroix, 2017). in addition, the articles also address concerns, like risks of missed diagnoses, lack of physical exams, differences in communicating via technology compared to in-person, monetisation of virtual care visits, and limitations of technology (limb, 2018; and milani, 2009). many of these pieces also question if there is a need to establish a vcpr virtually or if it must be established with a hands-on physical exam, or a timely visit to the premises where animals are maintained, in every instance (cary & massecar, 2017; and cushing, 2017). others accept virtual care is part of veterinary medicine, are ready to incorporate new technologies into their practice, and want regulatory bodies to keep pace (nelson-pratt, 2018). veterinary teams are encouraged to think outside the box and find ways to help their clinicians incorporate virtual care into the practice (cushing & lacroix, 2018; and rose, 2017). many veterinarians are interested in using telemedicine in their practices, but they have concerns about further infringement on their personal time or if telemedicine will disrupt their already busy day-to-day workflow (freiman, 2019). there are also legal and ethical concerns when it comes to virtual care cases between veterinarians and clients (flemming, 2003; and marshall, 2019). almost every jurisdiction around the world requires a license to practice veterinary medicine and most have some sort of definition in statute that defines the practice of veterinary medicine. some states in the u.s., like kentucky, consider the act of providing general advice to be the practice of veterinary medicine, whether there is an established vcpr or not. others consider general advice to be allowable, but there must be an established vcpr to make a diagnosis, create a treatment plan, or prescribe medications (flemming, 2003). there are also concerns about the location where the vcpr is established and where the veterinarian is licensed and how that will be enforced. this is important from both a regulatory perspective and a liability perspective (jack, 1999). it is generally accepted that technology and innovation advance more quickly than regulations and ethical considerations related to them. some ethical concerns to consider as virtual care and other technologies evolve include data usage, client privacy, and security of medical records and credit card data (marshall, 2019). professional regulatory agencies in europe have not paid much attention to veterinary telemedicine, and in portugal it is not considered an acceptable form of practice by the portuguese veterinary order (ordem dos médicos veterinários, omv) which prohibits virtual examinations and prescriptions, though these restrictions were temporarily lifted during the covid-19 pandemic (mãgalhaes-sant’ana et al., 2020). as part of its preparations for a new code of professional conduct, the omv conducted a policy delphi study in 2018 to determine the views of portuguese veterinarians about telemedicine to guide policymaking. the vast majority of respondents agreed that there should be limits on the use of telemedicine in practice, and they further believed that omv should encourage digital literacy and certification of telehealth providers. in the comments, ‘most participants acknowledged that the service provided by teleconsultations is complementary to that of physical consultations but stressed the need for having a face-to-face interaction before resorting to telematic means. others questioned this view; a small animal practitioner noted that in urgent cases, such as poisoning and heat stroke, performing a teleconsultation ‘can mean the difference between life and death.’ it was also mentioned, namely by a specialist respondent, that, in the case of behavioral medicine, since examining animals in their home environment is particularly beneficial, remote consultations should be allowed for both first consultations and follow-ups, according to the judgment of the specialist veterinarian.’ as this study was conducted before the covid-19 outbreak, the authors recommend further research to determine if opinions have evolved. they also recommend that more research be done on the impacts of telemedicine on animal welfare and antimicrobial resistance (mãgalhaes-sant’ana et al., 2020). kogan et al. (2016) surveyed veterinarians to determine how information and communication technologies are utilised in veterinary practices. responses from 967 veterinarians showed younger veterinarians were more comfortable with newer technologies, like texting, skype, and social media; however, they were the least likely to engage in consultations after hours and on weekends. older veterinarians were more likely to support the use of remote monitoring devices. many veterinarians felt that communicating with their clients via email or text could be less time-consuming than via phone or in-person if appropriate boundaries could be set. some scenarios they identified as requiring less time with a virtual visit were post-operative recheck visits, management of diabetic patients, and nutritional counselling. of note, older responders were more likely to identify several scenarios where virtual visits could be appropriate compared to their younger counterparts (kogan et al., 2016). in a survey of pet owners, that received 1,031 responses, who had had a dog or cat hospitalised for longer than 4 hours, many expressed the desire for more frequent updates than what they received. over two-thirds wanted updates every 2–6 hours and over half of the respondents were willing to pay a premium for regular updates. most updates were relayed via phone, but over 38% of owners would prefer text updates. it was noted that veterinarians may want to consider using more text updates, when appropriate, as those can be less time-consuming than phone updates. millennial pet owners have cited chat or texting as the most important veterinary service they want (kogan et al., 2019). one of the weaknesses of data collected by surveys is that the sample sizes may not adequately represent all cross-sections of the veterinary practitioner or pet-owning populations (kogan et al., 2019; and kogan et al., 2016). hawk (2018) surveyed facebook users to determine the perception and use of telemedicine by veterinarians and by owners. the sample size of 176 respondents included only seven veterinarians or veterinary students making that population statistically insignificant; however, pet owners responses indicated their three top concerns when interacting with a veterinary practice are the humane treatment of their pets, the ease of scheduling, and a timely response. the owners also had a positive attitude toward veterinary telemedicine, especially about potential emergencies. this was statistically significantly true for people aged 18–44 years old compared to those who were aged 45–75. the study also showed owners were willing to pay for virtual care visits (hawk, 2018). robben et al. (2016) evaluated the impact on pet owners and intensive care unit (icu) staff of a virtual pet visit system with live video streaming. when a pet was admitted to the icu, the clients were offered the ability to view their pet through a telepet live-streaming service (tps). the pet owners who utilised the tps were found to be more satisfied with the care their pets received than the pet clients who did not opt to use the service. the vast majority who took advantage of the tps felt less anxious about their pet and would be willing to pay for the service. the veterinary technicians working in the icu also had generally favourable responses to the use of the tps, though tempered by the negative comments they received from a few dissatisfied clients who were concerned about what they saw on the video footage. there was no way for this study to be blinded or randomised, but overall the results revealed clients had positive experiences with it. some clients were distressed by the video, so tps would not be appropriate for everyone (robben et al., 2016).  in addition to noting that consumers are willing to pay for telemedicine, it is also important to note that providing telemedicine does not have to costly. papageorges & hebert (2001c) recognised that telemedicine can be performed using standard technologies and available tools instead of purchasing expensive equipment from vendors. they summarise by stating; ‘we should harness the power of the internet to give us the communication tools and the freedom we need to practice medicine the way we believe is best.’ one of the most frequently recommended telemedicine techniques for veterinarians is post surgical recheck exams. bishop et al. (2018) randomised 30 client-owned dogs into two groups for examinations following surgical sterilisation. in one group, the dogs were rechecked virtually (telemedicine group) and the dogs in the other group were rechecked in the veterinary clinic (control group). none of the dogs randomised to the telemedicine group had a surgical complication necessitating a visit to the clinic. the most common problem was a slow internet connection reducing the quality of the audio-visual feed. the rechecks were still able to be completed virtually. there were two minor surgical complications in the control group randomised for the in-clinic rechecks. owners from both groups were satisfied with the recheck visits; however, the owners from the telemedicine group felt their dogs were less stressed or fearful than if they had taken them for the in-clinic recheck. these owners would strongly prefer to utilise telemedicine for similar appointments in the future, supporting the hypothesis owners found telemedicine visits to be a useful and satisfactory alternative to in-clinic appointments. the owners of the dogs in the telemedicine group also saved, on average, 50 minutes of travel time to and from the clinic. one of the advantages of telemedicine highlighted in this study was the ability of virtual care to reduce stress and anxiety in animal patients. one limitation to the study is, while the patients were randomised to the control or telemedicine groups, there was no way for the owners or practitioners to be blinded to the modality used for the recheck exams, which could bias responses (bishop et al., 2018). military working dogs (mwd) perform a wide variety of tasks including being deployed with u.s. military forces without access to veterinary care. donham & wickett (2018) documented the usefulness of virtual care when a mwd became ill at a remote outstation and sepsis was suspected. the dog was transferred to a canadian role ii medical facility where more medical resources were available but not a veterinarian. the staff interacted with the mwd’s veterinarian in the u.s., who was able to work with them, obtain diagnostic information, formulate a plan to stabilise the dog, facilitate evacuating the dog to a military base in germany then to his home station for more care. interestingly, it was the ability to videoconference that made the difference in this dog’s care because verbal descriptions did not adequately convey the severity of the dog’s condition and the visual impression did. the case report concluded that in ‘austere expeditionary settings where medical specialties are frequently unavailable, and given the spread of internet technology to rural settings, the use of video calling for virtual consultations has the potential to improve care in the deployed setting,’ (donham & wickett, 2018). veterinarians with exotic animal practices have debated the benefits and concerns with telemedicine too. they recognise the advantages of teleconsulting and the potential benefit for situations with a recent hands-on examination of the patient, but they have concerns about establishing a direct relationship with a client and providing care to the patient without a physical exam having taken place. many companion exotic animal practitioners see virtual care has a place in husbandry, environmental, and nutritional issues (hess, 2017).   mhealth, wearables, smartphone applications the growth of wearables, smartphone applications (apps), and other technology makes it easier than ever to collect data about an animal’s activity, mobility, food consumption, and other health data. cardiac arrhythmias can be difficult to diagnose in dogs, and frequently require the utilisation of a 24-hour holter monitor. these are not always readily available, do not support long-term monitoring, and some animals are intolerant of wearing them. recently several studies show promise for alternatives to the holter monitor in dogs. brloå¾nik & avbelj (2015) piloted a wireless body electrocardiogram (ecg) to investigate whether it could surmount the limitations of a holter monitor; the results showed great potential. the sample size was very small, and a study with a larger population of animals is pending (brloå¾nik & avbelj, 2015). lichtenberger et al. (2018) published a preliminary assessment of a single-lead, 14-day ecg adhesive patch monitor (apm). again, the sample size was small, and the results were comparable to those obtained with a 24-hour holter monitor. they found that the adhesive caused some mild skin irritation and walking, running or playing caused intermittent motion artefact, but they could still obtain analysable data over 93% of the time that the dogs wore the patch (lichtenberger et al., 2018). smartphone apps may also play a role in what information can be gathered and shared through a virtual visit. two independent prospective studies compared a smartphone-based ecg with a standard 6-lead ecg in dogs and cats. the ecgs were measured simultaneously with the smartphone app using a single-lead recorder coupled to it while the reference ecg was recorded with a standard 6-lead ecg machine. kraus et al. (2016) performed a study that included 51 dogs and 27 cats. three board-certified cardiologists read each ecg; there was 100% agreement in heart rates between the two methods, and intra-observer agreement for rhythm diagnoses was extremely high. the only time where there was significant disagreement was in the qrs polarity readings in cats. it is possible this occurred because the electrodes for the two devices were not placed in the same spots (kraus et al., 2016). vezzosi et al. (2016) performed a prospective, multi-centre study with a similar design and evaluated 166 dogs. 20% of the dogs in this study were healthy, and the remainder had a variety of morbidities, including heart disease, cancer, and respiratory, gastrointestinal or neurologic disease. this study found the smartphone ecg app had 100% sensitivity and 97.9% specificity in the detection of arrhythmias, and all cases of atrial fibrillation were correctly identified. the ecg app was also excellent at identifying ectopic beats and may be useful for screening or monitoring dogs with cardiomyopathies for arrhythmias. one limitation to the smartphone ecg app is mean electrical axis cannot be calculated because it captures a single lead (vezzosi, et al., 2016). however, the study authors concluded the smartphone ecg app may allow veterinarians to identify and manage patients at cage side and share the results via electronic means with specialists (kraus et al., 2016). further studies should be done to determine the diagnostic value of owners using the smartphone app in the home setting and sharing the results with the veterinarian. vezzosi et al. (2018) also recently validated a smartphone ecg app in a study with 50 horses. the study showed comparable findings to those in dogs, except there was not good agreement on the polarity of p waves. there was excellent agreement for heart rate and rhythm (vezzosi et al., 2018). dogs and cats are not the only animals where monitoring ecgs can be of benefit. changes in heart rate in cattle can provide warning signs for illness and disease, which require early detection and intervention to prevent spread through a herd. warren et al. (2008) studied a prototype electrocardiographic pill that would remain in the reticulum and allow for continuous and automatic acquisition of heart rate and core body temperature. the study showed promise in allowing the capture of information about the cattle’s health without requiring restraint (warren et al., 2008). the fever tag® is an ear tag that monitors a calf’s body temperature every 15 minutes and alerts when the temperature deviates from normal parameters which may happen up to 72 hours before the calf shows signs of illness, particularly pneumonia. by signalling the onset of illness, a rancher can intervene early in the course of disease, thus limiting morbidity, mortality, and the use of antimicrobials. mccorkell et al. (2014) tested the efficacy of the fever tag® in feedlot calves just obtained from auction and in specific pathogen-free calves experimentally infected with bovine viral diarrhoea virus. there were no instances of false positive diagnoses of bovine respiratory disease (brd), but there were significant instances of false negatives and inconsistent readings. the study concluded significant improvements were needed in fever tag® accuracy and reliability (mccorkell et al., 2014). however, 3 years later, mahendran et al. (2017) showed that by using the fever tag® to monitor calves’ body temperature, they could determine when the calves became ill and their response to therapeutic interventions. in addition to sensing body temperature changes from respiratory disease, the fever tag® was also useful in diagnosing navel ill and diarrhoea (mahendran et al., 2017). other technology that can aid in the early detection of brd is a computer-aided lung auscultation system, such as the whisper® stethoscope. the stethoscope is used to auscultate lung sounds of cattle and then score the sounds from 1–5, with 1 indicating no abnormalities and a low likelihood of brd. mang et al. (2015) tested the technology on 561 steers recently arrived at a feedlot. there was very good specificity and sensitivity when utilising the device, though there was a wide confidence interval. they further concluded, because of the higher specificity of this device, there were less falsely diagnosed cases of brd and thus less use of antimicrobials in the feedlot (mang et al., 2015). noffsinger et al. (2014) conducted field trials with the whisper® stethoscope to determine the relative accuracy of whisper® scores and rectal temperatures in diagnosing brd. two data sets were used. the first involved the correlation between rectal temperatures, manual lung scores, and case fatality rates in feedlot cattle pulled for brd. the second data set evaluated the relative accuracy of the whisper® scores and rectal temperatures. when taken alone, the whisper® score was a better predictor of brd than a rectal temperature ≥104.5ºf; however, a whisper® score of 1 and no fever was the best predictor of survival. manual lung scores better correlated with case fatality rates. using the whisper® score and rectal temperature in combination improved diagnosis and prognosis, and allowed for more judicious use of antimicrobials (noffsinger et al., 2014). cats may easily become stressed with restraint and repeated handling, especially when ill. this can be especially problematic when attempting to acquire a rectal temperature. quimby et al. (2009) compared digital rectal and microchip transponder thermometry in 40 cats that were experimentally infected with feline herpesvirus type 1 (fhv1). the cats’ temperatures were measured both before and after infection with fhv1. there was sufficient agreement between the digital rectal and the microchip transponder thermometry to consider the microchip a valid substitute for obtaining a rectal temperature (quimby et al., 2009). smartphones and accessories are utilised at cage-side in exotic animal practices. these devices are particularly useful when it may be difficult or dangerous to transport wild or zoo animals, or the animal may be in a fragile or debilitated state making transportation risky. huynh (2019) summarised the use of smartphone devices in exotic animals. as with cats and dogs, smartphone apps can obtain ecgs in exotic animals, like penguins, though dolphin vocalisations can create artefacts. there are also smartphone attachments for direct ophthalmoscopy; the structures in the posterior segment could be identified in all animals, though focal light artefacts were common when the tapetum lucidum was photographed with certain devices. non-clinically trained personnel were able to obtain acceptable images of the fundus, indicating potential for these devices in areas with limited resources. otoscopes, laryngoscopes, cystoscopes, and endoscopes are available as smartphone attachments. huynh (2019) states: the main advantage for using a smartphone over a conventional endoscopic unit is the increased portability, accessibility, transmission, and lower price. recording of the procedure and tele-transmission can be performed instantaneously.   there are also point-of-care ultrasound devices that can be utilised for obtaining sonograms of exotic animals which may be particularly useful for focused assessment with sonography for trauma (fast) exams (huynh, 2019). vallone (2019) wrote about using smartphone technology in clinical ophthalmology without expensive accessory equipment. current smartphone technology, teleophthalmology is expected to increase (vallone, 2019). kanemaki et al. (2017) also used a smartphone and an indirect ophthalmoscopy lens to obtain various fundic images in dogs and cats. it was noted the photographer may need to adjust the exposure to account for the range of tones in the bright tapetum lucidum and the darker, pigmented non-tapetal area (kanemaki et al., 2017). normal and abnormal brain functions include cognition, wakefulness, and sleep. these change during anaesthesia making it extremely difficult to determine the effects of trauma, disease, and epilepsy in animals. in human medicine, there have been advances with the use of electroencephalograms (eeg), but these are often difficult to obtain for animals. cousillas et al. (2017) created an ambulatory eeg system that would allow horses to freely move about in their home location. the preliminary study was done with five horses trained for competition events. the study authors were able to obtain analysable eegs from each horse and could identify alpha, beta, and gamma waves. the eeg system obtained its goal of being easily placed and fitted on each horse, the horse could be mobile in its home environment, and it did not put any more constraint on the animal than any usual gear. further studies will need to be done to determine accuracy when asleep or under anaesthesia (cousillas et al., 2017). maclarty et al. (2007) have compared a non-invasive biotelemetry shirt with whole body plethysmography in african green monkeys. the shirts provide a non-invasive method to continuously collect physiologic data, like respiration rate, ecg, activity, body temperature, blood pressure, eeg, and more without having to restrain the animal or surgically implant biotelemetric devices. the study concluded the biotelemetric shirt could be used in place of interpretive plethysmography studies and respiratory evaluation and allows for the animals to move about normally while continuously collecting data (maclarty et al., 2007). diabetes mellitus in cats and dogs is a common endocrine problem that can be difficult to monitor and control. home glucose monitoring is preferable to monitoring in the veterinary hospital because stress hyperglycaemia can lead to inaccurate results. many clients are reluctant or unable to obtain blood samples from their pets for frequent blood glucose checks. a continuous blood glucose monitor can make this easier for cat owners, though the only one that does not require the pet owners to calibrate at home is the freestyle libre (abbott laboratories, 2020). this sensor can be used to take multiple measurements for up to 14 days (gottlieb & rand, 2018). after gathering the data from an at-home glucose curve, the client can schedule a virtual visit with the veterinarian and adjustments in the treatment plan can be made as needed. there are studies that have shown the accuracy of the freestyle libre compared to glucose curves, and the clinical accuracy makes continuous glucose monitoring an attractive alternative for pet owners (corradini et al., 2016; and malerba et al., 2020). high-tech wearables are tracking activity and providing clues to the early-onset of problems as well. wearable devices can be attached to an animal’s collar and track how active a dog is, how often a cat uses the litterbox, or if pets are making more frequent trips to the water bowl. subtle changes may go unnoticed by the owner, but the data can reveal possible signs of infection, kidney disease, or an endocrinopathy. food bowls can read an animal’s microchip and be pre-programmed to open only for specific animals at set times to dispense a premeasured quantity of food. they also allow multi-pet homes to feed different foods and amounts to specific animals to assist with weight-loss plan or use of prescription foods. a report from grand view research states: in coming years, the combination of wearable devices, mobile application, and data analytics technology can be a mainstream option for the value-based care. some pet wearable companies are also providing cloud-based data analytics services along with their products, which can help veterinarians to diagnose and treat pets by providing valuable clinical information for real-time decision making (jergler, 2018).   one of the major limitations to wearables is battery life, though it improves with each iteration (jergler, 2018).   discussion this literature review identified increasing literature about veterinary telemedicine including both peer-reviewed studies and less rigorous articles in veterinary news magazines, like anecdotal reports, editorials, and opinion pieces. there is robust data to support virtual care for veterinary consults, as shown in a variety of studies, like those on radiology, pathology, cytology, behaviour, and cardiology. data also supports teleconsulting to improve animal care in areas where resources may be limited, including rural areas, developing countries, and other remote locations. there is also a growing body of evidence to support mhealth, the role and the use of wearable devices, and smartphone applications in veterinary medicine. teleconsulting and mhealth have been shown to be effective across many species, including companion animals, exotics, equids, and food animals. there are fewer published studies about direct-to-consumer (dtc) telemedicine visits. these have been favourable, but most information about this has been gleaned from human health care. if human paediatrics is used as an analogy to veterinary medicine, studies in paediatric telehealth can lead to cautious optimism for veterinary medicine to observe similar outcomes. veterinarians need to learn from paediatrician’s successes and their deficits, for example judicious use of antimicrobials. legal concerns will persist, though no published reports of veterinarians providing inadequate or substandard care via virtual care were identified. there was one lawsuit related to telemedicine, though that case involved the violation of vcpr laws, not the care actually provided (ronald s. hines, d.v.m., v. texas state board of veterinary medical examiners, n.d.). this review identified a number of published anecdotes of successful veterinary visits; however, those have not been analysed for publication in a peer-reviewed journal. the literature also lacks studies comparing in clinic visits with telehealth visits to determine if there is concordance between the findings of those exams. in general, the literature agrees telemedicine has a role in veterinary medicine. based on studies of newly-boarded veterinary radiologists, it may also be important new graduates obtain experience in practice before performing virtual care visits unless an experienced veterinarian is available for support. it is important to note that telemedicine is a tool, and as such, it is not appropriate for every healthcare issue, situation, client, or animal. the challenges of providing veterinary care during the onset of covid-19 and lockdowns in many areas led to a significant uptake in the utilisation of veterinary telehealth. this will lead to additional research and peer-reviewed publications that will further advance our knowledge of how telehealth is incorporated into veterinary practice, including benefits, risks, outcomes of those visits, including successes and adverse events.  the creation of guidelines like the american telemedicine association and the association of paediatrics would most likely benefit those in the profession who would like to use veterinary virtual care in practice. no one summed it up better than bath (2006), in a letter to editor, who wrote, ‘the conclusion is that telemedicine is not something abstruse and only for the boffins. it is useful and simple to use, even today. it can only get better and its use become more widespread…’ it is time to move forward with veterinary telemedicine using thoughtful consideration to the benefits and concerns that surround any tool integrated into veterinary practice.   conflict of interest this commissioned review was the basis for the 2019 vivet innovation symposium talk, ‘rcvs knowledge – evidence into practice & initial findings of the telemedicine study’ (teller, 2019; and vivet press office, 2020). the review was further expanded and updated for this paper. acknowledgements: the authors gratefully acknowledge l. m. rey for assistance with data and reference management. funding: this review received no funding. competing interests: moberly serves on the cabi publishing north american library advisory board and the vetstream academic advisory board. teller serves on the air.vet advisory board.   references abbott laboratories. 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(2019). glossary. in terrestrial animal health code (vol. 1–2). world organisation for animal health (oie). available from: https://www.oie.int/index.php?id=169&l=0&htmfile=glossaire.htm [accessed 6 october 2020] intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in female dogs undergoing elective neutering is ovariectomy or ovariohysterectomy superior? a knowledge summary by catrina pennington bvm&s mrcvs 1* 1the royal veterinary college, royal college street, london, nw1 0tu *corresponding author (trinpennington@gmail.com) vol 5, issue 2 (2020) published: 04 jun 2020 reviewed by: malcolm ness (bvetmed certsao dipecvs frcvs) and theophanes liatis (dvm mrcvs) next review date: 07 mar 2021 doi: 10.18849/ve.v5i2.303 pico question in female dogs undergoing elective neutering via midline coeliotomy is ovariectomy superior to ovariohysterectomy in terms of anaesthetic duration, incision length, complications and postoperative pain?   clinical bottom line category of research question treatment the number and type of study designs reviewed the number and type of study designs that were critically appraised were four prospective clinical trials (peeters et al., 2011; lee at al., 2013; harris et al., 2013; and tallant et al., 2016) and a retrospective cohort study (okkens et al., 1997) strength of evidence critical appraisal of the selected papers meeting the inclusion criteria collectively provide weak evidence in terms of their experimental design and implementation outcomes reported okkens et al. (1997) found no occurrence of pyometra/endometritis in 135 dogs receiving ovariectomy (ove) or ovariohysterectomy (ovh) over an 8–11 year follow-up period. this study also reported no significant difference in long-term postoperative complications in either group. of the four prospective clinical trials one (harris et al., 2013) had final year vet students perform the surgeries. this study found no difference in incision length, surgical time or incidence of intra-operative complications between techniques. however the relevance of this study to procedures performed by qualified veterinary surgeons is questionable. the remaining papers all evaluated incision length, surgical time and postoperative pain after surgeries performed by experienced vets. all three found mean incision length was shorter in the ove group and two (lee et al., 2013; and tallant et al., 2016) found that surgical duration was shorter in the ove group. only one paper (lee et al., 2013) revealed a significant difference in pain scoring between groups, with the ove group having lower scores at 1, 2, 4 and 6 hours post-surgery. lee at al. (2013) and tallant et al. (2016) also recorded intra-operative complications, however none were noted in either group conclusion in view of the strength of evidence and the outcomes from the studies the following conclusion is made; whilst the evidence does suggest ove may be associated with some modest improvement in surgical time and incision length, due to the small sample sizes and varying techniques used, further studies are required before definitive conclusions can be made. there is currently insufficient evidence to determine if there is a difference in complication rates or postoperative pain between procedures.   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision-making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario an 11-month-old, female entire crossbreed dog presents for elective neutering. you discuss surgical techniques with the client. you are confident at performing both ovariectomy and ovariohysterectomy via midline coeliotomy. other techniques, including minimally invasive surgery and surgery through a flank incision, are not locally available or financially feasible and so are not considered. when considering anaesthetic duration, incision length, complication rate and postoperative pain, what evidence is there to suggest ove is superior to ovh or vice versa? the evidence from the literature reviewed here there is some evidence to suggest that when performed by an experienced veterinary surgeon ove is associated with a shorter incision length and reduced surgical time compared to ovh. however the studies reviewed differ markedly in case selection, technique and study objectives. the sample sizes are typically small and the experience of the operating veterinary surgeons may not accurately reflect an ‘average’ general practitioner. additionally the differences in between procedures reported may not be clinically significant. there is convincing evidence that, when properly performed, ove is not associated with a risk of pyometra. there is currently insufficient evidence to determine if there is a difference in postoperative pain following ovh compared to ove. no papers reported an improvement in any outcome with ovh compared to ove. in conclusion, whilst the evidence does suggest ove may be associated with some modest improvement in surgical time and incision length, further studies are required before definitive conclusions can be made. summary of the evidence harris et al. (2013) population: female dogs of various breeds presented to a british veterinary teaching hospital for elective neutering. age range 6–120 months. weight range 2.9–51.5 kg. dogs were excluded from recruitment if there were signs of pregnancy, oestrus, pseudopregnancy or ill health on clinical examination. dogs were excluded at the time of surgery if pregnancy or abnormalities of the reproductive system were visualised or palpated. sample size: 108 dogs intervention details: dogs were randomly allocated to undergo ove (n=54) or ovh (n=54) via midline coeliotomy. a final year student was allocated to each case and given written instructions of the procedure to be performed based on a standard open protocol. the procedures were performed by the final year student assigned to the case with a qualified veterinary surgeon assisting, this assistant would complete the procedure if the total surgical duration exceeded 2 hours or major complications occurred. study design: prospective, single centre, randomised, controlled, clinical trial outcome studied: intra-operative complication rates. time of surgery: from first incision to start of closure from start to end of closure total surgical time. incision length. main findings (relevant to pico question): two dogs in the ovh group experienced major complications (one bladder laceration, one pedicle rupture prior to ligation) which required the assistant veterinary surgeon to complete the procedure, these were not included in the final analysis. 11/108 cases exceeded the 2 hour time limit, 8/51 of the ovh group and 3/53 of the ove group – this was not statistically significant. mean total surgical time was 88.7 +/20.6 minutes in the ove group and 92.0 +/27.6 minutes in the ovh group. this was not significantly different. mean incision length was 8.7 +/2.6 cm in the ove group and 9.6 +/3.4 cm in the ovh group. this was not significantly different. no significant difference was observed in time from first incision to start of closure or time of closure between groups. minor intra-operative complication rates occurred in 12/52 (23%) of the ovh group and 21/54 (39%) of the ove group – this did not differ significantly between groups. limitations: this is a single centre study which may limit application to other centres. surgeries were performed by final year students and so results may not be applicable to experienced veterinarians. students may have been more familiar with ovh from time in general practice where ovh is more commonly performed. an assistant veterinary surgeon more experienced in ovh was scrubbed in to procedures. analgesia used is not recorded. the text instructions supplied recommended a set incision length with extension at the discretion of supervising veterinary surgeon. incision length was recorded as an absolute length rather than as a proportion of the dog’s length. different supervising veterinary surgeons of different skill levels were assisting and this was not controlled between groups. there was no assessment of difference in skill levels of students, this was likely to be variable and was not controlled between groups. peeters et al. (2011) population: client-owned, female entire, healthy dogs admitted to a dutch veterinary teaching hospital for elective neutering. 12 mixed breed, 30 pedigree dogs of unspecified breed. dogs excluded if they were not classified as asa i (a normal healthy patient) on the american society of anaesthesiologists’ (asa) classification of physical health, or had shown signs of oestrus within the previous 6 weeks. two dogs were later excluded due to receiving medical management for epilepsy. mean age and weight were 2.8 years (standard error of mean +/3 years) and 26 kg (standard error of mean +/6 kg) in the ovh group and 1.9 years (standard error of mean +/1.2 years) and 24.4 kg (standard error of mean +/7.3 kg) in the ove group. sample size: 40 dogs intervention details: recruited dogs were randomly assigned to undergo ovh (20) or ove (20). induction and maintenance of anaesthesia was performed as per a set protocol with carprofen (4 mg/kg) given once intravenously prior to surgery. surgical procedure was standardised for both techniques. both ove and ovh were performed via an open approach midline coeliotomy. all surgeries were performed by the same veterinary surgeon with an assistant. buprenorphine (10 μg/kg) was administered subcutaneously every 6 hours for 24 hours after surgery. dogs hospitalised for > 24 hours received carprofen subcutaneously at a dose of 2 mg/kg. blood samples were collected immediately prior to and at 1 and 6, hours post-surgery via a preplaced jugular catheter. a final blood sample was collected at 24 hours post-surgery via venipuncture of the contralateral jugular vein. assessors were blinded to the type of procedure performed. study design: prospective, single centre, randomised, blinded, controlled, clinical trial outcome studied: body condition score. blood loss estimated by weight of surgical sponges and swabs. time of surgery: from skin incision until completion of closure from start of incision to counting of used swabs from start of closure until end of closure. incision length (both of skin and of fascia) relative to the length of the area from manubrium to cranial rim of the pubis. pain scores: determined by the glasgow composite measure pain scale (reid et al., 2007) long form (cmps-lf) and short form (cmps-sf) recorded at 2, 6, 12 and 24 hours post-surgery. postoperative wound characteristics: determined by subjective assessment of swelling, redness, dehiscence, discharge and pain on palpation performed by four senior veterinary students blinded to surgical technique assessed at 2, 6, 12 and 24 hours post-surgery scored from 0–4 with 0 indicating feature not detected and 4 being severe scores added to give total. main findings (relevant to pico question): the mean relative length of both the fascia and skin incisions were significantly shorter in the ove group (17.7 +/1.8% and 19.8 +/2.0% respectively) than in the ovh group (21.3 +/3.1% and 23.8 +/3.6% respectively). surgical time (any component), postoperative pain and wound scores at any time point were not significantly different between groups. limitations: this is a single centre study which may limit application to other centres. all procedures were performed by a single board certified veterinary surgeon which may limit application to general practice. wound appearance was assessed by subjective methods. collection of blood via a jugular catheter was performed at 1 and 6 hours post-surgery, and by venipuncture at 24 hours post-surgery, this may have affected pain scores. incision length was determined by the operating veterinary surgeon and may not reflect the required minimum incision length for each procedure. dogs received buprenorphine analgesia at 6 hourly intervals for 24 hours post-surgery. this is unlikely to reflect general practice and may have hindered ability to detect differences in pain scores between groups. tallant et al. (2016) population: adult, female entire dogs obtained from local humane society shelters (country of origin not specified). weight ranged from 3.3–30.1 kg. dogs were excluded if there were signs of illness or cardiovascular abnormalities, evidence of oestrus or pregnancy on physical examination. sample size: 20 dogs intervention details: dogs were individually kenneled a minimum of 24 hours prior to surgery. dogs were randomly assigned to receive either ove or ovh. anaesthetic protocol was standardised with carprofen (4 mg/kg) given once subcutaneously prior to surgery. surgery was performed as per a standardised technique via a median coeliotomy. haemostasis was achieved via a vessel sealing device, this was also used to seal and divide the uterine body where this was under 9 mm, where the uterine body exceeded 9 mm a single circumferential ligature was applied prior to transection. aftercare was standardised. rescue analgesia (buprenorphine) was administered to dogs with pain scores of 5/24 or greater. study design: prospective, single centre, randomised, blinded clinical trial outcome studied: total incision length. duration of each phase of surgery: phase 0: from induction to first incision phase 1: from first incision to grasping the first ovary phase 2: from manipulation of the first ovary to initiation of body wall closure phase 3: from initiation of body wall closure to completion of skin closure. heart rate, end-tidal isoflurane, systolic, mean and diastolic blood pressure measured at each phase. pain: assessed at 1, 2, 4, 6, 8, 12, 18 and 24 hours after surgery performed by single blinded assessor using the cmps-sf and a 10 cm visual analog scale wound sensitivity was measured using an algometer with readings given in newtons; for each time point three readings were obtained from a point 1 cm cranial to the cranial edge of the incision. complication rate up to 24 hours. main findings (relevant to pico question): the change in mean arterial pressure between phase 1 and 2 was greater in the ovh group (increase of 25 +/14 mmhg) than the ove group (increase of 9 +/15 mmhg). the change in diastolic pressure between phase 1 and 2 was greater in the ovh group (increase of 27 +/13 mmhg) than the ove group (increase of 6 +/14 mmhg). there were no significant differences between groups in blood pressure between other phases, or heart rate and systolic pressure changes between any phases. the mean heart rate of the ove group was significantly greater than that of the ovh group during phase 0 and during phase 3. the end-tidal isoflurane was significantly lower for the ovh group compared to the ove group during phase 1 and phase 2. there was no difference during phase 3 or between the phases. mean procedure time was significantly greater for the ovh group (17.5 +/2.4 minutes) compared to the ove group (15.4 +/1.7 minutes). there were no significant differences between groups in the duration of phases 0–2, however, the duration of phase 3 was longer in the ovh group than the ove group. mean skin incision length was significantly greater in the ovh group (6.4 +/0.7 cm) compared to the ove group (5.3 +/1.1 cm). one dog from each group required rescue analgesia – this was not significantly different. neither visual analog scores nor algometer readings were significantly different between groups. there were no complications in any of the dogs intra-operatively or up to 24 hours postoperatively. limitations: this was a single centre study, which may limit the application of results to other centres. all procedures were performed by the same veterinary surgeon which may limit application to other veterinary surgeons. the operating veterinary surgeon was board certified which may not reflect general practice. incision length was reported as an absolute value rather than percentage of body length. pre-operative overnight kenneling is not reflective of a typical general practice setting. the sample size was small, limiting power to detect differences between groups and increasing the effect of any individual variation. incision length was determined by the operating veterinary surgeon and may not reflect the required minimum incision length for each procedure. a vessel sealing device was used during the procedure and so results may not be applicable to procedures using ligatures. lee et al. (2013) population: female entire, purpose-bred, crossbreed dogs (country of origin not specified). dogs were excluded if abnormalities were found on clinical examination or serum biochemical profile/complete blood count 24 hours prior to surgery. sample size: 13 dogs intervention details: dogs were kenneled 24 hours prior to surgery. anaesthetic protocol was standardised. all surgeries were performed in the morning by a single experienced veterinary surgeon. ove (6 dogs) or ovh (7 dogs) were performed as per a standardised technique via midline celiotomy. butorphanol (4 mg/kg) was administered intravenously prior to extubation, no further analgesia was given. blood sampling was performed by jugular venipuncture prior to surgery then at 1, 2, 4, 6, 12 and 24 hours post-surgery. aftercare was standardised. study design: prospective, single centre clinical trial outcome studied: pain assessment: performed by blinded assessor using short form of the glasgow composite measure pain scale (cmps-sf) (reid et al., 2007) assessed prior to surgery then at 1, 2, 4, 6, 12 and 24 hours post-surgery. serum cortisol and glucose assessed prior to surgery then at 1, 2, 4, 6, 12 and 24 hours post-surgery. incision length. surgical duration. anaesthetic duration. intra and postoperative complications. main findings (relevant to pico question): no complications were observed intra or postoperatively in either group. incision length was significantly shorter in the ove group. mean incision length was 10.1 +/2.2 cm in the ovh group and 4.4 +/0.3 cm in the ove group. surgical duration was significantly shorter in the ove group. mean surgical time was 52.3 +/2.1 minutes in the ovh group and 35.8 +/2.8 minutes in the ove group. anaesthetic duration was significantly shorter in the ove group. mean anaesthetic time was 66.1 +/4.4 minutes in the ovh group and 47.1 +/4.0 minutes in the ove group. the ove group had a significantly lower cmps-sf score than the ovh group at 1, 2, 4 and 6 hours postoperatively. serum cortisol and glucose values did not differ significantly between groups. limitations: this was a single centre study which may limit application of results to other centres. all procedures were performed by the same veterinary surgeon which may limit application to other veterinary surgeons. venipuncture was performed regularly throughout the study which may have affected pain scores. incision length was reported as an absolute value rather than percentage of body length. the study population were purpose bred crossbreeds which may limit application to other breeds. pre-operative overnight kenneling is not reflective of a typical general practice setting. the sample size was small, limiting power to detect differences between groups and increasing the effect of any individual variation. incision length was determined by the operating veterinary surgeon and may not reflect the required minimum incision length for each procedure. dogs received one injection of butorphanol analgesia postoperatively only. this was in contrast to other studies where a non-steroidal anti-inflammatory drug (nsaid) was administered which may be more typical of general practice. this may account for the differences in pain score noted. okkens et al. (1997) population: female dogs of various breeds which had undergone either an ove or ovh procedure at a dutch, teaching hospital 8–11 years prior to the study. weight range at time of surgery 1.6–37.5 kg, age range at time of surgery 9.6 months to 9 years. sample size: 135 dogs intervention details: dogs had been randomly selected to receive either ovh (n=66) or ove (n=69). anaesthesia and surgical technique were standardised. a questionnaire was sent to owners 8–11 years post-surgery.  questions included whether the dog had experienced abdominal pain, vaginal discharge, endometritis/pyometra attractiveness to male dogs and urinary incontinence post-surgery. if any of the questions were answered positively a follow-up phone call was carried out. study design: retrospective single centre, cohort study outcome studied: incidence of urinary incontinence, ovarian remnant syndrome, attractiveness to male dogs, abdominal pain, vaginal discharge, endometritis/pyometra post-surgery. main findings (relevant to pico question): no attractiveness to male dogs or abdominal pain as a consequence of elective neutering was reported in any dog. asymptomatic vaginal discharge was observed in two dogs from either group. six dogs in the ove group and nine in the ovh group developed urinary incontinence. there was no incidence of endometritis/pyometra in either group. there was no significant difference between groups in the incidence of any of the urogenital problems studied during the follow-up period. limitations: the method of randomisation was not reported and thus cannot be critiqued. the questions asked were not reported and it is not clear if these may have biased client answers. the study is retrospective and follow-up was performed. group matching (of age, weight etc.) was not possible and therefore confounding factors may have influenced results. the study may be underpowered to detect differences in the rate of urinary incontinence between groups due to the relatively uncommon nature of the condition. due to the long follow-up time, accuracy of client recollection would be expected to have reduced. the level of experience of the veterinary surgeons performing the procedures is not reported. bias may have been introduced by cases with negative outcomes being less likely to have complete case records and therefore being more likely to be excluded. appraisal, application and reflection five papers were found to be relevant to this knowledge summary, four prospective clinical trials (peeters et al., 2011; lee at al., 2013, harris et al., 2013; and tallant et al., 2016) and a retrospective cohort study (okkens et al., 1997). the retrospective cohort study (okkens et al., 1997) reviewed long-term complications post ove and ovh and found no occurrence of pyometra/endometritis in 135 dogs 8–11 year post-surgery. this finding is anticipated as pyometra is known to occur secondary to cystic endometrial hyperplasia; a disorder which requires the presence of progesterone and would not be expected to occur in the absence of functional ovarian tissue or administration of exogenous hormones (de tora & mccarthy, 2011). likewise the group reported there was no significant difference in urinary incontinence between groups. the findings of this study must be considered with caution however, as there may be some inherent bias with dissatisfied owners less likely to provide follow-up and therefore to be included. harris et al. (2013), a prospective, randomised clinical trial, prospectively monitored ove and ovh surgeries performed by final year vet students. this study found no difference in incision length, surgical time or incidence of intra-operative complications between techniques; however the relevance of this study to procedures performed by qualified veterinarians experienced in routine neutering is disputable. the remaining papers all evaluated surgeries performed by experienced veterinarians. these studies all compared incision length, surgical time and postoperative pain between groups. all found mean incision length was shorter in the ove group and two (lee et al., 2013; and tallant et al., 2016) found that surgical duration was shorter in the ove group; however the clinical impact of these findings is not clear as the reduction in both parameters was small. additionally it should be noted that the surgeries reported by tallant et al. (2016) were performed with the aid of a vessel sealing device, therefore results may not be applicable to procedures performed with suture ligation. differences in pain scores reported by these papers are harder to interpret. only one paper (lee et al., 2013), found a significant difference in pain scoring between groups; with the ove group having lower scores at 1, 2, 4 and 6 hours post-surgery. however this was a small study (n=13) with purpose-bred dogs and procedures performed by a single veterinary surgeon. equally two of the three groups (peeters et al., 2011; and lee et al., 2013) also performed postoperative blood sampling at regular intervals which may have affected pain score accuracy. finally analgesia protocol varied between papers. pre-operative nsaid administration was performed by tallant et al. (2016) and peeters et al. (2011), but not by lee et al. (2013). tallant et al. (2016) administered buprenorphine at 6 hourly intervals for 24 hours post-surgery, whilst peeters et al. (2011) only included this as a rescue protocol and lee et al. (2013) administered a single butorphanol injection only. administration of additional analgesia beyond what is commonly used in general practice may hinder ability to detect differences in pain scores between groups, however withholding analgesia that is commonly used, may artificially increase differences in groups beyond what would be anticipated. lee et al. (2013) and tallant et al. (2016) also recorded intra-operative complications, however none were noted in either group.  gonadectomy in female dogs is generally performed to prevent misalliance and pyometra, for behavioural reasons and to reduce the risk of mammary and uterine neoplasia. removal of the ovaries alone would be expected to prevent unwanted pregnancy, pyometra and to have an equal impact on the risk of mammary neoplasia as ovh, due to the cessation of ovarian hormone production. the effect of leaving the uterus in situ on the development of uterine neoplasia has not been evaluated, however as this disease is rare the incidence of canine malignant uterine neoplasia is approximately 0.003% (van goetham et al., 2006) and anticipated to be at least in part hormonally mediated, the impact of a change in practice from ove to ovh on the uterine neoplasia related morbidity/mortality is likely to be negligible.   of the studies reviewed here only two major complications were reported, both by harris et al. (2013). of these complications one, bladder laceration, would be expected to occur more commonly in ovh procedures due to the more caudal placement of the distal ligature. however, this study did not find a significant difference in complications between groups overall. it has also been proposed that ove may be associated with a reduced risk of ureteral ligation; as the distal ureter is located caudal to the placement of the distal ovarian ligatures in ove, but in the vicinity of the uterine ligature when an ovh is performed (de tora & mccarthy, 2011). however serious complications secondary to neutering are rare and there is currently no evidence showing a difference in perioperative complications between techniques. this knowledge summary reviewed surgery performed via a midline coeliotomy incision only, surgery performed via flank incision was not considered as part of this knowledge summary and data may not necessarily be extrapolated to other approaches. in conclusion though the evidence reviewed within this knowledge summary suggests that ove may be associated with shorter surgical duration and incision length than ovh there are several major weaknesses which prevent definitive conclusions. firstly, where significant results are reported actual differences are not large and may be clinically insignificant. secondly, all but two of the papers (okkens et al. 1997; and harris et al., 2013) used sample sizes of 40 or fewer animals, thus confounding factors are more likely to affect results and extrapolation to a general population becomes more challenging. of the two papers which did use larger sample sizes, one (harris et al. 2016) reviewed surgeries performed by final year students; consequently the implication of results from unqualified vets is not clear; and the second was a retrospective study reviewing owner reported long-term complications only. finally, the population and techniques used between studies varied markedly and were often not representative of uk general practice; for example lee et al. (2013) used only purpose-bred cross breed dogs, tallant et al. (2016) used vessel-sealing devices rather than suture ligation, and peeters et al. (2011) regularly blood sampled patients to collect data for a separate study. no difference in complication rates between groups has been shown and differences in postoperative pain scores between procedures have not been convincingly demonstrated. no papers identified an advantage of performing ovh over ove. these results apply only to animals with grossly normal uteri at coeliotomy, and hysterectomy is still recommended when uterine pathology is present. further indicated research includes large scale studies allowing identification of differences in rare intra-operative complications and randomised, clinical trials in larger numbers of animals in a setting more reflective of general practice, to determine if a significant difference between procedures is found when power is increased.   methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform 1973 to 2019 week 08 pubmed accessed via the ncbi website (1910–2019) search strategy: cab abstracts: (dog or dogs or canine or canines or canis or bitch or bitches).mp. or exp dogs/ or exp bitches/ or exp canis/ [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (spey* or spay* or ovariohysterectom* or ovario-hysterectom*).mp. or exp hysterectomy/ [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] ovariectom*.mp. or exp ovariectomy/ [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] 1 and 2 and 3   pubmed: (canine or bitch or dog or bitches or dogs or canis) and (ovariectomy or ovariohysterectomy or spey or spay) dates searches performed: cab abstracts: 07/03/19 pubmed: 12/03/19 exclusion / inclusion criteria exclusion: single case reports duplicates laparoscopic surgeries inclusion: english language peer reviewed publication original data in vivo study canine patients comparative papers including both ovariectomy and ovariohysterectomy performed through a median coeliotomy reporting one or more of the following outcomes; complication rates, surgical time, post-operative pain search outcome database number of results excluded – non-canine patients excluded – not ovh/ove excluded – duplicate excluded – no original data excluded – non-surgical excluded – laparascopic approach excluded – not median coeliotomy excluded – non-comparative excluded – not comparing specified criteria total relevant papers cab abstracts 477 9 4 10 96 83 44 1 222 3 5 pubmed 1226 54 12 181 123 427 61 1 360 2 5 total relevant papers when duplicates removed 5 conflict of interest the author declares no conflicts of interest. references american society of anesthesiologists. (1963). new classification of physical status. anesthesiology. 24:111. detora, m. & mccarthy, r. (2011). ovariohysterectomy versus ovariectomy for elective sterilization of female dogs and cats: is removal of the uterus necessary? journal of the american veterinary medical association. 239(11):1409—1412. doi: http://dx.doi.org/10.2460/javma.239.11.1409 harris, k., adams, v., fordyce, p. & ladlow, j. (2013). comparison of surgical duration of canine ovariectomy and ovariohysterectomy in a veterinary teaching hospital. journal of small animal practice. 54(11):579–583. doi: https://doi.org/10.1111/jsap.12147 lee, s., lee, s., park, s., kim, y., seok, s., hwang, j., lee, h. & yeon, s. (2013). comparision of ovariectomy and ovariohysterectomy in terms of postoperative pain behavior and surgical stress in dogs. journal of veterinary clinics. 30(3):166–171. okkens, a.c., kooistra, h.s. & nickel, r.f. (1997). comparison of long-term effects of ovariectomy versus ovariohysterectomy in bitches. journal of reproduction and fertility supplement. 51:227–31 peeters, m.e. & kirpensteijn, j. (2011). comparison of surgical variables and short-term postoperative complications in healthy dogs undergoing ovariohysterectomy or ovariectomy. journal of the american veterinary medical association. 238:189–94. doi: http://dx.doi.org/10.2460/javma.238.2.189 reid, g., nolan, a., hughes, j., lascelles, d., pawson, p. & scott, e. (2007). development of the short-form glasgow composite measure pain scale (cmps-sf) and derivation of an analgesic intervention score. animal welfare, 16(s):97–104. tallant, a., ambros, b., freire, c. & sakals, s. (2016). comparison of intraoperative and postoperative pain during canine ovariohysterectomy and ovariectomy. the canadian veterinary journal. 57(7):741–746. van goethem, b., schaefers-okkens, a. & kirpensteijn, j. (2006). making a rational choice between ovariectomy and ovariohysterectomy in the dog: a discussion of the benefits of either technique. veterinary surgery. 35(2):136–143. doi: http://dx.doi.org/10.1111/j.1532-950x.2006.00124.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in dogs with uncomplicated corneal ulcers, do antibacterial eye drops reduce the risk of infection? a knowledge summary by sery johnson bs 1* wanda j gordon-evans dvm phd dacvs dacvsmr 1 1university of minnesota college of veterinary medicine, 1365 gortner ave, st paul, mn 55108, usa *corresponding author (joh10898@umn.edu) vol 6, issue 4 (2021) published: 17 nov 2021 reviewed by: kazuya oikawa (bvsc phd) and constance neville white (dvm phd) next review date: 07 dec 2022 doi: 10.18849/ve.v6i4.389 pico question in dogs with uncomplicated corneal ulcers does treatment with prophylactic antibacterial eye drops reduce the risk of secondary infection when compared to no treatment with prophylactic antibacterial eye drops?   clinical bottom line category of research question treatment the number and type of study designs reviewed zero strength of evidence zero outcomes reported none conclusion there were no published papers found to address the pico   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are presented with a 4 year old, female spayed dog of mixed breed with an acute onset of epiphora and blepharospasm of the right eye. ocular exam and fluorescein staining reveal a superficial corneal ulcer, which has not received any treatment prior to diagnosis. the dog’s owner has already spent more money than she would like just for the exam and wants to know whether the recommended antibacterial drops are necessary. the evidence there was no peer-reviewed evidence that met the inclusion criteria to summarise. appraisal, application and reflection in dogs with uncomplicated corneal ulcers, the administration of prophylactic topical ophthalmic antibacterials is well documented and recommended in textbooks on veterinary ophthalmology as the standard of care (maggs et al., 2018); for the purpose of this knowledge summary, an uncomplicated corneal ulcer was defined as a new onset superficial corneal ulcer. despite this recommendation, there have been no studies to demonstrate a significant difference in infection rates in affected dogs receiving prophylactic topical ophthalmic antibacterials compared to dogs that do not. however, the potential negative impacts of not treating uncomplicated corneal ulcers with topical ophthalmic antibacterials could be significant, possibly resulting in secondary ocular infections, melting deep corneal ulcers, and may eventually lead to loss of vision or loss of the eye. therefore, unless robust evidence is established to refute the current dogma, it is recommended that practitioners continue to uphold the current standard of care. methodology section search strategy databases searched and dates covered: pubmed on ncbi platform; 1950–2020 cab abstracts on ovid platform; 1973–2020 search strategy: cab abstracts and pubmed: ((dogs) and (((corneal ulcer) or (keratitis)) or (corneal abrasion))) and ((((treatment) or (therapy)) or (ophthalmic solutions)) or (antibiotic)) dates searches performed: 07 dec 2020 exclusion / inclusion criteria exclusion: articles not available in english, clinical review articles, book chapters, articles not available for review inclusion: articles relevant to the pico (involving uncomplicated corneal ulcers that were treated to resolution) search outcome database number of results excluded – did not address the pico excluded – not english language excluded – non-canine total relevant papers cab abstracts 331 223 97 11 0 pubmed 391 335 33 23 0 total relevant papers when duplicates removed 0 conflict of interest the authors declare no conflicts of interest. references maggs, d. j., miller, p. e. & ofri, r. (2018). slatter’s fundamentals of veterinary ophthalmology (6th ed.). elsevier. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. erratum to: does uk licensed nsaid administration reduce signs of postoperative pain in calves castrated without local anaesthesia? alexandra bartlett bsc (hons)1* 1the royal veterinary college, hawkshead lane, hatfield, hertfordshire, al9 7ta *corresponding author (abartlett7@rvc.ac.uk) vol 6, issue 3 (2021) erratum published: 19 jul 2021 original paper published: 08 jul 2021 the original article was published in veterinary evidence vol 6, issue 3 (2021): 10.18849/ve.v6i3.452 doi: 10.18849/ve.v6i3.525 erratum unfortunately the original version of the article had the following error.   within the appraisal, application and reflection section the date of one of the references was changed from: interestingly, daniel et al. (2015) used a dose of 2.0 mg/kg meloxicam but found no significant improvement in pain, however this study investigated band castration, which according to the appraised evidence was less amenable to pain relief via nsaids. to: interestingly, daniel et al. (2020) used a dose of 2.0 mg/kg meloxicam but found no significant improvement in pain, however this study investigated band castration, which according to the appraised evidence was less amenable to pain relief via nsaids.   this correction has been made in both the html and pdf versions. veterinary evidence apologises for this error.    intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. in cats and dogs with traumatic diaphragmatic rupture, does surgical timing affect outcome? a knowledge summary by alison robertson bvms pgdip (vcp) mrcvs 1* 1university of bristol, langford small animal referral hospital, langford house, langford, bristol, bs40 5du *corresponding author (alisonclrobertson@gmail.com) vol 6, issue 4 (2021) published: 10 nov 2021 reviewed by: amanda curtis (rvn) and april l paul (dvm dacvecc) next review date: 03 aug 2023 doi: 10.18849/ve.v6i4.494 pico question in cats and dogs with traumatic diaphragmatic rupture undergoing herniorrhaphy does surgical timing affect outcome?   clinical bottom line category of research question prognosis the number and type of study designs reviewed ten studies were critically appraised. all of these were retrospective case series strength of evidence zero outcomes reported overall, there is not sufficient evidence reporting if timing of surgical intervention has an effect on the mortality rate in dogs and cats with traumatic diaphragmatic rupture. mortality rate was 6.8–50% in all cases conclusion there is no statistically significant information available with only several retrospective studies published that are a low quality of evidence. clinical practice can be reviewed based upon current evidence assessing timing of herniorrhaphy of traumatic diaphragmatic rupture. however, there are no clear recommendations and future studies are warranted   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a 2 year old female neutered domestic short-hair presents 30 minutes after being hit by a car. on presentation the cat is dyspnoeic and tachycardic at 250 bpm with poor peripheral pulses. on thoracic auscultation heart sounds are dull on the left side and displaced caudodorsally on the right side. the abdomen feels ‘empty’ on palpation. thoracic radiography and ultrasonography reveal the presence of a diaphragmatic rupture. the cat requires surgical repair of the diaphragm. is the cat more likely to survive if herniorrhaphy is performed immediately, or if medical stabilisation is performed for 24 hours prior to surgery? the evidence evidence is lacking about the outcome of cats and dogs with traumatic diaphragmatic ruptures. there are few studies that assess outcome based on time from presentation to surgery. this may be due to many of these cases presenting to and being surgically repaired by their primary veterinarian. the papers discussed show no statistical correlation between length of time from presentation to surgery and survival to discharge. clinical practice can be reviewed based upon current evidence; however, there are no clear recommendations and future studies are warranted. there are currently no prospective studies published, these may find a more significant outcome as less variables may be present. summary of the evidence wilson et al. (1971) population: dogs and cats with diaphragmatic hernia admitted to the college of veterinary medicine at ohio state university (usa) from january 1959 to december 1969. sample size: 116 cases: 94 dogs and 22 cats intervention details: 113 dogs and cats had surgery attempted, three animals died or were euthanised prior to surgical intervention. all animals were diagnosed based on thoracic radiographs. type of diaphragmatic tear and herniated organs were noted.   study design: retrospective single-centre case series outcome studied: survival during hospitalisation. time from suspected trauma to surgery was recorded. follow-up time postoperatively varied. main findings (relevant to pico question): time from suspected trauma to surgery was from immediately following trauma to 6 years later (mean 109 days). most hernias were traumatic. 11 animals had congenital hernias, in 16 cases the cause was unknown. 76/116 (65.4%) animals survived to discharge from hospital. one animal was dead on arrival and two were euthanised prior to surgery 19/116 (16.8%) animals died prior to surgery – of these most hernias were present for 1 hour to 2 weeks prior to surgery. 6/116 (5.1%) animals died during surgery. 14/116 (12.1%) animals died postoperatively – 12/14 (85.7%) died within 24 hours of surgery. limitations: single-centre study. retrospective study. no statistical analysis or discussion of results. no discussion of stabilisation, surgical technique, anaesthetic protocol and postoperative management. since the paper was written, surgical, anaesthetic and medical management is likely to have changed a lot. clinical management, and therefore outcome of cases may be different in current practice. garson et al. (1980) population: dogs and cats with traumatic diaphragmatic hernia admitted to glasgow university veterinary school (uk) between january 1972 and august 1978. sample size: 56 cases: 23 dogs and 33 cats intervention details: 53 dogs and cats underwent surgery, three dogs died prior to anaesthesia for herniorrhaphy. all animals diagnosed based on thoracic radiographs. anaesthetic protocols and supportive treatment varied. midline celiotomy performed in all cases, two cases had lateral thoracotomy. type of diaphragmatic tear and herniated organs noted.   in cats evacuation of pneumothorax at the end of surgery was performed by maximally expanding lungs prior to tying of a purse string suture in the diaphragmatic tear. in dogs a chest drain was placed.  study design: retrospective single-centre case series outcome studied: duration of clinical signs and signalment of each case recorded. follow-up time postoperatively varied. discussed reasons patients had not survived to discharge.  main findings (relevant to pico question): 27/53 (50.9%) animals died or were euthanised.  most deaths occurred within 24 hours postoperatively, mostly due to pneumothorax.  time from admission to surgery was not recorded.  limitations: single-centre study. retrospective study. no statistical analysis or discussion of results. no discussion over time from presentation to surgery. some findings discussed as ‘unremarkable’, however these findings not presented and no statistical analysis performed. did not discuss method of diagnosis of the diaphragmatic rupture or the pathology leading to death or euthanasia. varied stabilisation, surgical technique, anaesthetic protocol and postoperative management. since the paper was written, surgical, anaesthetic and medical management is likely to have changed a lot. clinical management, and therefore outcome of cases may be different in current practice. schmiedt et al. (2003) population: cats that had surgical repair of traumatic diaphragmatic hernia at the university of tenessee and university of georgia college of veterinary medicine (usa) between 1991–2001. sample size: 34 cats intervention details: all cats underwent surgical repair of diaphragmatic rupture. study design: retrospective multi-centre case series outcome studied: cause of hernia, breed, age, sex, clinical signs, duration of hernia, location of diaphragmatic tear, organs herniated, level of training of veterinarian performing the surgery, placement of thoracic drain after surgery, postoperative complications, time to discharge were recorded. duration of hernia was subjectively assessed as time from traumatic event to surgical repair. long-term follow-up was obtained by telephone interview with the owner or referring veterinary surgeon or by review of medical records. main findings (relevant to pico question): there was no significant difference in mortality rates in cats that had diaphragmatic hernia for 0–24 hours (7/34 (20.6%) cats), 1–7 days (17/34 (50%) cats) or >7 days (10/34 (29.4%) cats) from trauma to repair.  mortality rate during hospitalisation was 6/34 (17.6%) cats. postoperative cardiac or respiratory arrest occurred in 5/34 (14.7%) cats within 48 hours postoperatively.  mean duration of traumatic diaphragmatic hernia was 17.6 days. concurrent injuries were present in 8/34 (23.5%) of cats, mortality was significantly greater in these cats.  long-term follow up available in 17/34 (50%) of cats, mean duration was 3.28 ± 2.28 years. 10/14 (71.4%) cats were healthy, one cat had dyspnoea after strenuous exercise. 3/14 (21.4%) cats were dead, one was euthanised due to urinary incontinence, one due to nasal haemorrhage, one had an unknown cause of death. limitations: retrospective study. cases collected over long time period (1991–2001), surgical procedures and medical management may have changed within this time. varied stabilisation, surgical technique, anaesthetic protocol and postoperative management. length of follow-up was variable and 17/34 (50%) cases were lost to long-term follow-up. minihan et al. (2004) population: cats and dogs that underwent surgical repair of a chronic traumatic diaphragmatic hernia at tufts university school of veterinary medicine or angell memorial animal hospital (usa) between 1987 and 1996.  diagnosis made by thoracic radiography in 48 animals, 10 animals had thoracic ultrasonography.  cases were considered chronic with: a history of known trauma, and clinical signs (coughing, tachypnoea, dyspnoea, vomiting, weight loss) for at least 2 weeks prior to surgery; or obvious signs of chronicity at surgery (body wall bruising, absence of haemothorax or haemoabdomen, presence of adhesions or fibrosis at hernia margins). sample size: 50 cases: 34 dogs and 16 cats intervention details: anaesthetic protocol varied, all cases were mechanically ventilated. all animals underwent exploratory laparotomy, 14/50 (28%) also underwent partial median sternotomy.  study design: retrospective multi-centre case series outcome studied: duration and type of clinical signs, initial clinical exam findings and time from trauma to surgery were recorded.  postoperative complications were recorded.  follow-up time was variable, with long-term follow-up available in 34 cases. main findings (relevant to pico question): duration of clinical signs was 1 day to 7 years. time from trauma to surgical correction was 2 weeks to 84 months (mean 14.5 months). 43/50 (86%) of animals survived to discharge. 2/50 (4%) of animals died or were euthanised during surgery. 5/50 (10%) of animals died or were euthanised postoperatively during hospitalisation.  30/43 (70%) of animals were alive at long-term follow-up with no clinical signs related to the diaphragmatic hernia (mean 47 months). 3/43 (7%) of animals had died or were euthanised at long-term follow-up (mean 56 months), the remainder were lost to follow-up.  limitations: retrospective study. cases collected over long time period (1987–1996), surgical procedures and medical management may have changed within this time.  varied stabilisation, surgical technique, anaesthetic protocol and postoperative management. groups outcome of all animals with diaphragmatic hernias over 14 days, does not discuss outcome of different length of clinical signs.  gibson et al. (2005) population: dogs and cats undergoing surgical repair of traumatic diaphragmatic hernia within 24 hours of admission to ontario veterinary clinic, university of guelph (canada), between january 1990 to december 2002. sample size: 92 cases: 63 dogs and 29 cats intervention details: cases underwent surgical repair of diaphragmatic rupture. all cases underwent repair via a midline celiotomy and were mechanically ventilated throughout the procedure. study design: retrospective single-centre case series outcome studied: to examine the effect of timing of surgical intervention on perioperative survival rate. intervention timing was objectively classified by:  time from trauma to admission time from trauma to surgery time from admission to surgery  this was then categorised as early intervention (<24 hours) or late (>24 hours). survival classified as discharge from hospital. grouped as alive or dead. euthanised animals were included in the dead group. cases with time from trauma to admission <14 days were considered acute.  cases with time from trauma to admission >14 days were considered chronic. main findings (relevant to pico question): 82/92 (89.1%) dogs and cats survived to discharge. 84/92 (91.3%) dogs and cats received surgery within 24 hours of admission. perioperative survival was not significantly associated with time from trauma to admission (admitted <24 hours vs >24 hours after trauma). perioperative survival was not significantly associated with time from trauma to surgery (undergoing surgery <24 hours vs >24 hours after trauma). perioperative survival was not significantly associated with time from admission to surgery (undergoing surgery <24 hours vs >24 hours after admission).  survival to discharge was not associated with time from trauma to admission, time from trauma to surgery or time from admission to surgery. limitations: retrospective study. single-centre study. cases collected over a long time period (1990–2002), surgical procedures and medical management may have changed within this time.  poor control group (animals undergoing surgery >24 hours after admission). did not present data or discuss findings of animals undergoing surgery >24 hours after admission. did not discuss how diaphragmatic hernia was diagnosed. varied stabilisation, surgical technique, anaesthetic protocol and postoperative management. ozer et al. (2007) population: cats undergoing diaphragmatic herniorrhaphy as treatment for suspected traumatic diaphragmatic hernia at istanbul university faculty of veterinary medicine (turkey). diagnosis made by positive contrast celiography.  sample size: 44 cats intervention details: all animals underwent general anaesthesia with a standard protocol of gaseous induction via face mask with isoflurane and positive pressure ventilation. a midline celiotomy was performed for diaphragmatic herniorrhaphy.  postoperative plain radiographs were obtained for all cats. study design: retrospective single-centre case series outcome studied: age, sex, breed, concurrent orthopaedic and soft tissue injuries, radiographic changes, biochemical abnormalities, duration of anaesthesia and surgery, organs herniated, location of rupture on the diaphragm, perioperative complications were recorded.  main findings (relevant to pico question): perioperative survival rate was 41/44 (93.2%). all deaths that occurred 3/44 (6.8%), were perioperative. limitations: retrospective study. single-centre. only perioperative survival is discussed, it is not clear what percentage of cats survived to discharge from hospital.  stabilisation of cases is not discussed. the type of positive pressure ventilation that was used is not stated. if manually ventilated there would be varied volume and pressure given with each breath.  anaesthetic length is not discussed.  the time frame that cases were collected over was not recorded. besalti et al. (2011) population: cats undergoing diaphragmatic herniorrhaphy as treatment for traumatic diaphragmatic hernia at ankara university, faculty of veterinary medicine (turkey), between may 2002 and april 2010. diagnosis made by radiography, with some cases requiring celiography or a barium swallow study for the confirmation of diagnosis.  sample size: 52 cats intervention details: acute diaphragmatic rupture was defined as the suspected trauma occurring <14 days prior to surgery. chronic diaphragmatic rupture was defined as the suspected trauma occurring >14 days prior to surgery.   all cats received prophylactic cephalosporin and dexamethasone prior to surgery. they all received standard protocols for general anaesthesia, mechanical ventilation, and midline celiotomy for diaphragmatic herniorrhaphy. all cats were prescribed ketoprofen for 3 days postoperatively. study design: retrospective single-centre case series outcome studied: age, sex, timing from suspected trauma to presentation, clinical signs, concurrent injuries, location of diaphragmatic tear, organs herniated, perioperative and postoperative complications were recorded. survival was classified as survival to discharge. follow-up was performed in all cats to assess rate of recurrence within the first 10 days postoperatively. main findings (relevant to pico question): 82.7% (43/52) of cases survived to discharge. acute diaphragmatic hernia occurred in 31/52 (59.6%) cats; mortality rate was 5/31 (16.1%). chronic diaphragmatic rupture occurred in 21/52 cats (40.4%); mortality rate was 4/21 (19%). of the cases that died, 4/9 (44.4%) occurred intraoperatively and 5/9 (55.6%) occurred postoperatively (within 5 hours after surgery). when assessing location of diaphragmatic tear, death occurred in 4/7 (57%) of cases with a centrally located tear, 1/2 (50%) of cases with tears in multiple locations,2/9 (22%) with ventrally located tears, 2/13 (15%) with left sided tear. no cases with a right sided tear died. 8/9 (33.3%) non-survivors had multiple organs herniated into the thorax. limitations: retrospective study. single-centre. pre-operative stabilisation and postoperative care were not discussed. although it is discussed that cases were more likely to not survive based on location of tear and having multiple organs herniated, it is a small number of cases and therefore not possible to assess causation. igna et al. (2014) population: cats and dogs undergoing diaphragmatic herniorrhaphy as treatment for traumatic diaphragmatic hernia at the faculty of veterinary medicine timiåÿoara (romania), between 2001 and 2013. diagnosis made by thoracic radiography and/or confirmed at surgery. sample size: 43 cases: 17 cats and 26 dogs. all dogs and 13/17 (76.5%) of cats had traumatic diaphragmatic rupture. three cats had a peritoneopericardial hernia and one cat had a pleuroperitoneal hernia. intervention details: all animals underwent general anaesthesia, manual or mechanical ventilation, and midline celiotomy for diaphragmatic herniorrhaphy. four cases required a partial median sternotomy. study design: retrospective single-centre case series outcome studied: age, sex, concurrent orthopaedic and soft tissue injuries, clinical signs, organs herniated, timing from trauma to surgery, organs herniated, type of diaphragmatic tear and location, survival to discharge. main findings (relevant to pico question): 32/43 (74.4%) of cases received surgical intervention within 24 hours of trauma. survival to discharge was 38/43 (88.4%) cases. limitations: retrospective study. single-centre study. cases collected over a long time period (2001–2013), surgical procedures and medical management may have changed within this time. stabilisation, surgical technique, anaesthetic protocol and postoperative management are not discussed. some cases were manually ventilated, varied volume and pressure would be given each breath. survival is described for all cases. there is no differentiation between the outcome of traumatic versus congenital diaphragmatic hernias. this is a limitation as cases with traumatic hernias may present with concurrent injuries which may affect patient stability and outcome. legallet et al. (2017) population: cats and dogs undergoing diaphragmatic herniorrhaphy as treatment for traumatic diaphragmatic hernia at texas a&m veterinary teaching hospital (usa) between 1 october 2001 and 31 april 2014. sample size: 96 cases: 17 cats and 79 dogs intervention details: diagnosis made by thoracic radiography and ultrasonography and confirmed at surgery. all animals underwent general anaesthesia, manual ventilation, and midline celiotomy for diaphragmatic herniorrhaphy. study design: retrospective single-centre case series outcome studied: age, sex, sp02 (oxygen saturation), blood lactate at presentation, concurrent orthopaedic and soft tissue injuries, duration of anaesthesia and surgery, organs herniated, additional surgical procedures performed during herniorrhaphy, perioperative and postoperative complications were recorded. intervention timing was objectively classified by: time from admission to surgery time from trauma to surgery time from trauma to admission acute diaphragmatic hernias were present for <14 days duration. chronic diaphragmatic hernias were present for >14 days duration. animals grouped into survival to discharge or death during hospitalisation, including euthanised animals. main findings (relevant to pico question): time between trauma and admission, trauma and surgery, and admission to surgery did not affect survival. perioperative survival rate was 78/96 (81.3%) (15/17 (88.2%) cats and 63/79 (79.8%) dogs). in acute cases 10/12 (83.3%) cats and 38/48 (79.2%) dogs survived to discharge. in chronic cases 5/5 (100%) cats and 25/31 (80.6%) dogs survived to discharge. animals that were oxygen dependent prior to surgery had a 5 times higher likelihood of mortality. animals with concurrent soft tissue injuries had a 4.3 times higher likelihood of mortality. animals with concurrent orthopaedic and soft tissue injuries had a 7.3 times higher likelihood of mortality. increased anaesthetic and surgical time, due to concurrent orthopaedic and soft tissue injuries, was associated with higher mortality rates. limitations: retrospective study. single-centre study. cases collected over a long time period (2001–2014), surgical procedures and medical management may have changed within this time. varied stabilisation, surgical technique, anaesthetic protocol and postoperative management. all cases manually ventilated, varied volume and pressure would be given each breath. many animals underwent other procedures at the same time as diaphragmatic herniorrhaphy, including elective procedures such as neutering and portosystemic shunt ligation. this likely affected outcome by increasing anaesthetic length. yaygingül et al. (2019) population: cats undergoing diaphragmatic herniorrhaphy as treatment for traumatic diaphragmatic hernia at adnan menderes university, faculty of veterinary medicine (turkey), between 2016 and 2017. diagnosis made by thoracic radiography, positive contrast celiography was performed in one case. sample size: 15 cats intervention details: all animals were admitted to the intensive care unit and received oxygen therapy and prophylactic antibiosis for 24 hours prior to surgery. they all received standard protocols for general anaesthesia, manual ventilation, and midline celiotomy for diaphragmatic herniorrhaphy. all cases remained hospitalised for 3 days postoperatively. during this time, they all received oxygen therapy, methyprednisolone and salbutamol via nebulisation. all cats were prescribed cefazolin for 1 week postoperatively. study design: retrospective single-centre case series outcome studied: age, sex, body weight, timing from suspected trauma to presentation, clinical signs, radiographic findings, biochemical changes, location of diaphragmatic tear, organs herniated, perioperative and postoperative complications were recorded. main findings (relevant to pico question): four cases died perioperatively; all of these had lung lacerations and pleural effusion. mortality rate was 4/15 (26.7%). limitations: retrospective study. single-centre study. no discussion over timing from presentation to surgical intervention. appraisal, application and reflection overall, there is low quality of evidence assessing if performing herniorrhaphy within 24 hours of presentation affects the outcome of cats and dogs with traumatic diaphragmatic hernia. in the studies that assessed the time between trauma or hospital admission and surgical repair the timing of herniorrhaphy was not associated with survival to hospital discharge (gibson et al., 2005; legallet et al., 2017; and schmiedt et al., 2003). in one study assessing surgical repair of chronic diaphragmatic hernia, defined as being present for over 2 weeks prior to surgical repair, in-hospital mortality was 7/50 (14%) (minihan et al., 2004). another study found no difference in mortality in cats undergoing surgical repair within 24 hours, 1–7 days or over 7 days since trauma, with overall mortality of 6/34 (17.6%) (schmiedt et al., 2003). overall mortality is variable, with the lowest reported rate 3/44 (6.8%) (ozer et al., 2007). the highest reported mortality rate was 27/53 (50.9%) (garson et al., 1980); survival in this population was markedly worse that the cases in the remainder of the studies. this may reflect a change in approach to case management and treatment options available since publication. however, another older publication reported a mortality rate similar to more recent studies (wilson et al., 1971). the published data are retrospective studies with many clinical variables, with differences in individual disease severity and case management (besalti et al., 2011; garson et al., 1980; gibson et al., 2005; igna et al., 2014, legallet et al., 2017; minihan et al., 2004; ozer et al., 2007; schmiedt et al., 2003; wilson et al., 1971; and yaygingül et al., 2019). varied disease severity is to be expected in this condition as it has a traumatic aetiology, and many cases presented with concurrent soft tissue and orthopaedic injuries. multiple injuries were associated with outcome in two studies (legallet et al., 2017; and schmiedt et al., 2003), with an increase in mortality of these patients. animals with concurrent injuries that underwent herniorrhaphy also had other surgical procedures performed under the same general anaesthesia. several also had elective procedures performed, such as neutering. increased anaesthesia time was linked with an increase in mortality (legallet et al., 2017). in the same study, animals that required oxygen supplementation prior to surgery were less likely to survive. these findings suggest that systemic disease severity is associated with outcome in cats and dogs with traumatic diaphragmatic rupture. variables not assessed was the association between number and type of organs herniated into the thorax or the location of diaphragmatic tear and outcome. these were not linked to the pico question to assess the timing of surgical intervention, therefore were not investigated as part of this review. in conclusion, in reviewing the available literature, there is no evidence to support that time to surgical intervention is associated with outcome in cats and dogs with traumatic diaphragmatic rupture. methodology section search strategy databases searched and dates covered: cab abstracts 1973–2021 week 31 pubmed 1966–2021 week 31 search strategy: cab abstracts and pubmed: dog or dogs or canine or cat or cats or feline diaphragm* hernia or hernia or rupture or tear or injury outcome* or prognosis* or survival* or mortality* 1 and 2 and 3 and 4 dates searches performed: 03 aug 2021 exclusion / inclusion criteria exclusion: not relevant, foreign, case reports, abstracts, reviews, book chapters, repeat of same relevant result within search inclusion: relevant journal articles, accessed through university of glasgow library search outcome database number of results excluded – not relevant excluded – foreign (without translation to english) excluded – case report excluded – review excluded – congress proceedings (abstract only) excluded – book chapter excluded – repeated result in same search total relevant papers cab abstracts 229 188 3 12 11 3 1 1 10 pubmed 83 68 1 7 1 0 0 0 6 total relevant papers when duplicates removed 10 conflict of interest the authors declare no conflicts of interest. references besalti, o., pekcan, z., caliskan, m. & aykut, z.g. (2011). a retrospective study on traumatic diaphragmatic hernias in cats. ankara üniversitesi veteriner faukültesi dergisi. 58(3), 175–179. doi: https://doi.org/10.1501/vetfak_0000002470 garson, h.l., dodman, n.h. & baker, g.j. (1980). diaphragmatic hernia. analysis of fifty-six cases in dogs and cats. journal of small animal practice. 21, 469–481. gibson, t.w.g., brisson, b.a. & sears, w. (2005). perioperative survival rates after surgery for diaphragmatic hernia in dogs and cats: 92 cases (1990–2002). journal of the american veterinary medicine association. 227(1), 105–109. igna, c., schuszler, l., sala, a., bumb, d., proteasa, a. & dascalu, r. (2014). diaphragmatic hernia in dogs and cats: a report of 43 cases (2001–2013). lucräƒri åžtiiå£ifice medicinäƒ veterinaräƒ. 47(4), 48–51. available from: https://usab-tm.ro/utilizatori/medicinaveterinara/file/2014/simpozion/vol_%20xlvii-4_2014_complet.pdf [accessed 03 aug 2021]. legallet, c., theiman makin, k. & selmic, l.e. (2017). prognostic indicators for perioperative survival after diaphragmatic herniorrhaphy in cats and dogs: 96 cases (2001–2013). bmc veterinary research. 13(16). doi: https://doi.org/10.1186/s12917-016-0926-y minihan, a.c., berg, j. & evans, k.l. (2004). chronic diaphragmatic hernia in 34 dogs and 16 cats. journal of the american animal hospital association. 40, 51–63. ozer, k., guzel, o., devecioglu, y. & aksoy, o. (2007). diaphragmatic hernia in cats: 44 cases. medycyna weterynaryjna. 63(12), 1564–1567. available from: http://www.medycynawet.edu.pl/images/stories/pdf/pdf2007/122007/200712s15681571.pdf [accessed 03 aug 2021]. schmeidt, c.w, tobias, k.m. & mccrackin stevenson, m.a. (2003). traumatic diaphragmatic hernia in cats: 34 cases (1991–2001). journal of the american veterinary medicine association. 222(9), 1237–1240. wilson, g.p., newton, c.d. & burt, j.k. (1971). a review of 116 diaphragmatic hernias in dogs and cats. journal of the american veterinary medicine association. 159(9), 1142–1145. yaygingül, r., bozkan, z., bilgen åžen, z., kibar kurt, b. & belge, a. (2019). traumatic diaphragmatic hernia in cats: a retrospective study of 15 cases (2016–2017). kocatepe veterinary journal. 12(2), 205–212. doi: https://doi.org/10.30607/kvj.493594 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. cryotherapy of the distal limbs: an effective treatment for equine laminitis following onset of lameness? a knowledge summary by lucy ryde bvmsci (hons) mrcvs fcmgr acmi 1* 1university of surrey school of veterinary medicine, vsm building, university of surrey, daphne jackson road, guildford gu2 7al *corresponding author (lucyryde@gmail.com) vol 6, issue 4 (2021) published: 09 dec 2021 reviewed by: joanne ireland (bvms phd certavp(em) fhea mrcvs) and david ramey (dvm) next review date: 27 may 2023 doi: 10.18849/ve.v6i4.480 pico question in horses with acute laminitis, does cryotherapy of the distal limbs applied after onset of clinical signs lead to improved clinical outcomes compared to horses treated without cryotherapy?   clinical bottom line category of research question treatment the number and type of study designs reviewed four papers were critically appraised; there were three randomised, controlled trials, and one retrospective cohort study strength of evidence weak outcomes reported there were reduced histological changes and lamellar injury in limbs treated with cryotherapy in the randomised controlled trials and reduced clinical severity of laminitis in horses treated with cryotherapy in the retrospective cohort study conclusion in horses with acute laminitis there is weak evidence to suggest that cryotherapy of the distal limbs is an effective treatment option when applied following onset of clinical signs. further randomised, controlled trials should be performed to assess clinical outcomes of cryotherapy in order to draw definitive conclusions   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. the evidence a literature search returned a total of 302 papers, of which four met the inclusion criteria. these papers consisted of three prospective, blinded, experimental, randomised controlled trials (rcts) (van eps et al., 2014; dern et al., 2018; and dern et al., 2017), where laminitis was induced in horses using the oligofructose model and the effects of cryotherapy studied. the remaining paper was a retrospective cohort study (d’arpe, 2010), which evaluated the outcomes of various treatment protocols for laminitis in the field rather than in an experimental setting. the quality of evidence of the papers included is variable. all were published within ten years of this paper being written, meaning that they are likely to be representative of treatment protocols used at the present day. experimental rcts generally produce strong evidence due to the nature of the study type used (cockcroft, 2019), and the utilisation of blinding in the papers studied will have contributed to the strength of the evidence (guyatt et al., 2008). however, the study populations used in these rcts comprised solely a small number of standardbred horses from research herds, which brings into question the generalisability of results obtained. for this reason, evidence yielded from the rcts should be categorised as moderate to weak. the retrospective cohort study will have produced weaker evidence than the rcts (cockcroft, 2019) due to both the nature of the cohort study design and the fact that it was retrospective, meaning that many variables were not able to be controlled and so significant biases, such as selection bias, may have interfered with the results (sauerland et al., 2002). for these reasons, the retrospective cohort study included is likely to have yielded weak evidence. summary of the evidence d’arpe (2010) population: horses diagnosed with laminitis between 2001 and 2010 analysed retrospectively. sample size: 85 horses. intervention details: cases were divided into two groups: group 1 of 53 horses that were not treated with cryotherapy. group 2 of 32 horses that were treated with cryotherapy. of the horses in group 1, 33 were graded as low-severity laminitis and were treated conservatively. 19 horses were graded as medium–high severity, and one as high severity, and these were treated surgically. 22 horses underwent partial or complete wall ablations, 14 underwent a deep digital flextor tendon (ddft) tenotomy, and seven underwent transcortical casting. all others were treated conservatively. the horses in group 2 were treated with cryotherapy for at least 72 hours. additional cryotherapy was applied for a further 48 hours if heat reoccurred in the foot. 17 of these horses were treated with a cryotherapy machine at -5 to -7oc whilst the remaining 15 were treated with ice cubes at 0–4o additional treatments were provided to horses in both groups as required, including antibiotics, controlled diets, and pain management. the severity of laminitis was then assessed based on pain management, radiographic changes, and clinical assessment. study design: retrospective cohort study. outcome studied: subjective assessment – clinical outcome of each case based on pain management, radiographic changes, and clinical assessment. main findings (relevant to pico question): cryotherapy reduced or eliminated clinical signs within 12–24 hours of initiation in all horses treated and none developed rotation of the pedal bone or required further, more severe treatment interventions. white line disease developed 2–3 months later in 10/15 (67%) of the horses treated with ice cubes, which was deemed to be a result of the wet condition of the foot. only 1/17 (6%) of the horses treated with the cryotherapy machine developed white line disease. limitations: additional treatments, such as antibiotics and dietary changes, were not controlled between the groups. this is a variable that could have impacted the results. it was a retrospective study, so the horses were not randomly assigned to their respective groups. group 1 did not receive cryotherapy as it was not available at the time, meaning that selection bias was present; horses treated between 2001–2007/2008 did not receive cryotherapy, with its use commencing in 2008. it is probable that other variables changed over this time period, increasing the potential for confounding in this study. twelve out of thirty-two (38%) of the horses treated with cryotherapy were unable to be followed up after the study. this means that the longer-term effects of cryotherapy are unknown in 12 of the subjects. there was also a substantial loss to follow-up in group 1, weakening the evidence the paper provides as the longer-term effects of either treatment are unknown. van eps et al. (2014) population: standardbred geldings aged 3–11 years, ranging from 430–548 kg, with no lameness and no gross or radiographic abnormalities of the hooves. sample size: eight horses. intervention details: all horses were housed and fed in stables for 4 weeks prior to the study. laminitis was induced in all horses using the oligofructose model via nasogastric administration of the bolus dose (10 g/kg bodyweight of oligofructose, up to a maximum dose of 4.2 kg). immediately after induction, each horse was confined to stocks for the remainder of the study. forelimb hoof temperature was monitored using hoof wall thermistors, and human pedometers were attached to both forelimbs to monitor the frequency of weight-shifting as a marker for pain. 12 hours after induction of laminitis, horses were monitored for the development of lameness by pedometer counts and gait analysis by two individuals every 4 hours. once lameness was detected at walk by both investigators, one forelimb was continuously cooled, and the other forelimb was maintained at ambient temperature. the forelimbs designated for each treatment alternative were randomly assigned. perineural analgesia via palmar nerve block was given to all horses using 2.5 ml of 0.25% bupivacaine and 2.5 ml of 2% mepivacaine per site, and all horses received phenylbutazone (4.4 mg/kg bodyweight iv) at the onset of lameness and again between 12–24 hours after the onset of lameness. cryotherapy was achieved by placing the limb in a rubber boot containing 50% cubed ice and 50% water to a level just below the carpus. 36 hours after the detection of lameness, horses were euthanised via pentobarbital sodium (20 mg/kg bwt iv) and the forelimb dorsal lamellae were dissected from the hoof of both forelimbs and processed for light microscopy. study design: prospective, randomised, controlled, blinded, experimental trial. outcome studied: objective assessment ― dorsal lamellar sections were examined 36 hours after onset of lameness by two blinded observers to determine histological score (0–4 [normal to severe]) and a morphometric analysis was performed on each. main findings (relevant to pico question): continuous digital hypothermia significantly reduced the severity of lamellar injury in the horses studied. four out of eight (50%) of the lamellar sections at ambient temperature had a histological score of 4 (most severe) compared with 0 of the iced sections and the median histological scores of the ambient sections were significantly higher than those of the iced sections. the histological changes noted in the limbs treated with cryotherapy were limited to only the mildest histological changes able to be observed using light microscopy. pain, as judged by the weight-shifting monitored by the pedometers, was found to be significantly reduced in the limbs treated with cryotherapy compared to those treated at ambient temperature – horses were noted to stand still on the cryotherapy-treated limb and weight shift on the ambient limb. limitations: hypothermia was initiated immediately after onset of lameness. in clinical scenarios, there is likely to be a delay in initiation of hypothermia. the researchers only performed histological analysis of the lamellae, rather than any study of clinical progression of the laminitis. this makes extrapolation of the results to clinical outcomes more difficult. the decreased pain noted in the limbs treated with cryotherapy could have been due to the analgesic properties of cryotherapy rather than any disease-modifying effects of the treatment. the study only continued for 36 hours for humane reasons, so conclusions cannot be drawn on the progression of laminitis after 36 hours and whether the laminitis lesions present in the limbs would have deteriorated after the cessation of cryotherapy. results were obtained using artificially induced laminitis and so it may not be possible to directly extrapolate the results to naturally occurring laminitis. a small sample size was studied, with the study population comprising eight standardbred geldings, which is unlikely to be representative of the wider population. dern et al. (2017) population: standardbred geldings aged 3–11 years with no lameness and no abnormalities of the hooves detectable by gross or radiographic examination. this is a secondary analysis of the same horses used in van eps, 2014. sample size: eight horses intervention details: all eight horses had laminitis induced using the oligofructose model via nasogastric administration of the bolus dose (10 g/kg bodyweight of oligofructose, up to a maximum dose of 4.2 kg). the horses were all confined to stocks for the duration of the study and pedometers were attached to each forelimb to monitor frequency of weight-shifting as a marker for pain. hoof wall temperature was measured using hoof wall thermistors. horses were closely monitored for the onset of lameness by pedometer counts and gait evaluation performed by two observers every 4 hours. lameness of one or both forelimbs at walk was the timepoint for initiation of cryotherapy – one forelimb was cooled and the other maintained at ambient temperature. all horses were given perineural analgesia in both forelimbs via palmar nerve block using 2.5 ml of 0.25% bupivacaine and 2.5 ml of 2% mepivacaine per site. phenylbutazone (4.4 mg/kg bodyweight iv) was also given to all horses at the onset of lameness and again between 12–24 hours after the onset of lameness. 36 hours after the initiation of cryotherapy, all horses were euthanised with pentobarbital sodium (20 mg/kg bodyweight iv) and lamellar tissue samples were collected from both forelimbs and fixed and processed for light microscopy. study design: prospective, controlled, blinded, experimental trial. outcome studied: objective assessment – horses were euthanised after 36 hours to study concentrations of inflammatory markers in the lamellae to compare the differences between the limbs treated with cryotherapy with those treated at ambient temperature. the results were also compared with the data from a previous study (van eps et al., 2014) which utilised data from a study conducted by leise et al. (2011), documenting inflammatory markers present in the lamellae of normal horses that had not had laminitis induced. main findings (relevant to pico question): digital cryotherapy had no significant effect on increasing or decreasing the number of inflammatory markers present in the lamellae. limitations: the researchers only studied inflammatory markers present in the lamellae, rather than looking at clinical signs or pathology of the lamellae. results were obtained using artificially induced laminitis and so the results may not be directly extrapolatable to naturally occurring laminitis. a small sample size of eight standardbred geldings was studied, which is unlikely to be representative of the wider population. a power calculation was not carried out to determine whether the sample size was large enough. the study only continued for 36 hours for humane reasons, so conclusions cannot be drawn on the progression of laminitis after 36 hours and whether the laminitis lesions present in the limbs would have deteriorated after the cessation of cryotherapy. dern et al. (2018) population: standardbred geldings aged 3–11 years with no evidence of lameness or gross abnormalities of the hooves. sample size: 15 horses: seven horses administered oligofructose to induce laminitis, eight horses which acted as controls. intervention details: horses were randomly assigned to one of two groups seven horses underwent laminitis induction via nasogastric administration of the bolus dose (10 g/kg bolus of oligofructose, up to a maximum dose of 4.2 kg). eight horses acted as the control group and did not have laminitis induced. all horses were placed in stocks for the duration of the study and had constant access to hay and water. cryotherapy was performed on one randomly assigned forelimb on all horses 12 hours after induction of laminitis. twelve hours was chosen as it represents the timeframe during which horses consistently start to show clinical signs of laminitis. in the control group, cryotherapy was initiated 12 hours after the beginning of confinement in stocks. cryotherapy was achieved by maintaining one forelimb in a rubber boot containing 50% ice and 50% water to the level of the proximal metacarpus. forelimb hoof temperature was monitored using thermistors and human pedometers were attached to each forelimb to monitor the frequency of weight-shifting as a marker for pain. two-hourly recording of vital parameters was also performed. a single dose of phenylbutazone was administered to all horses in the treatment group at the onset of signs of laminitis (determined by evidence of weight-shifting). all horses were euthanised 24 hours after initiation of cryotherapy with pentobarbital sodium (20 mg/kg bodyweight iv) and lamellar tissue samples collected from both forelimbs to study inflammatory mediators and leukocyte numbers, which were assessed using qpcr and immunohistochemistry. the sections were either snap frozen or fixed and processed for light microscopy. study design: prospective, randomised, controlled, blinded, experimental trial. outcome studied: objective assessment – lamellar tissue samples were obtained 24 hours after initiation of continuous digital hypothermia. concentrations of inflammatory mediators and leukocyte numbers in the lamellar tissue were assessed using qpcr and immunohistochemistry. subjective assessment – histopathological scores were assigned to each section from 0–4 (normal to severe) by two blinded observers. main findings (relevant to pico question): pedometer data showed increased weight-shifting in the limbs treated at ambient temperature compared with those treated with cryotherapy, signifying increased pain in the ambient limbs. median histological scores were significantly lower in the horses treated with cryotherapy than those maintained at ambient temperature. lamellar leukocyte numbers were significantly decreased in horses treated with cryotherapy. no difference was seen in lamellar mrna concentrations of inflammatory cytokines. two inflammatory chemokines were found to be decreased in horses treated with cryotherapy. limitations: the study was only conducted for 24 hours for humane reasons so conclusions cannot be drawn on the progression of laminitis after 24 hours and whether the laminitis lesions present in the limbs would have deteriorated following cessation of cryotherapy. the researchers only performed histological analysis of the lamellae, rather than any study of clinical progression of the laminitis. this makes extrapolation of the results to clinical outcomes more difficult. the decreased pain noted in the limbs treated with cryotherapy could have been due to the analgesic properties of cryotherapy rather than any disease-modifying effects of the treatment. only one horse was lame at the time that cryotherapy was commenced and three of seven horses only showed obel grade 1 lameness 24 hours post-laminitis induction. this means that cryotherapy would have been given prophylactically in these horses. results were obtained using artificially induced and so the results may not be directly extrapolatable to naturally occurring laminitis. a small sample size of 15 standardbred geldings was studied – this is unlikely to be representative of the general population. appraisal, application and reflection cryotherapy of the distal limbs is a fairly new treatment option for laminitis. it has come to the fore in recent years as an effective prophylactic measure to prevent the onset of laminitis in horses treated during an at-risk period (kullmann et al., 2013). however, cryotherapy has had somewhat limited clinical use thus far, as the majority of laminitis cases occur without warning and so treatment prior to onset is not usually feasible in a clinical setting. the efficacy of cryotherapy as a treatment option once clinical signs of laminitis are apparent is yet to be determined. if cryotherapy were shown to be effective at halting the progression of structural changes in the lamellae and reducing the severity of the condition, its use could potentially change the way laminitis is managed and improve outcomes for affected horses. this knowledge summary seeks to determine whether cryotherapy of the distal limbs is an effective treatment for laminitis when applied following the onset of clinical signs. of the three papers deemed to produce ‘moderate-to-weak’ evidence (as noted in the ‘evidence’ section above), two found positive effects of cryotherapy (van eps et al., 2014; and dern et al., 2018) and one found no effect (dern et al., 2017). dern et al. (2017) studied the effect of cryotherapy on inflammatory signalling in the lamellae during an episode of laminitis and found no significant difference between treating the distal limbs with cryotherapy and treating at ambient temperature. however, whilst inflammation is thought to play a role in the pathology of laminitis, it is possible that cryotherapy is still effective at treating laminitis, but that the cryotherapy works via a different mechanism than by controlling inflammatory signalling. this may explain why no significant differences were found in this study. thus, the results of this study do not necessarily negate the use of cryotherapy as a treatment for laminitis, although they do not support it. dern et al. (2018) also studied the effect of cryotherapy on inflammatory signalling in the lamellae in horses with laminitis. in addition, lamellar histological grade and leukocyte numbers were also studied. similarly, dern et al. (2018) found limited effects of cryotherapy on inflammatory signalling, but did note a slight decrease. this study did, however, find significantly lower histological grades and leukocyte numbers in limbs treated with cryotherapy. a lower histological grade indicates that there was reduced stretching and deterioration of the secondary lamellae, the cause of displacement and rotation of the pedal bone in laminitis (belknap, 2015), and so suggests that cryotherapy would be an effective treatment. this study supports the conclusions drawn by dern et al. (2017) that cryotherapy of the distal limbs likely acts to treat laminitis via a mechanism other than by reducing inflammatory signalling. it should, however, be noted that dern et al. (2018) initiated cryotherapy at a ‘clinically relevant timepoint’, rather than at the onset of clinical signs. a ‘clinically relevant timepoint’ was defined as 12 hours post induction of laminitis, as this was deemed to be the most likely time for clinical signs to develop following induction with the oligofructose model. this assumption is supported by the literature (van eps & pollitt, 2010), but it is important to note that in the study performed by dern et al. (2018) only one horse was lame at the time that cryotherapy was commenced, and three of the seven horses only showed obel grade 1 lameness at 24 hours post-induction. this means that cryotherapy would have been given prophylactically in these horses, rather than as a treatment. this weakens the evidence provided by dern et al. (2018) in showing that cryotherapy of the distal limbs is an effective treatment option for laminitis when initiated after the onset of clinical signs. van eps et al. (2014) initiated cryotherapy following the onset of lameness at walk in horses induced with the oligofructose laminitis model. the study found that cryotherapy significantly reduced the severity of lamellar injury and prevented all limbs treated from progressing to the most severe grade of lamellar degradation. this was in stark contrast to 50% of the ambiently treated limbs being classified at this most severe grade. this study provides moderate evidence for the use of cryotherapy of the distal limbs as an effective treatment for laminitis, limited by the lack of clinical progression of the cases as the horses were euthanised before this could be assessed. all of the papers discussed thus far (dern et al., 2017; dern et al., 2018; and van eps et al., 2014) have been rcts. this is a strength, as it means they are likely to have robust study designs and produce strong evidence (cockcroft, 2019). however, there are a number of limitations associated with these studies. all of the studies artificially induced laminitis using the oligofructose laminitis model. this model is based on sepsis-related laminitis (godman et al., 2016) and so may not be reflective of naturally occurring cases, of which the vast majority occur due to endocrinopathies and hyperinsulinaemia (belknap, 2015). additionally, small sample sizes of young, healthy, standardbred horses were used, meaning that the horses studied are unlikely to be representative of the wider equine population, particularly of the population at greatest risk of laminitis (faber & fonseca, 2014). both of these limitations weaken the basis for the application of the results to clinical cases of laminitis occurring in the field. furthermore, each of the rcts studied not the clinical outcome of the trial, but the histological effects on the lamellae and the presence of inflammatory mediators. whilst the pathology of laminitis is understood to be associated with elongation and deterioration of the lamellae (belknap, 2015), without clinical assessment of the subjects, it would be problematic to infer from these studies that cryotherapy of the distal limbs will improve clinical outcomes of affected horses. this further limits the ability to claim that cryotherapy is an effective treatment for horses with laminitis in the field. moreover, in the studies performed by van eps et al. (2014) and dern et al. (2017), cryotherapy was initiated immediately following onset of lameness (these studies utilised the same horses, with dern et al. (2017) using the data collected in 2014 to perform additional analysis). this is not necessarily reflective of how laminitis is treated in the field ― in a naturally occurring case of laminitis, there would likely be a delay in initiation of treatment (for example, lameness may not be detected instantly and there may be a delay between noticing the problem, calling a veterinarian for advice, and performing any diagnostics before beginning treatment). these studies do not allow for extrapolation of the efficacy of cryotherapy when a number of hours or days have passed before treatment is commenced. in addition, the studies only continued for 36 hours, so conclusions cannot be drawn on the longer-term progression of laminitis and whether the laminitis lesions present in the limbs would have deteriorated after the cessation of cryotherapy. a retrospective cohort study was performed to explore treatment outcomes of naturally occurring cases of laminitis in the field, with a larger sample size of 85 horses (d’arpe, 2010). d’arpe (2010) found that 0/32 (0%) of horses treated with cryotherapy developed subsequent rotation of the pedal bone, whereas some horses treated with ambient limb therapy did develop pedal bone rotation. this may suggest that cryotherapy is a beneficial treatment option. however, the reporting of results in this paper does not allow for direct comparison between treatment groups, meaning that it is difficult to draw conclusions on whether treatment with cryotherapy resulted in better outcomes than treatment without. no deleterious effects were seen in horses treated with cryotherapy, indicating that it is safe to use. additionally, as the study was performed in the field, there would likely have been a delay between the onset of clinical signs and initiation of treatment, which reflects a more feasible use of cryotherapy in clinical practice than that which is performed in the rcts. the results of this study suggest that cryotherapy of the distal limbs may be an effective treatment for laminitis. however, retrospective cohort studies have significant limitations which can lead to bias (sauerland et al., 2002). little detail is provided on decisions regarding the allocation of horses to treatment groups in d’arpe (2010). however, it can be inferred that the horses were not randomly assigned to treatment groups, as all the horses treated with cryotherapy were those who developed laminitis after cryotherapy became available as a treatment option in 2008. horses who developed laminitis prior to 2008 were treated with alternative therapies, as cryotherapy was not available. this may have given rise to bias in the treatment groups and thus weakens the strength of conclusions able to be drawn from the study. it is also possible that the horses treated with cryotherapy in this study were treated so because they were assessed to be good candidates for cryotherapy (i.e. perhaps they had less severe laminitis, or perhaps the laminitis was identified particularly early in the disease course). the paper indicates that 20/53 (38%) of the non-cryotherapy cases were moderate to highly severe or very high severity whereas that information is not provided for the cryotherapy cases. the possibility for bias here further weakens the conclusion that cryotherapy is a good treatment option for all horses with laminitis. furthermore, additional treatment protocols (e.g., dietary restriction, length of box rest and pain relief) were not controlled between groups. a lack of control of these variables could have impacted the results. there may also be a further possibility of bias in this study given that the author of the study invented the boots used in the 17 successful cryotherapy cases, representing a potential financial conflict of interest that may have biased the results. these limitations weaken the argument for application of cryotherapy to the wider equine population. in conclusion, there is weak evidence to support the use of cryotherapy of the distal limbs as a treatment for acute laminitis in horses after the onset of clinical signs. the evidence from the rcts largely supports the use of cryotherapy, and, importantly, no studies found negative effects associated with its use. whilst rcts can produce strong evidence (cockcroft, 2019), they do have certain limitations, mostly surrounding their artificial nature. these limitations are particularly problematic when attempting to extrapolate results found on histology to clinical outcomes of cases; there is certainly strong evidence that cryotherapy of the distal limbs reduces structural degradation of the secondary lamellae during acute laminitis, but it is more difficult to draw definitive conclusions regarding clinical outcomes from these studies. many of these limitations of rcts can be overcome by field studies, as was discussed regarding the study performed by d’arpe (2010). however, field studies produce much weaker evidence than rcts, and this particular field study has a number of important limitations including selection bias and poor reporting. considering each of these studies in relation to one another, it appears that there is evidence to support the use of cryotherapy of the distal limbs as a treatment for laminitis after the onset of clinical signs. the evidence should be categorised as weak, as this conclusion can only be drawn when the studies are viewed in combination with each other in order to account for their respective limitations. further randomised, controlled trials should be performed to assess the efficacy of cryotherapy on improving clinical outcomes of laminitis cases when applied after the onset of clinical signs. methodology section search strategy databases searched and dates covered: cab abstracts on cab direct 1973–may 2021 pubmed on nih platform 1949–may 2021 scopus 1984–may 2021 search strategy: cab abstracts: (equine* or horse* or pony or ponies) and (laminiti*) and (cryotherapy or hypothermia or “cold therapy” or ice or icing or cold)   pubmed: (equine* or horse* or pony or ponies) and (laminiti*) and (cryotherapy or hypothermia or “cold therapy” or ice or icing or cold)   scopus: (equine* or horse* or pony or ponies) and (laminiti*) and (cryotherapy or hypothermia or “cold therapy” or ice or icing or cold) and not (bovine*) and (limit-to (doctype, “ar”)) dates searches performed: 27 may 2021 exclusion / inclusion criteria studies were limited to in vivo studies, which evaluated the use of cryotherapy applied only after the onset of clinical signs of laminitis. exclusion: non-english language publication; in vitro studies; study group received prophylactic cryotherapy only; study group did not have laminitis. inclusion: any study of horses or ponies undergoing treatment for laminitis using cryotherapy administered after the onset of clinical signs. search outcome database number of results excluded – by preliminary title screen excluded – non-english language publication excluded – in vitro study excluded – study group received prophylactic cryotherapy only excluded – study group did not have laminitis excluded – duplicate paper total relevant papers cab abstracts 80 60 1 1 9 3 2 4 pubmed 36 23 0 1 6 2 0 4 scopus 186 166 2 1 9 4 0 4 total relevant papers when duplicates removed 4 conflict of interest the author declares no conflicts of interest. references belknap, j. 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(2010). equine laminitis induced with oligofructose. equine veterinary journal. 38(3), 203–208. doi: https://doi.org/10.2746/042516406776866327 van eps, a.w., pollitt, c.c., underwood, c., medina-torres, c.e., goodwin, w.a. & belknap, j.k. (2014). continuous digital hypothermia initiated after the onset of lameness prevents lamellar failure in the oligofructose laminitis model. equine veterinary journal. 46(5), 625–630. doi: https://doi.org/10.1111/evj.12180 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. does physical therapy after a tplo lead to improvement of the 1-year post-operative peak vertical force? a knowledge summary by andrea faure beaulieu bvsc1* antonio pozzi dmv1 1vetsuisse faculty, university of zurich, rämistrasse 71, 8006 zürich, switzerland *corresponding author (andrea.fb@hotmail.ch) vol 1, issue 3 (2016) published: 21 sep 2016 reviewed by: adam swallow (bvsc mrcvs) next review date: 20 sep 2018 doi: 10.18849/ve.v1i3.31 clinical bottom line based on the lack of sufficient clinical studies investigating the pico question, it is not possible to conclude if physical therapy should be recommended as a routine postoperative treatment after tplo. question does postoperative rehabilitation improve 1-year postoperative peak vertical force (pvf) after a tibial plateau levelling osteotomy (tplo) in dogs? clinical scenario a dog needs to undergo a tplo as a result of a ruptured cranial cruciate ligament. the owner, an ambitious footballer, coincidentally had to operate his knee two years ago for the same reason. he would like to know if the postoperative rehabilitation is comparable and if there is any evidence that physical therapy in dogs provides similar benefits as in humans (van melick 2016). summary of the evidence wucherer (2013) population: overweight dogs with unilateral cranial cruciate ligament rupture (cclr) sample size: 40 dogs n = 40 intervention details: two treatment groups: n = 19 nonsurgical treatment group (physical therapy, weight loss, and non-steroidal anti-inflammatory drugs [nsaid] administration) n = 21 surgical treatment group (tplo + nonsurgical treatment) study design: randomised controlled trial outcome studied: subjective: owners had to complete questionnaires (canine brief pain inventory [cbpi] and vas [visual analogue scale]) at each outcome measure time. objective: functional and clinical scores (peak vertical force [pvf], vertical impulse [vi], body weight and body fat). main findings (relevant to pico question): dogs with cclr treated with surgical and nonsurgical interventions had better outcomes than dogs only with nonsurgical treatment significant (p < 0.05) improvements of pain severity and interference score at the 52-week evaluation of the questionnaires significant (p < 0.05) higher mean pvf at the 24and 52-week evaluations limitations: surgery wasn't performed by the same person (board-certificated veterinary surgeon or a surgical resident under the direct supervision of a board-certified veterinary surgeon) and different surgical procedures (arthroscopy vs. arthrotomy) due to complications during the time of follow-up (most common cause was the development of contralateral cclr) dogs were successively excluded from the study. of the initial 40 dogs only data of 23 were used at the 52-week evaluation. au (2010) population: medium to large breed dogs with naturally occurring cranial cruciate ligament (crcl) injury sample size: 65 dogs n = 65 intervention details: two treatment groups with different surgical interventions and the same postoperative physical rehabilitation: n = 35 had lateral fabellar suture (lfs) n = 30 had tplo study design: non-randomised controlled trial outcome studied: objective: radiographic osteoarthritis (oa) and functional/clinical scores (pvf, stifle joint range of motion and thigh circumference) main findings (relevant to pico question): increase of pvf from 3 weeks to 24 months but no significant difference between both groups mean pvf at 3 weeks evaluation: lfs group (17.57 ±70) and tplo group (20.65 ± 1.73) mean pvf at 24 months evaluation: lfs group (32.27 ±81) and tplo group (39.00 ± 2.75) increase of radiographic oa scores from preoperative to 24 months in both groups but no significant difference between both groups (potential oa scores ranged from 0 to 63): radiographic score at preoperative evaluation: lfs group (18.5 ±59) and tplo group (16.38 ± 1.91) radiographic score at 24-month evaluation: lfs group (28.21 ± 2.84) and tplo group (24.31 ± 2.42) limitations: significant differences between the groups at the start of the trial: age, weight, breeds and thigh circumference. dogs were nonrandomly allocated to groups: owners decided the surgical treatment. surgery wasn’t performed by the same person (surgery residents under the direct supervision of board certified surgeons). identical physical rehabilitation regime for all dogs. non-exclusion of dogs which developed crcl injury in the opposite limb or other complications considered to affect function (e.g. implant removal because of infection) during the postoperative period of the study. follow up incomplete. only approximately 50% of the dogs returned for the 24-month postoperative re-evaluation.   appraisal, application and reflection only two papers relevant to the pico were found in the literature analysing the ground reaction force (grf) over a longer time period of dogs with unilateral cclr after a tplo and/or physical therapy. wucherer et al. (2013) compared, in a randomised controlled trial, overweight dogs with cclr which were assigned to a non-surgical (physical therapy, nsaid administration and weight loss) and a surgical (tplo) + physical therapy treatment group. both groups received the same non-surgical therapy. the physical therapy, which was conducted by the same person, was individually designed for each dog and included at least 6 supervised sessions over 12 weeks. while the non-surgical treatment group had its first session at the beginning of the trial, the surgical group started 2 weeks after the surgery.   the study was able to show that the mean pvf of the dogs in the surgical treatment group was significantly higher after 24 and 52 weeks after the start of the study, compared with the non-surgical treatment group.    in the nonrandomised controlled trial from au et al. (2010) dogs with cclr underwent either a tplo or a lfs as surgical intervention. both groups were followed by an identical physical rehabilitation regime performed by the same experienced handler. even if the pvf scores were recorded during 2 years on a regular basis no significant differences between the two groups could be shown. this work has some bias since the two groups were not similar (different age, weight, breeds), the follow up was incomplete and the dogs having developed crcl injury on the opposite limb or other complications during the study period, were kept in the group.  moreover, the surgeries in both studies were done by different surgeons and were not conducted identically. this will additionally compromise the strength of the results. in conclusion, there is currently insufficient evidence to prove the benefit of postoperative physical therapy after a tplo based on an increase in pvf at 1 year recheck follow-up. however, there is some preliminary evidence that rehabilitation may be beneficial for the postoperative period, although further studies are needed. to provide evidence that rehabilitation should be included as routine postoperative treatment after tplo, a prospective, randomised study should be performed. dogs should undergo tplo and rehabilitation by the same individuals following consistent protocols to reduce variability. dogs should be followed for at least 1 year after surgery.   methodology section search strategy databases searched and dates covered: cab abstracts on the cab direct interface, date range: 1973 2016 and pubmed accessed via the ncbi interface, date range: 1971 2016 search terms: ( dog or dogs or canine or canines or canis or puppy or puppies ) and (tplo or "tibial plateau leveling osteotomy" or "tibial plateau levelling osteotomy" or "tibial plateau leveling" or "tibial plateau levelling") and ("vertical force" or "ground reaction force" or grf or "force plate" or "pressure platform" or plate or platform or compression or force or pressure) dates searches performed: december 7th 2015 exclusion / inclusion criteria exclusion: non english language, non-systematic review, conference papers or summary updates. inclusion: studies which include rehabilitation, tplo and grf at the same time. search outcome database number of results excluded – non-english language publication excluded – as didn’t include the criteria rehabilitation, tplo and grf at the same time total relevant papers cab abstracts 80 11 67 2 ncbi pubmed 66 0 65 1 total relevant papers when duplicates removed 2 conflict of interest the authors declare no conflicts of interest. references van melick, n. et al. (2016) evidence-based clinical practice update: practice guidelines for anterior cruciate ligament rehabilitation based on a systematic review and multidisciplinary consensus. british journal of sports medicine, [in process] http://dx.doi.org/10.1136/bjsports-2015-095898 wucherer, k. l. et al. (2013) short-term and long-term outcomes for overweight dogs with cranial cruciate ligament rupture treated surgically or nonsurgically. journal of the american veterinary medical association, 242 (10), pp. 136-472. http://dx.doi.org/10.2460/javma.242.10.1364 au, k. k. et al. (2010) comparison of short­ and long­term function and radiographic osteoarthrosis in dogs after postoperative physical rehabilitation and tibial plateau leveling osteotomy or lateral fabellar suture stabilization. veterinary surgery, 39 (2), pp. 173-180. http://dx.doi.org/10.1111/j.1532-950x.2009.00628.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. supraspinatus tendinopathy in 327 dogs: a retrospective study sherman orye canapp, jr. dvm, ms, ccrt, dacvs, dacvsmr1* debra ann canapp dvm, cva, ccrt, dacvsmr1 brittany jean carr dvm, ccrt1 catherine cox ms1 jennifer genevieve barrett phd, dvm, dacvs, dacvsmr2 1veterinary orthopaedic and sports medicine group, 10975 guilford road, annapolis junction, md 20701 2marion dupont scott equine medical center, virginia-maryland college of veterinary medicine, 17690 old waterford road leesburg, va 20176 *corresponding author (scanapp@vosm.com) vol 1, issue 3 (2016) published: 04 july 2016 reviewed by: wanda gordon-evans (dvm, phd, dacvs dacvsmr) doi: 10.18849/ve.v1i3.32 section index:    abstract | introduction | methods | results | discussion | conflict of interest | references | supplementary files abstract objective: to report clinical findings and treatments for dogs with supraspinatus tendinopathy (st). background: st is a term used to describe tears, calcifying tendinopathy, tendinosis and/or injuries in and around the tendon of the supraspinatus muscle, and is a cause of forelimb lameness, especially in sporting and performance dogs. evidentiary value: this is a retrospective study of 327 dogs diagnosed with st. methods: medical records (2006 to 2013) were reviewed for history, signalment, prior treatments, physical examination findings, diagnostic imaging and arthroscopic findings, concurrent shoulder and elbow pathologies, and treatments performed. results: dogs aged 4 months to 14 years (average 6.5 years; median 6 years) were diagnosed with st. performance and sporting dogs were 39.4% of the population, with 58.1% of them being agility dogs. pain was elicited on palpation of the supraspinatus tendon in 49.3% of dogs. shoulder radiographs in 283 dogs showed mineralisation in 13% of cases. mri of the shoulder was performed in 31 cases and revealed findings indicative of st, including hyperintensity of signal on t1 weighted image (or “spin-lattice”) and short t1 inversion recovery (stir) sequences of the supraspinatus tendon at its insertion on the greater tubercle and mineralisation of the supraspinatus tendon. common ultrasonographic findings included increased tendon size (76%), irregular fibre pattern (74%), and non-homogeneous echogenicity (92.5%). the most common findings on shoulder arthroscopy were supraspinatus bulge (82.2%) and subscapularis pathology (62.4%). elbow pathology was recorded in 54.5% of dogs. treatment outcomes showed 74.6% of dogs failed to respond to non-steroidal anti-inflammatory drugs (nsaid) and 40.8% failed to respond to rehabilitation.  conclusions: these findings suggest concurrent shoulder and/or elbow pathology is not uncommon in dogs with st. further, st often fails to respond to nsaid therapy and rehabilitation therapy.  application: other treatments such as regenerative medicine should be considered. future studies are still needed to assess the use and efficacy of regenerative medicine for st. introduction the shoulder joint of the dog is distinct in its ability to withstand large forces and allow for great mobility while maintaining the control needed for stable and precise function of the forelimb. both the stability and function of the shoulder joint relies on a complex network of supportive soft tissue structures, specifically those of the rotator cuff which include the supraspinatus, infraspinatus, teres minor, and subscapularis (1-4). the supraspinatus is an important passive stabiliser of the shoulder joint, and is responsible for shoulder extension and advancing the limb (3,4). several degenerative disorders have been identified in both humans and dogs involving the supraspinatus tendon including rotator cuff tears, calcifying tendinopathy (bony mineralisation within the tendon) and tendinosis (microtears within the tendon) (3,5-7).  st is a term used to describe these clinical conditions and/or injuries in and around the tendon of the supraspinatus muscle, and is a cause of forelimb lameness, especially in human athletes and performance dogs (5,8-14).             the aetiology of st in performance dogs is thought to be repeated strain activity and overuse from chronic repetitive activity, with a failure of adequate remodeling (8,10,13,14). while inflammation may play a role in the initiation of st, it generally does not in the propagation and progression of the disease process. histology of pathologic supraspinatus tendons shows either absent to minimal inflammation with hypocellularity, a loss of tightly bundled collagen appearance, an increased proteoglycan content, and lack of neovascularisation in response to injury (5,14-22).  tendons damaged from repeated strain demonstrate discontinuous, disorganised tendon fibres with little to no inflammation and occasional mineralisation within the tendon and bony remodeling at its insertion site in chronic cases (14,21). in chronic cases, calcification at the site of insertion has been well documented in both humans and dogs (17,22-25).               diagnosis of st can be made on the basis of a combination of orthopaedic examination, imaging, and diagnostic arthroscopic findings. on initial presentation dogs with st typically present with a weight bearing lameness on the affected limb that often worsens with activity. direct palpation of the tendon and flexion of the shoulder commonly produces pain, and the supraspinatus muscle may be atrophied (10,22,25,26-28).  mineralisation of the supraspinatus tendon can be identified with diagnostic imaging modalities such as radiography, computerised tomography, magnetic resonance imaging (mri), and diagnostic ultrasonography (10,17,24,29-31). the most common finding on mri is enlargement and increased signal in the area of insertion of the supraspinatus tendon over the greater tubercle of the humerus on t2 weighted image (t2-w) and stir sequences (10,32). diagnostic musculoskeletal ultrasonography is a relatively new technique that has been used and validated for the diagnosis of st in both humans and dogs (8,33-40). musculoskeletal ultrasound provides a non-invasive definitive diagnosis of st, and allows for facile and cost-effective sequential exams to assess response to treatment (8,33-40). changes in size, shape, and echogenicity of the tendon found on diagnostic ultrasounds indicate st.   conservative treatment of st includes medical management of acute inflammation, controlled activity, rehabilitation therapy, acupuncture, deep cross-friction massage, heat, ultrasound therapy, range of motion (rom) and stretching, and therapeutic laser therapy. extracorporeal shockwave therapy has also been used in chronic calcified st in both humans and dogs (2,14,42-44). as in humans, other treatment options include regenerative medicine therapy and surgery (10,14,16,17). platelet-rich plasma (prp), stem cell therapy (sct), or a combination of these may be directly injected into the tendon under ultrasonographic guidance. surgical intervention (debulking or releasing the supraspinatus tendon) has been documented in chronic cases that do not respond to conservative management and rehabilitation therapy. in addition, arthroscopic evaluation of the shoulder can be performed to rule out concurrent pathologies, such as medial shoulder syndrome. rehabilitation therapy as previously described is crucial following any surgical treatment (45). healing can be confirmed by improvement in lameness, pain on palpation, improved range of motion, and improvement in appearance of the tendon using mri and/or musculoskeletal ultrasonography.              while there is a great deal of literature regarding the presentation, clinical findings, diagnostic imaging characteristics of st in humans, to the authors’ knowledge there is limited literature describing st in dogs.  the purpose of this retrospective study is to describe clinical findings and diagnostic imaging characteristics for dogs with st. methods medical records of client-owned dogs diagnosed with st were reviewed from 2006-2013. data collected included signalment, history, limb involvement, prior treatments, physical and orthopaedic examination, diagnostic imaging results (radiography, mri, diagnostic musculoskeletal ultrasound), arthroscopy findings, presence of concurrent shoulder and elbow pathologies, and treatments performed.  dogs were included if a diagnosis of st was made based on a combination of orthopaedic examination findings and diagnostic imaging findings. dogs were excluded if medical records were incomplete. results dogs: a total of 327 dogs were diagnosed with st from 2006-2013. all records were found to be complete. ages ranged from 4 months to 14 years (average 6.5 years; median 6 years). no sex predisposition was apparent, as there were 142 female dogs (20 intact) and 185 male dogs (41 intact). the different breed representations are displayed in table 1. performance and sporting dogs accounted for 39.4% of the population, and companion animals accounted for the remaining 60.6%. of the performance and sporting dog population, 58.1% participate in agility. at presentation, a majority (74.6%) of dogs failed to respond to nsaid therapy, and 40.8% failed to respond to a dedicated rehabilitation therapy program for st, which consisted of weekly rehabilitation therapy sessions for a minimum of 8 weeks. unilateral lameness was more common than bilateral, 62.4% and 37.6% respectively. the average lameness score, graded from 0 (sound) to 6 (non-weight bearing lame), was 2.1 (median 3). duration of lameness at initial presentation ranged from one week to over one year. less than one third of dogs (26.6%) had a chronic (>1 year) lameness. of the remaining, average duration was 14.7 weeks (median 13 weeks). physical examination findings: a physical examination was performed on all 327 dogs. on physical examination, pain on direct palpation of the supraspinatus was found in 49.3% of dogs. pain/spasm on shoulder extension and abduction was noted in 59.5% and 59.9%, respectively. pain/spasm on shoulder flexion was recorded to be found in 64.1%, and pain on biceps stretch was recorded in 48% of dogs. radiography: shoulder radiographs were performed in 283 dogs (86.5%). mineralisation was noted in 37 cases (13%) (figure 1). in the 123 dogs with bilateral st, mineralisation was noted in 10 cases; 8 unilateral and 2 bilateral. elbow radiographs were performed in 267 dogs (480 elbows), and 76 of those dogs (28.3% of total st dogs) had signs of elbow disease. sclerosis was noted in 28.3% of elbows and degenerative joint disease (djd) in 15.9%. magnetic resonance imaging: mri of the shoulder was performed on 31 dogs. all mri images were reviewed by an american college of veterinary radiology certified veterinary radiologist. of these 31 dogs, 50% of dogs had findings indicative of st including hyperintensity of signal on t1 and stir sequences of the st at its insertion on the greater tubercle (figure 2). a flattened or oval appearance of the biceps tendon, loss of fluid around the biceps tendon within the bicipital groove at the level of insertion of the supraspinatus, and/or displacement of the biceps tendon from the bicipital groove characterised biceps impingement secondary to st in 50% of cases (figures 3 and 4). fatty replacement at the myotendinous junction (seen on the t1 weighted image) of the supraspinatus was present in 30% of cases. mineralisation of the st was noted in 16% of cases. diagnostic musculoskeletal ultrasonography: diagnostic musculoskeletal ultrasonography was performed in 255 dogs (78%). the supraspinatus tendon was evaluated in both the longitudinal and sagittal plane for each of the following characteristics: size, shape, echogenicity, and boney irregularity at the insertion. the following changes were also reported if present: biceps tendon pathology, synovial proliferation, and increases in synovial fluid volume within the biceps sheath and/or shoulder joint. of the 255 cases, mixed echogenicity was found in 89.2% of cases, irregular fibre pattern was found in 52.5% of cases, the supraspinatus appeared enlarged in 50.6% of cases, a core lesion was identified in 23.6% of cases, boney irregularity was found in 19.3% of cases, bicipital tenosynovitis was found in 15.7% of cases, and mineralisation of the supraspinatus tendon was appreciated in 15% of cases (figures 5 and 6). arthroscopy: shoulder arthroscopy was performed in 218 dogs. of these, elbow arthroscopy was performed in 168 dogs; 23 dogs had elbow arthroscopy only. a total of 271 shoulders were evaluated via arthroscopy. of the 271 shoulders, a supraspinatus bulge was noted in 82.2% of dogs (figure 7). of these, biceps tendon impingement was noted in 38.7% of dogs. while 29.2% of dogs had bicipital tenosynovitis, biceps pathology was noted in 37.6%. pathology of the subscapularis was observed in 62.4% of dogs; medial glenohumeral ligament (mgl) pathology was present in 44.6%; labral tear in 32.8%; cartilage defects in 21.8%; and bone eburnation or osteophytosis in 11.1% of dogs. of the 168 dogs evaluated via elbow arthroscopy, 257 elbows in total were evaluated.  of the 257 elbows evaluated, 54.5% had elbow pathology, of which 34.6% had fragmented medial coronoid processes, 5.1% had evidence of medial coronoid disease, and 14.8% had end stage medial compartment disease. the remaining 45.5% were within normal limits. discussion a total of 327 dogs were diagnosed with st from 2006-2013 representing the largest accumulation of supraspinatus tendon injuries in a retrospective study to date. there was no apparent age, sex, or breed predisposition. diagnostic musculoskeletal ultrasonography of the shoulder was performed in 255 of the 327 dogs. changes consistent with st were noted on diagnostic musculoskeletal ultrasound in the majority of cases. while the diagnostic musculoskeletal ultrasonographic grading scores and their significance are still being assessed, diagnostic musculoskeletal ultrasonography should be considered as a useful imaging modality in diagnosing st. musculoskeletal ultrasonography has several advantages over mri. it is quicker, more economical, and can be performed without anesthesia or sedation in most instances. also, sequential ultrasonographic examinations during the course of treatment allows for monitoring of treatment response. recently, the ultrasound shoulder pathology rating scale (usprs) has been developed in humans (41). this scale provides an objective quantification of the pathology observed and is used not only for diagnosis but also monitoring treatment and progression of disease. further study is needed to establish an usprs for dogs. diagnostic arthroscopy was useful in the identification of st, which has not been described in the primary literature. a supraspinatus bulge was noted in 82.2% of the 218 dogs that had shoulder arthroscopy performed highlighting the importance of a thorough evaluation of the shoulder during arthroscopic exploration. additionally, concurrent shoulder and/or elbow pathology was a common finding on arthroscopy. pathology consistent with medial shoulder syndrome was found in 62.4% of dogs. of the 257 elbows in 191 dogs that were evaluated via arthroscopy, elbow pathology (fragmented medial coronoid process and/or medial compartment disease) was found in 54.5% of dogs. these findings suggest that concurrent shoulder and/or elbow pathology is not uncommon in dogs with st. our finding that concurrent injury to other forelimb structures is common also suggests the same repetitive actions that cause st can also cause other forelimb injuries, such as traumatic fragmentation of the medial coronoid process (tfmcp), thereby increasing lameness of the affected limb (4,15). however, it is also possible that pathologies such as non-traumatic fragmented medial coronoid process (fmcp) or medial compartment disease (mcd) may not only exist concurrently but also potentially predispose patients to compensatory shoulder pathology, such as st (4,15). this suggests that st may be secondary in these cases and that treating the primary pathology should be considered when formulating a treatment plan. when considering treatment options for st dogs, it is important to note that many of the patients failed to respond to conservative management prior to presentation as 74.6% of patients failed to respond to nsaid therapy and 40.8% failed to respond to rehabilitation therapy. this may suggest that conservative management is often insufficient to treat st. while dogs treated surgically have been shown to have improvements in gait and overall comfort, regenerative medicine therapy also shows promising results and should be considered for dogs with st (2,10,27). treatment of acute cases of st consists of conservative management including medical management, rehabilitation therapy, controlled activity, and acupuncture; however, treatment of chronic cases of st is somewhat different. dogs tend to take longer to recover due to the chronic nature of the changes in the tendon, as well as take longer to heal and progress through the different stages of exercises. the inflammatory process must be reinitiated in order to break down scar tissue and remodel the fibres of the tendon into their proper orientation, thus increasing its load capacity. nsaids are not recommended for chronic cases of st because of the need to reinitiate the inflammatory response (2,4). treatment of chronic cases of st often includes deep cross-friction massage, heat, ultrasound therapy, rom and stretching. acupuncture and cold laser therapy can also be utilised to increase circulation and reduce pain. extracorporeal shockwave therapy has also been used in chronic calcified st in both humans and dogs (2,14,42-44). regenerative medicine therapy has also been utilised for st in both humans and dogs, especially for cases where a core lesion is present (1,7,14,43,44,48-51). platelet-rich plasma (prp), stem cell therapy (sct), or a combination of these may be directly injected into the tendon under ultrasound guidance. severe cases may require a second injection (1,44,49,50). this therapy may be used as a primary treatment, however; arthroscopic exploration of the shoulder is recommended in conjunction since concurrent pathologies are not uncommon. arthroscopic treatments may be combined with an intra-articular injection of regenerative medicine therapy to aid in and speed the healing and recovery process (2). future studies are needed to evaluate the use of regenerative medicine therapy for st and other tendon injuries in the canine. the major limitation of this study is that it is a retrospective study. shortcomings can include recall bias, missing data points and lost follow-up. for evaluation of treatments and outcomes, lack of randomisation and the influence of bias and confounders also come into play. however, the large number of cases identified in this study contributes a significant database to the current literature, until further controlled studies that objectively measure treatment outcomes are performed. of note, the common clinical findings and diagnostic imaging characteristics of st have been thoroughly described.           in conclusion, these findings suggest concurrent shoulder and/or elbow pathology is not uncommon in dogs with st. further, chronic st often fails to respond to nsaid therapy and rehabilitation therapy, suggesting that other treatments such as regenerative medicine should be considered. future studies are still needed to assess the use and efficacy of regenerative medicine for st. conflict of interest the authors declare no conflicts of interest. references marcellin-little, d.j.  levine, d. and canapp s.o. 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(2011) diagnostic accuracy of ultrasound for rotator cuff tears in adults: a systemic review and meta-analysis. clinical radiology, 66 (11), pp. 1036-1048. http://dx.doi.org/10.1016/j.crad.2011.05.007 teefey, s.a. et al. (2004) detection and quantification of rotator cuff tears. the journal of bone & joint surgery, 86 (4), pp. 708-716. brose, s.w. et al. (2008) shoulder ultrasound abnormalities, physical examination findings, and pain in manual wheelchair users with spinal cord injury. archives of physical medicine and rehabilitation, 89 (11) pp. 2086-2093. http://dx.doi.org/10.1016/j.apmr.2008.05.015 danova, n.a. and muir, p. (2003) extracorporeal shock wave therapy for supraspinatus calcifying tendinopathy in two dogs. veterinary record, 152 (7), pp. 208-209. http://dx.doi.org/10.1136/vr.152.7.208 benell, k. s. et al. (2007) efficacy and cost-effectiveness of a physiotherapy program for chronic rotator cuff pathology: a protocol for randomized, double-blind, placebo-controlled trial. bmc musculoskeletal disorders, 8 (1), pp. 86. http://dx.doi.org/10.1186/1471-2474-8-86 cookson, j.c. and kent, b.e. (1979) orthopaedic manual therapy, an overview. part 1. the extremities. physical therapy, 59 (2), pp. 136-146. devor, m. and sorby, r. (2006) fibrotic contracture of the canine infraspinatus muscle: pathophysiology and prevention by early surgical intervention. veterinary and comparative orthopaedics and traumatology, 19, pp. 117-121. kesikburun, s. et al. (2013) platelet-rich plasma injections in the treatment of chronic rotator cuff tendinopathy: a randomized controlled trial with 1-year follow up. the american journal of sports medicine, 41 (11), pp. 2609-2616 http://dx.doi.org/10.1177/0363546513496542 canapp, s.o. (2013) regenerative medicine for tendinopathies in the canine. in: proceedings acvs symposium. san antonio, tx 24 -26 april. american college of veterinary sports medicine and rehabilitation, pp. 343-347. brosseau, l. et al. (2002) deep transverse friction massage for treating tendonitis. cochrane database system reviews (4):cd003528. http://dx.doi.org/10.1002/14651858.cd003528 wernham, b.g. warman, g.a. and jarram, r.m. (2008) bicipital tenosynovitis in dogs. compendium on continuing education for the practising veterinarian, 30 (10), pp. 537-552. gilley, r.s. wallace, l.j. and hayden, d.w. (2002) clinical and pathologic analyses of bicipital tenosynovitis in dogs. american journal of veterinary research, 63 (3), pp. 402-407. http://dx.doi.org/10.2460/ajvr.2002.63.402 jo, c.h. et al. (2011) does platelet-rich plasma accelerate recovery after rotator cuff repair: a prospective cohort study. the american journal of sports medicine, 39 (10), pp. 2082-2090. http://dx.doi.org/10.1177/0363546511413454 supplementary files, images & tables table 1: breed representation of 327 dogs with supraspinatus tendinopathy figure 1: shoulder radiograph with mineralisation of the supraspinatus tendon insertion. figure 2: stir sagittal image of a shoulder mri in a patient with a st showing an inflamed supraspinatus tendon. figure 3: stir transverse image of a shoulder mri in a patient with a st showing a flattened or oval appearance of the biceps tendon and loss of fluid around the biceps tendon within the bicipital groove at the level of insertion of the supraspinatus. figure 4: t1 mri image of a patient with a st showing fatty replacement at the myotendinous junction of the supraspinatus tendon. figure 5: diagnostic musculoskeletal shoulder ultrasound image depicting an enlargement of the supraspinatus tendon. figure 6: diagnostic musculoskeletal shoulder ultrasound image showing a supraspinatus tendon with a mixed echogenicity, suggestive of active inflammation. figure 7: shoulder arthroscopy demonstrating a supraspinatus bulge and secondary biceps impingement.   intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. comparison of the safety of alfaxalone and propofol as anaesthetic induction agents in bitches undergoing c-section a knowledge summary by ben haythornthwaite ba 1* 1cambridge university veterinary school, madingley rd, cambridge cb3 0es *corresponding author (bhaythornthwaite@hotmail.co.uk) vol 5, issue 3 (2020) published: 19 aug 2020 reviewed by:jane alexander (bvetmed, certva, mrcvs) and myra forster-van hijfte (certvr certsam dipecvim-ca frcvs) next review date:15 nov 2021 doi: 10.18849/ve.v5i3.313 pico question in bitches and their puppies undergoing caesarean section, is an alfaxalone or a propofol induction safer?   clinical bottom line category of research question risk the number and type of study designs reviewed six papers were critically reviewed. there were two randomised controlled trials directly comparing alfaxalone and propofol inductions, two randomised controlled trials including a propofol induction in one of the experimental groups and two non-comparative studies. strength of evidence moderate outcomes reported propofol and alfaxalone can both be used safely for the anaesthesia of bitches and their puppies undergoing caesarean section. there is evidence that alfaxalone may provide better anaesthesia quality for the bitches, and the puppies may be delivered with higher indicators of puppy vitality following its use. further research into the beneficial clinical outcomes of alfaxalone should be investigated. conclusion the use of both propofol and alfaxalone for the induction of bitches undergoing caesarean section can be recommended.   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision-making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario for canines undergoing a caesarean section, anaesthesia can be a risk to both the bitch and the puppies. silva et al. (2009) recorded significantly lower apgar scores for puppies born from caesarean section, for which anaesthesia may be partially responsible. supporting this, luna et al. (2004) found that multiple anaesthetic protocols have profound effects on neonatal neurological function postpartum due to passage of anaesthetic agents across the placenta following administration. propofol in particular has been found to rapidly cross the placenta into the foetal circulation (sánchez‐alcaraz, 1998). in a study by moon et al. (1998), 58% of caesarean sections were carried out on an emergency basis. this highlights the importance of having a safe anaesthetic protocol in place for swift treatment of patients who may already be compromised. propofol is frequently used as an induction agent in caesarean sections and alfaxalone is becoming more commonly used in the anaesthesia of pregnant bitches. this review aims to compare the safety of these two induction agents, both in the bitches and the puppies. the evidence six studies in total were found relevant to the pico, including four randomised controlled trials (metcalfe et al., 2014; doebeli et al., 2013; vilar et al., 2018; and luna et al., 2004) and two non-comparative studies (de cramer et al., 2017; and funkquist et al., 1997). one of the randomised controlled trials was blinded (doebeli et al., 2013). the variables measured included puppy survival and vitality (metcalfe et al., 2014; doebeli et al., 2013; vilar et al., 2018; luna et al., 2004; de cramer et al., 2017; and funkquist et al., 1997) and anaesthetic variables in the bitch (metcalfe et al., 2014; doebeli et al., 2013; vilar et al., 2018; de cramer et al., 2017; and funkquist et al., 1997). however, different measures of puppy vitality and anaesthetic variables in the bitches were recorded in each study. two of the studies directly compared the use of alfaxalone and propofol as induction agents (metcalfe et al., 2014; doebeli et al., 2013). these studies will be most useful when comparing the safety of the two drugs. the other studies (vilar et al., 2018; luna et al., 2004; de cramer et al., 2017; funkquist et al., 1997) included the use of propofol as an induction agent in one of their experimental groups. although it will be useful to assess the safety of propofol in these studies to compare with the results found in the studies by metcalfe et al. (2014) and doebeli et al. (2013), they will not offer evidence of as high a quality as in the two comparative randomised controlled trials. unfortunately as alfaxalone is only recently becoming more commonly used in caesarean sections, i found fewer studies including it in one of the experimental groups. summary of the evidence metcalfe et al. (2014) population: bitches undergoing caesarean section and the puppies born to them. no exclusions were made for breed, parity, urgency or whether any pups had been born naturally prior to presentation. the mean age for alfaxalone group was 48.9 ± 21.4 months. the mean age for the propofol group was 58.3 ± 18.1 months. sample size: 74 bitches intervention details: cases were randomised in blocks of three so that two in three would receive alfaxalone induction and one in three would receive propofol induction: alfaxalone induction n = 48/74 (65%) propofol induction n = 26/74 (35%) experimental details: before anaesthesia was induced, the clinical status of each patient was determined by physical examination. ultrasonographic examination of the bitch was performed. venous blood samples for haematology and biochemistry were collected immediately prior to induction. no patients received a premedication. patients in the alfaxalone group received an induction volume equalling 2 mg/kg body weight intravenously (iv). patients in the propofol group received an induction volume equalling 7 mg/kg body weight iv. the dose was administered until the investigator determined the depth of anaesthesia to be sufficient for endotracheal intubation or until the whole dose had been administered over 60 seconds. if intubation was not possible 60 seconds after the induction dose was given, one further induction dose could be administered to effect. mean induction dose for the alfaxalone group was 1.87 ± 39 mg/kg and for the propofol group was 5.46 ± 1.05 mg/kg. the quality of induction, maintenance and recovery was assessed in each patient. apnoea during maintenance was recorded if more than 30 seconds occurred between inspirations. general anaesthesia was maintained in all patients using inhalational isoflurane and oxygen. respiratory rate, pulse rate and oxygen saturation of haemoglobin were recorded during the procedure and assigned to one of three time categories: after induction, during the anaesthesia and during the recovery phase. following delivery of the pups, local anaesthesia, analgesia, anti-emetics, antibiotics, procoagulants and tocomimetics were administered as indicated by the needs of the bitch and the preference of each investigator. as soon as possible after delivery, each pup was assessed as live or dead. each live pup was then scored as positive or negative for withdrawal reflex, sucking reflex, anogenital response and flexion reflex. at 24 hours after delivery, each pup was reassessed as live or dead. study design: prospective, non-blinded, randomised, positive controlled trial outcome studied: quality of anaesthetic induction, maintenance and recovery in the subjects. this was measured as percentage of bitches in which apnoea was recorded and by a subjective scoring system as described by ko et al. (1998). puppy survival measured as percentage alive at birth and 24 hours after. puppy vigour measured by being scored as either positive or negative for four health vigour assessments – withdrawal reflex, sucking reflex, anogenital response and flexion reflex. main findings (relevant to pico question): induction apnoea was recorded in 7/48(15%) bitches in the alfaxalone group and 6/26(25%) bitches in the propofol group. maintenance apnoea was recorded in 2/48 (4%) bitches in the alfaxalone group and 4/26 (17%) bitches in the propofol group but only on one of these occasions was the duration of apnoea recorded. of bitches in the alfaxalone group, 47/48 (98%) scored a top score for induction, 39/48 (81%) for anaesthetic effectiveness and 35/48 (73%) for recovery. with propofol, 23/26 (88%) scored a top score for induction, 17/26 (65%) for anaesthetic effectiveness and 18/26 (69%) for recovery. a greater percentage of alfaxalone group puppies (n = 213) were positive for all four health vigour assessments compared with the propofol group (n = 131): withdrawal reflex (95.8% in alfaxalone group vs 93.1% in propofol group) suction reflex (93.9% vs 84.0%) anogenital reflex (82.7% vs 80.9%) flexion reflex (90.1% vs 83.2%) the mean number of puppies per litter with normal withdrawal reflex (4.25 ± 2.94 vs 4.69 ± 3.16), suction reflex (4.17 ± 2.93 vs 4.23 ± 3.29), anogenital reflex (3.67 ± 3.04 vs 4.08 ± 3.26) and flexion reflex (4.00 ± 2.89 vs 4.19 ± 3.35) did not differ between the alfaxalone and propofol group respectively (p = 0.5, 0.9, 0.6 and 0.8). the alfaxalone group puppy survival percentages at birth did not differ from those in the propofol group (93% vs 94% respectively; p = 0.7). the alfaxalone group puppy survival percentages at 24 hours did not differ from those in the propofol group (89% vs 89% respectively; p = 0.9). there was no effect detected of treatment group on the total number of deaths (p = 0.7). limitations: not blinded. the number of brachycephalic bitches (12/26) in the propofol group was recorded as 25% of the population. it truly represents 46% of the propofol population. 9/48 (19%) of the alfaxalone group were represented by brachycephalic breeds whereas 12/26 (46%) of the propofol group was represented by the same. brachycephalic breeds tend to be more unstable under anaesthesia (gaynor et al., 1999) so this difference in demographics may have affected anaesthetic scores. this study was carried out between four different locations with seven different veterinary surgeons in total, which may have had an effect particularly on scoring anaesthetic quality due to its subjective measurement. however, the use of a scoring system (ko et al., 1998) will have reduced the amount of inter-investigator variation. apnoea was recorded in six bitches during anaesthetic maintenance but the duration of this apnoea was only recorded on one occasion possibly impacting scores for quality of anaesthesia. withholding of analgesics and local anaesthetics may have affected the quality scores for anaesthetic maintenance and recovery. the propofol sample size was half the size of the alfaxalone sample size. no analysis of respiratory rates, pulse rates, oxygen saturations and rectal temperatures. doebeli et al. (2013) population: bitches presenting with dystocia for which caesarean section was indicated and the puppies born to them. mean age of the bitches was 3 years, ranging from 1 to 11 years. mean body weight of the bitches was 7.3 kg, ranging from 1.6 to 51 kg. sample size: 22 bitches 81 puppies intervention details: cases divided in half between those receiving alfaxalone induction and those receiving propofol induction: alfaxalone group n=11 (50%) propofol group n=11 (50%) experimental details: all bitches received iv fluids (lactated ringer’s solution, 10–20 ml/kg/h) immediately after presentation until after recovery. in those bitches with poor general condition or severe dehydration, haes-steril 10% was added (1–2 ml/kg/h). before induction, all bitches were preoxygenated for 5 minutes using flow by oxygen at 2 l/minute and received a 20 mg/kg iv dose of cefazolin. bitches in the alfaxalone group received an induction volume equaling 1–2 mg/kg body weight iv. bitches in the propofol group received an induction volume equaling 2–6 mg/kg body weight iv. the surgeons and the observer who performed the evaluations after anaesthesia induction were blind to the agent used. anaesthesia maintained using isoflurane to effect. immediately after the last puppy was delivered, all bitches were started on 5 mcg/kg/h continuous rate infusion of fentanyl. all bitches received 14 mcg/kg buprenorphine and 4 mg/kg carprofen iv 20 minutes before the end of surgery. after delivery, all puppies had fluid cleared from the upper airways using suctioning. they were actively warmed and were oxygenated using flow by oxygen at 2 l/m. if breathing was inadequate, respirot was given at a dose of 1–2 drops orally and 3–5 ml/100g 5% glucose was given subcutaneously. body weight was recorded and a clinical examination of each puppy was performed.  study design: prospective, blinded, randomised, positive controlled trial outcome studied: neonatal viability determined using a modified apgar score developed by veronesi et al. (2009) at 5, 15 and 60 minutes after delivery. heart rate, respiratory effort, reflex irritability, motility and mucous membrane colour were rated 0 (absent), 1 (detectable, weak) or 2 (detectable, strong). puppy survival measured as percentage alive at birth, 60 minutes, 24 hours, 3 days and 3 months after. pre and intra-operative parameters in bitches including temperature, heart rate, respiratory rate, packed cell volume (pcv), total protein, anaesthesia duration, mean blood pressure and delivery time. main findings (relevant to pico question): puppy survival did not differ between the alfaxalone and the propofol group at any of the measured time intervals. 4 puppies from each group were born dead over the course of the study. at the first assessment 5 minutes after birth, the proportion of puppies in the alfaxalone group (n = 36) with high (7–10), medium (4–6) and low (0–3) apgar scores were 68%, 15% and 17% respectively. the same proportions for the propofol group (n = 45) were 19%, 31% and 50% respectively. the apgar scores at 5, 15 and 60 minutes after delivery were greater in the alfaxalone group than in the propofol group. the overall estimated score difference between the groups was 3.3 (p<0.001). pre and intra-operative parameters did not differ between the alfaxalone and the propofol group. maternal recovery was uneventful and rapid in both groups. limitations: a rather small sample size was used. although a significant difference in apgar scores was found between the alfaxalone and propofol groups, a larger population may provide better information on the range of patients seen in practice. ranges were given for alfaxalone and propofol induction dose but no indication as to how doses were chosen. no indication as to how patients were distributed between study groups. although the authors report maternal recovery as uneventful and rapid, no values are provided with regards to recovery time. the value of apgar scores in predicting short-term survival of puppies is not fully known. vilar et al. (2018) population: bitches undergoing elective caesarean section. sample size: 45 bitches from four different breeds (french bulldog, yorkshire terrier, chihuahua and bull terrier). intervention details: bitches assigned uniformly to three experimental groups: group p: propofol induction and maintenance (n = 17) group ps: propofol induction, sevoflurane maintenance (n = 14) group pes: propofol induction and maintenance, lidocaine epidural analgesia (n = 14) all bitches premedicated with morphine (0.2 mg/kg) ten minutes before induction with 3 mg/kg propofol. bitches in group p were taken straight to surgery and maintained on repeated boluses of propofol. once the last neonate was removed, maintenance was swapped to sevoflurane (0–8%) in oxygen. bitches in group ps were intubated following induction and maintained on sevoflurane (0–8%). bitches in group pes were intubated and then epidural anaesthesia was performed using lidocaine (2%) into the lumbosacral intervertebral space. once the last neonate was removed, maintenance was swapped to sevoflurane (0–8%) in oxygen. intramuscular tramadol and postoperative oral amoxicillin plus clavulanic acid was given to all patients. in all groups 1–2 mcg/kg fentanyl iv was provided when required to manage intraoperative pain. once the bitch was transferred to the surgical area, heart rate, respiratory rate, oxygen saturation, rectal temperature and blood pressure were monitored every 5 minutes. at 60 and 120 minutes after surgery, it was assessed whether the female was conscious, able to get up and/or walk and accept the puppies. immediately following delivery, the puppies were evaluated and apgar scored using a modified apgar score model (batista et al., 2014). puppies with an apgar score < 5 were provided with neonatal resuscitation protocols. puppies were classified as born dead, born alive but with severe defects, born alive but dead within 6h or viable and still alive after 6h. neonatal viability was also assessed at 12, 24 and 48h after birth. study design: non-blinded, randomised controlled trial outcome studied: intra and postoperative parameters in bitches including heart rate, respiratory rate, oxygen saturation, rectal temperature, consciousness, ability to get up and/or walk and accept the puppies. anaesthetic variables in bitches including number of propofol boluses required, time taken to start surgery following intubation and sevoflurane concentration required intra-operatively. puppy survival measured as percentage alive at birth and percentage mortality after 12 hours and 48 hours. puppy vitality measured via a modified apgar scoring system (batista et al., 2014) at birth and 60 minutes after. numbers of neonates requiring neonatal resuscitation was also recorded. main findings (relevant to pico question): the ps group is the only group in this study satisfying my inclusion/exclusion criteria and are therefore the only findings included here. mean values of parameters measured between the beginning of inhalatory anaesthesia and the end of surgery in the ps group were: heart rate –7 ± 3.1 beats per minute blood pressure –7 ± 3.5 mmhg oxygen saturation –1 ± 0.1 % rectal temperature –4 ± 0.1 °c 51/52 (98.1%) of puppies in the ps group were born alive. there was a mortality of 2/52 (3.8%) at 12 and 48 hours after delivery. at birth, 4/52 (7.7%) of puppies in the ps group had an apgar score between 0–3 (classed as critical neonates). this decreased to 1/51 (1.9%) at 60 minutes after delivery. mean apgar score at birth in the ps group was 7.0 ± 2. mean apgar score 60 minutes after birth in the ps group was 9.0 ± 1. the number of puppies in the ps group requiring different types of resuscitation was: tactile stimulation – 28/51 (54.9%) breathing stimulation – 21/51 (41.2%) drugs administration – 6/51 (11.7%) limitations: not blinded. comparisons drawn between groups are not relevant for the purposes of this review. bitches were premedicated with morphine which may have affected puppy vitality. brachycephalics were heavily represented, however this may correlate with the relevant clinical population. a scoring system for the quality of anaesthesia experienced by the bitches may have been useful, for example that described by ko et al. (1998). results were not provided for some of the parameters measured in the bitches – consciousness, ability to get up and/or walk and accept the puppies. it would be useful to know the longer term outcome of the puppies, for example over a few weeks or months. de cramer et al. (2017) population: bitches selected from the general obstetric population as being at increased obstetric risk. sample size: 292 caesarean sections in 256 bitches total. this included 133 boerboel, 68 english bulldog and 55 other purebred bitches. intervention details: in all cases an attempt at unassisted labour was declined by the owners. bitches were admitted 3–4 days prior to predicted parturition date (calculated as day 57 following day 0 of pregnancy). in these days bitches were observed for signs of impending parturition and by 6 hourly vaginal speculum examinations of the cervix. the decision on when to perform a caesarean section was based upon the first appearance of any dilation of the cervix. medetomidine was given as a predmedicant at 7 mcg/kg iv. induction performed 1 minute later with a 1 mg/kg iv bolus of propofol. top ups were given if required up to 2 mg/kg total. patients were intubated immediately after induction but were not connected to a closed circuit until surgical preparation had been carried out (averaging 3–5 minutes). all bitches were given a set amount of lactated ringers commencing following induction and finishing when 35 mll/kg had been infused. 10 mg/kg cefazolin was administered iv at induction. antibiotics were continued postoperatively with 20 mg/kg bid oral amoxicillin for 5 days. 0.1 mg/kg meloxicam was administered iv only when the last puppy had been removed. following removal of the puppies, atipamezole hydrochloride was given subcutaneously (sc) to each puppy at the dose of 50 mcg/puppy. 10% povidone iodine was applied to the umbilicus. puppies were dried, fluid was shaken from the airways and they were placed in an incubator set at 35°c. after surgery 20 mcg/kg atipamezole hydrochloride was administered iv to the bitch. it was recorded whether the bitches were fully ambulatory at 15 minutes following extubation. after delivery of the puppies, records were made of total puppies delivered, live, dead, deformed and euthanised. apgar scores were assessed 15 minutes after delivery of the last puppies using the system described by veronesi et al. (2009). puppy survival was recorded at delivery, 2 hours and 7 days after surgery. maternal survival was recorded after delivery of the last puppy, 2 hours and 7 days after surgery. the glasgow composite pain scale (gcps) evaluation was performed at the time of discharging the bitch (usually 2–3 hours after surgery). study design: non-comparative, retrospective study outcome studied: puppy survival measured as percentage alive at birth, 2 hours and 7 days postoperatively. puppy vitality measured using an apgar scoring system described by veronesi et al. (2009). variables relating to the bitches including whether they were ambulatory 15 minutes after extubation, haematocrit following surgery and comfort of bitches at discharge using the glasgow pain scale evaluation. surgical timings including total delivery time, average time to deliver individual puppies and average surgery time. main findings (relevant to pico question): percent live at delivery for the boerboel 97.39% (n = 1378), english bulldog 96.67% (n = 541) and other purebreed 91.69% (n = 313). after correction for foetuses discovered dead on ultrasound and malformed euthanised puppies, the survival rates for boerboel, english bulldog and other purebreed puppies were 98.21%, 95.60% and 94.30% respectively at 2 hours and 91.78%, 87.17% and 88.26% at 7 days. average surgery time for the boerboels and english bulldogs was 38 and 33 minutes respectively. the average apgar scores for the boerboels, english bulldogs and other purebreed puppies respectively was 9.77, 9.35 and 9.68. 2 hour survival rate was negatively correlated with the proportion of puppies in a litter with apgar scores of 8 or below (p = 0.01) but was not correlated to the mean apgar score of litters (p = 0.11). maternal survival rate was 291/292 with one boerboel bitch dying from gastric dilation and volvulus 2 days following surgery. the average gcps for bitches at discharge was 6.4. no bitch had a haematocrit of below 30% after surgery. all bitches were fully ambulatory 15 minutes after extubation. limitations: non-comparative study therefore hard to assess how a different protocol may compare under the same conditions. there was little measurement of the safety of anaesthesia for bitch. although number of bitches ambulatory at 15 minutes gives some indication of recovery, it would be useful to know intraoperative parameters or to use an anaesthetic scoring system. it could be useful to include gcps following recovery as well as at discharge. the pain score at discharge is presented as an average score of all bitches included in the study. this is broad and is not particularly useful in knowing if bitches who underwent a more complicated anaesthesia were more painful postoperatively for example. the population in this study was made predominantly of two breeds which is not representative of the full clinical population. however, english bulldogs are commonly among those presenting for caesarean section. all caesarean sections in this study were elective and results may differ to animals undergoing an emergency surgery. the medetomidine premedication may contribute to changes in puppy vitality. puppies given sc atipamezole prior to apgar scoring. funkquist et al. (1997) population: bitches undergoing caesarean section when indicated due to dystocia. sample size: 141 bitches – age ranged from 13 months to 9 years and represented 60 breeds. 412 puppies. intervention details: the veterinary surgeon on duty determined when caesarean section was indicated and performed the surgery. in some cases, puppies had been delivered per vaginum prior to caesarean section. anaesthesia was induced using propofol given iv to effect. 5 mg/kg was drawn up. estimated weight of the puppies was deducted from the bitch’s weight before calculating this dose. 20 minutes was allowed to elapse following induction before delivery of the puppies was begun. patients were immediately intubated and maintained using gaseous isoflurane (0.5 –0%) in a mixture of 65:35 oxygen:nitrous oxide. immediately after delivery, each puppy’s nasal passages, mouth and pharynx were cleared of mucus. puppies were also gently swung to remove fluid. in some puppies, a combination of crotethamide and cropropamide were given orally (2 – 12 mg of each drug). viability of puppies were monitored during a period of 1–3 hours until bitches and puppies were discharged. postoperative condition of the bitches and puppies were determined by telephone interview of owners 3 months after caesarean section. study design: non-comparative study outcome studied: status of the bitches – during anaesthesia and in recovery, whether they could care for their puppies postoperatively and complications encountered. puppy survival measured as percentage born alive and percentage alive after the 3 month observation period. puppy vitality by looking at how many puppies required more active resuscitation than usual. main findings (relevant to pico question): bitches induction and maintenance of anaesthesia was uneventful in all bitches. bitches recovered quickly from anaesthesia and without excitation. 101/141 of the bitches were considered by the owners to be alert and were unaffected by the anaesthesia. the other 40 were lethargic for 1–2 days after surgery. one brachycephalic bitch developed dyspnoea after surgery and a tracheotomy was performed following extubation. it subsequently recovered. one bitch had aggressive behaviour toward her puppies and was unwilling to care for them for 2 days after surgery. she then cared for them but had less interest than was considered normal. her milk production was also insufficient. one bitch developed metritis and mastitis 24 hours after surgery. two bitches developed metritis within 1 week of surgery and another developed mastitis 4 weeks after surgery. also after surgery, two bitches had slight bleeding, one had peritonitis and diarrhoea and another had diarrhoea and dehydration. puppies 74% (306/412) puppies delivered by caesarean section were born alive (26% (106/412) puppies delivered by caesarean section were stillborn). 4% (13/306) of puppies born alive died within 20 minutes. of the 293 surviving puppies, 36 (12%) were euthanised or died during the 3 month postoperative period. most puppies had evidence of some respiratory depression and required more active resuscitation. the degree of respiratory depression did not differ between the first and last puppy delivered during each caesarean section. limitations: non-comparative study therefore hard to assess how a different protocol may compare under the same conditions. several vets were involved in performing the caesarean sections and accompanying anaesthesia. there were no values given relating to how many puppies needed more active resuscitation. there was no indication of what measurements were used when determining if bitches had a good anaesthetic induction, maintenance and recovery. the follow-up was done by telephone communication. it may not be reliable to count on owners to give an accurate assessment of their animals. in some cases variable numbers of puppies had been removed from the uterus before caesarean section and in others none had. some puppies were given crotethamide and cropropamide if required and others were not which may influence mortality over the course of the study. luna et al. (2004) population: healthy 2–5 year old bitches requiring caesarean section due to lack of uterine contractions or inadequate vaginal dilation. bitches weighed between 7 and 14 kg. sample size: 24 bitches intervention details: bitches divided into four groups: group 1 – thiopentone (8 mg/kg) induction (n = 6) group 2 – midazolam (0.5 mg/kg) + ketamine (2 mg/kg) induction (n = 6) group 3 – propofol (5 mg/kg) induction (n = 6) group 4 – lidocaine with adrenaline 2% (2.5 mg/kg) + bupivicaine with adrenaline 0.5% (0.625 mg/kg) epidural (n = 6) experimental details: all bitches sedated with 0.5 mg/kg chlorpromazine iv. groups 1–3 were given their induction and then immediately intubated and given gaseous enflurane maintenance anaesthesia. group 4 underwent epidural anaesthesia at the lumbosacral space and were not intubated. 10 ml/kg/hr lactated ringer’s solution infused into all bitches during the anaesthetic. equal numbers of each group were operated on by one of two experienced veterinary surgeons. following removal from the uterus, the airways of the neonates were cleared and the following measurements were recorded: heart and respiratory rates, rectal temperature and neurological reflexes (including pain reflex, suction reflex, anogenital reflex, magnum reflex and flexion reflex). the puppies were examined 7 days later and the numbers which had died were recorded. study design: non-blinded randomised controlled trial outcome studied: puppy vitality measured using various parameters including heart and respiratory rate, temperature, and presence or absence of the reflexes mentioned above. puppy mortality. main findings (relevant to pico question): the only group relevant to this evidence summary is the propofol induction group and are therefore the only results included here. the following was found in this group: mean values for heart and respiratory rate of the puppies were 123 beats/minute and 16 breaths/minute respectively. mortality was 1/24 puppies (4%). the percentage of puppies testing positive for each of the reflexes tested was as follows: pain – 96% suction – 88% anogenital – 88% magnum – 58% flexion – 46% limitations: not blinded. the epidural group does not utilise inhalational anaesthesia, making it difficult to draw comparisons to the other groups. narrow weight range of dogs (7–14 kg) may not be representative of a clinical population. small sample sizes for each group. cases were divided between two veterinary surgeons. however, cases in each group were divided equally and each veterinary surgeon was described as experienced. although the paper was primarily focused on the effects on the puppies, it may have been useful to record parameters in the bitches to better evaluate the safety of the protocols on them too. no follow-up of puppy vitality/mortality following the initial measurements. appraisal, application and reflection i found six studies involving the use of alfaxalone or propofol inductions that were relevant to this question (metcalfe et al., 2014; doebeli et al., 2013; vilar et al., 2018; luna et al., 2004; de cramer et al., 2017; and funkquist et al., 1997), two of which were randomised controlled trials which directly compared propofol and alfaxalone inductions (metcalfe et al., 2014; and doebeli et al., 2013). these two studies looked to measure similar variables (maternal anaesthetic quality, neonatal mortality and neonatal vitality), but used different methods to determine them. this will be discussed under the headings relating to maternal safety and puppy safety below. these two studies offer the highest quality evidence relevant to my question due to the direct comparison of the two anaesthetic agents. the other four studies included two randomised controlled trials (vilar et al., 2018; and luna et al., 2004) which included a propofol induction as one of the experimental groups, and two non-comparative studies (de cramer et al., 2017; and funkquist et al., 1997) in which the anaesthetic protocol included a propofol induction. these studies recorded measures of maternal and puppy mortality and vitality which may be comparable to the two studies including the use of alfaxalone. one variable which may make it difficult to compare results between studies is the range of anaesthetic and surgical protocols used. three studies included a premedication in their anaesthetic protocol – chlorpromazine (luna et al., 2004), medetomidine (de cramer et al., 2017) and morphine (vilar et al., 2018). as we have previously established, any anaesthetic agent will have a varying effect on the bitch as well as pass across the placenta and affect neonatal function. therefore, drawing comparisons between these three studies and the three which do not involve the use of a premedication (metcalfe et al., 2014; doebeli et al., 2013; and funkquist et al., 1997) may be unreliable. despite this, in a clinical environment many choose to use a premedication in their anaesthetic protocols for caesarean sections therefore these studies are useful to draw conclusions from. safety of anaesthesia can be defined in many different ways and in the case of caesarean sections, relates to both the bitches and the puppies individually; i will therefore consider each of these in turn.   maternal safety with regards to the bitches, perioperative mortality is one potential measure of safety. however, there was a single bitch mortality in only one of the studies (de cramer et al., 2017), which was a gastric dilation 2 days postoperatively, likely unrelated to the anaesthesia. the relatively small sample sizes used by most of the studies make it difficult to assess differences in mortality between a propofol and alfaxalone induction. in a study by moon et al. (1998) of 808 bitches undergoing caesarean section, a maternal mortality rate of 1% (n=9) was found. we can therefore see that differences in mortality may not be apparent with the sample sizes used in these studies. five of the studies attempted in some way to measure the effect of the anaesthetic protocol on the bitches intraoperatively and postoperatively (metcalfe et al., 2014; doebeli et al., 2013; vilar et al., 2018; de cramer et al., 2017; and funkquist et al., 1997). one study using propofol (funkquist et al., 1997) subjectively assessed the status of the bitches, reporting induction and maintenance of anaesthesia to be uneventful in all cases. they also found that 101/141 of the bitches were considered by the owners to be alert and unaffected by the anaesthesia in the 1–2 days following surgery. one brachycephalic bitch developed dyspnoea postoperatively which may be related to the anaesthetic protocol, however this probably falls in line with the expected anaesthetic risks in brachycephalic dogs (gaynor et al., 1999). low numbers of other postoperative complications were seen in this study, all of which were unlikely to be related to the anaesthesia. three studies recorded objective variables pre, intra or postoperatively. de cramer et al. (2017), one of the propofol studies, found a maternal survival rate of 291/292, with the death due to a gastric dilation and volvulus 2 days postoperatively which is unlikely to be related to the anaesthesia. all bitches were ambulatory 15 minutes after extubation and no bitches had a haematocrit below 30% following the surgery. average pain score at discharge was 6.4 which is on the boundary of requiring further pain relief but is probably to be expected following abdominal surgery. vilar et al. (2018), one of the propofol studies, recorded heart rate, respiratory rate, oxygen saturation, rectal temperature, consciousness, ability to get up and/or walk and accept the puppies. only results for heart rate, respiratory rate, oxygen saturation and rectal temperature were reported and there were no adverse findings. in the comparison study by doebeli et al. (2013) temperature, heart rate, respiratory rate, pcv, total protein, anaesthesia duration, mean blood pressure and delivery time were recorded. no differences were found between the propofol and the alfaxalone group. although reporting objective variables such as in these three studies is useful, i believe an anaesthetic scoring system such as that used in the study by metcalfe et al. (2014) to be much more useful at deciding the quality of anaesthesia undergone by the patient. the scoring system in this study was described by ko et al. (1998). they found that of bitches in the alfaxalone group, 47 (98%), 39 (81%) and 35 (73%) scored a top score for induction, anaesthetic effectiveness and recovery respectively. for the same parameters with propofol, 23 (88%), 17 (65%) and 18 (69%) scored top scores, lower in every category when compared to the alfaxalone group. also in this study, induction apnoea was recorded in 15% of bitches in the alfaxalone group compared to 25% of bitches in the propofol group. maintenance apnoea was recorded in 4% of bitches in the alfaxalone group compared to 17% of bitches in the propofol group. although these values differ, the sample sizes may be too low to draw meaningful conclusions. from these studies, very few anaesthetic complications were encountered, highlighting that with regards to the bitches, both propofol and alfaxalone are relatively safe to use. this is the conclusion found by the two randomised controlled trials (metcalfe et al., 2014; and doebeli et al., 2013) which are the most reliable studies to consider when answering this question. the only real differences between the two induction agents was found by metcalfe et al. (2014), with the anaesthetic scoring system suggesting that patients induced using alfaxalone may have a slightly better quality of anaesthesia than those induced using propofol. the differences in the numbers of bitches experiencing apnoea in each of the groups may be relevant as both alfaxalone and propofol can cause respiratory depression. however, we probably can’t draw conclusions about this from this study alone so further investigation with larger sample sizes may be required to see if apnoea is more apparent using either induction agent.   puppy safety all six studies looked at two major variables when assessing safety of the anaesthesia relating to the puppies – puppy survival, which is directly comparable between studies, and puppy vitality, which each study assessed in different ways. in the four studies including a propofol but not an alfaxalone experimental group (vilar et al., 2018; luna et al., 2004; de cramer et al., 2017; and funkquist et al., 1997), puppy mortality can likely be compared to that found in the alfaxalone groups in the two comparative studies (metcalfe et al., 2014; doebeli et al., 2013) as it was measured as percentage mortality in all studies. with regards to puppy vitality, in most studies one of two measures was used: apgar scoring or presence of reflexes, both of which can be compared. the two randomised controlled trials (metcalfe et al., 2014; and doebeli et al., 2013) found no significant difference in the puppy survival between the alfaxalone and propofol groups at birth (93% vs 94% respectively; p = 0.7) or at 24 hours after (89% vs 89% respectively; p = 0.9). in light of the strength of evidence of the other papers, these studies are more reliable, indicating that alfaxalone and propofol probably have similar effects regarding puppy mortality. perioperative puppy mortality in the propofol groups of the other studies ranged from 1.79–28.9% (vilar et al., 2018; luna et al., 2004; de cramer et al., 2017; and funkquist et al., 1997). one study (funkquist et al., 1997) found a much higher puppy mortality rate than in any of the others and when discounting this study puppy mortality would range from 1.79–5.7%. therefore, puppy mortalities when undergoing a propofol induction fell within acceptable limits for a majority of the studies evaluated. nevertheless, it is difficult to use these values in context when comparing the two induction agents due to large differences in study protocols and populations. we are therefore best drawing conclusions from the two randomised controlled trials directly comparing alfaxalone and propofol, which found that both agents perform similarly with regards to puppy mortality perioperatively. puppy vitality is harder to quantify and compare between groups. metcalfe et al. (2014) recorded the reflexes that each puppy showed following delivery and found that a greater percentage of alfaxalone group puppies were positive for all four health vigour assessments compared with the propofol group. luna et al. (2004) recorded similar reflexes and found slightly higher percentages in their propofol group compared to the propofol group in the study by metcalfe et al. (2014). doebeli et al. (2013) measured apgar scores of puppies at 5, 15 and 60 minutes after delivery and found significantly higher scores at all times in the alfaxalone group compared with the propofol group. vilar et al. (2018) found a higher apgar score in their propofol and sevoflurane group which was more comparable with the alfaxalone group in the study by doebeli et al. (2013). however, they used a morphine premedication which reduced the dose of propofol used in some cases which may explain this difference. de cramer et al. (2017) recorded very high apgar scores in their cases. this could be due in part to their anaesthetic protocol in which they used a medetomidine premedication and comparably low doses of propofol. as well as this, puppies were given atipamezole following removal, prior to apgar scoring.   conclusion taking all studies into account, puppy mortality was generally in accepted proportions and there were few examples of bitch mortality and anaesthetic complications. as there were six studies involving the use of a propofol induction (metcalfe et al., 2014; doebeli et al., 2013; vilar et al., 2018; luna et al., 2004; de cramer et al., 2017; and funkquist et al., 1997) and only two involving the use of an alfaxalone induction (metcalfe et al., 2014; and doebeli et al., 2013), we can be more certain that propofol is safe for this purpose. however, current evidence suggests that alfaxalone is a safe alternative and further research with regards to its use will increase certainty of this. the most reliable studies from those i found, the two randomised controlled trials (metcalfe et al., 2014; and doebeli et al., 2013), suggested that there may be small differences between the safety of alfaxalone and propofol inductions in bitches undergoing caesarean section, both for the bitches and the puppies. there is evidence to suggest that alfaxalone may provide a slightly better quality of anaesthesia for the bitches, although only one study supported this (metcalfe et al., 2014). with regards to the puppies, no significant differences in mortality was observed. doebeli et al. (2013) found significantly higher apgar scores in the alfaxalone group compared to the propofol group in the first 60 minutes of life. metcalfe et al. (2014) found a greater percentage of puppies in the alfaxalone group were positive for each of the reflexes tested, however this was not statistically significant. therefore there is some evidence that alfaxalone may also be associated with increased neonatal viability in the first 60 minutes following parturition, however further investigation would help to clarify this. both alfaxalone and propofol inductions appear to be relatively safe in the anaesthesia of bitches undergoing caesarean section, suggesting that the current widespread use of propofol is acceptable. however, there is evidence to suggest that alfaxalone may provide bitches with a safer anaesthetic period, and puppies may be delivered with higher indicators of puppy vitality following its use. further research with regards to the use of alfaxalone for this purpose would be useful to further support this evidence in order to provide the best clinical advice for patients undergoing caesarean section. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform 1973 – week 45 2019 pubmed 1973 – 2019 web of science 1973 – 2019 search strategy: cab abstracts: (dog* or bitch* or canine) and (cesarean or caesarean or section or assis* or birth* or parturition) (alfaxalone or alphaxalone or alphaxolone or anaesthesia or induction) (propofol or anaesthesia or induction) (survival or pupp* or outcome* or morbidity or mortality or result or safe* or success* or (adverse and effect*)) 1 and (2 or 3) and 4   pubmed: ((dog* or bitch* or canine) and (cesarean or caesarean or section or assis* or birth* or parturition) and (alfaxalone or alphaxalone or alphaxolone or propofol or anaesthesia or induction) and (survival or pupp* or outcome* or morbidity or mortality or result or safe* or success* or (adverse and effect*)))   web of science: ((dog* or bitch* or canine) and (cesarean or caesarean or section or assis* or birth* or parturition) and (alfaxalone or alphaxalone or alphaxolone or propofol or anaesthesia or induction) and (survival or pupp* or outcome* or morbidity or mortality or result or safe* or success* or (adverse and effect*))) dates searches performed: 15 nov 2019 exclusion / inclusion criteria i chose to exclude studies not using gaseous maintenence anaesthesia as anaesthetic protocols such as total intravenous anaesthesia or including epidural analgesia may have a more profound difference in outcomes. by including studies looking at propofol or alfaxalone induction individually as well as comparing the two, i hope to obtain more relevant papers which i can then compare myself at the point of analysis. exclusion: no full text available not relevant to pico non-english language publications the use of epidural analgesia, co-induction or total intravenous anaesthesia effect on puppies not recorded single case studies published more than 25 years ago papers relevant to human medicine inclusion: studies including propofol or alfaxalone induction either individually or comparing the two studies maintaining animals on gaseous anaesthesia english language papers relevant to pico full text available papers relevant to veterinary medicine search outcome database number of results excluded – not relevant to pico excluded – inaccessible excluded – single case studies excluded – non-english language publications excluded – published more than 25 years ago excluded – duplication total relevant papers cab abstracts 174 156 2 1 6 1 2 6 pubmed 485 478 0 0 1 0 0 6 web of science 241 234 0 0 1 0 0 6 total relevant papers 6 conflict of interest the author declares no conflicts of interest. references batista, m., moreno, c., vilar, j., golding, m., brito, c., santana, m. and alamo, d. (2014). neonatal viability evaluation by apgar score in puppies delivered by cesarean section in two brachycephalic breeds (english and french bulldog). animal reproduction science, 146(3–4):218–226. doi: https://doi.org/10.1016/j.anireprosci.2014.03.003 de cramer, k.g.m., joubert, k.e. and nöthling, j.o. (2017). puppy survival and vigor associated with the use of low dose medetomidine premedication, propofol induction and maintenance of anesthesia using sevoflurane gas-inhalation for cesarean section in the bitch. theriogenology, 96:10–15. doi:  https://doi.org/10.1016/j.theriogenology.2017.03.021 doebeli, a., michel, e., bettschart, r., hartnack, s. and reichler, i.m. (2013). apgar score after induction of anesthesia for canine cesarean section with alfaxalone versus propofol. theriogenology, 80(8):850–854. doi: https://doi.org/10.1016/j.theriogenology.2013.07.006 funkquist, p.m., nyman, g.c., löfgren, a.j. and fahlbrink, e.m. (1997). use of propofol-isoflurane as an anesthetic regimen for cesarean section in dogs. journal of the american veterinary medical association, 211(3):313–317. gaynor, j.s., dunlop, c.i., wagner, a.e., wertz, e.m., golden, a.e. and demme, w.c. (1999). complications and mortality associated with anesthesia in dogs and cats. journal of the american animal hospital association, 35(1):13–17. doi: https://doi.org/10.5326/15473317-35-1-13 ko, j.c., nicklin, c.f., melendaz, m., hamilton, p. and kuonen, c.d. (1998). effects of a microdose of medetomidine on diazepam-ketamine induced anesthesia in dogs. journal of the american veterinary medical association, 213(2):215–219. luna, s.p.l., cassu, r.n., castro, g.b., neto, f.t., silva, j.r. and lopes, m.d., 2004. effects of four anaesthetic protocols on the neurological and cardiorespiratory variables of puppies born by caesarean section. veterinary record, 154(13), pp.387-389. doi: http://dx.doi.org/10.1136/vr.154.13.387 metcalfe, s., hulands‐nave, a., bell, m., kidd, c., pasloske, k., o'hagan, b., perkins, n. and whittem, t. (2014). multicentre, randomised clinical trial evaluating the efficacy and safety of alfaxalone administered to bitches for induction of anaesthesia prior to caesarean section. australian veterinary journal, 92(9):333–338. doi: https://doi.org/10.1111/avj.12223 moon, p.f., erb, h.n., ludders, j.w., gleed, r.d. and pascoe, p.j. (1998). perioperative management and mortality rates of dogs undergoing cesarean section in the united states and canada. journal of the american veterinary medical association, 213(3):365–369. sánchez‐alcaraz, a., quintana, m.b. and laguarda, m. (1998). placental transfer and neonatal effects of propofol in caesarean section. journal of clinical pharmacy and therapeutics, 23(1):19–23. doi: https://doi.org/10.1046/j.1365-2710.1998.00124.x silva, l.c.g., lucio, c.f., veiga, g.a.l., rodrigues, j.a. and vannucchi, c.i. (2009). neonatal clinical evaluation, blood gas and radiographic assessment after normal birth, vaginal dystocia or caesarean section in dogs. reproduction in domestic animals, 44:160–163. doi: https://doi.org/10.1111/j.1439-0531.2009.01392.x veronesi, m.c., panzani, s., faustini, m. and rota, a. (2009). an apgar scoring system for routine assessment of newborn puppy viability and short-term survival prognosis. theriogenology, 72(3):401–407. doi: https://doi.org/10.1016/j.theriogenology.2009.03.010 vilar, j.m., batista, m., pérez, r., zagorskaia, a., jouanisson, e., díaz-bertrana, l. and rosales, s. (2018). comparison of 3 anesthetic protocols for the elective cesarean-section in the dog: effects on the bitch and the newborn puppies. animal reproduction science, 190:53–62. doi: https://doi.org/10.1016/j.anireprosci.2018.01.007 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in dogs undergoing anaesthesia do pre-anaesthetic gastroprotectants reduce gastro-oesophageal reflux? a knowledge summary by leanne june barry rvn cert vnecc pgcert apvn 1* 1university of glasgow, glasgow, g12 8qq *corresponding author (leanne_barry@hotmail.com) vol 5, issue 4 (2020) published: 12 nov 2020 reviewed by: zofia lisowski (bvsc phd afhea mrcvs) and james swann (ma vetmb dacvim decvim mrcvs) next review date: 14 may 2022 doi: 10.18849/ve.v5i4.340 pico question in dogs undergoing anaesthesia do pre-anaesthetic gastroprotectants reduce gastro-oesophageal reflux?   clinical bottom line category of research question treatment the number and type of study designs reviewed five papers were critically reviewed. there was a randomised prospective study, two randomised blinded prospective studies, randomised non-blinded prospective study and a randomised, double blinded and placebo-controlled prospective study. strength of evidence moderate outcomes reported evidence of high quality suggests omeprazole or cisapride with esomeprazole decrease the incidence of gastro-oesophageal reflux (gor) in the anaesthetised dog. in addition, a study of lower quality showed that continuous infusion of metoclopramide at a higher than normal dose rate decreased the incidence of gor. conclusion omeprazole or cisapride with esomeprazole decreases the incidence of gor in the anaesthetised dog.   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision-making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care clinical scenario a 5-year-old labrador undergoing elective arthroscopy under general anaesthesia developed regurgitation and nausea following recovery from anaesthesia. the dog was otherwise healthy with no history of vomiting or regurgitation. the dog developed oesophagitis as a complication of this. does the administration of pre-anaesthetic gastroprotectants reduce the risk of gor? the evidence there is evidence to support that pre-anaesthetic gastroprotectants prevent gor. the peer-reviewed studies are generally prospective studies. there is no consistency between the trials of patient sex, breed, depth of anaesthesia, surgery being performed and position during surgery. the choice of anaesthetic drugs can also influence the risk of gor. panti et al. (2009) studied the effects of omeprazole administration pre-operatively on 47 dogs undergoing orthopaedic surgery. compared to the control group, the dogs that received pre-operative omeprazole had a significant decrease in the occurrence of gor. in contrast, zacuto et al. (2012) found that esomeprazole (an isomer of omeprazole) had no effect on gor. however, cisapride with esomeprazole decreased reflux events. the study by favarato et al. (2012) evaluated metoclopramide or ranitidine on 90 anaesthetised dogs and concluded that there was no influence on the effect of gor. however, wilson et al. (2006) concluded that whilst a low dose of metoclopramide had no effect on the incidence of gor, administering a higher than normal dose of metoclopramide as a continuous infusion resulted in a 54% reduction in relative risk of developing gor. although the same dose rates of metoclopramide were used for both studies they produced conflicting results. in the study by johnson (2014) the administration of maropitant in 26 dogs undergoing surgery showed that it prevented vomiting but not the occurrence of gor. the gastroprotectant used should be tailored to the patient and the clinical scenario presented (marks et al., 2018). summary of the evidence favarato et al. (2012) population: healthy female dogs undergoing general anaesthesia for ovariosalpingohysterectomy. age range 0.5–9 years. weight range 1.5–34 kg. sample size: 90 dogs intervention details: 30 dogs were the control group – received only the anaesthetic protocol. 30 dogs received metoclopramide – an intravenous bolus of 1 mg/kg 5 minutes before induction, and continuous infusion (1 mg/kg/h intravenously) immediately after anaesthetic induction. 30 dogs received ranitidine – intravenous bolus of 2 mg/kg, 6 hours before anaesthesia. all dogs received acepromazine (0.1 mg/kg), propofol (6 mg/kg) and isoflurane for anaesthetic protocol. all received a 12 hour food and water fast. dogs were randomly assigned to groups. study design: randomised prospective study outcome studied: evaluation of metoclopramide or ranitidine on the number of acid and non-acid reflux events during anaesthesia in dogs. oesophageal ph values were monitored using intraluminal oesophageal phmetry placed cranially to the oesophagogastric junction and recorded throughout the procedure. ph values lower than 4 was considered an acid reflux episode. a non-acid reflux was confirmed by oesophagoscopy immediately after surgery. chi-squared test was used to compare the frequency of gor events between groups. main findings (relevant to pico question): reflux episodes were presented in seven dogs: control group – 4/30 dogs; ranitidine group – 2/30 dogs; metoclopramide group – 1/30 dog. pre-anaesthetic metoclopramide and ranitidine did not reduce gor. no difference of reflux episodes (p>0.05) was found between the groups. limitations: study was not stated to be blinded. low reflux events in the control group made it difficult to determine a difference compared to the treatment groups – a larger sample size could determine a different result. higher doses (more than normally used) of metoclopramide were used in the study. johnson (2014) population: dogs undergoing general anaesthesia for elective soft tissue or orthopaedic surgery. average age 3.1 years (range 6 months to 10 years). average weight 20.5 kg (range 3.6–49.8 kg). no history of vomiting. mix of 18 purebred dogs and eight mixed breed dogs. 18 females and eight males. sample size: 26 dogs intervention details: treatment group (n= 13 dogs) received maropitant (1 mg/kg−1) intravenously (5–7 minutes) 45–60 minutes before premedication. control group (n= 13 dogs) received saline 0.9% (0.1 ml/kg−1) intravenously (5–7 minutes) 45–60 minutes before premedication. premedication consisted of hydromorphone (0.1 mg/kg−1) and acepromazine (0.03 mg/kg−1) intramuscularly followed by propofol (2–6 mg/kg−1) and isoflurane (19 dogs) and sevoflurane (seven dogs) for anaesthesia. food, not water was withheld for 12 hours before anaesthesia. dogs were randomly assigned to groups. observer blinded to treatment monitored for retching or vomiting before induction. study design: randomised and blinded prospective study outcome studied: objective study to evaluate the efficacy of maropitant for prevention of vomiting and gor in dogs undergoing anaesthesia measuring oesophageal ph flexible oesophageal ph probe placed into distal oesophagus (measured to assume tip was near gastro-oesophageal junction) detected for gor. measurements were taken using a ph recorder and uploaded at study completion. gor defined as a ph less than 4 for gastric acid reflux or more than 7.5 ph for bile reflux for around 30 seconds. initial ph values were measured immediately on probe placement. the fisher exact test was used to compare gor in the groups. main findings (relevant to pico question): vomiting and retching was prevented in the maropitant group (treatment group – 0 dogs and control group – 6/13 dogs retched or vomited). gor was not prevented as no difference in frequency between the groups (treatment group – 4/13 dogs and control group – 6/13 dogs had a reflux event). limitations: small sample size – a larger group could have shown a difference between the control group and the treatment group. panti et al. (2009) population: dogs (asa risk 1–2, american society of anesthesiologists classification) undergoing general anaesthesia for pelvic limb orthopaedic surgery. weight range 9–85 kg. no history of reflux, regurgitation, vomiting or gastrointestinal disturbances. sample size: 47 dogs intervention details: treatment group – 22 dogs were given 1 mg/kg omeprazole orally (p.o) at least 4 hours before anaesthesia. control group – 25 dogs received only premedication. pre-anaesthetic – acepromazine (0.03 mg/kg) and methadone (0.2 mg/kg) intramuscularly followed by approximately 4 mg/kg propofol intravenously 1 hour later and maintained on isoflurane. each dog received an epidural – 37 dogs received preservative free morphine and a local anaesthetic and 10 dogs received preservative free morphine and sterile normal saline. 31 dogs breathed spontaneously, and 16 dogs breathed with a ventilator. clinician (not involved in probe placement or anaesthetic) allocated patient to treatment group using a random number generator. food, not water, withheld for 12 hours. patient positioning: in dorsal recumbency was in 16/22 dogs in the treatment group and 15/25 dogs in the control group; in lateral recumbency was in 6/22 dogs in the treatment group and in 10/25 dogs in the control group. mechanical ventilation was performed in the treatment group on 5/22 dogs and in the control group on 11/25 dogs; the remainder breathed spontaneously. ph probe placed into distal oesophagus after induction by the same operator using a set measurement. it was placed once adequate depth of anaesthesia was reached (15 to 20 minutes) to prevent gor on placement. parameters were recorded every 5 minutes during anaesthesia by an anaesthetist unaware of the group the patient was in. if regurgitation occurred (food up into the mouth) probe was washed with water. anaesthesia duration was between 120 and 330 minutes. the fisher exact test was used to compare gor in the groups. study design: randomised and blinded prospective study outcome studied: investigate the effect of pre-operative administration of omeprazole on oesophageal ph. gor is defined as an abrupt decrease in ph below 4. main findings (relevant to pico question): gor was decreased in dogs with the addition of omeprazole. treatment group – 4/22 (18%) dogs less than 4 ph. control group – 13/25 (52%) less than 4 ph. gor was 4.7 times more likely in the control group compared to the treatment groups (logistic regression, 95% cl 1.1 to 24.7, p = 0.032). the number needed to treat with omeprazole to prevent gor was 2.95 (95% cl 1.69 to 11.83). limitations: long duration between each anaesthesia. large weight range between dogs. wilson et al. (2006) population: healthy dogs undergoing elective orthopaedic surgery. weight > 4.4 kg. age over 6 months. any dogs with a history of dysphagia, regurgitation or vomiting were excluded. sample size: 52 dogs intervention details: control group – 18 dogs received a saline (0.9% sodium chloride (nacl)) infusion before and during anaesthesia. treatment group 1 – 16 dogs received a low dose metoclopramide – bolus of 0.4 mg/kg intravenously followed by a continuous rate infusion of 0.3 mg/kg/hr before and during anaesthesia. treatment group 2 – 18 dogs received a high dose metoclopramide – bolus of 1mg/kg intravenously followed by a continuous infusion of 1 mg/kg/hr before and during anaesthesia. premedication of acepromazine (0.044 mg/kg and morphine (0.66 mg/kg) intramuscularly, followed by thiopental to effect and maintained by isoflurane. food was withheld overnight (11–23.5 hours) but water was available. dogs were randomly assigned into groups however personnel knew their treatment status. if vomiting occurred (54%), it was recorded following premedication. all patients were placed into dorsal recumbency. patients breathed spontaneously. flexible ph probe taped to oesophageal stethoscope was inserted into oesophagus to measure gor by 1 of 3 trained people using a standardised placement system. placement was near to gastroesophageal junction and data continually collected by a computer. gor was defined as a ph less than 4 or more than 7.5 for more than 30 seconds. the fisher exact test was used to compare gor in the groups. study design: randomised, non-blinded prospective trial outcome studied: the effect of two doses of metoclopramide on the incidence of gor in anaesthetised dogs measuring oesophageal ph. main findings (relevant to pico question): higher doses of metoclopramide was associated with a 54% reduction in relative risk of developing gor. dogs that had a gor episode during anaesthesia: control group – 12/18 dogs; treatment group 1 – 7/16 dogs; treatment group 2 – 6/18. limitations: morphine was used which could result in increased gor. study was not blinded. higher doses (more than normally used – normal range of 0.5 mg to 1 mg/kg once daily (noah, 2020)) of metoclopramide were used in the study. zacuto et al. (2012) population: healthy dogs undergoing elective orthopaedic surgery. age range 0.5–12 years. weight range 3.6–52 kg. pure breeds and mixed breeds. all dogs with a history of gor, regurgitation, vomiting, oesophagitis or coughing were excluded. sample size: 61 dogs intervention details: control group – 21 dogs received saline (0.9% nacl) 10ml over 3 minutes intravenously. treatment group 1 – 22 dogs received esomeprazole (1 mg/kg) over 3 minutes intravenously. treatment group 2 – 18 dogs received a combination of esomeprazole (1 mg/kg) over 3 minutes intravenously and cisapride (1 mg/kg diluted with sterile saline to a total of 100 ml) over 15 minutes intravenously all were given 12–18 hours and 1–1.5 hours before anaesthetic induction. premedication of hydromorphone (0.05 mg/kg) and atropine (0.02 mg/kg) subcutaneously followed by propofol (4 mg/kg) and diazepam (0.3 mg/kg) intravenously and maintained on isoflurane. each dog received a loading dose of fentanyl (5 μg/kg) followed by a constant rate infusion (0.4 μg/kg/min) intravenously for analgesia. all dogs were fasted for 12 hours. patients were randomly assigned to groups using a random number generator. anaesthetist was blinded to treatment group of patients. patients did not have a standard positioning. oesophageal ph/impedance probe was placed into oesophagus and external reference pad placed in axillary region to measure gor. the probe was placed by 1 of 2 persons proximally to the gastroesophageal junction. a one-way analysis of variance (anova) and nonparametric mann-whitney u test to evaluate statistical differences. study design: randomised, double blinded and placebo-controlled prospective study outcome studied: the influence of esomeprazole and cisapride on gastroesophageal reflux during anaesthesia in dogs. the data was collected via a computer and gor defined when the ph was less than 4. main findings (relevant to pico question): preanesthetic administration of cisapride and esomeprazole decreases the number of reflux events (per dog) in anesthetised dogs compared to placebo but esomeprazole alone does not. the proportion of dogs having a gor episode did not differ significantly among groups. dogs that showed reflux episodes in each group: control group 8/21 dogs; treatment group 1 8/22 dogs; treatment group 2 2/18. limitations: small group of participants. appraisal, application and reflection gor is common in dogs and studies have shown a range of 12% to 78.5% incidences occur under general anaesthesia in studies in referral hospitals (rodríguez-alarcón et al., 2015). the patients in all the studies were fasted of food overnight or for at least 12 hours for consistency and is compatible with a normal clinical setting (favarato et al., 2012; johnson, 2014; panti et al., 2009; wilson et al., 2006; and zacuto et al., 2012). the johnson (2014) study concluded pre-anaesthetic maropitant can assist in reducing vomiting but not the incidence of gor as the two groups showed a similar gor event rate. further studies of a larger group would be required to prove this because the study was underpowered. a study of preoperative omeprazole was performed by panti et al. (2009). results show a significant difference between the control group and the treatment group showing that omeprazole decreases gor events in the anaesthetised dog. the study uniquely looked at the number needed to treat, showing three dogs would be given omeprazole prophylactically to prevent one of them from having gor. this study therefore provides a good argument for the prophylactic treatment of all dogs undergoing general anaesthesia. morphine was used as an epidural in panti et al. (2009) and wilson et al. (2006) used it as a premedication. morphine has been known to increase gor when given intramuscularly and so should be avoided in patients undergoing anaesthesia (wilson et al., 2005). high doses of metoclopramide trialed by wilson et al. (2006) in dogs undergoing anaesthesia was associated with a 54% reduction in relative risk of developing gor. the study consisted of neutered male dogs and a mixture of spayed and entire female dogs. although the trial was randomised the study was not blinded. the results do not show a significant difference in low dose metoclopramide. conversely, a trial by favarato et al. (2012) using pre-anaesthetic metoclopramide (same dose as wilson et al. (2006)) or ranitidine concluded no influence in incidence of gor. the difference between studies was that wilson et al. (2006) used morphine as a premedication and that could have increased the incidence of gor showing a discrepancy between the findings. had morphine been used in favarato et al. (2012) there is a possibility that a higher gor event would be present in the control group and may have increased the chances in finding the beneficial effects of metoclopramide or ranitidine. in addition, favarato et al. (2012) could have been underpowered compared to the wilson et al. (2006) trial and that could have determined different results. esomeprazole with the addition of cisapride (prokinetic drug) has resulted in a decrease in gor (zacuto et al., 2012). the trial was randomised with a placebo-control. the difference to the other studies was that it was given 12–18 hours and 1–1.5 hours before anaesthesia. esomeprazole itself increased the ph significantly but a noticeable difference with cisapride decreased gor. the patients were not exposed to morphine as per previous studies but were similarly starved for 12 hours. a limitation of the studies evaluated is the inclusion of all breeds. brachycephalic breeds are more susceptible to gor due to the increase in negative intrathoracic pressure as a result of overcoming upper respiratory tract obstruction associated with brachycephalic obstructive airway syndrome (downing and gibson, 2018). therefore, the inclusion of brachycephalic breeds, which is unknown in these studies may bias the results. it would be prudent for future studies into gor to consider this breed disposition. another limitation is that dogs in each study were undergoing either soft tissue or orthopaedic surgery. patients that undergo abdominal and orthopaedic surgeries are thought to be at higher risk of developing gor (rodríguez-alarcón et al., 2015). furthermore, other factors to consider that can increase the incidence of gor include; the anaesthetic drugs given, patient signalment (breed, sex, age and weight) and positioning of the patient (rodríguez-alarcón et al., 2015). finally, if there was mucosal abutment at the probe tip then this could potentially cause a false negative (wilson et al., 2006). in conclusion, studies suggest that high doses of metoclopramide, or omeprazole, or a combination of esomeprazole and cisapride have an effect on reducing gor episodes in the anaesthetised dog. however, further trials would be beneficial. a new study factoring in trial number, patient positioning, sex, breed and type of surgery being performed could result in supporting previous studies. methodology section search strategy databases searched and dates covered: cab abstracts on cab direct 1973 – 2020 week 18 pubmed on ncbi interface 1920 – may 2020 search strategy: cab abstracts: (canine or canines or dog or dogs) (anaesthe* or anesthe*) (gastroprotectant* or gastro-protectant* or protectant* or omeprazole or esomeprazole or cisapride or maropitant or metoclopramide or ranitidine) (((gastro* or gastric) and reflux) or gor or ger) 1 and 2 and 3 and 4   pubmed: (canine or canines or dog or dogs) (anaesthesia or anesthesia or anaesthetic or anesthetic) (gastroprotectant or gastro-protectant or protectant or omeprazole or esomeprazole or cisapride or maropitant or metoclopramide or ranitidine) ((gastro or gastric) and reflux) or gor or ger 5. 1 and 2 and 3 and 4 dates searches performed: 14 may 2020 exclusion / inclusion criteria exclusion: studies that did not include anaesthesia, were not english, wrong species or were not related to pico inclusion: peer-reviewed journals, veterinary journals, full papers, dogs search outcome database number of results excluded – not peer-reviewed excluded – did not answer the pico question excluded – anything other than veterinary journals excluded – not in english total relevant papers cab abstracts 9 1 3 0 0 5 pubmed 10 0 6 0 0 4 total relevant papers when duplicates removed 5 conflict of interest the author declares no conflicts of interest. acknowledgements – dr mary fraser (bvms certvd phd fhea cbiol mibiol frcvs), samantha fontaine (msc pgcap bsc dipavn(med) rvn fhea) and dr desiree scott (bvm&s mrcvs). university of glasgow – post graduate certificate in advanced practice in veterinary nursing. clare boulton (rcvs knowledge) for her assistance with finalising the search strategy and the reviewers. references downing, f. & gibson, s. (2018). anaesthesia of brachycephalic dogs. journal of small animal practice, 59(12), 725–733. doi: https://doi.org/10.1111/jsap.12948 favarato, l. s. c., favarato, e. s., souza, m. v., costa, p. r. s., nehme, r. c., monteiro, b. s. & bonfá, l. p. (2012). evaluation of metoclopramide and ranitidine on the prevention of gastroesophageal reflux episodes in anesthetized dogs. research in veterinary science, 93(1), 466–467. doi: https://doi.org/10.1016/j.rvsc.2011.07.027 johnson, r. a. (2014). maropitant prevented vomiting but not gastroesophageal reflux in anesthetized dogs premedicated with acepromazine-hydromorphone. veterinary anaesthesia and analgesia, 41(4), 406–410. doi: https://doi.org/10.1111/vaa.12120 marks, s. l., kook, p. h., papich, m. g., tolbert, m. k. & willard, m. d. (2018). acvim consensus statement: support for rational administration of gastrointestinal protectants to dogs and cats. journal of veterinary internal medicine, 32(6), 1823–1840. doi: https://doi.org/10.1111/jvim.15337 noah compendium (noah). (2020). emeprid, clinical particulars. panti, a., bennett, r., corletto, f., brearley, j., jeffrey, n. & mellanby, r. (2009). the effect of omeprazole on oesophageal ph in dogs during anaesthesia. journal of small animal practice, 50(10), 540–544. doi: https://doi.org/10.1111/j.1748-5827.2009.00818.x rodríguez-alarcón, c., beristain-ruiz, d., rivera-barreno, r., díaz, g., usón-casaús, j., garcía-herrera, r., pérez-merino, e., universidad autónoma de ciudad juárez & universidad de extremadura. (2015). gastroesophageal reflux in anesthetized dogs: a review. revista colombiana de ciencias pecuaria, 28(2), 144–155. doi: https://doi.org/10.17533/udea.rccp.v28n2a03 wilson, d., evans, a. & mauer, w. (2006). influence of metoclopramide on gastro-esophageal reflux in anesthetized dogs. american journal of veterinary research, 67(1), 26–31. doi: https://doi.org/10.2460/ajvr.67.1.26 wilson, d., evans, a. & miller, r. (2005). effects of preanesthetic administration of morphine on gastroesophageal reflux and regurgitation during anesthesia in dogs. american journal of veterinary research, 66(3), 386–390. doi: https://doi.org/10.2460/ajvr.2005.66.386 zacuto, a. c., marks, s. l., osborn, j., douthitt, k. l., hollingshead, k. l., hayashi, k., kapatkin, a. s., pypendop, b. h. & belafsky, p. c. (2012). the influence of esomeprazole and cisapride on gastroesophageal reflux during anesthesia in dogs. journal of veterinary internal medicine, 26(3), 518–525. doi: https://doi.org/10.1111/j.1939-1676.2012.00929.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. delayed versus on arrival modified live viral vaccination in stocker cattle on bovine respiratory disease a knowledge summary by ashlee ambs ms 1 heather k. moberly msls ahip fhea pgcert (vet ed) 2 sarah capik dvm phd 1, 3* 1texas a&m university college of veterinary medicine and biomedical sciences, 660 raymond stotzer pkwy, college station, tx 77843 usa 2202 olsen blvd, university libraries, texas a&m university, college station, tx 77843–4462 usa 3texas a&m agrilife research, 6500 w amarillo blvd, amarillo, tx 79106 usa *corresponding author (sarah.capik@ag.tamu.edu) vol 7, issue 1 (2022) published: 04 mar 2022 reviewed by: nathan erickson (bsc dvm wcvm mvsc) and john fishwick (ma vetmb dchp dipecbhm mrcvs) next review date: 27 oct 2023 doi: 10.18849/ve.v7i1.503 pico question in auction market calves at high risk of developing bovine respiratory disease (brd), does delayed (14–30 days) vaccination with a modified live vaccine (mlv) for viral respiratory pathogens versus administration of mlv on arrival (within 24 hours of arrival) to the stocker operation, result in less calves with brd morbidity diagnosed based on visual signs and rectal temperature >40°c, or less calves with brd mortality?   clinical bottom line category of research question treatment the number and type of study designs reviewed four papers were critically reviewed. all were randomised complete block designs strength of evidence moderate outcomes reported in stocker calves, delaying administration of a mlv for respiratory viruses may result in numerically lower initial brd morbidity rates, while giving at arrival may result in numerically lower brd retreatments. one study shows statistically lower cases of brd morbidity after the third antimicrobial treatment in cattle vaccinated on arrival with both a clostridial and mlv for respiratory viruses compared to cattle vaccinated on arrival with clostridial vaccine and delayed mlv for respiratory viruses. no conclusion about mortality can be drawn due to inconsistent numerical conclusions between studies conclusion due to conflicting evidence and a general lack of statistically significant differences in morbidity and mortality outcomes, a definite answer regarding the impact of delayed mlv respiratory vaccination in stocker calves cannot be made   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario stocker cattle are young and lightweight calves (often somewhere in the range of 204–250 kg) purchased to utilise pasture for frame-growth before moving to a feedlot for the finishing phase of their production life. since this is often also a situation where recently weaned calves are commingled, bovine respiratory disease (brd) is a concern. modified live vaccines (mlv) containing viral respiratory pathogens are commonly administered to calves on arrival to stocker operations as a way to manage brd risk. recently, vaccine protocols have been reexamined in the interest of reducing brd morbidity and several research projects have explored changing the timing of vaccine administration. in particular, delaying mlv administration for viral respiratory pathogens may allow an adjustment period for calves before challenging their immune system with a live vaccine. stocker operations and veterinarians should review the research evidence and consider the financial and production impact of any changes in mlv timing on their operations. the evidence there is no statistical evidence that delayed mlv administration for viral respiratory pathogens reduces brd morbidity or mortality in stocker calves. while there is some evidence of numerical reductions in brd morbidity, there is disagreement in the numerical differences in retreatment and mortality rates between arrival and delayed vaccinated calves between studies. summary of the evidence poe et al. (2013) population: high-risk beef steer and bull calves at 202 ± 4.1 kg. sample size: n = 393, (15–23 calves / pen, seven pens / treatment). intervention details: treatments: on arrival respiratory vaccination (day 0) with growth-promoting implant. on arrival respiratory vaccination (day 0) without growth-promoting implant. delayed respiratory vaccination (day 14) with growth-promoting implant. delayed respiratory vaccination (day 14) without growth-promoting implant. vaccine: pentavalent modified live vaccine (mlv) containing infectious bovine rhinotracheitis virus (ibrv), bovine viral diarrhoea virus (bvdv) type i and ii, bovine respiratory syncytial virus (brsv), parainfluenza-3 virus (pl3); (bovi-shield gold® 5, subcutaneously; pfizer animal health). metaphylaxis: none, but calves could receive treatment with florfenicol if their rectal temperature was ≥40°c during processing regardless of clinical signs. study design: randomised complete block design with a 2x2 treatment factorial. outcome studied: morbidity measured as: first brd treatment % (cattle exhibiting ≥2 clinical signs of brd (ocular or nasal discharge, depressed appearance, gaunt or lacking normal fill, coughing, laboured breathing, or lack of appetite were pulled and rectal temperature taken, and antimicrobial treatment was administered if rectal temperature was ≥40°c) – subjective assessment; unblinded personnel. second, third, and fourth brd treatment % (cattle with symptoms of brd and a rectal temperature of ≥40°c at 72 hours after the previous treatment) – subjective assessment; unblinded personnel. main findings (relevant to pico question): brd-related morbidity did not differ statistically due to vaccine timing. limitations: no blinding of personnel. pens had varying numbers of calves between blocks. the study reports that if any steers were identified as brd cases >21 days following their previous treatment, they were restarted on the brd treatment protocol as if they had never been diagnosed previously and considered a new incident case of brd. however, it is unclear how new incidence of brd after >21 days without clinical signs was managed statistically and if / where those animals are represented in the results. study did not evaluate mortality. it is unclear whether calves were processed immediately upon arrival or after an overnight rest following arrival at the facility. there appear to be two acceptable case definitions that could have qualified calves for first treatment for brd. one being having a rectal temperature ≥40°c at processing, regardless of the presence of other symptoms, and the other having ≥2 clinical signs of brd plus meeting temperature criteria as outlined above after day 0 processing. this makes interpreting brd incidence and comparison between studies potentially complex. this study did not describe any efforts to reduce potential cross-contamination between vaccinated and unvaccinated calves during treatment application, housing, subsequent sampling, and evaluation for and treatment of morbid animals. richeson et al. (2008) population: high-risk beef steer and bull calves at 197 ± 2.4 kg. sample size: n = 528; (10–19 animals/pen, 18 pens/treatment). intervention details: treatments: initial vaccination on arrival processing (day 0) with a booster at day 14. delayed initial vaccination (day 14) with a booster at day 28. vaccine: pentavalent modified live vaccine (mlv) for respiratory pathogens containing infectious bovine rhinotracheitis virus (ibrv), bovine viral diarrhoea virus (bvdv) types i and ii, bovine respiratory syncytial virus (brsv), and parainfluenza-3 virus (pl3) in combination; (express 5, subcutaneously; boehringer-ingelheim vetmedica inc). metaphylaxis: calves received tilmicosin for metaphylaxis only if they had a rectal temperature of ≥40°c at arrival processing and were not included in subsequent morbidity outcomes. study design: randomised complete block design. outcome studied: bovine respiratory disease (brd) morbidity in the first 42 days on feed (cattle with visual symptoms of respiratory illness -depression, lethargy, rapid breathing, nasal or ocular discharge, slowness in going to feed bunk, and a gaunt or emaciated appearanceand with a rectal temperature ≥40°c – subjective assessment by blinded personnel. second and third morbidity (cattle were re-evaluated 72 hours after first or second treatment and were eligible for retreatment if they had a rectal temperature ≥40°c at that time) – objective assessment by blinded personnel. percentage of death loss over 56 day study. main findings (relevant to pico question): no statistically significant differences were observed. calves that received the mlv on arrival processing had higher initial brd morbidity (71.65% vs 63.5%; standard error (se) 7.61; p-value: 0.12) but required less second treatments than cattle that received the mlv on day 14 (25.1% vs 30.8%; se 9.80; p-value: 0.17), and also experienced increased death loss numerically (2.3% vs 0.8%; se 0.75; p-value: 0.16). limitations: animals per pen varies almost two-fold. unclear whether reported death loss is brd-specific or overall mortality. case definition is vague as there is no description of how many clinical signs were required for first treatment and it is unclear whether any clinical signs (other than a rectal temperature above their cut-off) were required in order to be eligible for second or third treatment. numerical differences are difficult to interpret in a meaningful manner and are not necessarily broadly applicable or repeatable. confidence intervals for estimates were not provided. cattle were received on day -1 and ear tags were placed and weights were obtained prior to arrival processing on day 0. this study did not describe any efforts to reduce potential cross-contamination between vaccinated and unvaccinated calves during treatment application, housing, subsequent sampling, and evaluation for and treatment of morbid animals. richeson et al. (2009) population: high-risk beef steer and bull calves at 239 ± 1.2 kg. sample size: n = 263 (10–12 calves/pen, six pens/treatment). intervention details: vaccines: clos: clostridium chauvoei, clostridium septicum, clostridium novyi, and clostridium sordellii and clostridium perfringens types c & d bacterintoxoid in a special oil adjuvant; alpha-7, subcutaneously; boeringer ingleheim vetmedica. resp: pentavalent modified live vaccine (mlv) containing infectious bovine rhinotracheitis virus (ibrv), bovine viral diarrhoea virus (bvdv) type 1a and type 2a, parainfluenza-3 virus (pl3), and bovine respiratory syncytial virus (brsv); (express 5, subcutaneously; boeringer ingelheim vetmedica). treatments: acar: arrival clos (day 0) and arrival (day 0) resp. acdr: arrival clos (day 0) and delayed resp (day 14). dcar: delayed clos (day 14) and arrival resp (day 0). dcdr: delayed clos (day 14) and delayed (day 14) resp. a resp vaccine booster was given 14 days after initial dose in all treatment groups. metaphylaxis: all calves received tilmicosin metaphylaxis on arrival with a 48 hour post-treatment interval where they were not eligible for bovine respiratory disease (brd) treatment. study design: randomised complete block design with a 2x2 treatment factorial. outcome studied: brd morbidity rate (cattle with two or more visual signs of brd with rectal temperature ≥40°c) – subjective assessment, unblinded personnel. second brd treatment (cattle with rectal temperature ≥40°c at 48 hours after initial treatment – objective assessment, unblinded personnel. third brd treatment (cattle with rectal temperature ≥40°c at 72 hours after second treatment – objective assessment, unblinded personnel. percentage of chronic animals (displayed brd symptoms after third antibiotic treatment) – subjective assessment; unblinded personnel. percentage of dead (not brd-specific) in 56-day study. main findings (relevant to pico question): no statistical differences between delayed versus arrival vaccine administration in percentage of dead calves (resp p-value: 0.7). brd morbidity rates were not statistically different but were numerically less in calves with delayed administration of the mlv (65.1%) versus those vaccinated on arrival (73.4%; no standard error of the mean (sem) reported for resp contrast; resp p-value: 0.23). percentage of chronic animals (cattle that displayed signs of brd after the third antibiotic treatment) was greatest statistically in cattle administered clostridial vaccine on arrival and delayed respiratory vaccine (acdr: 11.4%) compared to those receiving clostridial vaccine and respiratory vaccine on arrival (acar: 1.5%; p=0.04), and numerically higher than those receiving a delayed clostridial vaccine with either arrival (dcar: 6.3%; p = 0.26) or delayed respiratory vaccine (dcdr: 3.2%; p = 0.08). the sem was 4.7 with the interaction between clos and resp having a p-value of 0.05. the percentage of animals treated a second time for brd out of the total population did not differ significantly between groups (acar: 38.5%, acdr: 39.5%, dcar: 36.1%, dcdr: 25.5%; sem: 8.7; resp p-value: 0.43; interaction p-value: 0.34). the percentage of animals treated a third time for brd out of the total population did not differ significantly between groups (acar: 20.5%, acdr: 22.4%, dcar: 19.8%, dcdr: 10.8%; sem: 9.4; resp p-value: 0.61; interaction p-value: 0.43). limitations: no blinding of evaluators for subjective outcomes. unclear whether reported death loss is brd-specific or overall mortality. numerical differences are difficult to interpret in a meaningful manner and are not necessarily broadly applicable or repeatable. overall means in delayed vs arrival resp were not provided for all outcomes. there were no sems available for main effects. confidence intervals for estimates were not provided. cattle appear to have been processed the same day they arrived at the facility. this study indicated that fenceline contact between vaccinated and non-vaccinated calves was possible. it did not describe efforts to reduce potential cross-contamination between vaccinated and unvaccinated calves during treatment application, subsequent sampling, and evaluation for and treatment of morbid animals. richeson et al. (2015) population: high-risk beef steer and bull calves at 211 ± 2.6kg in fall, 213 ± 5.4kg in spring. sample size: n = 184 fall, 186 spring (two blocks / season, two pens / treatment / block). intervention details: treatments: amlv: initial modified live respiratory pathogen vaccine (mlv) on day 0. dmlv: initial mlv vaccine on day 14. nmlv: no vaccination with mlv vaccine until the end of the 42-day receiving period. both amlv and dmlv calves were revaccinated 14 days after initial vaccination. vaccine: pentavalent modified live vaccine (mlv) containing infectious bovine rhinotracheitis virus (ibrv), bovine viral diarrhoea virus (bvdv) types i and ii, parainfluenza-3 virus (pl3), and bovine respiratory syncytial virus (brsv); (bovi-shield gold 5, unspecified route; zoetis). metaphylaxis: all calves received tilmicosin metaphylaxis on arrival with a 24 hour post-metaphylaxis interval observed during which they were not eligible to be treated for bovine respiratory disease (brd). study design: randomised complete block design. outcome studied: percentage of cattle diagnosed with brd at least once (cattle observed with ≥2 visual signs of brd (depression, lethargy, rapid breathing, nasal or ocular discharge, and lack of appetite) and a rectal temperature ≥40°c were considered morbid and were treated) – subjective assessment, blinded personnel. relapses (percentage of cattle treated for brd that required ≥ 1 retreatment; counted once for statistical analysis) – subjective assessment, blinded personnel: cattle were eligible for retreatment 72 hours after previous treatment if they again had ≥2 visual signs of brd and a rectal temperature of ≥40°c. each animal was eligible for up to five total treatments for brd. percentage of mortality associated with clinical brd in 42-day study. main findings (relevant to pico question): morbidity associated with brd was not significantly affected by mlv timing (amlv: 35.4% vs dmlv: 34.9%; standard error (se) of the least square means (lsm): 11.2; p-value = 0.94), however a lower percentage of delayed vaccination calves was considered morbid and relapsed, than calves who were vaccinated on arrival (dmlv: 23.3% vs amlv: 30.1%; se of lsm: 9.1; p-value = 0.51). though not statistically evaluated, the percentage of calves treated three times for brd was lower in arrival vaccination calves (0.5%) versus delayed (3.6%). mortality percentage was higher numerically in calves receiving delayed vaccination than those vaccinated on arrival, but not statistically significant (dmlv: 1.6% vs amlv: 0.9%; se of lsm: 1.1; p-value = 0.67). limitations: blocks did not contain the same number of calves (block 1 = 93; block 2 = 91; block 3 = 71; block 4 = 118) and the number of calves in each pen within each block was not specified. authors did not indicate the route of vaccine administration. numerical differences are difficult to interpret in a meaningful manner and are not necessarily broadly applicable or repeatable. confidence intervals for estimates were not provided. cattle appear to have been processed the same day they arrived at the facility. this study did not describe efforts to reduce potential cross-contamination between vaccinated and unvaccinated calves during treatment application, housing, subsequent sampling, and evaluation for and treatment of morbid animals. appraisal, application and reflection overall, we identified no statistical evidence that delayed modified live vaccination (mlv) for viral respiratory pathogens lowered bovine respiratory disease (brd) morbidity or mortality rates. one study (richeson et al., 2009) indicated statistically lower cases of brd morbidity in chronic animals (displaying clinical signs of brd after the third antimicrobial treatment) vaccinated on arrival with both a clostridial vaccine and mlv for respiratory viruses compared to cattle vaccinated on arrival with clostridial vaccine and delayed mlv for respiratory viruses. however, there were several interesting numerical differences in initial brd morbidity favouring delayed vaccination in several of the studies that suggest perhaps additional, well-powered studies on this question are warranted. mortality and retreatment numerical differences were inconsistent between studies. additionally, there were numerous other differences between studies including brd case definition, vaccines used, different treatment regimens employed, and other management differences that made comparing results between studies difficult.  although we did not specifically limit our search geographically, all four studies that met our criteria and are discussed in this knowledge summary were performed in the united states. although, numerical differences cannot be used to support study conclusions they are important to report for discussion. two studies showed numerical differences in retreatment and relapses (richeson et al., 2009; and richeson et al., 2015). in one study (richeson et al., 2015) with blinded observers, all cattle that relapsed and required retreatment were counted once regardless of the number of times this occurred, while in the other (richeson et al., 2009) which did not have blinded observers, retreatment rates were measured as a percentage treated with second or third antibiotic treatments and each retreatment was analysed individually. including all the relapses in one analysis, as in richeson et al. (2015), does not allow evaluation of multiple retreatments and limits our ability to compare this study to others that specifically separate evaluations of subsequent treatments. given the potential impact that delayed vaccination could have on the resulting immune responses of the cattle, it would be beneficial to evaluate second and third treatment rates separately. limitations related to study design, such as lack of blinding or small sample sizes, increase the chances for biased results and the results, especially numerical differences, must be interpreted with caution. bovine respiratory disease morbidity is inherently a subjective assessment of health, because identifying a potentially ill animal is largely accomplished via visual signs and sometimes followed by an objective measurement of temperature. blinding of individuals that are evaluating subjective outcomes like brd morbidity helps prevent unintentional biases that could impact those subjective outcomes in unpredictable ways. two of the four papers evaluated (poe et al., 2013; and richeson et al.,2009), indicated that evaluators were not blinded when evaluating subjective outcomes. three of the four papers evaluated had varying, or uneven, numbers of animals in pens or between blocks among treatments (poe et al., 2013; richeson et al., 2008; and richeson et al., 2015). it remains uncertain whether the density of a pen influences the risk of brd for the animals in it, potentially due to a decrease in available space and resources or due to stress from the commingling experience. additionally, three of the studies (poe et al. 2013; richeson et al., 2009; and richeson et al., 2015) had smaller sample sizes than the other (richeson et al., 2008) which may have impacted their ability to detect smaller differences in morbidity. even though each study provided evidence for a very specific question, there are multiple differences between the four studies that must be considered when interpreting the results. a notable difference is that two studies (richeson et al., 2008; and richeson et al., 2009) evaluated one mlv for respiratory viruses (express 5) while the other two studies (poe et al., 2013; and richeson et al., 2015) evaluated another mlv for respiratory viruses (bovishield gold® 5). these are only two of multiple mlv for respiratory viruses available on the market in the us and there are differences in the adjuvant used, different pathogen loads, different virus types and strains included, routes of administration, etc., between manufacturers and vaccines that could impact the results. therefore, although the studies provide evidence for our question related to delayed versus on-arrival mlv use, the evidence each provides is not necessarily externally valid when considering all mlv for respiratory viruses. another area of variability between studies is the difference in the definition of ‘arrival’. two studies appear to have processed calves on the day they arrived (richeson et al., 2009; and richeson et al., 2015); one indicates they were processed the day after they arrived (richeson et al., 2008), and one seems to indicate calves were processed after resting ‘overnight’ on grass and hay (poe et al., 2013). further potential variability exists regarding the amount of potential cross-contamination possible via direct or fomite contact between calves that were and were not vaccinated in each study during the period when they may have shed vaccine virus; mitigation strategies were not well-described. treatment and prophylaxis regimens are an additional area of variability in these protocols and throughout different feeding operations; it is possible that the impact of delayed vaccination could vary between operations due to differences in these other important health management factors. the two studies that used the express 5 mlv (richeson et al., 2008; and richeson et al., 2009) gave prophylactic tilmicosin and treated for internal and external parasites on arrival to all cattle, and boostered the mlv 14 days after they were first administered. however, one study (richeson et al., 2009) was also evaluating timing of clostridial vaccine while the other (richeson et al., 2008) gave all calves a clostridial vaccine on arrival. for prophylaxis, one (richeson et al., 2008) only administered tilmicosin if arrival rectal temperature was ≥40°c and those cattle were excluded from further morbidity assessment, while the other (richeson et al., 2009) administered it to all cattle on arrival and all were able to be evaluated for morbidity the next day. there was not a statistical difference in the number of cattle in each treatment that were excluded in richeson et al. (2008), which should have prevented a differential bias in morbidity outcomes between vaccine treatments. however, those cattle appear to have remained with their pen mates who did not receive prophylaxis, which may have differentially influenced the morbidity during the study in general and especially when compared to studies that provide metaphylaxis to all calves equally. these differences in arrival management between the two studies makes them difficult to compare. additionally, in both studies, cattle were able to be evaluated for retreatment due to brd morbidity after 72 hours, when they could be administered a different antibiotic. each allowed up to three retreatments. however, each study used different antibiotics as their first, second, and third treatments (richeson et al. [2008] used tilmicosin, enrofloxacin, and florfenicol, respectively; richeson et al. [2009] used florfenicol, ceftiofur, and danofloxacin, respectively), which also makes comparison of retreatment rates between studies difficult. the two studies that evaluated bovishield gold® 5 mlv (poe et al. 2013; and richeson et al., 2015) administered a clostridial vaccine and treated for internal and external parasites on arrival to all animals but differed in other parts of their protocols. for prophylaxis, richeson et al. (2015) administered tilmicosin to all cattle on arrival and cattle were able to be evaluated for brd morbidity after 24 hours. in poe et al. (2013) cattle with a rectal temperature that was ≥40°c at processing received their first treatment of florfenicol at processing regardless of clinical signs. they were presumably then able to be reevaluated after 72 hours when they could receive the second antibiotic treatment in their protocol, though this was not explicitly described. however, cattle who were not treated at processing seemed to be eligible to be evaluated the next day to determine if initial brd treatment should be administered. additionally, it does not appear that treatment during processing was a criteria for randomising nor is it clear whether delayed or arrival vaccinated calves had similar incidences of calves treated at processing. the differential treatment of calves in this study complicates assessment of brd incidence. in both papers, morbid cattle could be evaluated for retreatment due to brd morbidity after 72 hours, when they could be administered a different antibiotic (richeson et al. [2015] used florfenicol, enrofloxacin, tilmicosin, ceftiofur, then tulathromycin; poe et al. [2013] used florfenicol, tilmicosin, enrofloxacin, then tulathromycin).however, one study (poe et al., 2013) described that cattle going >21 days following treatment before exhibiting additional brd symptoms, were considered a new case of brd and their treatment regimen began again at florfenicol. selection of an antibiotic protocol is often a producer or veterinarian preference based on known efficacy, availability, pharmacology, etc. due to the different spectrums and modes of action associated with these drugs their use as metaphylaxis or treatment may impact brd morbidity outcomes (o’connor et al., 2019). case definition and criteria that make a calf eligible for brd treatment or retreatment was also a notable difference between studies that complicated comparisons. poe et al. (2013) actually used two different case definitions, one during processing where calves could receive treatment if they had a rectal temperature ≥40°c regardless of clinical signs, and then after day 0 when they had to have ≥2 clinical signs plus a rectal temperature of ≥40°c. richeson et al. (2008) required an unspecified number of visual signs plus rectal temperature of ≥40°c for initial treatment while richeson et al. (2009; and 2015) required ≥2 clinical signs plus a rectal temperature of ≥40°c to be eligible for initial treatment. retreatment criteria also varied between studies with some requiring some form of clinical signs plus a temperature threshold to be met (poe et al., 2013; and richeson et al., 2015) while others evaluated only the rectal temperature of calves at predetermined intervals after initial or subsequent treatment (richeson et al., 2008; and 2009). these different criteria, while externally valid, highlight one of the reasons why repeatability of brd research is so difficult to realise and how variable identification and management of brd cases can be within the literature. all four studies evaluated male calves that were either procured already castrated or castrated on arrival. although they all accounted for castration status in their analyses, three of the four studies (poe et al., 2013; richeson et al., 2008; and richeson et al., 2015) used a california banding technique for castration while the other study (richeson et al., 2009) used surgical castration. cattle react differently to alternate castration methods and the variable inflammatory response plus the impact castration can have on clinical signs such as depression, decreased appetite, etc., could alter the impact of delayed vaccination in a commercial setting (roberts et al., 2018). the lack of representation of heifers in the study populations also limits our ability to extrapolate these results to high risk heifer calves in stocker operations. mortality was evaluated in three studies (richeson et al., 2008; richeson et al., 2009; and richeson et al., 2015) but none found a statistical difference between delayed versus on arrival vaccine administration treatment groups. in richeson et al. (2009) there were inconsistent numerical differences due to the added variable of clostridial vaccine timing. the other two studies had opposing numerical differences, where one (richeson et al., 2008) showed a higher percentage of death loss over the 56 day study in calves vaccinated on arrival and the other (richeson et al., 2015) had a higher percentage of mortality associated with clinical brd in delayed vaccination calves during the 42 day study. the latter study revealed an association with brd and death loss while the former did not describe a cause for death. therefore, it cannot be concluded that all deaths were related to brd making comparison of the two studies more complicated. since these studies disagreed numerically, it is important to recognise these differences as well as those previously mentioned, such as the use of prophylaxis in richeson et al. (2015) which was not used in richeson et al. (2008). given the small percentages in death loss among the treatments in these studies, which ranged from 0.8–2.3%, it is also possible that they were underpowered to truly evaluate mortality. even with a similar goal for these studies and some with the same vaccines administered, there are many aspects of a protocol that can introduce variability and make it difficult to interpret outcomes. producers and veterinarians should use the information provided in this summary to make vaccine protocol decisions considering the limitations listed above. since the evidence differed among studies and no statistical difference between arrival versus delayed vaccine administration was identified, no answer can be given to the clinical question. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform: 1910–2021 week 42 search run with no limits or filters limit results to english and 2000–current pubmed on ncbi website: 1946–27 october 2021 search run with no limits or filters limit results to english and 2000–current search strategy: cab abstracts: ((exp cattle/ or (calf or calves or steer or steers or heifer or heifers or bull or bulls or bovine or bovines or cattle or youngstock or young-stock or (young adj2 stock)).mp.) and (exp vaccines/ or vaccin*.mp. or exp immunization/ or immuni*.mp.) and (delay or delays or delayed or arrive or arrives or arrived or arrival or postarrival or "post arrival" or post-arrival).mp. and (pneumon*.mp. or (respiratory adj1 disease*).ti,ab. or "respiratory diseases".sh. or (respiratory adj2 disease*).ti,ab. or ((shipping or undifferentiated) adj1 fever).ti,ab. or (brd or brdc).ti,ab. or (bovine adj1 respiratory adj1 disease*).ti,ab. or (bovine adj1 respiratory adj1 disease* adj1 complex).ti,ab. or (summer adj1 pneumon*).ti,ab. or (enzootic adj1 pneumon*).ti,ab. or pleuropneumon*.mp. or bronchopneumon*.mp. or (respiratory adj1 tract adj1 disease*).mp.))   pubmed: (("pneumonia"[mesh terms] or "pneumonia"[title/abstract] or "pneumoniae"[title/abstract] or "pneumonias"[title/abstract] or "respiratory diseases"[all fields] or "respiratory disease"[title/abstract] or "shipping fever"[title/abstract] or "undifferentiated fever"[title/abstract] or "brd"[title/abstract] or "brdc"[title/abstract] or "bovine respiratory disease"[title/abstract] or "bovine respiratory disease complex"[all fields] or "summer pneumonia"[title/abstract] or "enzootic pneumonia"[title/abstract] or ("pleuropneumonia"[mesh terms] or "pleuropneumonia"[title/abstract] or "pleuropneumonias"[title/abstract] or "pleuropneumoniae"[title/abstract]) or ("bronchopneumonia"[mesh terms] or "bronchopneumonia"[title/abstract] or "bronchopneumonias"[title/abstract] or "bronchopneumoniae"[title/abstract]) or "respiratory tract disease"[title/abstract] or "respiratory tract diseases"[all fields]) and ("calf"[title/abstract] or "calves"[title/abstract] or "steer"[title/abstract] or "steers"[title/abstract] or "heifer"[title/abstract] or "heifers"[title/abstract] or "bull"[title/abstract] or "bulls"[title/abstract] or "bovine"[title/abstract] or "bovines"[title/abstract] or "cattle"[title/abstract] or "cattle"[mesh terms] or "youngstock"[title/abstract] or "young stock"[title/abstract] or "young-stock"[title/abstract]) and ("immunization"[mesh terms] or "immunization"[title/abstract] or "immunisation"[title/abstract] or "immunizations"[title/abstract] or "immunisations"[title/abstract] or "immunize"[title/abstract] or "immunise"[title/abstract] or "immunized"[title/abstract] or "immunised"[title/abstract] or "vaccination"[mesh terms] or "vaccine"[title/abstract] or "vaccines"[title/abstract] or "vaccination"[title/abstract] or "vaccinating"[title/abstract] or "vaccinated"[title/abstract]) and ("delay"[title/abstract] or "delayed"[title/abstract] or "delays"[title/abstract] or "post-arrival"[title/abstract] or "post-arrival"[title/abstract] or "postarrival"[title/abstract] or "arrive"[title/abstract] or "arrival"[title/abstract] or "arrives"[title/abstract] or "arrived"[title/abstract]) dates searches performed: 27 oct 2021 exclusion / inclusion criteria exclusion: publication date prior to 2000, is a systematic review and / or meta-analysis, is conference proceedings, does not evaluate the bovine species, does not compare arrival versus delayed vaccine administration groups, does not evaluate the same vaccine given on arrival versus delayed administration, the delayed time was less than 14 days post-arrival, does not evaluate brd morbidity, or calves not evaluated in a stocker operation. inclusion: brd morbidity assessment, respiratory vaccine used when evaluating vaccine timing, and comparison of effects of delayed modified live vaccine administration and administration of vaccine on arrival to the stocker operation. search outcome database number of results excluded – not a research trial excluded – not an mlv respiratory vaccine study in calves excluded – does not compare arrival versus delayed (14–30 days) administration of the same mlv vaccine excluded – calves not evaluated or administered treatment at stocker operation total relevant papers cab abstracts 94 17 35 35 3 4 pubmed 50 7 16 24 1 2 total relevant papers when duplicates removed 4 conflict of interest ambs was advised and led by dr. john richeson (one of the authors or co-authors of all papers that are evaluated within this summary) to obtain her master’s degree at west texas a&m university from january 2016 to may 2017. capik collaborates regularly with dr. john richeson (one of the authors or co-authors of all papers that are evaluated within this summary) and has collaborated with two of the co-authors on richeson et al. 2009 (kegley and powell) and on co-author on poe et al. 2013 (kegley). moberly serves on the cabi publishing north american library advisory board and the vetstream academic advisory board. references o’connor, a.m., hu, d., totton, s.c., scott, n., winder, c.b., wang, b., wang, c., glanville, j., wood, h., white, b., larson, r., waldner, c. & sargeant, j.m. (2019). a systematic review and network meta-analysis of injectable antibiotic options for the control of bovine respiratory disease in the first 45 days post arrival at the feedlot. animal health research reviews. 20, 163–181. doi: https://doi.org/10.1017/s1466252320000031 poe, k.d., beck, p.a., richeson, j.t., gadberry, m.s., kegley, e.b., hess, t.w. & hubbell, d.s. (2013). effects of respiratory vaccination timing and growth-promoting implant on health, performance, and immunity of high-risk, newly received stocker cattle. applied animal science. 29(4), 413–419. doi: https://doi.org/10.15232/s1080-7446(15)30254-0 richeson, j.t., beck, p.a., gadberry, m.s., gunter, s.a., hess, t.w., hubbell, d.s. & jones, c. (2008). effects of on-arrival versus delayed modified live virus vaccination on health, performance, and serum infectious bovine rhinotracheitis titers of newly received beef calves. journal of animal science. 84(4), 999–1005. doi: https://doi.org/10.2527/jas.2007-0593   richeson, j.t., kegley, e.b., gadberry, m.s., beck, p.a., powell, j.g. & jones, c.a. (2009). effects of on-arrival versus delayed clostridial or modified live respiratory vaccinations on health, performance, bovine viral diarrhea virus type i titers, and stress and immune measures of newly received beef calves. journal of animal science. 87(7), 2409–2418. doi: http://dx.doi.org/10.2527/jas.2008-1484 richeson, j.t., beck, p.a., poe, k.d., gadberry, m.s., hess, t.w. & hubbell, d.s. (2015). effects of administration of a modified-live virus respiratory vaccine and timing of vaccination on health and performance of high-risk beef stocker calves. the bovine practitioner. 49(1), 37–42. doi: https://doi.org/10.21423/bovine-vol49no1p37-42 roberts, s.l., powell, j.g., hughes, h.d. & richeson, j.t. (2018). effect of castration method and analgesia on inflammation, behavior, growth performance, and carcass traits in feedlot cattle. journal of animal science. 91(1), 66–75. doi: https://doi.org/10.1093/jas/skx022 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. should we prescribe oral metronidazole or probiotics for acute gastroenteritis in dogs? a knowledge summary by emily moore dvm 1* wanda j gordon-evans dvm phd dacvs dacvsmr 2 1tufts cummings school of veterinary medicine, 200 westboro rd, north grafton, ma 01536, usa 2university of minnesota college of veterinary medicine, 1365 gortner ave, st paul, mn 55108, usa *corresponding author (moor1662@umn.edu) there is an erratum to this paper published in veterinary evidence vol 7, issue 2 (2022): 10.18849/ve.v7i2.626 vol 7, issue 2 (2022) published: 18 may 2022 reviewed by: louise buckley (phd fhea rvn) and silke salavati (dipl.ecvim-ca phd fhea mrcvs) next review date: 19 dec 2023 doi: 10.18849/ve.v7i2.393 pico question in dogs with acute gastroenteritis, is metronidazole faster, slower, or comparable in resolving clinical signs when compared to probiotic administration?   clinical bottom line category of research question treatment the number and type of study designs reviewed five studies total, all were blinded, randomised controlled trials strength of evidence moderate outcomes reported the use of probiotics as a treatment for acute, uncomplicated diarrhoea in dogs may improve clinical signs faster when compared to a placebo, but showed no difference when compared directly to metronidazole. metronidazole, when compared to a placebo, produced mixed results with one study finding that treatment with metronidazole did significantly reduce the time to resolution of diarrhoea, while another study found the difference with placebo was not significant conclusion based on the evidence evaluated, the use of oral metronidazole will not decrease time to resolution of clinical signs in cases of acute, uncomplicated diarrhoea in dogs when compared to probiotic administration and thus should not be a first-line treatment in such cases   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are presented with an 18 month old, female spayed labrador retriever with a 1 day history of watery, unformed stool with increased frequency. the patient does not have a previous history of diarrhoea. physical examination is normal, aside from faecal staining around the anus; her appetite and behaviour are unchanged to mildly decreased. faecal float and smear tests are negative for parasites and there is no apparent blood in the faecal sample. the owner would like a treatment that will return the dog’s stools to normal consistency in the shortest amount of time and asked about prescribing metronidazole, as this has worked for her other dogs with similar presentations previously. you know that not all cases of acute gastroenteritis need to be treated with antimicrobials and will resolve with time, but the owner wants a treatment today. you wonder if prescribing a probiotic / synbiotic would be as efficacious at treating the acute diarrhoea as metronidazole is and if this would be the better option for today’s visit. the evidence while the shmalberg et al. (2019), langlois et al. (2020), herstad et al. (2010), nixon et al. (2019), and kelley et al. (2009) studies were all randomised controlled clinical trials, the evidence directly comparing the time for resolution of clinical signs in dogs treated for acute gastroenteritis is inconclusive. shmalberg et al. (2019) is the only study that compared both treatments directly, but was underpowered and did not show statistical difference for the two treatments when compared to each other and to no intervention. the herstad et al. (2010), nixon et al. (2019), and kelley et al. (2009) studies compared time to resolution of clinical signs with probiotics compared to placebo and suggest that there is faster resolution of clinical signs when a dog is treated with probiotics in cases of acute, uncomplicated diarrhoea. langlois et al. (2020) reported that metronidazole may shorten the course of diarrhoea by 1.5 days. however, this study used an unvalidated faecal scoring system and small sample size. based on the results of shmalberg et al. (2019) and langlois et al. (2020), there is no unequivocal evidence that metronidazole reduces the duration of clinical signs associated with acute, uncomplicated diarrhoea, and thus should not be used as a first-option treatment in such cases. summary of the evidence shmalberg et al. (2019) population: client-owned dogs that presented for acute diarrhoea (≤7 days) with or without vomiting, between 4–45 kg, and lacking any clinically relevant comorbidities (endocrinopathies, organ dysfunction, immune-mediated disease, suspected pancreatitis). excluded were dogs with signs consistent with severe acute haemorrhagic diarrhoea syndrome (significant dehydration, hypovolemia, large volumes of haemtochezia). sample size: 63 dogs enrolled; 60 dogs completed study. intervention details: there were three groups: placebo (20 dogs), probiotic treatment (20 dogs), and metronidazole treatment (20 dogs). synbiotic (classified as probiotic in original article) treatment group: vital vetô (vital planet, palm harbor, fl, usa) probiotic capsules: probiotic composition: bifidobacterium bifidum vpbb-6, bifidobacterium longum vpbl-5, bifidobacterium animalis vpba-4, bifidobacterium infantis vpbi-6, lactobacillus casei vplc-1, levilactobacillus brevis vplb-5, limosilactobacillus reuteri vplr-1, and lactobacillus bulgaricus vplb-7. prebiotic composition: 425 mg organic acacia gum and fructo-oligosaccharides. 30 billion colony forming units (cfu) given by mouth twice daily for 10 days. metronidazole treatment group: metronidazole powder given in gelatin capsules: oral metronidazole capsules given twice daily for 10 days. dogs 4–10 kg received 125 mg; 12.5–25 mg/kg dose range. dogs 10.1–20 kg received 250 mg; 12.5–25 mg/kg dose range. dogs 20.1–45 kg received 400 mg; 8.9–20 mg/kg dose range. typical dose range for metronidazole in cases of giardiasis is 25 mg/kg and clostridial infections is 10–15 mg/kg when given orally. placebo group: capsules of sucrose equal in volume to probiotic and metronidazole capsules: oral capsules given twice daily for 10 days. rescue treatment (treatment given to dogs that still had diarrhoea after 10 days or experienced worsening frequency of diarrhoea, worsening faecal score, increased haematochezia, or worsening straining) for any dog was tylosin, 30 mg/kg by mouth twice daily for 10 days. three dogs were eliminated from the study, one due to significant parasite burden (metronidazole group) and two due to failure of owners to give the treatment (one in the probiotic group and one in the placebo group). a predetermined sample size of n = 20 per group was determined by power analysis prior to study. randomisation was performed using a schedule obtained from a random sorting feature of a commercial software program (excel for mac). study design: double blinded, placebo controlled, randomised clinical trial. outcome studied: outcome = number of days until first formed stool, as measured by a faecal score ≤3. main findings (relevant to pico question): treatment group did not significantly affect the duration of diarrhoea when all dogs were included. neither metronidazole treatment nor probiotic treatment significantly reduced the number of days until the first formed stool was appreciated in the dogs. probiotic group: acceptable faecal score after 3.5 ±2 days (mean value with standard deviation). metronidazole group: acceptable faecal score after 4.6 ±4 days (mean value with standard deviation). placebo group: acceptable faecal score after 4.8 ±9 days (mean value with standard deviation). p-value measured between the placebo group and the two treatment groups was p = 0.17. after dogs positive for parasite ova on faecal float were removed, there was no significant difference between this finding and the findings when parasite ova positive dogs were included in the statistics (p = 0.56): acceptable faecal score probiotic group after 3.5 ±2 days. acceptable faecal score metronidazole group after 4.5 ± 2 days. acceptable faecal score placebo group after 4.8 ± 3 days. no dogs needed rescue treatment. limitations: the outcome was only one formed stool, which could be a sign of resolution, but could also represent an anomaly during treatment. while complete blood count (cbc), chemistry panel, faecal floatation, and polymerase chain reaction (pcr) panels were done on most dogs, some dogs received empirical treatment (fenbendazole) or supportive care (maropitant, iv or sq fluids) prior to study enrolment. owners received financial compensation for participating. dogs with a low parasite burden were included in the study (dogs with a high parasite burden were excluded). the probiotic also contained prebiotics that were not found in the placebo and could have had an effect on the microbiome. metronidazole is typically given in the form of a tablet, capsule, or oral solution when used in a non-hospital setting, so the bioavailability of the powder form is unknown in this study. langlois et al. (2020) population: dogs with acute, uncomplicated diarrhoea ± vomiting not due to parasitism, giardia spp infection, or parvoviral enteritis. dogs >6 months with diarrhoea <7 days duration, between 4–50 kg. all dogs were up to date on core vaccinations. the study excluded dogs that received probiotics, antimicrobials, or anti-inflammatory treatments within the preceding 30 days prior to diarrhoea onset, pregnant or nursing dogs, and dogs with moderate to severe abdominal pain, complete anorexia, or moderate to severe dehydration (>8%). sample size: 48 dogs recruited; 31 dogs completed study. intervention details: there were two groups: treatment with metronidazole (14 dogs) and no treatment (placebo) group (17 dogs): metronidazole group: eight dogs received either intravenous (iv) fluids (≤1 day) or subcutaneous (sc) fluids (no dose given). six dogs received one dose of maropitant citrate (cereniaô, zoetis, kalamazoo, mi, usa). metronidazole target dose = 10–15 mg/kg by mouth twice daily for 7 days. metronidazole was compounded in gel capsules by unichem laboratories ltd. (mumbai, india). placebo group: seven dogs received either iv (≤1 day) or sc fluids (no dose given). six dogs received one dose of maropitant citrate (cereniaô, zoetis, kalamazoo, mi, usa). placebo dose = capsules of microcrystalline cellulose by mouth twice daily for 7 days. rescue treatment (metronidazole) was given if diarrhoea persisted after 7 days. any dog that presented with vomiting could receive one dose of maropitant 1 mg/kg sc (clinician’s discretion). hematochezia (p = 0.48), fluid therapy treatment (p = 0.48), maropitant citrate treatment (p = 0.72) were not different between the two populations of dogs. a predetermined sample size of n = 15 per group was determined by power analysis prior to study. dogs were randomised using a computer-generated log created by the pharmacist. the dog owner and clinician were blinded to treatment. 14 dogs were excluded from the study. 10 dogs were excluded for gastrointestinal parasitism, two dogs for inability to obtain sufficient faeces for faecal testing, one dog for normal faecal score prior to therapeutic initiation, and one for ultrasonographic evidence of acute pancreatitis. three dogs were removed from the study. one dog for severe vomiting (test population), one dog for failure to provide faecal scores and return at day 7 for diagnostics, and one for failure of faecal scoring and adherence of dietary guidelines. study design: double blinded placebo controlled randomised clinical trial. outcome studied: outcome = time in days until resolution of diarrhoea, measured as two consecutive faecal scores ≤4. main findings (relevant to pico question): metronidazole significantly reduced the number of days until resolution of diarrhoea (p = 0.04) in dogs when compared to the placebo group. metronidazole population resolution of diarrhoea average (mean and standard deviation) = 2.1 ±6 days. 13/14 dogs receiving metronidazole had resolved diarrhoea by day 4. placebo population resolution of diarrhoea average (mean and standard deviation) = 3.6 ±1 days: 2/17 dogs in the control group received metronidazole due to persistent diarrhoea at day 7. limitations: bristol scoring system is not validated in dogs nor is it commonly used, but it is validated and commonly used in human diarrhoeal studies. all dogs ate their normal diet, although one dog was excluded due to lack of owner compliance. dogs with persistent diarrhoea at day 7 were included in statistical analysis as ‘resolved at day 7’ for statistics. only 18/31 dogs had biochemical analysis or further diagnostic work up (abdominal us). lead author is affiliated with zomedica, inc. small sample size. herstad et al. (2010) population: dogs with acute self-limiting gastroenteritis. the dogs had either diarrhoea or diarrhoea and vomiting. the study excluded dogs with diarrhoea ± vomiting for over 2 weeks, dogs treated with a probiotic product within a month of presentation, and dogs that required hospitalisation. sample size: 36 dogs; it was not stated if any dogs did not complete or were withdrawn from the study. intervention details: the study had two groups: treatment with probiotics (15 dogs) and no treatment (placebo) group (21 dogs): probiotic treatment = zoolac propaste ô (chem vet a/s, denmark): probiotic composition: lactobacillus farciminis, pediococcus acidilactici, bacillus subtilis, licheniformis, and thermo-stabilised lactobacillus acidophilus. placebo treatment = pasta-base with vegetable oil, lecithin, and e551b (stabiliser). 22 dogs also presented with vomiting: 12 in placebo group; 10 in probiotic group (no statistical analysis provided). doses for both placebo and probiotic paste was based on weight: 1 ml for 1–10 kg; 2 ml for 10–25 kg; 3 ml for 25–50 kg. given by the owner by mouth three times daily (every 8 hours) until normalisation of stools. first dose was a double dose in both placebo and probiotic group. randomisation protocol was not described, only stated that there was block randomisation. calculation of a predetermined group size (n) was not performed prior to study enrolment. no adverse effects in either group were reported. study design: double-blind placebo control randomised clinical trial. outcome studied: outcome = day (whole or half) until last abnormal stool and days until normalisation of stool. main findings (relevant to pico question): probiotic treatment was a significant factor for time to diarrhoea resolution (p = 0.045) but was not significant for time until resolution of signs if diarrhoea and vomiting were both present (p = 0.55). the time to first normal stool after starting treatment was not significant between the two groups (p = 0.14). probiotic group: time until last abnormal stool: 1.3 days (95% confidence interval (ci): 0.5–1). time until last clinical sign (vomiting or diarrhoea): 1.4 days (95% ci: 0.5–4). time until first normal stool: 2.9 days (95% ci: 2.1–7). mean duration of vomiting: 0.9 days (95% ci: 0.5–3). placebo group: time until last abnormal stool: 2.2 days (95% ci: 1.3–1). time until last clinical sign (vomiting or diarrhoea): 2.2 days (95% ci: 1.4–1). time until first normal stool: 3.4 (95% ci: 2.6–2). mean duration of vomiting: 1.2 days (95% ci: 0.2–2). both probiotic and placebo groups had significantly reduced number of stools during the first 3 days of treatment (p ≤0.01), but were not different from each other (p = 0.19). both probiotic and placebo groups had significantly reduced number of vomiting incidences during the first 3 days of treatment (p ≤0.01), but were not different from each other (p ≥0.16). limitations: faecal samples for bacterial and parasitic analysis were only collected from some patients, not all, and only at the initial enrolment in the clinical trial. there was no standardised way to assess normalisation of stool consistency, only done by owner opinion and relied upon owner’s recollection during interview on day 4 or 8. no clearly stated definition of ‘normalised stool’, normalisation of stool was defined by owner’s interpretation and was only subjective. small sample size. all of the products used (probiotics and placebo paste) were supplied by the manufacturing company directly. nixon et al. (2019) population: client owned dogs with acute diarrhoea ≥1 occurrences within 24 hours of presentation to primary care veterinarian. dogs were excluded if their signs were deemed unsuitable for conservative management, if they received antimicrobial or probiotic treatment within 4 weeks before day 0 of enrolment. dogs with comorbidities that did not affect diarrhoea were included in the study. sample size: 148 dogs initially enrolled, 118 dogs remained with no dosing errors, 107 dogs completed the entire study. intervention details: the study consisted of two groups: synbiotic (classified as probiotic in original article) group (57 dogs) and a placebo group (61 dogs). treatment group = enterococcus faecium 4b1707, preplex® (pka, protexin veterinary, somerset, uk) prebiotics, combined kaolin and montmorillonite clay, psyllium, pectin, and beta glucan: given by mouth three times daily (every 8 hours). placebo group = placebo composed of soya oil, colloidal silica, dextrose, liver flavour: given by mouth three times daily (every 8 hours). dosing by body weight for probiotic and placebo group: <5 kg = 2 ml 5–15 kg = 2 ml 15–30 kg = 5 ml 30–45 kg = 7 ml ≥45 kg = 10 ml all dogs ate hill’s® i/d (topeka, kansas, usa) for duration of study. a predetermined group size of 43 cases based on a power calculation. randomisation was performed using block randomisation with a block size of 2 stratified by site. 41 dogs did not complete the study. 10 were included inappropriately (no episode of diarrhoea), 10 had dosing errors (inappropriate therapy dose or failure to accept new diet), 10 did not receive a confirmed dose of therapy, and 11 for worsening or non-improvement of signs. the number of dogs excluded from each group was not specified. study design: double-blinded, placebo controlled, randomised clinical trial. outcome studied: outcome definition: time until passage of three consecutive faeces of normal consistency (faecal score ≤3) measured from initial presentation to the veterinary clinic within 10 days of initial study enrolment. main findings (relevant to pico question): probiotic treatment was significant (p = 0.008) in decreasing time to resolution of diarrhoea as measured as the passage of three consecutive normal stools (faecal score ≤3). probiotic group duration of diarrhoea median time: 32 hours (range 2–118 hours; n = 51). placebo group duration of diarrhoea median time: 47 hours (range 4–167 hours; n = 58). fewer dogs in the probiotic group required additional medical intervention when compared to the placebo group. additional treatment could include antiemetics, gastrointestinal (gi) motility modulating drugs, antimicrobials, and corticosteroids. probiotic group requiring additional treatment: two dogs with five total treatments. placebo group requiring additional treatment: nine dogs with 15 total treatments. the dogs were withdrawn from the study and there was no significant difference in time until withdrawal between the probiotic group (61 hours ± 41 hours) and the placebo group (45 hours ± 3 hours) and there was not a significantly different relative risk of needing additional medical treatment in either group. limitations: while the data is significantly different, the result may not be clinically different (only 0.5 day) for the owner. no diagnostic testing to rule out infectious causes of diarrhoea or unknown comorbidities, which could impact the responsiveness of the diarrhoea to a probiotic alone. while the mann-whitney test was used to determine differences in median age between the group was not significantly different, the value was very close to p and may confer a clinical difference. the median age of the treatment group was 45 months, while the median age of the placebo group was 24 months. dogs were allowed to be removed from the trial if they needed additional medical intervention; more were removed from the placebo group and could represent attrition bias. dogs that missed one dose in a day in either the placebo or treatment group were not excluded, which may impact results given the timing of resolution of diarrhoea was measured in hours and was around four doses for the treatment group (specific numbers were not given). this lack of strict compliance may mimic the realities of daily life (in respect to client compliance) therefore, it is not unreasonable to still include these dogs. the placebo had a different composition than the probiotic; it would be a stronger study if the placebo was the same composition as the probiotic without the probiotics and prebiotics. two authors were employees of the company that produced the probiotic. kelley et al. (2009) population: young, adult dogs that presented to their veterinarian with acute idiopathic diarrhoea with a stool score of 4; all dogs from a guide dog organisation from a single training campus. excluded dogs that had other medical conditions, were being treated with other medications, or had stool scores <3. sample size: 45 recruited; 36 met inclusion criteria, 31 dogs completed study. intervention details: the study consisted of two groups: probiotic group (13 dogs) and a placebo group (18 dogs): probiotic group = canine derived bifidobacteerium animalis ahc7 (procter and gamble pet care, lewisburg, oh, usa) in cocoa butter treats: dose = 2 x 1010 colony forming units (cfu) / day by mouth twice daily for 14 days or until resolution of diarrhoea. placebo = same vehicle as the test agent without probiotic (cocoa butter treats): placebo dose = by mouth twice daily for 14 days or until resolution of diarrhoea. both groups ate either eukanubaô (procter & gamble, cincinnati, oh, usa) or iamsô (procter & gamble, cincinnati, oh, usa) maintenance diets. at the beginning of the study, any dog could be prescribed metronidazole at dvm’s discretion for number of abnormal stools, degree of stool looseness, health of dog, and if dog was housed nearby outbreaks of diarrhoea. metronidazole dose = 750 mg, by mouth twice daily for 7 days. nine dogs in the control group received metronidazole. four dogs in the treatment group received metronidazole for gi disease. five dogs were excluded from statistical analysis – four dogs had missing stool scores; one dog had been previously enrolled in the study. the kennel staff performing the stool scoring were blinded to the dog’s treatment group. randomisation protocol was not stated. study design: blinded, placebo controlled randomised clinical trial. outcome studied: outcome = time, in days, until resolution of diarrhoea. resolution of diarrhoea was defined as stool scores that improved from 4 to ≤2 and remained ≤2 for at least 5 consecutive days. main findings (relevant to pico question): treatment with probiotic significantly reduced days to resolution of diarrhoea when compared to the placebo group in all dogs, and in both german shepherds and labrador retrievers, while the labrador-golden retrievers or golden retrievers did not show a significant difference due to small sample size. probiotic group all dogs: mean days to resolution of diarrhoea was 3.9 ±3., placebo group all dogs: mean days of resolution of diarrhoea was 6.6 ±7 days. p-value for all dogs, p = <0.01. probiotic group german shepherds: mean days to resolution of diarrhoea was 3.3 ±9. placebo group german shepherds: mean days of resolution of diarrhoea was 7.7 ±8 days. p-value for german shepherds, p = 0.03. probiotic group labrador retrievers: mean days to resolution of diarrhoea was 3.3 ±3. placebo group labrador retrievers: mean days of resolution of diarrhoea was 6.3 ± 2.4 days. p-value for labrador retrievers, p = 0.05. probiotic group labrador-golden retrievers: mean days to resolution of diarrhoea was 5.3 ±5. placebo group labrador-golden retrievers: mean days to resolution of diarrhoea was 6.0 ±5 days. p-value for labrador-golden retrievers, p = 0.73. probiotic group golden retrievers: mean days to resolution of diarrhoea was 1.0 ±0. placebo group golden retrievers: mean days of resolution of diarrhoea was 6.0 ±0 days. p-value for golden retrievers not calculated, only one dog per group. 5/13 dogs in the treatment group received metronidazole: mean days of resolution of diarrhoea in probiotic dogs that did not receive metronidazole: 3.33 ±26 days (based on reviewer’s calculation). 9/18 dogs in the control group received metronidazole: mean days to resolution of diarrhoea in placebo dogs that did not receive metronidazole: 6.11 ±88 days (based on reviewer’s calculation). when dogs receiving metronidazole were excluded from the study, resolution of diarrhoea by day 4 occurred in 3/9 dogs in the control group and 7/9 dogs in the probiotic group – statistical analysis was not presented. limitations: funded by procter and gamble pet care, which produced the probiotic used in the treatment group. all dogs were from the same facility, which could be a confounder (a bias in management or population). dogs receiving metronidazole were included in the statistics and were more commonly in the control group. giardia positive dogs were included in the statistics and received metronidazole (standard of care for giardiasis); these dogs should have been eliminated from the study as the cause is infectious and not idiopathic. small samples sizes when considering the data with and without the metronidazole treated dogs. very small sample size in some subgroups. appraisal, application and reflection dogs with cases of acute gastroenteritis are commonly seen at first opinion clinics (singleton et al., 2019). two commonly used options for treatment of dogs with acute, uncomplicated diarrhoea are systemic antimicrobials, mainly metronidazole (although in the uk potentiated amoxicillin is more commonly used), and nutraceuticals, including various formulations of probiotics / synbiotics (singleton et al., 2019). many cases of acute diarrhoea are self-limiting (shmalberg et al., 2019), yet many mild cases are still treated with metronidazole (singleton et al., 2019). the continued prescribing of metronidazole may be related to a perception that metronidazole administration resolves a patient’s diarrhoea in a more timely manner and satisfies an owner’s expectation of medication administration. however, there is also a rising concern about veterinary use of antimicrobials and the effects on human health (herstad et al., 2010; and prescott, 2019). the use of antimicrobials in all fields of veterinary medicine can have effects on the microbial population, which in turn can impact human health. research in companion animals shows the close relationship between humans and their pets allows for the transfer of microbes between the species, thus increasing the potential for transfer of methicillin-resistant bacteria between the human and pet. with increased antimicrobial resistance, the treatment of infections may become more challenging in both human and veterinary medical fields (lloyd & page, 2018). thus an alternative treatment regimen needs to be established for uncomplicated acute diarrhoea in the veterinary population that both alleviates the patient’s condition and placates the client. the practice of prescribing probiotics for treatment of acute diarrhoea in veterinary patients may offer an alternative solution. the direct study of the time to resolution of clinical signs (diarrhoea) using metronidazole compared to probiotics has not been studied adequately in dogs that present for acute, uncomplicated diarrhoea. only one study directly compares time to resolution of diarrhoea in dogs treated with metronidazole or probiotics, while the remaining data must be extrapolated from studies comparing either oral metronidazole use to a placebo, or probiotic use to a placebo. shmalberg et al.’s (2019) study directly comparing treatment with metronidazole, a probiotic product, and a placebo, found there was no significant reduction in time to resolution of acute diarrhoea when the dog received a probiotic or metronidazole. the metronidazole-treated group had a very similar average to the placebo-treated group, but probiotic average days until resolution of diarrhoea was 1 day shorter than both, which may be clinically important for a client. langlois et al. (2020) found that metronidazole treatment for cases of acute, uncomplicated diarrhoea did have a significant impact on time to resolution of diarrhoea when compared to a placebo. metronidazole treatment was found to resolve clinical diarrhoea 1.5 days sooner than the placebo. a limitation of the study is that the participants’ diet was not controlled, which is also a mainstay of common treatment (singleton et al., 2019). the sample sizes were small for this study as well. herstad et al. (2010), nixon et al. (2019), and kelley et al. (2009) performed randomised clinical trials comparing the use of probiotics and a placebo to evaluate timing of resolution of clinical signs. while herstad et al. (2010) found no significant improvement in the probiotic treated group over the placebo group when the dogs presented with both vomiting and diarrhoea, herstad et al. (2010), nixon et al. (2019), and kelly et al. (2009) found that probiotic administration did provide an improvement over the placebo by reducing time in days to resolution of diarrhoea. herstad et al. (2010) did not provide clients with a standard faecal scoring system to use and only based faecal consistency on client opinion, while also not eliminating parasitic or infectious causes of diarrhoea. the placebo used in the nixon et al. (2019) study varied in composition from the probiotic formulation, which could be a confounding factor. again, nixon et al. (2019) failed to remove dogs with infectious causes of diarrhoea as well. the population of dogs used in the kelley et al. (2009) study may not be representative of the general population of dogs but does remove confounding differences in environment and owner compliance as seen in shmalberg et al. (2019), langlois et al. (2020), herstad et al. (2010), and nixon et al. (2019). kelley et al. (2009) found that probiotic administration reduced time of resolution of diarrhoea by 2.5 days, which may be significant to many owners. overall, the results of studies by shmalberg et al. (2019), langlois et al. (2020), herstad et al. (2010), nixon et al. (2019), and kelley et al. (2009) provided weak evidence for the efficacy of metronidazole compared to placebo for treatment of acute, uncomplicated diarrhoea. given the lack of clear benefit for resolution of diarrhoea with a course of metronidazole, the long-term effects of antimicrobials (specifically metronidazole) on the microbiome of the gastrointestinal tract must also be considered when prescribing antimicrobial / antibacterials as they could be unfavorable for the patient. pilla et al. (2020) and igarashi et al. (2014) found that oral metronidazole treatment for cases of acute diarrhoea led to changes in the gastrointestinal microbiome composition, particularly bacteria responsible for bile acid metabolism, that persisted for up to 1 month post antibacterial treatment in some dogs. during oral metronidazole treatment, the faecal dysbiosis index was increased, but returned to normal after 2 weeks of metronidazole treatment (pilla et al., 2020; and nogueira et al., 2019). in contrast, probiotic use generally appears to be safe in veterinary species. the potential risk of probiotic use must be extrapolated from human research. the greatest apparent risk is the potential of a bacterium to become pathogenic, particularly if the intestinal barrier is not fully developed, but appeared safe when used in patients with a history of immunosuppression (either iatrogenic or infectious in origins) (butel, 2014). additionally, natural bacterial behaviours, such as genetic material transfer, can occur and could be detrimental if the probiotic bacterium conveyed antimicrobial resistant genetic material to the normal flora, though evidence of this occurring is lacking (butel, 2014). further research needs to be performed in order to clinically answer this pico question. shmalberg et al. (2019) is the only study that directly compares the use of metronidazole and a probiotic product and did not show a significant advantage of either treatment compared to each other or a placebo. there is insufficient evidence to answer whether or not metronidazole affects the duration (shorter, or longer, or no difference) of clinical signs when compared to probiotic administration in cases of acute, uncomplicated diarrhoea. additionally, when evaluating the use of probiotics / synbiotic products as treatment to reduce the duration of acute, uncomplicated diarrhoea, the evidence remains weak. shmalberg et al. (2019) showed that probiotics were equivalent to metronidazole in timing of resolution of diarrhoea. while herstad et al. (2010) and nixon et al. (2019) showed earlier time to clinical resolution of diarrhoea, they did not show a significant advantage when compared to placebo. only kelly et al. (2009) showed a significant reduction in days to resolution of diarrhoea, but only in certain dog breeds. given the clinical scenario of an otherwise healthy dog presenting for acute and uncomplicated diarrhoea, prescribing probiotic / symbiotic products to satiate owner expectations (in insistence) would be a reasonable choice as the risk associated with these products is low and no long-term effects have been reported or studied. methodology section search strategy databases searched and dates covered: pubmed on ncbi platform, 1999–2021. cab abstracts on ovid platform, 1999–2021. search strategy: pubmed: acute and (diarrhea or diarrhoea or gastroenteritis) and (canine or dog or dogs) and (metronidazole or probiotic or probiotics or nutraceutical)   cab abstracts: (acute and (diarrhea or diarrhoea or gastroenteritis) and (dog or dogs or canine or canines) and (metronidazole or probiotic or probiotics or nutraceutical)) dates searches performed: 19 dec 2021 exclusion / inclusion criteria exclusion: articles not in english, review articles, articles that did not measure the desired outcome, articles that studied diarrhoea that was not acute, or articles that studied diarrhoea of a known cause. inclusion: articles available in english which were relevant to the pico. articles had to involve more than one dog and compare the pico pharmacologics to a placebo or each other. search outcome database number of results excluded – articles not in english excluded – clinical review article excluded – desired outcome not measured excluded – studied non-acute diarrhoea excluded – known cause of diarrhoea unable to access article total relevant papers pubmed 28 1 6 6 5 5 0 5 cab abstracts 37 7 9 8 2 5 1 5 total relevant papers when duplicates removed 5 conflict of interest the authors declare no conflicts of interest. references butel, m. j. (2014). probiotics, gut microbiota and health. médecine et maladies infectieuses. 44(1), 1–8. doi: https://doi.org/10.1016/j.medmal.2013.10.002 herstad, h. k., nesheim, b. b., l'abée-lund, t., larsen, s. & skancke, e. (2010). effects of a probiotic intervention in acute canine gastroenteritis – a controlled clinical trial. journal of small animal practice. 51(1), 34–3 doi: https://doi.org/10.1111/j.1748-5827.2009.00853.x igarashi, h., maeda, s., ohno, k., horigome, a., odamaki, t. & tsujimoto, h. (2014). effect of oral administration of metronidazole or prednisolone on fecal microbiota in dogs. plos one. 9(9). doi: https://doi.org/10.1371/journal.pone.0107909 kelley, r. l., minikhiem, d., kiely, b., o'mahony, l., o'sullivan, d., boileau, t. & park, j. s. (2009). clinical benefits of probiotic canine-derived bifidobacterium animalis strain ahc7 in dogs with acute idiopathic diarrhea. veterinary therapeutics. 10(3), 121–130. langlois, d. k., koenigshof, a. m. & mani, r. (2020). metronidazole treatment of acute diarrhea in dogs: a randomized double blinded placebo-controlled clinical trial. journal of veterinary internal medicine. 34(1), 98–104. doi: https://doi.org/10.1111/jvim.15664 lloyd, d. h. & page, s. w. (2018). antimicrobial stewardship in veterinary medicine. microbiology spectrum. 6(3). doi: https://doi.org/10.1128/microbiolspec.arba-0023-2017 nixon, s. l., rose, l. & muller, a. t. (2019). efficacy of an orally administered anti-diarrheal probiotic paste (pro-kolin advanced) in dogs with acute diarrhea: a randomized, placebo-controlled, double-blinded clinical study. journal of veterinary internal medicine. 33(3), 1286–1294. doi: https://doi.org/10.1111/jvim.15481 nogueira, j. p. s., he, f., mangian, h. f., oba, p. m. & de godoy, m. r. c. (2019). dietary supplementation of a fiber-prebiotic and saccharin-eugenol blend in extruded diets fed to dogs. journal of animal science. 97(11), 4519–4531. doi: https://doi.org/10.1093/jas/skz293 pilla, r., gaschen, f.p., barr, j. w., olson, e, honneffer, j., guard, b. c., blake, a. m., villanueva, d., khattab, m. r., alshawaqfeh, m. k., lidbury, j. a., steiner, j. m. & suchodolski, j. s. (2020). effects of metronidazole on the fecal microbiome and metabolome in healthy dogs. journal of veterinary internal medicine. 34(5), 1853–1866. doi: https://doi.org/10.1111/jvim.15871 prescott, j. f. (2019). veterinary antimicrobial stewardship in north america. australian veterinary journal. 97(7), 243–248. doi: https://doi.org/doi:10.1111/avj.12811 shmalberg, j., montalbano, c., morelli g. & buckley, g. j. (2019). a randomized double blinded placebo-controlled clinical trial of a probiotic or metronidazole for acute canine diarrhea. frontiers in veterinary science. 6(163), 1– doi: https://doi.org/10.3389/fvets.2019.00163 singleton, d. a., noble, p. j. m., sánchez-vizcaíno, f., dawson, s., pinchbeck, g. l., williams, n. j., radford, a. d. & jones, p. h. (2019). pharmaceutical prescription in canine acute diarrhoea: a longitudinal electronic health record analysis of first opinion veterinary practices. frontiers in veterinary science. 6(218), 1–14. doi: https://doi.org/doi:10.3389/fvets.2019.00218 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in horses with osteoarthritis, is mesenchymal stem cell therapy more effective at managing lameness than intra-articular corticosteroids? a knowledge summary by laura pratley bvsc1* 1university of liverpool institute of veterinary science, neston ch64 7te *corresponding author (laupratley@gmail.com) vol 5, issue 3 (2020) published: 23 jul 2020 reviewed by: guy hinnigan (bvsc certes(orth) dipecvs mrcvs) and roger smith (ma vetmb phd deo fhea dipecvsmr dipecvs frcvs) next review date: 10 nov 2021 doi: 10.18849/ve.v5i3.317 pico question in horses with osteoarthritis, is mesenchymal stem cell therapy more effective at managing lameness than intra-articular corticosteroids?   clinical bottom line category of research question treatment the number and type of study designs reviewed nine papers were critically reviewed; seven experimental trials and two randomised controlled double-blinded trials. strength of evidence weak to moderate outcomes reported there is moderate evidence to suggest that chondrogenically induced mesenchymal stem cells combined with equine allogenic plasma have a good efficacy at reducing lameness in the short-term, in horses with mild to moderate lameness associated with osteoarthritis. however, there is no definitive evidence directly comparing mesenchymal stem cell therapy and corticosteroids, to identify if mesenchymal stem cell therapy is more effective than intra-articular corticosteroids. conclusion in horses with mild to moderate lameness associated with osteoarthritis, there is moderate evidence to suggest that mesenchymal stem cell therapies are effective at managing lameness. however, it is undetermined whether they are more efficacious than intra-articular corticosteroids.   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision-making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.   introduction osteoarthritis (oa) is one of the most common causes of lameness, reduced athletic function and performance in both leisure and sports horses (rossdale et al., 1985; and clegg & booth, 2000) and it will affect approximately 25% of horses in their lifetime (neundorf et al., 2010; and broeckx et al., 2019b). oa is the degenerative and progressive degradation of the joint, caused by overloading of a normal joint or normal loading of an abnormal joint, leading to inflammation, which reduces the capacity for proteoglycan synthesis (kidd et al., 2001). this induces oa due to a cascade of inflammatory mediators (clutterbuck et al., 2010). there are many different treatment and management options available for veterinary surgeons and owners, including intra-articular (ia) corticosteroids, non steroidal anti-inflammatories and nutraceuticals. these treatments are aimed at reducing inflammation and clinical signs associated with oa, however, these treatments do not alter the disease progression. long-term use of nsaids  can be associated with adverse effects, such as colitis (mcconnico, 2008), and their use is prohibited in competing horses. ia corticosteroids are commonly used in both highand low-motion joints, with success at reducing lameness in the short and medium term (frisbie et al., 1997; and mcilwraith, 2010), however they have been shown to have deleterious effect on cartilage, in vitro, particularly methylprednisolone acetate (mpa) (bryon, 2008; and mcilwraith, 2010). other treatment options include disease modifying osteoarthritic drugs, which can be defined as drugs which do not just alleviate symptoms, but help hyaline cartilage repair and restoration (mcilrwaith, 2011) and slow or prevent structural disease progression, such as polysulfated glycosaminoglycans, and pentosan polysulfate. these have been shown to modulate disease progression in vitro (ghosh et al., 1993; little & ghosh, 1996; and mcilwraith et al., 2012), however this has not been repeated in vivo. they have shown little efficacy at reducing lameness, unless combined with ia corticosteroids (frisbie et al., 2009). hyaluronic acid (ha) is also commonly used for management of oa and can be used effectively alongside ia corticosteroids and has been shown to have anti-inflammatory effects within the joint (caron, 2005), and provides viscoelasticity to synovial fluid (howard & mcilwraith, 1993). in more recent years, there has been increased interest in mesenchymal stem cell (msc) therapies, which are thought to have regenerative properties within the joint and stop the progression of the disease (trumble, 2008; and zayed, 2016). there are now two stem cell based veterinary medicines that have been granted eu-wide marketing authorisation: arti-cell forte®, (boehringer ingelheim), allogenic mscs combined with equine allogenic plasma (eap), which is authorised for the reduction of mild to moderate recurrent lameness associated with non-septic joint inflammation in horses, and horstem® (equicord), equine allogenic umbilical cord mscs, which is authorised for the reduction of lameness associated with mild to moderate degenerative joint disease (djd) in horses. see table 1 for definitions. this knowledge summary aims to determine whether msc therapies are more effective at managing and reducing lameness in horses, compared to ia corticosteroids, and can therefore effectively allow horses to return to, and remain, in work for longer.   cell type derivation autologous derived from the patient’s own tissues allogenic derived from the tissue of a donor of the same species table 1: definition of type of msc in relation to the donor.   the evidence the literature search returned a total of 604 publications, of which nine met the criteria for inclusion (summarised in the search outcome tables). there were no publications that directly compared corticosteroids against msc therapies which met the inclusion criteria. this meant that publications comparing ia corticosteroids and msc therapies to a placebo were used to compare these interventions. the publications comprised of four papers comparing ia corticosteroids to placebo (foland et al., 1994; frisbie et al., 1997; frisbie et al., 1998; and kawcak et al., 1998) , and five papers comparing msc therapies to a placebo  (frisbie, 2009; barrachina et al., 2018; marinas-pardo et al., 2018; broeckx et al., 2019a; and broeckx et al., 2019b). of the nine included publications, seven were experimental trials, where oa was induced using surgical or chemical techniques. one publication was a non-randomised controlled trial (foland et al., 1994), whereas the remaining six were randomised controlled trials. the final two publications were large double-blinded randomised controlled trials (marinas-pardo et al., 2018; and broeckx et al., 2019b). the quality of the evidence comparing corticosteroids to a placebo is weak to moderate in strength, based on the study types and the publication’s methodology (randomised, controlled, experimental trials).  furthermore, all of these studies were published over 20 years ago, and despite still being relevant today, these results are less valid than more recent randomised controlled double-blinded trials, comparing the treatment effects of msc therapies to a placebo (foland et al., 1994; frisbie et al., 1997; frisbie et al., 1998; and kawcak et al., 1998). the evidence identified for msc therapy provided moderate evidence with good reliability, because the evidence was made up of recent publications, including two randomised controlled double-blinded trials, in addition to the randomised controlled experimental trials. however, in relation to the hierarchy of evidence, used to identify the efficacy of treatments, randomised controlled double-blinded trials are weaker in evidence than systematic reviews and meta-analyses, which are used to critically appraise evidence found in randomised controlled trials (cockcroft, 2019).   summary of the evidence foland et al. (1994) population: horses between 2–5 years, free of lameness and carpal effusion, had oa induced by osteochondral fragmentation in distal radio-carpal joints in both limbs. sample size: 12 horses intervention details: on day 14 and 35, one middle carpal joint on each horse received 2.5 ml of 12 mg/ml ia betamethasone, with the contralateral limb receiving 2.5 ml ia saline. horses were split into groups, six horses were stabled for the entire study period, and six were exercised on a treadmill for 5 days a week from day 14 to day 56. study design: randomised, controlled, experimental study outcome studied: subjective assessment: lameness was studied on day 17, and 6 and 8 weeks post intervention. main findings (relevant to pico question): no significant difference in the degree of lameness between treated and non-treated limbs of either stabled or exercised horses. lameness was present in 5/6 horses in treated limb of exercised horses, 4/6 were lame in the control limb, 1/6 lame in the treated limb at day 56. 5/5 were still lame in the rested group at day 56. limitations: no power calculation shown so small or significant differences may not be able to be identified between groups. lameness was only followed up until day 56, meaning the longer-term effects of betamethasone could not be identified. lameness is not examined at intervals throughout the study to identify changes in lameness over 56 days, and no objective measures of lameness were used. the non-fragmented joint was the control, which may affect results as the systemic effects of ia of betamethasone are unknown and a difference in lameness between limbs is difficult to identify. does not state if there was any blinding of examiners. results obtained using an induced oa model may not be directly extrapolated to naturally occurring oa in equids. the group size is small, and therefore may not be representative to the rest of the population. no randomisation of the study groups was described. there is no outcome provided for the sixth horse in exercised group. frisbie et al. (1997) population: horses between 2–7 years, free of lameness and carpal effusion, had oa induced by osteochondral fragmentation in one intercarpal joint on one limb. each horse underwent treadmill exercise for 5 days a week, from day 15 to day 72. sample size: 18 horses intervention details: triamcinolone acetonide (ta) treatment group: six horses received 12 mg (2 ml) ia ta into the fragmented intercarpal joint on days 13 and 27 post osteochondral fragmentation and ia polyionic fluid into the non-fragmented joint. ta control group: six horses received 12 mg (2 ml) ia ta into the non-fragmented carpal joint on days 13 and 27 post osteochondral fragmentation and ia polyionic fluid into the fragmented joint. control group: six horses received 2 ml ia polyionic fluid into both carpi on days 13 and 27 post osteochondral fragmentation. study design: randomised, controlled, experimental trial outcome studied: subjective assessment: lameness was scored in all the horses on day 72, using standardised american association of equine practitioners (aaep) scoring system. main findings (relevant to pico question): mean lameness score in the fragmented joint, in horses treated with ta in the fragmented joint was significantly lower than the control group. mean lameness score in the ta treatment group was 0.7/5 ±3. mean lameness score in the ta control group was 1/5 ±3. mean lameness score in control group was 1.6/5 ± 0.3. limitations: no power calculations shown, so small or significant differences between groups may not be identified. not stated if lameness examinations were blinded to the clinicians undertaking the scoring, so interpretive bias could have affected the results. selection bias likely as horses selected for the study may not be representative to horses with oa in the general population. results obtained using an induced oa model may not be directly extrapolated to naturally occurring oa in equids. randomisation technique was not identified in the methods. lameness was only followed up until day 72, meaning the longer-term effects of ta could not be identified, and no objective measures of lameness were used. the group size is small, and therefore may not be representative to the rest of the population. frisbie et al. (1998) population: horses between 2–7 years, free of lameness and carpal effusion, had oa induced by osteochondral fragmentation in one middle carpal joint on one limb. each horse underwent treadmill exercise for 5 days a week, from day 15–day 72. sample size: 18 horses intervention details: on day 14: mpa treatment group – six horses were treated with 100 mg ia mpa into the fragmented joint, and polyionic fluid into the contralateral carpal joint. mpa control group – six horses received 100 mg ia mpa into the non-fragmented joint and polyionic fluid into the contralateral fragmented joint. control group – six horses received ia polyionic fluid into both the fragmented joint and contralateral joint. study design: randomised, blinded, controlled, experimental trial outcome studied: subjective assessment: lameness was scored in all the horses on day 72, using standardised aaep scoring system. main findings (relevant to pico question): mean lameness score in the horses treated with mpa in the fragmented joint was 1/5, this was significantly lower than the control group. mean lameness score in control group was 2/5. clinical improvement was not associated with mpa treatment. limitations: no power calculations shown so small or significant differences may not be able to be identified between groups. selection bias likely as horses selected for the study may not be representative to horses with oa in general population. results obtained using an induced oa model may not be directly extrapolated to naturally occurring oa in equids. randomisation technique was not identified in the methods. lameness was only followed up until day 72, meaning the longer-term effects of mpa could not be identified, and no objective measures of lameness were used. the group size is small, and therefore may not be representative to the rest of the population. kawcak et al. (1998) population: horses aged 2–5 years had oa induced via osteochondral fragmentation in one distal radio-carpal bone and were then exercised on a treadmill 5 days a week from days 15 to 72. sample size: 12 horses intervention details: ta treatment group – six horses were treated with 12 mg ia ta in the oa affected joint, with the contralateral joint receiving saline. ta control group – six horses received ia ta in the non-fragmented joint, with their contralateral fragmented joint receiving saline. study design: randomised, blinded, controlled, experimental trial outcome studied: subjective assessment: lameness was scored in all the horses on day 72, using standardised aaep scoring system. main findings (relevant to pico question): horses treated with ta treatment group in the fragmented joint were significantly less lame than horses receiving saline in the fragmented joint at day 72. control group mean lameness score at day 72 was 1.5/5 ±5. ta treatment group mean lameness score at day 72 was 0.6/5 ± 0.5. limitations: lameness was not examined at intervals throughout the study to identify a change in lameness over time, only at day 72. no power calculations were shown, so small or significant differences between groups may not be identified. selection bias likely as horses selected for the study may not be representative to horses with oa in the general population. results obtained using an induced oa model may not be directly extrapolated to naturally occurring oa in equids. randomisation technique was not identified in the methods. lameness was only followed up until day 72, meaning the longer-term effects of ta could not be identified, and no objective measures of lameness were used. the group size is small, and therefore may not be representative to the rest of the population. frisbie et al. (2009) population: 2–5 year old horses who were otherwise healthy, each had oa surgically induced in one randomly chosen middle carpal joint, with the contralateral joint being sham operated on. sample size: 24 horses intervention details: control group – eight horses received ia 2 ml sterile saline in their oa affected joint. eight horses received 2 ml (10 x 106 cells) unmodified bone-marrow derived msc in their oa affected joint. eight horses received 2 ml adipose-derived stromal vascular fraction in their oa affected joint. horses had treatment on day 14, then started exercise on day 15, for 5 days a week to imitate race training, until the end of the study. study design: randomised, controlled, double-blinded experimental trial outcome studied: subjective assessment: lameness scoring was undertaken every 2 weeks until day 70, using the aaep scoring system. main findings (relevant to pico question): after surgery, there was a significant lameness increase in the oa affected limb compared to the sham operated joint in all horses. there was no significant improvement in lameness score in the treatment groups compared to the control group. limitations: selection bias likely as horses selected for the study may not be representative to horses with oa in general population. results obtained using an induced oa model may not be directly extrapolated to naturally occurring oa in equids. the study was partially funded by a pharmaceutical company producing stem cell-based products. small sample size and lack of power calculation identified in the methods so small or significant differences may not be able to be identified between groups. the study period was only over 10 weeks, meaning only short-term effects of msc can be identified. blinding of examiners was not described, meaning interpretive bias may have affected the results. no objective measure of lameness was used (i.e. use of a lameness locator). the group size is small, and therefore may not be representative to the rest of the population. barrachina et al. (2018) population: 18 healthy shetland ponies aged 3–7years, free of lameness and joint effusion, each had arthritis induced in a randomly assigned radio-carpal joint by ia injection of 25 mg of amphotericin b on day 0 (phase 1). at 4 months, (phase 2) the contralateral limb also had oa induced by the same method. horses were placed in paddocks 15 day post oa induction. sample size: 18 horses (36 radio-carpal joints examined) intervention details: control group – four horses received ia lactated ringers solution in the oa affected radio-carpal joint on weeks 2 and 5 post lesion induction. primed msc treatment group – seven horses received allogenic pooled bone marrow mscs (bm-mscs) (10 x 106 cells) primed by tumour necrosis factor alpha and interferon gamma in 2 ml of solution at weeks 2 and 5, ia into their radio-carpal joint. naïve msc treatment group – seven horses received unstimulated (10 x 106 cells) bm-msc cells in 2 ml solution at weeks 2 and 5, ia into their radio-carpal joint. at 4 months post lesion induction, oa lesions were induced in the contralateral radio-carpal joint of each horse (phase 2) and the same treatment corresponded respective to the initial treatment in the other joint. study design: randomised, blinded, controlled experimental trial outcome studied: subjective assessment: lameness exams, using aaep scoring system, were undertaken weekly until week 6, at 2 months (phases 1 and 2), 4 months and 6 months (for phase 1) post oa induction of each joint, respectively. main findings (relevant to pico question): no statistically significant difference found between groups at day 0. post induction, at week 1, the groups had statistically significant differences in average lameness, of 4.5/5 in the control group, 4.5/5 in naïve msc treatment group and 4/5 in the primed msc treatment group. 2 weeks after treatment, primed msc and naïve msc treatment groups had a significantly lower lameness score than the control group. after 2 months, average lameness score was 1.25/5 in the control group, 1.5/5 in the naïve msc treatment group and 1/5 in the primed msc group. the lameness score in the primed msc treatment group is significantly lower than the control and naïve msc treatment groups. after 6 months, average lameness score was 0.5/5 in the control group, 1/5 in the naïve msc treatment group and 0.5/5 in the primed msc group. the naïve msc treatment group has a significantly higher lameness score than the control and primed msc treatment groups. limitations: selection bias likely as horses selected for the study may not be representative to horses with oa in general population. no power calculation shown so small or significant differences may not be able to be identified between groups. results obtained using an induced oa model may not be directly extrapolated to naturally occurring oa in equids. no objective measure of lameness used (i.e. use of a lameness locator). the group size is small, and therefore may not be representative to the rest of the population. marinas-pardo et al. (2018) population: horses over the age of 2 years, from seven equine clinics, had oa in one or more joints in the fore or hind limbs, at a lameness grade between 2–5 on aaep scale. the joints with oa had not received any local or systemic anti-inflammatory drugs 2 weeks prior to the study. sample size: 72 horses intervention details: msc treatment group – 39 horses received treatment with 2 ml of (10 x 106 cells) allogenic mscs, ia in two different joints on day 0, the same joints were treated on day 15 and 20. horses received another dose of treatment if at day 45 ± 2 if they were non-responsive to treatment. placebo group – 33 horses received 2 ml ia phosphate buffered saline or dulbecco’s modified eagle’s medium (dmem + 10% dimethyl sulfoxide (dmso) on day 15 and 20. motion restriction after treatment was left to the discretion of the veterinary surgeon. study design: randomised, controlled, double blinded multi-centre clinical trial outcome studied: subjective assessment: lameness examination using standardised aaep scoring system at day 0, 15, 45, 60 and 90. comparison of responders versus non-responders. a responsive horse was deemed as an improvement of one or more lameness grades. main findings (relevant to pico question): horses treated with mscs had a significantly greater reduction in lameness from day 60 to 90, to those treated with placebo. there was a significantly increased number of responders to treatment and lower mean lameness grades on days 15, 60 and 90 compare to the placebo group. 4/37 (30.77%) of treatment group required a second dose to improve lameness grade. on day 90, 25.97/37 (70.2%) of horses that were treated with mscs had a reduction in lameness score by one or more grades. on day 90 average lameness score for treated horses was significantly lower at 1.44/5 ±44, compared to the placebo treated group 1.97/5 ± 0.36 significantly increased number of adverse events, such as transient swelling or heat of the joint, were recorded in the treatment group compared to the placebo group. limitations: no power calculation shown, so small or significant differences may not be able to be identified between groups. horses still could have been included in the study if they had been treated with ia corticosteroids 2 weeks before the study started, which may have influenced the results. the variable of motion restriction after treatment is difficult to account for due to the decision being left to the veterinary surgeon’s discretion. two horses were lost to follow-up before the end of the study. no objective measure of lameness was used (i.e. use of a lameness locator). broeckx et al. (2019)a population: healthy warmblood horses, with a median age of 8.5 years that were free of lameness and radiographic abnormalities and had oa surgically induced in the right metacarpophalangeal (mcp) joint on day 0, by osteochondral fragmentation. 7 days post-surgery, horses were exercised daily on a treadmill for the remainder of the study. sample size: 12 horses intervention details: control group – six horses received 2 ml ia sterile saline into their right mcp joint at week 5. msc treatment group – six horses received 2 ml ia equine allogenic chondrogenically induced msc (2 x 106 cells in 1 ml dmem with 10% dmso) combined with eap (1 ml plasma with 98 x 106 platelets/ml) at week 5. study design: randomised, double blinded, controlled experimental trial outcome studied: subjective assessment: weekly lameness examination occurred on a treadmill, whilst lunging on a soft surface and after distal forelimb flexion, using aaep scoring system until week 11. objective assessment: using an inertial sensor-based lameness locator software lameness was assessed weekly, where a positive vector sum represented right forelimb lameness. on weeks 0, 5 and 11, pressure plate analysis was performed. main findings (relevant to pico question): equine allogenic chondrogenically induced msc combined with eap significantly reduced lameness compared to control. from week 7, the lameness scores were significantly lower in the treatment group compared to the control group. from weeks 9 to 11, the average vector sums on a treadmill were significantly lower in the treatment group compared to the control group, but were not statistically significant on a straight line or on the lunge. no significant difference was found in the symmetry indices between groups using pressure plate analysis. limitations: the study period was short (11 weeks), meaning only short-term effects of msc combined with eap can be identified. the authors are employed by global stem cell technology and were inventors of the patents for arti-cell forte®. results obtained using an induced oa model may not be directly extrapolated to naturally occurring oa in equids. this was the only paper to use an objective measure of lameness, with a lameness locator and pressure plate, alongside aaep lameness scoring. however, the pressure plate analysis did not show a significant difference in lameness. there is reporting bias, as no vector sum data is reported or shown for the results on the right rein lunge, which is more likely to exacerbate right forelimb lameness, if present in this limb. it is important for the lameness locator to be used, and vector sum reported, on both reins, to be able to calculate the difference between the two. the group size is small, and therefore may not be representative to the rest of the population. broeckx et al. (2019)b population: warmblood horses between 3 to 23 years with recurrent grade 2 or 3 lameness associated with mcp joint oa, that had lasted for over 2 months. the horses had no pre-treatment and lameness only in one limb. horses were included using ia anaesthesia and radiographs sample size: 75 horses intervention details: control group – 25 horses received 2 ml sterile saline ia into their oa affected mcp joint on day 1. msc treatment group – 50 horses received 2 ml allogenic chondrogenically induced mscs and eap (2 x 106 cells/ml), suspended in dmem with 10% dmso ia into their oa affected mcp joint on day 1. after the first 3 days of box rest horses underwent light walking out for 1 week, followed by walking and trotting up until week 3. horses were gradually returned to work, depending on clinical evaluation, between weeks 4 to 6 under the owner’s care. study design: randomised, controlled, double-blinded clinical trial outcome studied: subjective assessment: lameness scoring was undertaken at day 0, weeks 3 and 6 using the aaep scoring system. at weeks 12 and 18 horses would be assessed, and if they could not be presented for assessment their owner would fill in a questionnaire. at 6, 12 and 18 weeks, and 1 year owners were contacted about their horse’s improvement and work status. main findings (relevant to pico question): at week 3, the treatment group had a significantly improved lameness score compared to the control group, with a score of 0/5 or 1/5 in 35/50 (70%) of the horses in the treatment group. at week 6, 39/50 (78%) of the horses in the treatment group had a lameness score of 0 or 1 which was significantly different to 6/25 (24%) with score 0 or 1 in the control group. at week 12, 46/50 (92%) of horses in the treatment group had a lameness score of 0 or 1, compared to 9/25(36%) in the control group. at week 18, 42/50 (84%) of horses in the treatment group had a lameness score of 0 or 1, compared to 4.25/25 (17%) in the control group. at week 6, 15/50 (30%) of the treatment group had returned to previous of level work and this rose to 21/50 (42%) by week 18, compared to 0% of the control group at both periods. at week 6, owners rated an 80% or above improvement in 36/50 (72%) of the treated horses, which was significantly more than the control horses. after 1 year, 23.5/50 (47%) of the treatment group had returned to their previous level of work and 18.5/50 (37%) were working at training level, compared to 2/25 (8%) at training level and 0% who had returned to their previous level of work in the control group. limitations: the rehabilitation occurred in the owner’s care, therefore there would be many different variables involved. at weeks 12 and 18 horses would be assessed, but if they could not be presented for assessment their owner would fill in a questionnaire. at 1 year the outcome was measured using a questionnaire to the owner about the work status of their horse, which can be biased, subjective and cannot be interpreted with any degree of accuracy. no objective measure of lameness was used (i.e. use of a lameness locator). appraisal, application and reflection the aim of this knowledge summary is to critically appraise published evidence to identify the efficacy of msc therapies, compared with ia corticosteroids, for managing lameness associated with oa in equids. it is beyond the scope of this review to evaluate and appraise systematic reviews on the treatment of oa in equids, or any non-lameness outcomes in the studies, such as radiographic and synovial fluid assessments. of the nine publications that met the inclusion criteria, seven were experimental trials and two were randomised controlled trials. from seven experimental trials, six induced oa using an osteochondral fragment model and one using ia amphotericin (barrachina et al., 2018). experimentally induced oa does not resemble the clinical pathology of naturally occurring oa or individual variation in the disease process, such as the stage of disease, innate healing response and disease progression. therefore, the experimental research cannot be extrapolated to natural oa in the population, which is a limitation identified in seven of the nine studies. furthermore, the experimental design with oa induced surgically is ethically questionable, with none of these studies being conducted in the united kingdom. within the nine publications that are reviewed within this paper, there is a limited number of researchers that have produced multiple papers each within this field of study. there are likely to be more reliable conclusions made about the treatment efficacy of corticosteroid and mscs, if a larger base of researchers were able to emulate similar results using the same treatment in their own randomised controlled trials, to eliminate any bias (i.e. interpretive). one publication, used chondrogenically-induced mscs combined with eap, to treat naturally occurring oa in 75 horses (broeckx et al., 2019b) and assessed the horses at 18 weeks, with a further follow-up at 1 year. this was the only long-term study. however, the method of follow-up at 1 year could not be reliably or accurately interpreted because it comprised of a phone call with the owner on the current state of work the horse was in. these results are likely to be biased and unreliable, compared to a blinded lameness examination of all study participants at 1 year. from the remaining publications, one paper followed the horses for 8 weeks (foland et al., 1994), four for 10 weeks (frisbie et al., 1997; frisbie et al., 1998; kawcak et al., 1998; and frisbie, 2009), one for 11 weeks (broeckx et al., 2019a), one for 12 weeks (marinas-pardo et al., 2018), and one for 6 months (barrachina et al., 2018). therefore, no study reliably identifies any medium or long-term effects of msc therapy or corticosteroids, which is an important consideration for both clinicians and owners in clinical practice. oa most commonly affects mcp, metatarsophalangeal, distal interphalangeal (van weeren, 2016), distal intertarsal and tarsometatarsal joints (mcilwraith, 1987). therefore another important consideration in practice, is for a treatment to be efficacious in both the high-motion and low-motion joints that most commonly develop oa in the equid. the versatility of msc therapies have been identified in two recent studies, where horses with naturally occurring oa in mcp, carpal, distal interphalangeal and tarsal joints were treated, and showed a significant reduction in lameness compared to a placebo (marinas-pardo et al., 2018; and broeckx et al., 2019b). furthermore msc therapy, with or without eap has shown efficacy in high-motion joints, such as mcp, carpal, distal interphalangeal, tarsocrural joints, as well as low-motion joints, such as tarsometatarsal and distal intertarsal joints (barrachina et al., 2018; marinas-pardo et al., 2018; and broeckx et al., 2019b). corticosteroids have been shown some efficacy in reducing lameness in both high (frisbie et al., 1997; and kawcak et al., 1998) and low-motion joints (labens et al., 2007) most commonly affected by oa. however, the evidence for corticosteroid efficacy in low-motion joints is weak, because there are a lack of publications comparing ia corticosteroid treatment in low-motion joints, to a placebo control. there is a distinct lack of evidence for the efficacy of either corticosteroids or mscs in other high-motion joints, such as the stifle joint, within the studies reviewed, compared with mcp and carpal joints. therefore, it cannot be definitively concluded that either corticosteroids or mscs are efficacious in all types of highand low-motion joint. oa has commonly been treated with ia corticosteroids which can reduce joint inflammation and pain. however, corticosteroids do not contribute to cell repair, or the slowing or reversal of disease progression (de souza, 2016). four publications studying the efficacy of ia corticosteroids (foland et al., 1994; frisbie et al., 1997; frisbie et al., 1998; and kawcak et al., 1998) were all published over 20 years ago and therefore provided moderate to weak evidence for the efficacy of corticosteroids based on the study type and methods used, but have provided repeated anecdotal clinical success in the field (mcilwraith, 2011). these are the most recent randomised, controlled trials and have been the basis of many systematic reviews evaluating the use of corticosteroids. these papers also use very similar experimental methods to those which are used in more recently published papers, such as surgically inducing oa by osteochondral fragmentation or using aaep lameness scoring (keegan, 2010), therefore these publications are still relevant today. however, due to the experimental design, it is difficult to know the severity of oa induced in study populations between different studies, which may affect the treatment success. the main limitations of these publications were that each had small sample sizes (n= ≤18) and showed no power calculations, meaning these study populations are not likely to be representative of the general population. furthermore, the experimental methodology of these studies means the results cannot be fully extrapolated to naturally occurring oa. these publications were published before the development of the lameness locator, and therefore were not able to use an objective method of lameness examination alongside aaep lameness scoring. lameness locators are objective measures of lameness and are more reliable than subjective examinations (donnell et al., 2015). two of the publications (randomised, controlled, experimental trials) identified that treatment with ia ta led to significantly lower lameness scores at 10 weeks, than treatment with the control (frisbie et al., 1997; and kawcak et al., 1998). in these two papers, the mean lameness score in the treatment group were within the aaep lameness score 0, compared to the controls, who had a mean score of within lameness score 1. this identifies a clinical, as well as statistical significance between the treatment and control groups, because score 0 means there is no identifiable lameness, compared to score 1, which means lameness is present, but inconsistently, and only under certain conditions (table 2).   lameness score grading 0 lameness not perceptible under any circumstances. 1 lameness is difficult to observe and is not consistently apparent, regardless of circumstances (e.g. under saddle, on a circle, on inclines, hard surface). 2 lameness is difficult to observe at a walk or when trotting in a straight line but is consistently apparent under certain circumstances (e.g. under saddle, on a circle, hard surface). 3 lameness is consistently observable at a trot under all circumstances. 4 lameness is obvious at a walk. 5 lameness produces minimal weight bearing in motion or at a rest, or a complete inability to move. table 2: a description of the aaep lameness scoring system.   one further study identified that treatment with ia mpa led to significantly lower lameness scores at 10 weeks compared to a placebo (frisbie et al., 1998). horses treated with betamethasone did not have significantly lower lameness than the control group after 8 weeks (foland et al., 1994). this suggests that this corticosteroid is not as effective as ta and mpa at managing lameness. clinical significance if difficult to interpret and identify, but there are clinical differences, especially with regards to athletic function, between score 0 and 1, as well as 1 and scores >1. clinical significance is important to differentiate from the statistical significance in lameness scores, to recognise the actual impact that the treatment has on the horse and its ability to return to its previous or required level of work. only one paper used return to function as an outcome measure (broeckx et al., 2019b), therefore this outcome cannot be compared between studies and only clinical significances can be interpreted. two randomised, controlled, double-blinded trials were included from the literature search. both studies provide high quality, reliable evidence in terms of the study design and methods. however, in terms of the pyramid of evidence, meta-analyses and systematic reviews provide much stronger evidence than randomised controlled trials, when looking at the efficacy of treatments, which needs to be considered when identifying the quality and strength of evidence provided for mscs. each compared msc therapies to a control, identifying the efficacy of msc therapies in the short-term. in one study, 46/50 (92%) of horses with mcp joint oa, treated with mscs combined with eap, had a lameness score of 0 or 1 at 12 weeks, which was significantly higher than 9/25 (36%) in the control group. furthermore, after 1 year 23.5/50 (47%) of the treatment group had returned to their previous level of work compared to 0% of the control group, based on a phone call follow-up with owners (broeckx et al., 2019b). this study identifies a likely significant clinical improvement in the treatment group at 1 year, as 23.5/50 (47%) had returned to their previous level of work, compared to 0% in the control group. another study, consisting of 76 horses with one or more joint affected by oa, found that at 90 days, horses treated with allogenic mscs, had a significantly lower average lameness score of 1.44/5, compared to the control group at 1.97/5 at a 95% confidence interval (marinas-pardo et al., 2018). despite a statistical significance being identified between the treatment and control groups, both groups have a mean lameness score within aaep score 1. therefore, the two groups are very similar within a clinical setting. these studies suggest that there is moderate evidence for the effectiveness of msc therapy in the management of lameness in horses with naturally occurring oa, in the short-term. two experimental publications provided further evidence for the efficacy of msc therapies at managing lameness in the short-term. one publication assessed 12 horses with surgically induced oa in their right mcp joint. mscs were used to treat the affected joint, and a lameness locator and force plate were used to objectively measure lameness, in addition to aaep lameness scoring (broeckx et al., 2019a). from week 7 of the study, lameness scores were significantly lower in the treatment group compared to the control group. a positive vector sum on the lameness locator indicates right forelimb lameness. from weeks 9 to 11 of the study, the average vector sums on a treadmill were significantly lower in the treatment group compared to the control group, but no statistical difference was found on a straight line or on the lunge. subjective lameness assessments are historically unreliable because there are likely to be differences in the way the examiners score lameness, despite the use of the more standardised aaep scoring system (table 2) across most of the studies. lameness locators, used in one publication (broeckx et al., 2019a) are an objective measure of lameness. they are sensitive and the most reliable method of lameness assessment (donnell et al., 2015). the lack of objective lameness measurement (such as use of a lameness locator) was another major limitation of the studies reviewed. there was no objective comparison that could be drawn from the results in papers, even in the more recent studies, where lameness locators would have been available. all publications, except one (foland et al., 1994) used standardised methods of scoring lameness: the aaep scoring system (table 2). in a recent experimental study assessing the effectiveness of primed mscs, 18 shetland ponies had oa artificially induced with ia amphotericin. the study population were treated with either primed mscs, naïve mscs or a control. there was a significantly lower lameness score 2 weeks post-treatment in groups treated with primed or naïve mscs compared to the control group. at 2 months post-treatment, the primed msc treatment group had an average lameness score significantly lower to the control group, but the naïve msc treatment group had a significantly higher lameness score compared to the other two groups. at 6 months, there was no difference in lameness scores between the primed msc treatment group and control group. furthermore, the naïve msc treatment group had a significantly higher lameness score in comparison to the other two groups (barrachina et al., 2018). this suggests that mscs are more effective when primed in the short-term, compared to a placebo. however, an objective measure, such as a lameness locator would have been useful in this study to identify statistically significant lameness scores between the treatment groups. furthermore, there is not a clinical significance between all groups means after 2 months, despite a statistical significance shown in the study. this is because the mean lameness scores of each group is within lameness score 1. two publications, which did not meet inclusion criteria because they did not compare the intervention to corticosteroids or a control, compared the efficacy of different mscs and protein rich plasma (prp). in one study, 165 horses with at least a 2 month history of mild to moderate lameness, associated with oa of the stifle, mcp, distal interphalangeal or proximal interphalangeal joints, were treated with either naïve mscs and prp, or chondrogenically induced mscs and prp. the horses were evaluated at 6 and 18 weeks post-treatment. horses were scored on their return to work. at 18 weeks, 19.5/25 (78%) of horses treated with naïve mscs and prp had returned to work at or below their previous level, compared to 56.76/66 (86%) of horses treated with chondrogenically induced mscs and prp. however, there was not a statistical difference between treatment groups and the study did not identify any randomisation or blinding of either examiners or owners (broeckx et al., 2014a). furthermore, in one randomised, non-blinded, comparative study, 20 horses with mcp joint oa were treated with either naïve mscs, prp, naïve mscs combined with prp or chondrogenically induced msc combined with prp. the horses were scored based on lameness score and joint effusion, where score 5 is clinical soundness and 0 is worsening of lameness. at 12 months, horses treated with prp combined with chondrogenically induced mscs had the highest average score of 4.8, whereas horses treated with mscs or prp and naïve mscs had a lower score of 4.2. these scores were all statistically higher than prp alone, which scored 2.6 (broeckx et al., 2014b). overall, mscs combined with plasma have a higher efficacy at managing lameness compared to prp alone. however, there is no statistically significant difference between chondrogenically induced mscs and naïve mscs when combined with prp, or treatment with mscs alone. furthermore, these two studies were not controlled. this means that the efficacy of the different treatments, at managing lameness, can be compared to each other, but the direct efficacy on reducing lameness compared to a placebo cannot be determined. the evidence in these two studies is contrary to recent evidence in a randomised, controlled experimental trial (barrachina et al., 2018), as they identify that naïve mscs may have longer-term effects in the management of lameness in horses with naturally occurring oa and have no statistically significant effects on lameness compared to primed mscs (broeckx et al., 2014a; broeckx et al., 2014b). the contradiction in evidence may be due to the method of artificial oa induction. ia amphotericin was used (barrachina et al., 2018), compared to naturally occurring oa (broeckx et al., 2014a; broeckx et al., 2014b) or osteochondral fragmentation (broeckx et al., 2019a), which was used in all other experimental trials that met the inclusion criteria. in conclusion, there was moderate, reliable evidence to suggest that msc therapies, including mscs combined with eap, are effective at reducing and managing lameness in equids associated with oa, in the short term. however, there are no randomised, controlled, double-blinded studies directly comparing msc therapy to ia corticosteroids, which would be required to directly compare the efficacy of the interventions on lameness. furthermore, no publications appropriately follow-up horses in the long-term, and this would be required to make conclusions about the longer-term effects of msc therapies and whether they are practical in a clinical setting. therefore, despite the good quality evidence for the effectiveness of msc therapies it cannot be definitively concluded that mscs, with or without eap, are more effective at managing lameness in horses with oa, compared to ia corticosteroids in clinical practice.   methodology section search strategy databases searched and dates covered: scopus (1823–november 2019) cab abstracts (1973–november 2019) pubmed ncbi (1910–november 2019) further relevant records were identified from the bibliographies and reference list of retrieved publications search strategy: all searches were carried out on scopus, cab abstracts and pubmed ncbi: ((equine* or horse* or equid*) and (oa or osteoarthritis or djd or “degenerative joint disease”) and (glucocorticoid* or steroid* or corticosteroid* or triamcinolone or “triamcinolone acetonide” or methylprednisolone or “methylprednisolone acetate” or betamethasone) and (“biological therap*” or acs or “autologous conditioned serum” or msc or “mesenchymal stem cell*” or prp or “protein rich plasma” or irap or “interleukin-1 receptor antagonist protein” or “allogenic mesenchymal stem cell*”)) ((equine* or horse* or equid*) and (oa or osteoarthritis or djd or “degenerative joint disease”) and (glucocorticoid* or steroid* or corticosteroid* or triamcinolone or “triamcinolone acetonide” or methylprednisolone or “methylprednisolone acetate” or betamethasone)) ((equine* or horse* or equid*) and (oa or osteoarthritis or djd or “degenerative joint disease”) and (“biological therap*” or acs or “autologous conditioned serum” or msc or “mesenchymal stem cell*” or prp or “protein rich plasma” or irap or “interleukin-1 receptor antagonist protein” or “allogenic mesenchymal stem cell*”)) dates searches performed: 10/11/2019, 13/11/2019, 14/11/2019 and 15/11/2019 exclusion / inclusion criteria study designs were limited to in vivo, primary studies only (e.g.  randomised controlled trials, non-randomised controlled trials) exclusion: non-english language, not a primary study, outcome measure not comparative (lameness), study group did not have equines with oa or lameness associated with oa, treatments not compared to the comparative intervention or a placebo, papers published before 1990, in vitro experimental studies. inclusion: any primary study of equids with lameness associated with oa, that are being treated with ia corticosteroids or msc therapy, where the outcome measure is based on a change in lameness grade and compared to each other or a placebo control. search outcome database number of results excluded – by initial title screen excluded – non-english language publication excluded – paper published before 1990 excluded – non comparative outcome measure excluded – study group did not compare intervention to placebo or comparative intervention total relevant papers scopus 247 225 4 2 2 9 5 cab abstracts 206 189 6 1 2 3 5 ncbi pubmed 153 144 0 1 2 2 4 other sources 7 1 0 0 1 1 4 total relevant papers when duplicates removed 9 conflict of interest the author declares no conflicts of interest. references barrachina, l., remacha, a. r., romero, a., vitoria, a., albareda, j., prades, m., roca, m., zaragoza, p., vazquez, f. j. and rodellar, c. 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(eds.). the veterinary journal, 217, pp. 26–32. doi: http://dx.doi.org/10.1016/j.tvjl.2016.05.014 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. aural haematomas in dogs managed by local corticosteroid instillation compared to drainage alone a knowledge summary by rachel church ma vetmb certavp pgcertvps mrcvs 1* 1milton keynes veterinary group, fyfield barrow, milton keynes, mk7 7an *corresponding author (rachelc861@hotmail.co.uk) vol 7, issue 1 (2022) published: 31 mar 2022 reviewed by: kate griffiths (bvsc certvd pgdip[meded] mrcvs) and maureen o'mara (phd mgis) next review date: 02 dec 2023 doi: 10.18849/ve.v7i1.438 pico question in dogs with aural haematomas does draining and injecting corticosteroids versus drainage alone reduce the risk of recurrence?   clinical bottom line category of research question treatment the number and type of study designs reviewed three papers were critically reviewed, a retrospective multi-centre cohort study, a randomised case control trial and an observational survey strength of evidence weak outcomes reported drainage alone at daily or weekly frequency consistently resulted in aural haematoma (ah) recurrence and lack of resolution. corticosteroid instillation alongside drainage reduced the risk of rapid recurrence for ahs, across both the cohort and the case control studies, provided drainage was frequent conclusion the strength of evidence for local steroid instillation was weak given the type of studies reviewed, alongside small sample sizes and variations in treatment protocol. however, consistently drainage alone appears an insufficient means of addressing ahs in dogs. in cases where frequent drainage was the chosen treatment option, the addition of local corticosteroid application appeared to improve the outcome compared to drainage alone. however, as systemic treatment was often employed alongside local corticosteroid instillation, success cannot necessarily be attributed solely to local treatment. larger, randomised control trials would be required to assess the effect of each individual intervention providing clearer evidence for the most effective medical protocol for treating aural haematomas in dogs   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario an 11 year old male neutered labrador retriever presents to your clinic with an aural haematoma of the right ear. the owner wishes to discuss the options for management without surgical intervention and has asked about the scientific evidence for local treatment of aural haematomas to select the best protocol for the lowest risk of recurrence. the evidence a search of the literature revealed three papers relevant to the pico. they consist of a retrospective multi-centre cohort study (mikawa et al., 2005), a randomised non-blinded case control study (kuwahara et al., 1986b) and an observational survey (hall et al., 2016). in the cohort study (mikawa et al., 2005) aural haematomas (ahs) were managed with frequent drainage alone or drainage and local instillation of corticosteroid (dexamethasone or prednisolone). in all cases which underwent drainage alone the haematoma recurred, requiring additional surgical or medical management to elicit resolution. with repeated drainage and local corticosteroid instillation, all cases resolved within 35 days. the randomised case control study (kuwahara et al., 1986b) compared local and systemic corticosteroid treatment of ahs with daily drainage alone. there was an absence of healing in all cases that received daily drainage only. daily treatment with local and systemic corticosteroids showed satisfactory healing in the majority of cases, and resolution within 5 days. the observational survey (hall et al., 2016) detailed the commonly employed treatments for ahs. drainage with local corticosteroid instillation was more commonly employed for ahs on first presentation than drainage alone, and with improved perceived outcome. the strength of evidence was weak for the pico question given the small sample sizes, in addition to variables in the treatment protocols, size and chronicity of the ahs, and the presence of underlying ear and skin disease. large scale randomised blinded case control studies would be required to provide stronger evidence for the benefit of local corticosteroid instillation over drainage alone. summary of the evidence mikawa et al. (2005) population: 59 aural haematomas (ahs) in 49 dogs (25 males, 24 females) across five facilities in miyazaki prefecture in japan between january 1998 and march 2005. mixed breed, with higher incidence of medium to large breed dogs. 22/49 dogs (44.9%) were golden retrievers. 45/59 (76.2%) affected ears had concurrent otitis externa. cases of aural haematoma consolidation or ear deformity were excluded. sample size: 23 dogs received interventions specific to the pico, from a total of 59 ahs in 49 dogs in the full study. the remaining 26 dogs will not be commented on further in this knowledge summary. intervention details: ahs were treated conservatively in 23 cases, and surgically in 43 cases (nine of which were initially treated conservatively). two cases were untreated. of those treated conservatively, 14 cases were treated with needle aspiration alone, and nine cases received 0.4% dexamethasone (4–8 mg) or 1% prednisolone (0.5 mg) infusion after needle aspiration. in both groups the treatment was repeated if the haematoma recurred. the treatment endpoint for the group receiving local corticosteroid treatment was ah resolution. the treatment frequency and endpoint in the group undergoing needle aspiration alone were not detailed. the frequency of needle aspiration alongside local corticosteroid instillation was weekly in 5/9 (55.5%) cases. concurrent treatment for otitis externa in affected cases (based on cerumen examination) was performed alongside ah treatment, the details of which were not supplied. study design: a retrospective multi-centre cohort study. outcome studied: the treatment and progression of each ah was recorded, including whether the ah resolved, if surgical management was subsequently required, if aural deformity occurred, or if the progress was unknown. the duration of treatment was recorded in the group undergoing corticosteroid instillation alongside drainage. in 5/9 cases that received local corticosteroid instillation alongside drainage, recurrence and volume of fluid retention in ah was recorded over a 4 week period. the recurrence of ah was studied with a follow-up period of 2 years in 26 cases, 1–2 years in 13 cases, 6 months to 1 year in 17 cases, and no follow-up in three cases. main findings (relevant to pico question): in the 14 cases that underwent drainage alone, none achieved resolution by initial or repeat drainage, with nine then undergoing surgical management. in two cases a total of eight drainage attempts were made. the remaining five cases that were conservatively managed included three that led to aural deformity and two cases that were lost to follow-up. the treatment duration was not stated in the drainage only group. initial reaccumulation was seen in all nine cases which underwent corticosteroid instillation alongside drainage, but subsequently the ahs resolved in all cases within 35 days. the mean duration of treatment was 18.3 days in the corticosteroid injection group (range 4–35 days). in the five cases receiving corticosteroid instillation in which fluid recurrence was measured, four cases showed a decrease in the level of fluid by week 2 and resolution by week 4, and one case showed an increase until week 3 then a resolution by week 4. this suggests the corticosteroid suppresses the production of haematoma fluid. with corticosteroid instillation, 2/9 (22.2%) cases recurred more than 2 weeks after treatment, 1 and 2 months after treatment had been completed. limitations: the quality of evidence may be reduced by the retrospective and multi-centre nature of the study, with accuracy reliant on the rigor of record keeping. the sample size was small therefore detailed statistical analysis is not possible. there was variability in the chronicity and size of the ahs, and the extent of accompanying ear or skin disease, however, these factors were not detailed across the intervention groups. there was a variable follow-up period. the type and dose of steroids used varied. it was not clear which animals received which dose or type of steroid, and whether this was altered during the management of each case. the drainage frequency in the corticosteroid instillation was weekly in five cases, but unknown in the remainder and in the drainage only group. kuwahara et al. (1986b) population: 40 dogs and 20 cats seen in a veterinary hospital in japan, date unknown. sample size: the participants were divided randomly into five groups, of which three relate to pico, consisting of 21 dogs. the remaining 19 dogs allocated to other groups and the 20 cats will not be commented on further in this knowledge summary. intervention details: group 3 (eight dogs) underwent ah drainage once (complete aspiration performed aseptically with a 16-gauge needle and syringe to remove the dead space of the cavity created by the haematoma). the dogs then received intravenous (iv) dexamethasone 0.5 mg/kg and intramuscular (im) gentamicin 4 mg/kg. group 4 (nine dogs) underwent ah treatment consisting of a single flush with sterile saline to remove fibrin, clots and debris. this was followed by daily local instillation of 0.2–0.4 mg dexamethasone (0.2%) and 0.25 mg gentamicin diluted 5–10 times in sterile saline (0.4–1.8 ml) depending upon the extent of the cavity, decreasing to approximately 0.5 ml by the second or third day. systemic treatment was also given as per group 3. group 5 (four dogs) underwent daily ah drainage for 6 days, being flushed with sterile saline and repeat aspiration until the fluid was clear. the saline volume used was 10–50 ml depending on the size of the haematoma. there was no recorded systemic treatment for this group. the treatment end point was defined as complete healing of the lesion. the criteria for a tentative diagnosis of complete healing was an absence of fluid accumulation and clinical signs (e.g. oedema, inflammation, head shaking or ear scratching). definitive diagnosis was made using the same criteria at re-examination 2 months after the final treatment. all animals were investigated and treated for underlying ear canal disease with a combination of systemic and topical treatments, the details of which are not provided. study design: a randomised non-blinded case control study. outcome studied: chronicity of ah prior to treatment – acute (0–7 day duration), subacute (8–14 days) or chronic (>15 days). days required for successful treatment. satisfaction with healing based on pinnal morphology. a subjective assessment, graded a–d, was made when the ah had healed, in which grade a denoted no morphological changes to the pinna and grade d denoted severe changes. grades a and b were considered to represent satisfactory healing, whereas grades c and d represented unsatisfactory healing. extent and duration of ear canal disease was assessed based on clinical signs and otoscopic examination. recurrence of ear canal disease and ah – the results of treatment for otitis externa and ah were recorded on the day following the final treatment, and at follow-up at 2 months and 1 year after the final treatment to assess recurrence. main findings (relevant to pico question): chronicity of ah – the majority of dogs had acute or subacute haematoma development in this study. 7/8 dogs (87.3%) in group 3 had acute ahs, 1/8 (12.5%) subacute. in group 4, 8/9 (88.9%) were acute, 1/9 (11.1%) subacute. in group 5 all dogs had acute ahs. days required for successful treatment – dogs in group 3 had resolution in 100% cases within 9 days. group 4 dogs showed resolution in 100% of cases within 5 days. group 5 dogs all showed an absence of healing and subsequently underwent surgical management. satisfaction with healing based on pinnal morphology. satisfactory healing (grade a or b) was achieved in 3/8 (37.5%) cases in group 3, 8/9 (88.9%) cases in group 4 and no cases in group 5. in summary group 4 dogs (single drainage and daily local and systemic treatment) showed satisfactory healing in the majority of cases and with the shortest treatment duration of 5 days. group 3 dogs (single drainage and systemic treatment) healed within 9 days but fewer achieved satisfactory healing. extent and duration of ear canal disease – 32/40 (80%) of dogs were suffering from ear canal disease, showing a range of cases from severe otitis externa to mild ear disease affecting only the vertical canal. recurrence of ear canal disease and ah – there was no recurrence reported at follow-up examination 2 months after the final treatment. after 1 year, recurrence of otitis externa was seen in one case in group 3. limitations: the paper did not address the impact of local corticosteroid use alone, since systemic corticosteroids were also given. they may affect any associated otitis, but could also exert an effect via suppressing any immune-mediated process that may underlie the development of ahs. therefore, while it can be inferred that the treatment protocol for group 4 dogs gave a more favourable outcome to those in group 5, this success may not be solely attributable to local treatment. the inclusion of group 3 dogs (those that underwent drainage and systemic corticosteroid treatment) was not directly related to the pico. however, it has relevance as a comparison to group 4 which received the same treatment in addition to local corticosteroid instillation, and therefore was included in the analysis. the improved outcome in group 4 compared to group 3 may be attributable to the additional local treatment used in this group. in group 4, gentamicin was injected locally in addition to corticosteroids, and therefore successful outcome may not be entirely attributable to corticosteroid instillation. the severity of disease was detailed clearly but not correlated with individual case outcomes. the volume and concentration of corticosteroid instilled varied depending on the size of the haematoma but this was not correlated with outcome. the study size was small, reducing the power of the study and precluding statistical analysis. the study was randomised but the method was not detailed, and the study was not blinded, with subjective assessment of haematoma healing and resolution of ear disease. hall et al. (2016) population: veterinary surgeons and practices on the rcvs register in the uk and members of the association of veterinary soft tissue surgeon (avsts), treating small animal patients. sample size: 2386 veterinarians were emailed questionnaires, of which 312 email addresses were invalid, and 259 completed questionnaires were received, 259/2074 (12.5%) response rate. responses were excluded if the questions were not all completed. 251 questionnaires were included in the analysis. intervention details: veterinarians were asked to select which treatment option they would use for aural haematoma (ah) management at first presentation and for recurrent cases. treatment options were needle drainage alone, needle drainage with local deposition of corticosteroids, surgical management, placement of a penrose drain, and ‘other’ procedures. ‘other’ procedures included systemic corticosteroid treatment with or without needle drainage, needle drainage with local corticosteroid instillation 3–5 days later, medical treatment of otitis externa for 7–10 days before needle drainage with local administration of corticosteroids, bandaging and the haematoma being left to resolve naturally. there were no details provided regarding corticosteroid doses or frequency of drainage. study design: observational subjective survey. outcome studied: respondents were questioned to establish the preferred treatment for ahs on initial presentation, for recurrent or persistent haematomas and for multiple recurrent haematomas. the reason for the treatment selection was recorded (previous success, owner preference, cost, practice policy, convenience, other). perceived success of the treatment (prevention of recurrence, cosmetic outcome and predicted owner satisfaction) were subjectively rated by the respondents as excellent, good, satisfactory or poor. questions relating to the treatment of skin and ear disease were not included in the questionnaire. main findings (relevant to pico question): for the management of ahs at initial presentation, 109/251 (43%) of respondents used drainage with local instillation of corticosteroids, compared to 40/251 (16%) who used drainage only. 20/251 (8%) were in the ‘other’ category, which included elements relevant to the pico but was not detailed to allow further evaluation. recurrent haematomas were treated by needle drainage with local instillation of corticosteroids in 40/251 (16%) of cases, compared to needle drainage alone in 17/251 (7%) of cases. 168/251 (67%) cases underwent surgical management. in cases with multiple recurrence 12/251 (5%) underwent drainage and local steroid instillation, and 5/251 (2%) received needle drainage alone. 161/251 (64.3%) underwent surgical management. perceived success – 13/109 (12%) respondents stated excellent perceived success with corticosteroid instillation and drainage, 51/109 (47%) good, 33/109 (30%) satisfactory and 12/109 (11%) poor. in comparison, 5/40 (13%) stated excellent perceived outcome with needle drainage alone, 10/40 (25%) good, 22/40 (56%) satisfactory and 3/40 (8%) poor. expected recurrence – 56/109 (51%) of respondents who used local instillation of corticosteroids alongside drainage as a first line treatment expected recurrence. there was no comparison figure for drainage only. cosmetic outcome – this was stated as excellent for medical management and good for surgical management. owner satisfaction with chosen treatment option – stated as excellent 41/251 (16%) of cases, 141/251 (56%) good, 65/251 (26%) average, 4/251 (1.5%) poor. respondents’ reasons for the treatment choice – 193/251 (77%) made their choice based on previous success, followed by owner preference 15/251 (6%), cost 13/251 (5%), practice policy 10/251 (4%), convenience 10/251 (4%) and other 10/251 (4%). 153/251 (61%) respondents expected 0–25% chance of recurrence with their first treatment choice. limitations: this was a weak form of evidence as it was an observational and subjective study, based on previous experience and perceived success of participants, therefore subject to substantial bias. there was objective assessment by the authors collating the results, but based on subjective assessment of ah by participants. the study lacked description of the size and extent of the ahs, which could affect treatment options chosen and therefore their predicted success. concurrent treatment for skin or ear disease was felt to be mandatory by the authors, but not detailed in the questionnaire, which made the findings difficult to review, as systemic treatments such as corticosteroids may have been used concurrently. the predictions of recurrence across different treatment options were not clearly displayed, neither was the time frame for recurrence. there were limitations relating to a survey with potential for misinterpretation of the questions, bias towards those with a technological disposition due to its distribution only through email, and bias towards a subset of practitioners more inclined to complete such surveys. the inclusion of avsts members may also bias towards surgical options or more chronic cases. the ‘other’ category included use of local instillation of steroids delayed from the initial drainage, but no further details were provided to allow evaluation of this subset. appraisal, application and reflection aural haematomas (ahs) are caused by pinnal cartilage rupture resulting in serosanguinous fluid entering the cavity. however, their pathogenesis in dogs remains unclear and is likely to be multifactorial, with theories relating to trauma, an immune mediated process (kuwahara et al., 1986a; and lahiani & niebauer, 2020), and cartilage degeneration with involvement of immunological factors (joyce & day, 1997). there are numerous treatment options for ahs in dogs, with a wide range of medical and surgical techniques described (ahirwar et al., 2007; and swaim & bradley, 1996). the above putative causes have prompted the use of local corticosteroid instillation as a treatment option, while ensuring a sterile technique is employed, as corticosteroids can predispose to abscess formation (seibert & tobias, 2013). however, as concurrent otitis externa and allergic skin disease are common (macphail, 2016), systemic corticosteroids are frequently used alongside local ah management, complicating the analysis of local corticosteroid treatment efficacy (joyce, 1994). three papers have been found which provide weak evidence towards the use of local instillation of corticosteroids in canine ahs in comparison to drainage alone. drainage techniques beyond needle aspiration and flushing have not been included. these would be better assessed with a pico focusing on the comparison of different drainage techniques. furthermore, needle aspiration and local corticosteroid instillation can be performed in the conscious patient, with direct relevance to situations in clinical practice where chemical restraint would be best avoided, such as older patients or those with concurrent disease. the randomised control trial (kuwahara et al., 1986b) is the preferred study design for assessing treatment. the trial showed recurrence in all cases of ah treated with drainage alone, necessitating either surgical intervention or alternative conservative management. therefore, in cases where surgical management is not appropriate or suitable, the results of this trial suggest that a treatment protocol including daily steroid instillation alongside drainage would be more successful than drainage alone in preventing recurrence and achieving resolution. the study did not, however, provide a clear comparison of local instillation of corticosteroid to daily drainage alone, since systemic treatment was used in addition to local corticosteroid treatment. therefore, the outcome could not be solely attributed to the local treatment. furthermore, gentamicin was also instilled locally alongside corticosteroids and so the success of local treatment may not have been solely attributable to corticosteroid instillation in these cases. the study was randomised which improves the strength of evidence when assessing treatment interventions.  however, the outcomes were not matched to the severity of the disease, the sample size was small, and the amount of steroid instilled was variable. larger studies would be required to analyse this further and guide treatment selection based on the individual patient. the retrospective cohort study (mikawa et al., 2005) provides a moderate level of evidence for assessing treatment. it revealed that repeated aspiration and instillation of corticosteroids was more effective than aspiration alone, with all ahs being resolved over a period of 35 days. in comparison, drainage alone did not produce resolution of the ah in any of the 14 cases, in spite of additional systemic treatment in all cases with underlying ear and skin disease. however, the sample size was small and the population was not randomised. there was also variation in the amount and type of corticosteroid instilled, and the severity or size of the ah was not detailed, all of which may influence the results. frequent repeated treatment was required in many cases, therefore consideration should be given as to which patients would be most appropriate to manage in this manner. the frequency of treatment was variable and not clearly defined in all cases. this paper highlights a need for further studies to evaluate alternative corticosteroid preparations and frequencies, including longer acting preparations that could be instilled less frequently. the observational survey (hall et al., 2016) is a weak form of evidence for addressing the research question. it revealed a majority of practitioners used corticosteroid instillation alongside ah drainage at first presentation, but 56/109 (51%) predicted recurrence. this study concurred with the findings of the previous two papers that drainage alone was not sufficient for resolution, but also suggested that local corticosteroid treatment with or without systemic corticosteroids would not be adequate in some cases. the observational survey was, however, subjective and affected by respondent bias and variables relating to their experience, severity of the ah and / or the presence of underlying ear disease. furthermore, additional treatments for concurrent disease were not detailed but would be expected to influence the treatment outcomes. the frequency of drainage or corticosteroid instillation were also not discussed, though such variations in the frequency and type of treatment employed in conservative management of ahs in clinical practice would be likely to influence the outcome. across the three papers studied, there was evidence to suggest that drainage alone had a high recurrence rate, prompting the need for alternative treatment options. the use of local instillation of corticosteroids as part of alternative protocols was associated with an improved outcome. however, the small sample sizes and variables across the papers meant that assessment of whether it was the sole reason for the improved outcome was less clear. large scale randomised control trial studies would therefore be required to evaluate this further. methodology section search strategy databases searched and dates covered: cab abstracts on the ovid interface 1973–2021 week 47 pubmed accessed via the ncbi website 1920–december 2021 search strategy: cab abstracts: (dog or dogs or canine or canines or canis).mp. or exp dogs/ or exp canis/ (aural or ear* or pinna* or auric*).mp. and ((haematoma* or hematoma* or othaematoma or othematoma).mp. or exp haematoma/) (corticosteroid* or corticoid* or glucocorticoid* or steroid* or dexamethason* or dexadreson or dexafort or 'triamcinolone acetonide' or methylprednisolone acetate or depomedrone or prednisolone).mp. or exp glucocorticoids/ or exp steroids/ (drain* or remov* or fluid or aspirat* or nonsurg* or non-surg* or 'non surg*' or suction*).mp. 1 and 2 and (3 or 4)   pubmed: dog or canine or canis (aural or ear or ears or pinna or auricular or auris) and (haematoma or hematoma or othaematoma or othematoma) corticosteroid or corticoid or glucocorticoid or steroid or dexamethasone or dexamethason or dexadreson or dexafort or 'triamcinolone acetonide' or methylprednisolone acetate or depomedrone or prednisolone drain or drainage or remove or fluid or aspirate or nonsurgical or non-surgical or “non-surgical” or suction 1 and 2 and (3 or 4) dates searches performed: 02 dec 2021 exclusion / inclusion criteria exclusion: irrelevant to pico not in english language only one technique included surgical management not canine patients review articles, non-peer reviewed material, conference proceedings duplicates inclusion: peer-reviewed material english language comparative papers including both aural haematoma drainage with corticosteroid injection and aural haematoma drainage alone canine patients search outcome database number of results excluded – irrelevant to pico excluded – non-english excluded – not comparing specified techniques excluded – surgical management excluded – not canine excluded – not peer-reviewed, conference or review paper total relevant papers cab abstracts 55 15 3 11 14 4 5 3 pubmed 110 97 0 7 1 0 4 1 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflicts of interest. the search was developed by clare boulton. references ahirwar, v., chandrapuria, v. p., bhargava, m. k., swamy madhu, shahi apra & jawre shobha. (2007). a comparative study on the surgical management of canine aural haematoma. indian journal of veterinary surgery. 28(2), 98–100. hall, j., weir, s. & ladlow, j. (2016). treatment of canine aural haematoma by uk veterinarians. journal of small animal practice. 57(7), 360–364. doi: https://doi.org/10.1111/jsap.12524 joyce, j. a. (1994). treatment of canine aural haematoma using an indwelling drain and corticosteroids. journal of small animal practice. 35(7), 341–344. doi: https://doi.org/10.1111/j.1748-5827.1994.tb01711.x joyce, j. a. & day, m. j. (1997). immunopathogenesis of canine aural haematoma. journal of small animal practice. 38(4), 152–158. doi: https://doi.org/10.1111/j.1748-5827.1997.tb03453.x kuwahara, j. (1986a). canine and feline aural haematoma: clinical, experimental, and clinicopathologic observations. american journal of veterinary research. 47(10), 2300–2308. kuwahara, j. (1986b). canine and feline aural hematomas: results of treatment with corticosteroids. journal of the american animal hospital association. 22(5), 641–647. lahiani, j. & niebauer, g. w. (2020). on the nature of canine aural haematoma and its treatment with continuous vacuum drainage. journal of small animal practice. 61(3), 195–201. doi: https://doi.org/10.1111/jsap.13107 macphail, c. (2016). current treatment options for auricular haematomas. veterinary clinics of north america: small animal practice. 46(4), 635–41. doi: https://doi.org/10.1016/j.cvsm.2016.01.003 mikawa, k., ito, t., ishikawa, k., kushima, k. & shii, h. (2005). treatment and prognosis of 59 canine ear hematomas. veterinary anesthesia surgery magazine. 36(4), 93–96. doi: https://doi.org/10.2327/jvas.36.93 seibert, r. & tobias, k. m. (2013). surgical treatment for aural haematoma. north american veterinary conference clinicians brief. 3, 29–32. swaim, s. f. & bradley, d. m. (1996). evaluation of closed-suction drainage for treating auricular haematomas. journal of the american animal hospital association. 32(1), 36–43. doi: https://doi.org/10.5326/15473317-32-1-36 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. can i hang? ideal time to replace isotonic crystalloid intravenous fluids and sets to prevent fluid contamination and blood stream infection: a knowledge summary a knowledge summary by erik fausak ma, mslis, cvt, lvt, rlat 1* samantha spelts student 1 rebecca brown psy.m., student 1 1bel-rea institute of animal technology 1681 s dayton st, denver, co 80247, usa *corresponding author (efausak@gmail.com) vol 1, issue 4 (2016) published: 16 nov 2016 reviewed by: kelly hall (wilke) (dvm, ms, dacvecc) and christopher parratt (bvsc mres certvc certavp(ecc) mrcvs) next review date: 16 nov 2018 doi: 10.18849/ve.v1i4.47 clinical bottom line based on very poor veterinary and human evidence, fluid bags and iv sets should be changed every 96 hours whether on one or multiple patients. additionally, supportive evidence suggests that creating a routine of wiping ports with alcohol prior to injection or withdrawal may significantly decrease the likelihood of fluid contamination. this certainly seems to be an area that needs more research. question in dogs and cats does the changing of iv fluids every 96 hours, compared to changing fluids when they are empty, reduce the risk of contamination in the bag and nosocomial infection to the patient? clinical scenario in this particular shelter environment, iv fluids are used in surgery, and the bag is replaced when it is empty. while nosocomial infections have not been reported, the pets are discharged within four hours of surgery and follow up is based on reports from the shelter. is it better to replace the bag more frequently to reduce bacterial contamination of the bag and risk infection to the patient? the evidence results included two prospective studies, a prospective study abstract, and a cochrane systematic review for human patients. summary of the evidence ullman (2013) population: adult and neonatal human patients on central or peripheral iv and arterial lines with fluids being delivered over a period of time. sample size: 5001 (16 studies) intervention details: human adult and neonatal patients receiving fluid therapy had their fluid lines evaluated for contamination at varying frequencies. study design: meta-analysis outcome studied: iv fluid colonisation and blood stream infections of patients on iv fluids. main findings (relevant to pico question): 1% of patients get a fluid iv bag-related infection at 3.6% colonisation of bacteria. iv sets should be replaced every 96 hours (current cdc guidelines) unless containing blood products or parenteral nutrition. neonates may warrant special consideration and more frequent iv set changes. limitations: all studies included were not blinded and had a high risk of bias; they all received low quality scores. guillaumin (2013) population: fluid bags lactated ringers solution (lrs) sample size: 90 1-litre lrs bags intervention details: lrs iv bags were placed in an emergency room and intensive care unit of an icu. all bags were punctured three times daily and hung in the hospital's icu and er environment to simulate clinical usage. fluid sampling and port swabbing occurred on days 0, 2, 4, 7, and 10. study design: prospective trial (non-randomised, non-blinded) outcome studied: fluids and ports were cultured for colonisation of bacteria main findings (relevant to pico question): no bags in the icu had bacterial contamination of fluid but bags in the er were at 1.1% colonisation by day 4 and reached a maximum fluid colonisation of 4.4% by day 7 and 10. port colonisation occurred on day 0 at 4.4%, day 4 had 17.8%, and bacterial colonisation reached 31.1% by day 7. limitations: conditions of the two environments (icu and er) are not discussed; the trial was not blinded or randomised. only presented as an abstract. matthews (2011) population: lactated ringers solution (lrs) bags used for subcutaneous delivery sample size: 29 lrs bags intervention details: bags maintained at room temperature with random allocation to a control group where bags were not used but removed from their plastic covering and 1 ml was collected immediately with fluid and interior bag wall cultured and only sampled at 30 and 60 days. the other group was the injection group where the bag was punctured by a 3 ml syringe and 22g needle on a daily basis. culture of injection port was penetrated after being wiped with alcohol, and 1 ml was withdrawn with a 22 g needle (sterile) on 0, 7, 14, 21, 30, and 60 day intervals. study design: randomised controlled non-blinded trial outcome studied: bacterial culture from aseptic technique (wiping ports with alcohol before sampling and using sterile needle and syringe). main findings (relevant to pico question): day 60 resulted in bacterial growth of acinetobacter lwoffi and staphylococcus spp in two bags. no bags were contaminated before 60 days, and bags that were contaminated were in the injectable group, not the control group. limitations: methodology seems different from the previous two studies with alcohol prep of bag prior to culturing. appraisal, application and reflection fluid contamination that can lead to blood stream infections appear to be a fairly low risk to patients in human medicine (ullman et al. 2013). in active and less clean environments, contamination of fluids seem to occur within four days of use (guillaumin et al. 2013; ullman et al. 2013). one well-designed study found that even with multiple patients, fluids were not contaminated in 60 days, but the sampling site was wiped with alcohol which may have affected the culture sensitivity, and since the environment was experimental, the facilities may have been much cleaner than a typical veterinary environment (matthews & taylor 2011). one consistent theme the evidence suggests is that fluid contamination is directly related to the cleanliness of the surrounding environment. the bottom line is that most iv fluids can be safely changed every 96 hours without risk of blood stream infection, but the evidence-base to support it remains very poor. while contamination may occur within 72 hours according to guillamin (2013), this is not based on a culture on day three, but on the contamination of fluids on day four. pediatrics may need special consideration (perhaps because fluids may often have glucose content), and lipid emulsions should be changed daily. percent contamination in guillaumin’s (2013) study in the veterinary clinical environment seems to be similar to the human meta-analysis (ullman et al. 2013).  due to different study designs, it is hard to say where matthews & taylor’s (2011) study fits in this spectrum since fluid contamination was not reached for 60 days; except that the laboratory environment can be much cleaner than the clinical environment or that the sample size is much smaller. certainly, matthews & taylor’s (2011) study suggests that bags for subcutaneous fluids can be kept for a minimum of 30 days.  sabino and weese (2006) examined factors for multi-dose vial contamination, and based on two prospective control studies published in the article, vial contamination is one of the largest factors for contaminated drugs.  swabbing the port or vial top resulted in a decline of 42% vial contamination to 0% vial contamination, much like matthews & taylor’s (2011) study. one factor that probably contributes significantly to reducing fluid contamination besides changing fluid sets and iv bags every 96 hours is to make sure that any injection in the bag is done after wiping the ports in alcohol. guillamin (2013) found a 17.8% bacterial contamination of ports by day four; a likely source to introduce fluid contamination.  future research that examines the cleanliness of personnel handling fluids and contamination of the fluids might be a very interesting avenue of examination. methodology section search strategy databases searched and dates covered: pubmed, google scholar, vet med resource, cab abstracts (1973-2015) search terms: intravenous and set and replacement, intravenous and fluid and bag and contamination, “fluid therapy” and contamination dates searches performed: october 2nd 2016 exclusion / inclusion criteria exclusion: relevance based on title and abstract, access. we only utilised human studies at the highest level of evidence (loe) 1. if there were no human study of loe 1 (systematic review), we would saturate with 10 most relevant human studies (loe 2). inclusion: relevant articles we could access, english, french search outcome database number of results excluded – relevance excluded – duplicate excluded – human: non-systematic reviews total relevant papers vetmed resource 25 24 0 0 1 cab direct 23 23 0 0 0 pubmed 85 64 1 20 1 total relevant papers when duplicates removed 2 +1 outside source:carr, anthony p. 2015 conflict of interest the authors declare no conflicts of interest. references carr, anthony p. (2015) new studies in veterinary internal medicine: bacterial infections. dvm 360, 46 (4), pp.m1–m3. available at: http://veterinarynews.dvm360.com/new-studies-veterinary-internal-medicine-bacterial-infections?pageid=2 [accessed february 4, 2016]. guillaumin, j. et al. (2013) influence of hang time on bacterial colonization of intravenous bags in a veterinary emergency and critical care setting (abst). journal of veterinary emergency and critical care, 23, p.s6. matthews, k.a. and taylor, d.k. (2011) assessment of sterility in fluid bags maintained for chronic use. journal of the american association for laboratory animal science, 50 (5), pp.708–712. sabino, c. v. and weese, j.s. (2006) contamination of multiple-dose vials in a veterinary hospital. the canadian veterinary journal, 47 (8), p.779. ullman, a.j. et al. (2013) optimal timing for intravascular administration set replacement. the cochrane database of systematic reviews, 9 (9), p.cd003588. available at: http://www.ncbi.nlm.nih.gov/pubmed/24037784 [accessed october 1, 2016]. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. pet owners’ online information searches and the perceived effects on interactions and relationships with their veterinarians nanette lai bsc ba ma1* deep k. khosa bsc bvms manzcvs phd1 andria jones-bitton dvm phd1 cate e. dewey dvm msc phd1 1university of guelph, 50 stone road east, guelph, on n1g 2w1 *corresponding author (lain@uoguelph.ca) vol 6, issue 1 (2021) published: 08 jan 2021 reviewed by: suzanne rogers (bsc(hons) chbc) and david g. thomas (phd bsc) doi: 10.18849/ve.v6i1.345 section index:    abstract | introduction | methods | results | discussion | conflict of interest | references abstract objective: to explore pet owners’ online search experiences for pet health information and the perceived effects on their interactions and relationships with veterinarians. background: few studies have examined pet owners’ online searches for pet health information; even less is known about how these search experiences may impact pet owners’ interactions and relationships with veterinarians, including any effects on bond-centered care. methods: qualitative study consisting of five focus groups conducted with 26 pet owners in the greater toronto area, ontario, canada, between june to september 2016. all interviews were audio-recorded and transcribed verbatim. qsr nvivo 11® was used to facilitate organisation of focus group data for thematic analysis. results: participating pet owners frequently referred to their relationships with veterinarians when discussing experiences searching online for pet health information. owners reported choosing either to disclose or withhold declaring their online searches to veterinarians, depending on whether participants perceived a beneficial or detrimental impact on a “good” professional relationship with their veterinarian. perceptions of veterinarians' reactions towards declaration of online searches were mixed, and influenced pet owners’ views of the existing relationship. conclusion: pet owners viewed their veterinarians as their most trusted source of pet health information, but many owners also wanted supplemental information from online searches. owners preferred veterinarians refer them to online pet health resources, ideally those affiliated with the veterinary profession. searching for pet health information online does not displace veterinarians’ guidance. rather, the veterinarian-owner relationship was perceived to be strengthened when online searches were openly discussed with veterinarians. implications: findings offer insight into pet owners’ expectations of veterinarians within the context of online pet health information, providing ideas for veterinarians to strengthen bonds with owners such as; showing support of owners’ online pet health information searching by recommending resources and considerations about communicating professional opinions to owners regarding online information.   introduction an expanding body of literature documents research in relationship-centered healthcare which emphasises a collaborative healthcare model built on partnerships and joint decision-making between human healthcare providers, patients, and their families (1–4). arising from studies in human medicine (5) and social sciences (6), such relationship-centered care [rcc], acknowledges a growing need for equal participation in health decision-making. awareness for rcc has also become a focus of increasing research in veterinary medicine (7), where this collaborative healthcare model has also been termed bond-centered care [bcc] or bond-centered practice (8,9). bcc recognises the unique relationship and bond shared between a pet and its owners (8). in acknowledging the owner-pet bond, the veterinarian aims to understand the pet’s healthcare needs whilst concurrently meeting and addressing the needs of the owner (9–11). it is recognised that this type of holistic approach supports the development of a collaborative relationship or bond between owners and veterinary service providers, facilitating joint healthcare decisions for the pet (10,12).  the existing literature on bcc has largely focused on the veterinarian’s role in the veterinarian-pet owner interaction. for example, publications describe bcc’s underlying philosophy to provide guidance for veterinarians on integrating this healthcare model into daily practice (4,11), including some research that focused on the impact of practicing bcc on veterinarian wellness (12,13). other research emphasises the veterinarian’s contributions to bcc, highlighting the veterinarian as an educator and support person along with being the medical expert to help pet owners in decision-making (14). related publications offer ideas to veterinarians for enhancing their contributions in bcc, such as developing communication skills to build strong bonds with pet owners (4,10). in contrast, far less research has investigated pet owners’ contributions in bcc. the few publications focused on pet owner contributions in bcc demonstrate owners’ desire to have increased involvement in choosing treatments and therapies for their animals (10,15). to help with their participation and decision-making in their pets’ healthcare, pet owners are known to search for pet health information across a variety of resources, such as newspapers or generic pet care books and associated literature (16). more recently, the internet is recognised as a common and readily accessible resource that many owners report using for pet health information (16,17). for example, kogan et al. (2009) reported that nearly three-quarters of 1622 surveyed pet owners who were veterinary clients residing in or around two metropolitan areas in the united states (knoxville, tennessee and denver, colorado) had reported using the internet to search for pet health information. hofmeister et al. (2008) noted pet owners ranked the internet as their third most commonly accessed pet health information resource, behind general practice and specialist veterinarians. more recently, kogan et al. (2018) reported the internet as being the most frequently cited source of pet health information (78.6%), with veterinarians being a close second (77.2%) from a survey of 571 pet owners in the united kingdom. the extent of research about pet owners’ online pet health information seeking is particularly scant when compared to the extensive volumes of literature discussing online human health information seeking (21–29). human medical research shows that online information seeking behaviour impacts patients’ interactions and relationships with physicians. for example, human patients who found online information that contradicted their physicians’ clinical interpretations actively mentioned their online searches during consultations with physicians (30). other research shows patients avoided bringing up online health information searches during consultations with physicians to prevent damaging the professional relationship (31–33). it has also been reported that patients observed their physicians’ behaviours during clinical encounters to guide decisions about whether to reveal their online health information searches (34). in the veterinary context, pet health outcomes may be impacted by veterinarian-pet owner relationships and interactions, including the fact that owner decisions related to the use of veterinary services is influenced by the veterinary-client relationship (35–38). little is known about how online pet health information seeking influences pet owners’ interactions and relationships with veterinarians, factors involved in the veterinarian-owner bond component of bcc (10). the goal of this study was to add to the limited understanding of pet owners’ online pet health internet information searches, and owners’ perceived effects on veterinarian-owner interactions and relationships. the specific objectives were to explore; 1) pet owners’ online resource preferences for seeking pet health information; and 2) how online search experiences influence veterinary interactions and relationships from the owner’s perspective.   methods study design and participants this exploratory qualitative study involved a series of five focus groups, comprised of individuals who identified themselves as current owners of at least one cat or one dog. focus groups were conducted between june and september 2016 in the greater toronto area, ontario, canada. recruitment for participants began in june 2016 using diverse social media platforms (e.g. facebook, instagram, twitter) and snowball recruitment (37). pet owners were informed of the purpose and format of the study and were offered an honorarium ($50 cad gift card) and meal for participating. each focus group was run when three or more individuals had confirmed their availability to participate during specified dates. all participants were made aware of the risks, benefits and repercussions of their involvement in the study, and accordingly consented to their involvement before the start of each focus group discussion. the study protocol received ethics approval from the university of guelph research board (reb #016ap002). data collection at participants’ convenience, focus group discussions took place at private homes and one was held at a community centre. a semi-structured question guide was used to discuss topics pertaining to participants’ experiences searching online for pet health information, including: online resources they had accessed; methods participants used for evaluating quality and validity of online pet health information; experiences communicating with veterinarians regarding online pet health information; and participants’ opinions about online pet health information. questions were open ended and designed to stimulate discussion among the pet owners, facilitating the moderator (first author) to explore a range of perspectives and shared experiences. data saturation was achieved by the fourth focus group discussion, where new information was not presented by participants (39). the fifth focus group was conducted to confirm data saturation.  all discussions were audio-recorded, transcribed verbatim, and de-identified to ensure that transcribed material could not be linked to individuals. individual speakers were identified as o####. the prefix o indicates the speaker was an owner, and #### consists of a unique number assigned to the individual. participants completed a short demographic questionnaire post-interview to collect data on gender and age in order to describe the study population. validation techniques used to lend rigour to the study included field notes taken by the moderator to document observations and non-verbal behaviours with the use of thick, rich description (40). data analysis all transcripts were systematically checked for accuracy against the audio-recordings by the first author. the computer software qsr nvivo 11® was used to facilitate organisation of focus group data for thematic analysis (41). in brief, each transcript was examined multiple times for familiarisation with the data, and open codes were applied to sections of text. common codes occurring across transcripts were merged into themes and sub-themes and described in a codebook. the themes were then systematically reviewed, named and defined. for consistency and clarity, naming and definition of themes and sub-themes were reviewed and cross checked with codes by the second author. verbatim quotations are presented to illustrate codes. in some instances, “…” is used to denote where words were removed by authors for clarity; words included in square brackets were added by the authors for clarification purposes. demographic data were analysed using descriptive statistics (e.g. means, median, proportions) using microsoft excel®.   results demographics twenty-six pet owners participated in the five focus groups. each focus group ranged from 3 to 9 participants (mean: 5) and ran from 46 to 78 minutes each (mean: 58 minutes). pet owner ages ranged from 21 to 65 years old (mean: 40.8 years); 23 (88.5%) identified as female, and 3 (11.5%) as male. two major themes pertaining to the project objectives were identified in thematic analysis of the data. both themes, and their associated sub-themes, are described below. theme 1: owners viewed veterinarians as their most trusted source of pet health information and also wanted supplemental online pet health information  owners across all focus groups acknowledged that veterinarians they had relationships with were irreplaceable as a source of trustworthy pet health information. however, many were also clear in wanting to augment that information by way of online pet health information searches that involved their veterinarian. the following three sub-themes describe this theme: sub-theme 1.1: owners wanted online information to augment information provided by their veterinarians, but veterinarian referrals to online pet health information were rare while nearly all owners considered their veterinarians as their primary information resource for pet health information, they also searched online for supplemental information. for example, one owner stated that: “… being a university student i’m very picky about resources and i definitely go for vet first… i’ll go to the vet first and then go online for follow-up.” [o0105] similarly, other owners’ online pet health information searches occurred as follow-ups to veterinary consults. to further explore owners’ experiences with veterinarian-recommended online pet health information resources, participants were asked about online content that veterinarians had referred them to. nearly all participants reported that veterinarians rarely directed them towards online resources for retrieving pet health information, as demonstrated by one owner who stated: “i’ve never actually been recommended anything by the vet.” [o0523] other participants appeared to have similar experiences with veterinarians not directing them to specific online resources. one owner reported that “i only get the ‘be careful of people believing they’re vets because they’ve had pets for years’ kind of caution, but not a specific recommendation.” [o0105] similarly, one owner made the following contrast between veterinarians and physicians: “i don’t know if you guys experienced the same thing. but the vets never give us any sites to look up things… if you ask your doctor on something, they would give you something to reference. but vets never do that.” [o1037] another owner noted that she did not recall veterinarians referring her to a specific type of online resource: “i don’t recall any vet directing me to a study. would be nice.” [o0521] the participating pet owners’ statements appear to indicate that some may have information needs they wish veterinarians to meet. sub-theme 1.2: owners wanted veterinarians to verify and check online information owners described independently conducting online pet health information searches and wanting their veterinarians to verify the information they identified. for example, several owners explained that they would first go online for information, and then contact their veterinarians to verify accuracy of the content. this was depicted by multiple owners, such as one participant who explained: “i would link [the online source] to an email to my vet and say ‘… is this… true?’” [o0314] some owners opted to have verbal conversations with their veterinarians for the same purpose: “if i find something on the internet that causes me concern i’ll call them [my veterinarians] and run it by them.” [o0108] “i actually don’t trust the internet that greatly… i’d still bring the information to my vet.” [o1037] one owner expressed that information he encountered ultimately required his veterinarian’s approval: “… if i found something online, and he [the veterinarian] said, ‘no, that’s totally wrong,’ you know, i’ll trust him… i’ll disregard what i found on the internet. in our case, the vet has the final say.” [o1040] sub-theme 1.3: owners want veterinarians to recommend online information resources – ideally affiliated with the veterinary profession owners expressed a desire for their veterinarians to recommend online pet health resources that veterinarians themselves had appraised. one owner reported that her own veterinarian helped initiate the owner’s search by giving her a web link to access after the consult: “our puppy was diagnosed with one of the tick-borne diseases… the vet provided us a link to information… i copied and pasted the actual disease name. and just read up on… symptoms we should be looking for.” [o0314] several owners described wanting online resources that were created by the veterinary profession or that their veterinarian had contributed content to. for example, one owner expressed: “if i could find my veterinarian’s name on the website… if he is willing to place his name on this website then yes, i will also trust this website.” [o1040] the latter idea was further emphasised by owners wanting to be directed to online pet health resources affiliated with professional veterinary associations, as explained by another participant: “i don’t know if it’s… possible or something, but if [there was] like a vet association driven, kind of faqs… those you know that the doctors contribute to it, they have their own studies to back it up… if there’s… a centralised, accredited go-to site, or sites… that, i think that would be very helpful for pet owners.” [o1037] this idea of having a veterinarian-authored online pet health information resource appeared to be shared by other participants. for example: “for my own personal issues, i always go to the mayo clinic. ‘cause i know they always have the top research. best doctors. everybody looks to the mayo clinic for information. i’d love to see one for cats and dogs… [where] all the top vets are working together, putting their resources out there so that pet owners can actually go look at it and just go ‘okay now i have a better understanding of my animal’s disease’ or condition and you know, a little checklist of all the things and what to look for.” [o0936] another participant elaborated on the idea of having an online pet health resource connected to a professional veterinary association, noting: “for human health… you have… different sites… that you know are reputable and accurate. it’s kind of hard to know with the pet sites… there’s nothing that sticks out in my mind that… is the go-to site, that… their information would be accurate.” [o0317] theme 2: there was a relationship between owners’ perceptions of their relationships with their veterinarians and disclosure of online searches for pet health information the second theme identified in the analysis related to a relationship between owners’ perceptions of the veterinarian-client relationship and the disclosure of owners’ online searches for pet health information with their veterinarian. specifically, how the owners’ perceived the veterinarian-client relationship influenced whether they disclosed their online search information to their veterinarian (sub-theme 2.1). further, how veterinarians were perceived to respond to owners’ online searches influenced the quality of the veterinarian-client relationship (sub-theme 2.2). each sub-theme is further described below. sub-theme 2.1: owners’ perceptions of the quality of the veterinarian-owner relationship influenced owners disclosing online searches in discussing their most recent online pet health information searches, participants described how the perceived quality of the veterinarian-client relationship influenced their discussing online search results with veterinarians in multiple ways. some owners who depicted the relationships in a positive manner, such as describing their relationships with veterinarians as “good,” reported sharing their online pet health information search results with their veterinarian. for example, one owner described how having a good relationship with veterinarians facilitated conversations about searching online for pet health information; “… when you’re sifting through information and you have a good relationship with your vet… you can bring things up as discussion topics.” [o0523]. other participants agreed, with one owner commenting that, “i have a really good relationship with my vet… they don’t mind me bringing things [from the internet] to them.” [o0104]. in contrast, other owners who also considered their relationships with their veterinarians as “good” voiced hesitation about sharing their online pet health information search activities with their veterinarian, as they would usually defer to their veterinarian’s expertise regardless. for example; “i’ve got a really good relationship with my vets… at the end of the day… [i] defer to them and never really challenge them based on something i’ve read on the internet… that’d be a little foolish.” [o0108] another owner agreed, sharing her thoughts about why she preferred not telling her veterinarian about her online search results; “[the veterinarian is] good at what he does, and i’ve used him for all three dogs. they would rather i show up than… research on my own.” [o0936] these sentiments seemed to suggest a hesitancy amongst these owners about disclosing online searches with their veterinarian because they perceived it would not be well-received by the veterinarians. other participants were more clear in describing that they did not share online search information with their veterinarians because they believed doing so could harm the veterinarian-client relationship. for example, one owner explained that: “… i’ve been working with him [veterinarian] for a long time and i… get the sense that he, some vets don’t like when their clientele looking up things on the internet… i try to… approach that lightly with my vet and not bombard him with information.” [o0315] another owner stated; “i think you have to be very diplomatic when you’re giving information to your vet… it does depend on your relationship with your vet.” [o0102]. the same owner also shared the following thought; “when you’re seeing a new vet you… have to tread lightly. ‘cause i’m sure everybody’s going on the internet looking for stuff… they’re just reading it off the internet and then thinking that they know as much as the vet. which i could see from the vet’s point [of view] would be a little frustrating.” sub-theme 2.2: veterinarians’ reactions towards owners disclosing online searches impacted owners’ perceptions of the relationship multiple participants shared their experiences with presenting online pet health search findings to their veterinarians. the owners’ perceptions of their veterinarians’ reactions to this disclosure influenced the veterinarian-client relationship. in some instances, owners perceived their veterinarian’s reaction to being presented with online information as negative. for example; one owner recounted a past experience where she viewed the veterinarian as being unreceptive to her ideas, including her website recommendation; “i referred [the veterinarian] to [a dog care website] to start doing a little bit of research because the movement is to get away from vaccinations. i dropped him as a vet because he was toeing the party line and wasn’t willing to consider that [my] dog even had a reaction to the [rabies] vaccination.” [o0103] similarly, another participant reflected on a past attempt in sharing her online findings with a veterinarian; “i found... a university paper… i said ‘i’ve got this paper can i email it to you’ [the veterinarian said] ‘i’m not giving you my email.’… he was openly hostile… so i went to a different vet… and we switched.” [o0109] in these instances, the reaction of the veterinarian to the owner sharing their online search information was perceived so negatively such that it led to the owner terminating the veterinarian-client relationship. in contrast, veterinarians’ reactions that were perceived to be positive appeared to influence owners’ constructive views of the professional relationship. this was well-demonstrated by one owner’s comment regarding her pet that had chronic anal gland infections; ”… my vet was at the point of saying if he gets one more infection, we’re removing them. i’m like that’s a really risky surgery… if i don’t have to knock him out, i don’t want to… i did some independent research… studies had been going on for a couple of years… saying that any chronic dermalogical [sic] issue is usually food based. and my vet wasn’t even aware that anal glands were considered part of the dermis… he was going to go to the extreme of taking them out… i had to take him all kinds of reports.” [o0525] when asked to elaborate about the veterinarian’s response the owner stated; “… he was actually awesome about it. i know other vets would not be, but he was always willing to learn new things and never make me feel uncomfortable about taking him things that contradicted what he’d said to me.“ similarly, other participants discussed sharing online search information with their veterinarian as helping to facilitate a stronger veterinarian-client relationship. for example; “… it’s about you finding information… and them being willing to listen… discuss things with you… more of a relationship… together.” [o0109] “… at the end of the day, all that information… helps me to have a more intelligent conversation with my vet. i think it really helps to have a much deeper relationship with your… vet.” [o0108] “… before all the information was on the internet… you’d call and they [veterinarians] would say ‘you gotta bring the cat in.’… now they’re willing to discuss a bit more over the phone… i think it really helps you have a much deeper relationship with your vet.” [o0104] hence, owners’ interpretations of veterinarians’ reactions towards being presented with online pet health information affected how participants viewed the professional relationship. where veterinarians were perceived to react well to the online information, relationships were strengthened, but where the veterinarian’s response was perceived as negative, it harmed the veterinarian-client relationship.   discussion this research aimed to explore pet owners’ online searches for seeking pet health information, including how online search experiences influence veterinary interactions and relationships from the pet owner’s perspective. consistent with previous research (19,42), pet owners in the present study indicated that their preferred pet health information was that provided by veterinarians. at the same time, many owners wanted supplemental information from online searches, and expected veterinarians to provide guidance about online content. our findings support past research indicating pet owners would welcome website suggestions from veterinarians (43), yet, as with the views from the participants in our research, pet owners generally do not receive website recommendations from veterinarians (18,43). to the authors’ knowledge, website recommendation behaviours and patterns among veterinarians have not been investigated. however, investigations from the human medical field may offer some insight. similar to pet owners, human patients also have a predilection towards health information from healthcare providers rather than the internet (44). physicians have been reported to recommend websites to the patients who request them or when patients expressed that they used the internet for seeking health information (45,46). as a point of contrast, findings from the present research and one other pet owner related study (17) report that some pet owners tended to avoid mentioning internet use to their veterinarians. speculatively, pet owners not mentioning their internet use to veterinarians may affect whether veterinarians recommend online resources. more research is warranted for exploring when and why pet owners are or are not referred to web-based pet health resources by veterinarians. some pet owners in this study expressed being reticent about discussing their online pet health information searches for fear of disrupting what they considered to be a “good” relationship with their veterinarian. because previous research in veterinary medicine has not explored pet owners’ perspectives about the impact of their internet use on their relationships with veterinarians, literature from human medical studies have been cited here for comparison. human patients have been reported choosing not to convey their online search activities to their physicians in order to maintain a good quality professional relationship (23). other research indicates human patients perceive improvements in relationships with physicians from discussing online health information (48–50) when physicians’ had positive responses towards patient internet search efforts (49,53). for example, human patients associated physicians’ positive reactions with improved therapeutic relationships, whilst negative or dismissive reactions from physicians were considered damaging to the relationship (50,54). the findings from the present study support both premises; that disclosure of online information searches are perceived to harm relationships with health professionals in instances where the health professional was perceived to respond negatively to the disclosure, but improve relationships where the health professional’s response was perceived to be positive. moreover, reports document physicians’ negative reactions, such as being disparaging or acting threatened towards patients’ internet searches, may drive patients’ deciding to discontinue the professional relationship (54), again akin to reports by some of the pet owners in this study. the depth of research in human medicine offers further insights and directions for future research in veterinary medicine. research reports that human patients viewed physicians’ reactions to be positive when the physicians engaged with the internet information, such as validating and encouraging patients’ searches (54). even if physicians actively disagreed with the internet content or expressed a lack of knowledge, human patients viewed these as positive responses, much as was observed with the pet owners’ views in our study. moreover, and similar to the findings from the present study, human patients considered their physicians’ reactions to be mostly positive if they had a good prior relationship (55). the effect of a positive existing relationship consistently influenced human patients’ views even when the physicians were actually being critical (50). furthermore, physicians criticising online health information was considered by patients to be a positive reaction because the physicians demonstrated engagement with the information. inversely, human patients deemed physicians’ reactions to be negative if the physicians appeared disengaged with the internet materials, even if they agreed with the content (50). physicians appearing to patients as being disengaged with internet information was viewed as responding negatively by patients, and some opted to see other physicians or the patients left the practice entirely (50, 55). in light of responses by human patients, an avenue for future research may involve exploring pet owners’ views about veterinarians’ engagement with pet health information on the internet. specifically, the extent to which veterinarians engage in discussions about online information and the impact that discussions have on the veterinarian–pet owner interaction and relationship. implications the present research suggests conversations between veterinarians and pet owners regarding online pet health information can positively impact the professional relationship, provided pet owners view veterinarians’ reactions to the online information disclosure to be positive. specifically, akin to human research, pet owners may consider veterinarians’ reactions to be positive if the veterinarians demonstrate support of owners’ online searches, such as veterinarians verbally acknowledging owners’ information gathering efforts. pet owners’ perceptions of veterinarians’ responses may be affected by veterinarians’ communication skills (57). drawing from suggestions for physicians (58), veterinarians demonstrating openness towards online health information may encourage pet owners to share their online pet health information research. also, enabling owners to discuss online findings communicates that their opinions are valued, as seen with human patients (47), and further emphasises the equal participation in bond-centred care (8–10). another benefit from open discussions about online health information includes potential strengthening of the veterinarian-owner relationship, as was observed here and is also depicted among human patient-physician relationships (47). research links strong veterinarian-pet owner relationships to increased veterinary service use and owners following veterinary recommendations – factors which are associated with improved pet health outcomes (34) and veterinary business outcomes. practical applications for bond-centred care based on the present research focuses on strengthening the veterinarian-pet owner bond. based on evidence from the literature, ideas for supporting positive veterinarian-owner interactions centred around owner internet use include engaging with owners, such as verifying content together (59). veterinarians may also consider directing owners to specific online resources as part of the veterinary consult (60). related suggestions include veterinarians integrating internet use into consultations with owners (61) or referring owners to external online resources for pet health information (57). veterinarians can enhance their bonds with owners by providing strategies and educating owners about assessing websites for accuracy and reliability (17). arming owners with the skills to recognise valid information from the internet becomes even more important within the context of bond-centred veterinary care, given that existing research has demonstrated that health information online may be misleading and potentially influence health information seekers’ attitudes towards diseases, medical treatments, or procedures (45). limitations a limitation of this study is the potential for response bias since pet owners who agreed to be interviewed may be more comfortable sharing their experiences searching for online health information, and the challenges they had encountered during searches and wished to specifically voice this. as with all qualitative research, this study was not designed for establishing statistical generalisability; therefore, results cannot be generalised for all pet owners. outcomes of this study provide depth of understanding in a previously under explored phenomenon and will be used to guide the development of a quantitative questionnaire for measuring the frequency and distribution of some of the observed phenomena in the broader canadian pet owner population. conclusions pet owners viewed their veterinarians as their most trusted source of pet health information, but many owners also wanted supplemental information from online searches. owners described wanting to veterinarian referrals to credible sources of online information, but these were rare. there was a relationship between pet owners’ perceptions of their relationships with their veterinarians and how pet owners perceived their veterinarians’ reactions to their disclosure of online pet health information searches. searching for pet health information online does not displace veterinarians’ guidance. rather, veterinarians acknowledging, recognising and engaging in pet owners’ internet research efforts can serve to strengthen the veterinarian-owner relationship.   conflict of interest acknowledgements: research costs were supported by 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(2014). educating the patient for health care communication in the age of the world wide web: a qualitative study. academic medicine. 89(2), 318–25. doi: https://doi.org/10.1097/acm.0000000000000101 intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. can measurement of glucose levels in blood and peritoneal fluid be used to diagnose septic peritonitis in dogs? a knowledge summary by nicole d'mello bvmsci (hons) mrcvs 1* 1university of surrey school of veterinary medicine, vsm building, university of surrey, daphne jackson rd, guildford gu2 7al *corresponding author (nicoledmello@hotmail.com) vol 7, issue 1 (2022) published: 02 mar 2022 reviewed by: adam swallow (bvsc mrcvs) and theodora tsouloufi (dvm phd afhea mrcvs) next review date: 17 oct 2023 doi: 10.18849/ve.v7i1.382 pico question can the measurement of blood and peritoneal fluid effusion glucose levels be used to accurately diagnose septic peritonitis in dogs when compared to cytology and bacterial culture?   clinical bottom line category of research question diagnosis the number and type of study designs reviewed three papers were critically reviewed, all of which were diagnostic test evaluation studies strength of evidence moderate outcomes reported glucose measurements can be used to diagnose septic peritonitis when the blood plasma glucose level is >2.1 mmol/l higher than that of the peritoneal fluid glucose when using a veterinary point of care (poc) glucometer. if using a biochemistry analyser, a whole blood glucose >1.1 mmol/l higher than that of the peritoneal fluid can be used to diagnose septic peritonitis. this is only relevant when the peritoneal fluid is collected by abdominocentesis and not in a postoperative period conclusion at present, there is moderate evidence that glucose measurements are useful as a patient side test for the diagnosis of septic peritonitis and are especially useful in cases where intracellular bacteria cannot be identified on cytology. however, despite the so far promising accuracy results, the cut-offs reported are quite variable and overall, there is not a single diagnostic test that is 100% sensitive and specific in repeated studies. therefore, the results of the glucose measurements should be evaluated alongside other biomarker testing, imaging modalities and the clinical presentation of the patient. glucose measurements cannot currently replace culture / sensitivity and cytology as the gold standard for the diagnosis of septic peritonitis   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a veterinarian is working the out of hours shift when a client brings in their 5 year old golden retriever. the dog is a known scavenger and is now presenting with anorexia, lethargy and abdominal pain. a quick ultrasound scan shows a small amount of free fluid in the abdomen. the veterinarian suspects this is case of septic peritonitis but they could not find any intracellular bacteria in the peritoneal fluid sample they took and cannot wait for results from bacterial culture. the veterinarian wonders if they can measure the glucose levels in blood and peritoneal fluid instead to reliably confirm their working diagnosis. the evidence the search identified three diagnostic test evaluation studies that were related to the pico question. the experimental designs provide a moderate strength of evidence as the studies were generally well planned, the patient follow-up was good and all studies were carried out in a realistic clinical setting. the main limitation in all the studies was the small sample size. summary of the evidence bonczynski et al. (2003) population: mixed population of dogs and cats with naturally occurring peritoneal effusions, presenting at a referral practice. sample size: 18 dogs: seven septic peritoneal effusions 11 nonseptic peritoneal effusions (control group) intervention details: minimum of 1 ml of venous blood and 1 ml of peritoneal effusion collected from all patients and placed into heparinised tubes. the samples were frozen immediately and analysed by the same person each time within 24 hours. study design: diagnostic test validation study. outcome studied: all objective assessments (relevant to the pico question): glucose was measured on all blood and peritoneal fluid samples using a blood chemistry analyser; vettest 8008 analyser (vettest analyzer; idexx). total nucleated cell count was measured on peritoneal fluid in all patients. the blood to fluid glucose (bfg) were measured by subtracting the peritoneal fluid concentration from the blood concentration. all peritoneal fluid samples were submitted for cytology (for presence of intracellular bacteria) and bacterial culture to determine if patients had septic peritonitis (sp) or nonseptic peritonitis (nsp). sensitivity, specificity, positive predictive value (ppv) and negative predictive value (npv) were determined. other biomarkers were measured in this study however they were not directly relevant to the pico question and therefore will not be commented on further in this knowledge summary. main findings (relevant to pico question): peritoneal fluid glucose concentration was significantly lower (p = 0.008) in dogs with septic effusion than those with nonseptic effusion. the median bfg difference was significantly higher in dogs with septic effusion than those with nonseptic effusion (p = 0.0005). a bfg difference >20 mg/dl (>1.1 mmol/l) was 100% sensitive and specific for diagnosis of sp in dogs, with ppv and npv of 100%. in septic dogs, peritoneal fluid glucose measurements <50 mg/dl (<2.8 mmol/l) were 57% sensitive and 100 % specific, with a ppv and npv of 83%. bfg difference is more reliable for diagnosis of sp than peritoneal fluid glucose measurements alone. limitations: small sample size of 18 dogs reduces the reliability of the results. there is an absence of descriptive statistics (breed, age, gender, etc.) for the study population. this is relevant as a more varied population has a greater applicability to general clinical practice. the glucose concentration was determined using a blood chemistry analyser which is not always practical for emergency patient side testing. the control population of dogs were not matched based on clinical history, exam findings or severity of illness and were not that clinically similar to dogs with sp. not all the controls had an inflammatory effusion, some were neoplastic. animals were sampled only once (at presentation). this does not allow for mapping of the changes in biomarker concentration over time. time since onset of disease may affect biomarker concentrations and therefore may reduce the reliability and significance of the results. this study was conducted in a referral practice. patients presenting are typically at a severe stage in the disease process. results from this study may not be directly applicable to patients with the same disease at an earlier or milder stage in the disease process, as is often seen in first opinion general practice. koenig & verlander (2015) population: mixed population of dogs with naturally occurring peritoneal effusions presenting at referral hospitals. sample size: 39 dogs: 17 septic peritonitis (sp); of which six were receiving antibiotics at the time of sampling; 22 nonseptic peritonitis (nsp) (control group); of which 10 were receiving antibiotics at the time of sampling. intervention details: all samples were collected concurrently on first presentation of peritoneal effusion: collection of venous whole blood, kept in heparinised tube. collection of peritoneal fluid via aseptic abdominocentesis. all samples were analysed with a veterinary point of care (poc) glucometer immediately after collection. samples were then centrifuged to obtain plasma and peritoneal supernatant and then tested with a veterinary poc glucometer. study design: diagnostic test validation study. outcome studied: objective outcomes studied (relevant to pico question): glucose concentration in whole blood and peritoneal fluid using a veterinary poc glucometer. glucose concentration in plasma and peritoneal fluid supernatant using a veterinary poc glucometer. peritoneal fluid cytology for bacterial identification and bacterial culture for diagnosis of sp. sensitivity, specificity, positive predictive value (ppv) and negative predictive value (npv) of glucose concentration differences for whole blood to peritoneal fluid (wb-pf), plasma to peritoneal fluid (p-pf) and plasma to peritoneal fluid supernatant (p-pfs) for the diagnosis of sp was determined. other biomarkers were measured in this study however they were not directly relevant to the pico question and therefore will not be commented on further in this knowledge summary. main findings (relevant to pico question): there was a significant and clinically relevant difference in glucose concentration when measured with a veterinary poc glucometer in whole blood versus plasma (p < 0.001) but not between peritoneal fluid and peritoneal supernatant (p = 0.140). when using a veterinary poc glucometer with a cut off of >20 mg/dl (>1.1 mmol/l): wb-pf difference was not an acceptable method of diagnosing sp with a sensitivity of 41.2%, specificity of 100%, ppv of 100% and npv of 68.8%. p-pf difference improved the diagnostic accuracy with sensitivity of 88.2%, specificity of 80%, ppv of 78.9% and npv of 88.9%. when using a veterinary poc glucometer with a cut-off of >38 mg/dl (>2.1 mmol/l): p-pf difference improved the diagnostic accuracy with sensitivity of 88.2%, specificity of 100%, ppv of 100% and npv of 90.9%. p-pf difference had the best diagnostic accuracy at 94.6%. limitations: one dog included in the study was administered dextrose before blood glucose was measured which can elevate blood glucose measurements therefore causing a greater difference between blood and peritoneal fluid glucose concentrations. it may have been assumed that this difference was due to the disease process rather than the administration of dextrose. for a diagnosis of sp, patients had to have bacteria identified on cytology or a positive culture result. however, only 3/22 dogs with nonseptic peritoneal effusion had peritoneal fluid sent for culture. this could have led to a misdiagnosis of a sterile effusion based on a combination of results from cytology and post mortem findings but without the added negative culture result. this may have affected the sensitivity and specificity of the study. if the glucose level in any sample was too low to give an objective reading, the patient would be assigned a glucose level of 20 mg/dl (1.1 mmol/l). in one case this meant there was a minimal difference in fluid glucose as the patients’ blood glucose was 28 mg/dl (1.55 mmol/l) and so the cut-off value of >20 mg/dl could not be reached. therefore, the patient would have been misdiagnosed with a nonseptic effusion. this reduces the sensitivity of the data in terms of using a veterinary poc glucometer and may explain why using a biochemistry analyser is more sensitive. the small sample size reduces the reliability of the results. the researcher conducting the fluid analysis was not blinded to the patient presentation, clinical signs or any other test results. researcher bias will affect the validity of the result, although in this case it may be less significant as the fluid analysis is an objective measure. this study was conducted in a referral practice. patients presenting are typically at a severe stage in the disease process. results from this study may not be directly applicable to patients with the same disease at an earlier or milder stage in the disease process, as is often seen in first opinion general practice. martiny & goggs (2019) population: mixed population of dogs with naturally occurring systemic inflammatory response syndrome and / or peritoneal effusion, presenting at primary and referral practice. sample size: 37 dogs: 18 with septic peritonitis (sp); diagnosed by either positive bacterial culture, intracellular bacteria on cytology or gross evidence of gastrointestinal perforation at surgery. 19 with nonseptic ascites (nsa) (age-matched controls). intervention details: peritoneal fluid sampled via abdominocentesis and placed into heparinised, ethylenediaminetetraacetic acid (edta), 2% sodium citrate and plain tubes. blood samples were collected via venipuncture or intravenous catheterisation and placed into heparinised, edta, 3.2% sodium citrate and plain tubes. study design: diagnostic test evaluation study. outcome studied: samples from sp (18) were paired with (19) age-matched controls for statistical analysis. objective assessments: after sample collection, glucose measurements were immediately obtained using a rapidpoint 405 (siemens medical solutions, norwood), on all heparinised blood and effusion samples (not supernatant). main findings (relevant to pico question): blood-effusion glucose gradient of <37 mg/dl (<2.06 mmol/l) was 89.5% sensitive for the diagnosis of sp but had a low specificity of 66.7%. blood-effusion gradient of glucose in sp dogs had a mean of 3.3 mmol/l and in nsa dogs a mean of 0.3 mmol/l which was a statistically significant difference. blood-effusion gradient of glucose had an area under the receiver operating characteristics (auroc) value of 0.809 which was significant (p = 0.0013) when compared to the line of identity auroc value of 0.5. no single biomarker is completely discriminating for sp and no cut-off offers 100% sensitivity and specificity. limitations: animals were sampled only once however the biomarker concentrations can vary as the disease progresses. this can affect the validity of the results. the small sample size reduces the reliability of the results. the personnel carrying out cytological evaluation of peritoneal fluid varied in their levels of training and experience which could lead to either false negative or false positives in the diagnosis of sp or nsa which would affect the reliability of the results. a standardised approach ensuring people with the same level of training in cytological evaluation carried out the analysis, would achieve more reliable results. the researcher conducting the fluid analysis was not blinded to patient presentation, clinical signs and other test results, although the effects of not blinding will have less of an impact when using objective measurements. this study was conducted in a referral practice. patients presenting are typically at a severe stage in the disease process. results from this study may not be directly applicable to patients with the same disease at an earlier or milder stage in the disease process, as is often seen in first opinion general practice. appraisal, application and reflection the literature search revealed three papers that were directly relevant to the pico question outlined. these were three diagnostic test evaluation studies (bonczynski et al., 2003; koenig & verlander, 2015; and martiny & goggs, 2019). there were two prospective clinical trials (szabo et al., 2011; and guieu et al., 2016) that analysed blood and peritoneal fluid samples following the placement of closed-suction abdominal drains (csad) after surgery, rather than evaluating patients in an acute presentation. although glucose measurements were analysed, both studies did not identify the sensitivity, specificity, positive predictive value (ppv), negative predictive value (npv) or diagnostic accuracy of any of the tests used and so the studies were not included for summary in this report. however, the outcomes highlighted from these studies were that glucose measurements were not reliable in diagnosing septic peritonitis (sp) in postoperative cases in which the peritoneal fluid sampled was collected from a closed suction drain. the study by szabo et al. (2011) used an experimental design in which healthy patients underwent abdominal surgery and were then monitored, which reduces the validity of the results to be applied to clinical practice. the results from these studies are specific to these clinical scenarios and the data should not be applied to patients presenting in an acute scenario or with fluid collected by abdominocentesis. the diagnostic test evaluation studies (bonczynski et al., 2003; koenig & verlander, 2015; and martiny & goggs, 2019) all provided a moderate level of evidence. the studies admitted patients to the study group consecutively over a time period and in accordance to pre-defined inclusion criteria which minimises selection bias. in terms of patients selection, bonczynski et al. (2003) included a wider range of inclusion criteria which meant that all patients with effusions (inflammatory or neoplastic) were admitted to the study group, which may be more representative of cases seen in practice. this study identified a diagnostic sensitivity and specificity of 100% when using blood to fluid glucose (bfg) differences of >1.1 mmol/l to diagnose sp (bonczynski et al., 2003). however, martiny & goggs (2019) identified that bfg gradients did not have a sensitivity, specificity or diagnostic accuracy of 100%. this was likely due to the patient selection for this study. all patients had to have an effusion as well as systemic inflammatory response syndrome (sirs) diagnosed at presentation. this meant that the sp group and the control group of nonseptic ascites (nsa) were clinically very similar and were also age-matched. this study identified that blood-effusion gradients were higher in dogs with sp compared to nsa and this was a statistically significant difference. they also identified that blood-effusion gradients had an area under the receiver operating characteristics (auroc) value of 0.809 which was significant (p-value of 0.0013) when compared to the line of identity auroc value of 0.5, which means that blood-effusion gradients are able to discriminate between sp and nsa (martiny & goggs, 2019). however, the study did not identify a cut-off value for blood-effusion glucose gradients with reasonable sensitivity or specificity, although they did identify that a cut-off of <2.06 mmol/l had a poor specificity of 66.7% but reasonable sensitivity of 89.5%. it is important to note that the studies by bonczynski et al. (2003) and martiny & goggs (2019) both analysed glucose measurements using blood chemistry analysers and blood gas analysers respectively. this can limit the application of the findings in each study to clinical practice as these diagnostic tools are not always readily available. the study by koenig & verlander (2015) overcame this by measuring glucose using a veterinary point of care (poc) glucometer, a tool commonly available in veterinary practice. the study identified that whole blood to peritoneal fluid (wb-pf) concentration differences were insensitive for diagnosis of sp as was plasma to peritoneal fluid, if a cut-off value of >1.1 mmol/l was used. however, this study did identify that a plasma to peritoneal fluid (p-pf) glucose concentration difference greater than >2.1 mmol/l (>38 mg/dl) supported an accurate diagnosis of sp in dogs with peritoneal effusions, with a diagnostic sensitivity of 88.2%, specificity of 100%, ppv of 100% and npv of 90.9% giving a diagnostic accuracy of 94.6% (koenig & verlander, 2015). it is also important to note that when using a veterinary poc glucometer, plasma rather than whole blood produced significantly relevant differences (p <0.001). however, there was no relevant difference when using peritoneal fluid rather than peritoneal fluid supernatant (p = 0.140) (koenig & verlander, 2015). all of the diagnostic test evaluation studies (bonczynski et al., 2003; koenig & verlander, 2015; and martiny & goggs, 2019) carried out a variety of diagnostic tests, including the gold standard reference tests of either cytology and culture and sensitivity, on all patients. this meant that every case of sp was confirmed by cytology and bacterial culture, so the accuracy of the index diagnostic test (blood and peritoneal fluid glucose measurements) was less likely to be overestimated. each study also contained sufficient information for replicability if needed. however, in the studies by koenig & verlander (2015) and martiny & goggs (2019), the researcher carrying out the fluid analysis was not always blinded to the clinical signs, presentation or results of the other diagnostic test. this can lead to an element of conscious bias due to lack of blind independent interpretation, although the significance of this is less important when the diagnostic tests are measuring an objective variable such as glucose concentrations, as in this case. the main limitation for all the studies analysed in this paper is the small sample size which can result in larger confidence intervals, decreasing the power of the study and potentially, its clinical relevance. it is also important to note that all of the studies (bonczynski et al., 2003; koenig & verlander, 2015; and martiny & goggs, 2019) collected data from patients in referral practice. it can be argued that these patients may be presenting with a more severe disease status than those seen in first opinion practice, therefore not being representative of all patients presenting at varying stages of disease. this can make it difficult to make direct applications from the data from these studies to first opinion general practice. furthermore, it is important to note that all the studies (bonczynski et al., 2003; koenig & verlander, 2015; and martiny & goggs, 2019) only sampled the animals once, typically at the initial presentation. single time point sampling does not allow for identification of any changes in biomarker concentration over time therefore, the effect of disease progression on biomarker concentrations cannot be determined, limiting the reliability of these results. the current gold standard for the diagnosis of sp in the pre-operative patient is either the identification of intracellular bacteria on cytology of peritoneal fluid or a combination of a positive bacterial culture of peritoneal fluid alongside cytology results confirming an inflammatory peritoneal effusion. cytology for diagnosis of sp has a reported accuracy of between 57% (mueller et al., 2001) to 87% (lanz et al., 2001) with bacterial culture results yielding an accuracy of between 50% (lanz et al., 2001) to 83% (mueller at al., 2001). the wide range in diagnostic accuracy shows a clear limitation to the gold standard. furthermore, cytological evaluation is subjective and dependent on the skill and expertise of the person analysing the sample. results from bacterial cultures of peritoneal fluid will require around 2–3 days to yield bacterial growth. this is a clear limitation for the critical patient in which decisions must be made in a timely manner to improve patient outcomes. therefore, an accurate patient side diagnostic test would be useful in aiding the diagnosis of sp. in summary, three papers were identified in the literature search, providing a moderate level of strength of evidence. the research has highlighted that a p-pf glucose difference of >2.1 mmol/l (>38 mg/dl) can be used to aid in diagnosis of sp, with a sensitivity of 88.2%, specificity of 100% and diagnostic accuracy of 94.6%, when the peritoneal fluid has been acquired directly from abdominocentesis during the pre-operative period and if measured using a veterinary poc glucometer (koenig & verlander, 2013). however, when using a biochemistry analyser the difference can be lowered to 1.1 mmol/l (>20 mg/dl) with 100% specificity and sensitivity (bonczynski et al., 2003). throughout the research presented there is a large variety in suggested cut-off values when measuring glucose differences. this is due to different studies using biochemistry analysers rather than veterinary poc glucometers as well as comparing whole blood versus plasma and peritoneal fluid versus peritoneal supernatant. this makes it challenging to easily generalise the results to clinical practice. a further study could be carried out to directly compare the sensitivity, specificity and diagnostic accuracy when using different analysers and sample types which may make the results easier to summarise and apply to general practice. based on the strength of the studies analysed, there is only moderate evidence that glucose measurements are useful as a patient side diagnostic test for septic peritonitis therefore this should not be the sole diagnostic test carried out. instead, glucose measurements should be used to build the clinical picture, alongside the patients clinical presentation, information gathered from imaging modalities and any results from cytology and / or bacterial culture of peritoneal fluid. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform (2000–2021) pubmed ncbi (2000–2021) search strategy: cab abstracts: (dogs or dog or canine or canines) and (septic) and (peritonitis or effusion) and (glucose)   pubmed: (dogs or dog or canine or canines) and (septic) and (peritonitis or effusion) and (glucose) dates searches performed: 17 oct 2021 exclusion / inclusion criteria exclusion: papers not written in english. papers not measuring blood and peritoneal fluid glucose or not diagnosing septic peritonitis via the gold standard of culture and sensitivity. this includes any papers not identified as a diagnostic test evaluation study in which diagnostic sensitivity and specificity was not identified (not relevant to pico question). review articles or conference proceedings. papers with no author name, abstract or doi number. inclusion: papers that measured glucose in blood and peritoneal fluid as well as confirmed the diagnosis of septic peritonitis via cytology and / or bacterial culture. the paper must determine diagnostic sensitivity and specificity for using glucose measurements to diagnose septic peritonitis. search outcome database number of results excluded – not written in english excluded – not relevant to pico question excluded – review articles or conference proceedings excluded – no author name, abstract or doi total relevant papers cab abstracts 17 4 9 1 0 3 pubmed 10 0 7 0 0 3 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflicts of interest. references bonczynski, j. j., ludwig, l. l., barton, l. j., loar, a. & peterson, m. e. (2003). comparison of peritoneal fluid and peripheral blood ph, bicarbonate, glucose, and lactate concentration as a diagnostic tool for septic peritonitis in dogs and cats. veterinary surgery. 32(2), 161–166. doi: https://doi.org/10.1053/jvet.2003.50005 guieu, l-v. s., bersenas, a. m., brisson, b. a., holowaychuk, m. k., ammersbach, m. a., beaufrère, h., fujita, h. & weese, j. s. (2016). evaluation of peripheral blood and abdominal fluid variables as predictors of intestinal surgical site failure in dogs with septic peritonitis following celiotomy and the placement of closed-suction abdominal drains. journal of the american veterinary medical association. 249(5), 515–525. doi: https://doi.org/10.2460/javma.249.5.515 koenig, a. & verlander, l. l. (2015). usefulness of whole blood, plasma, peritoneal fluid, and peritoneal fluid supernatant glucose concentrations obtained by a veterinary point-of-care glucometer to identify septic peritonitis in dogs with peritoneal effusion. journal of the american veterinary medical association. 247(9), 1027–1032. doi: https://doi.org/10.2460/javma.247.9.1027 lanz, o. i., ellison, g. w., bellah, j. r., weichman, g. & vangilder, j. (2001). surgical treatment of septic peritonitis without abdominal drainage in 28 dogs. journal of the american animal hospital association. 37(1), 87–92. doi: https://doi.org/10.5326/15473317-37-1-87 martiny, p. & goggs, r. (2019). biomarker guided diagnosis of septic peritonitis in dogs. frontiers in veterinary science. 6, 208. doi: https://doi.org/10.3389/fvets.2019.00208 mueller, m. g., ludwig, l. l. & barton, l. j. (2001). use of closed-suction drains to treat generalized peritonitis in dogs and cats: 40 cases (1997–1999). journal of the american veterinary medical association. 219 (6), 789–794. doi: https://doi.org/10.2460/javma.2001.219.789 szabo, s. d., jermyn, k., neel, j. & mathews, k. g. (2011). evaluation of postceliotomy peritoneal drain fluid volume, cytology, and blood-to-peritoneal fluid lactate and glucose differences in normal dogs. veterinary surgery. 40(4), 444–449. doi: https://doi.org/10.1111/j.1532-950x.2011.00799.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. non-clinical benefits of evidence-based veterinary medicine a knowledge summary by sarah hauser bsc (hons) mpa mpp1* elizabeth l. jackson bag (hons) mba phd sfhea1 1royal veterinary college, 4 royal college st, london nw1 0tu *corresponding author (shauser@rvc.ac.uk) vol 1, issue 3 (2016) published: 22 aug 2016 reviewed by: dr sebastian arlt next review date: 20 aug 2018 doi: 10.18849/ve.v1i3.34 clinical bottom line there are few studies addressing business benefits of evidence-based veterinary medicine (ebvm) while the need for a wider adoption of ebvm has been highlighted and linked to commercial benefits, further empirical studies are needed to identify and quantify such linkages question does the adoption of ebvm by uk veterinary practices (versus the non-adoption) provide commercial benefits? summary of the evidence vandeweerd et al (2012) population: veterinarians (who work in the french-speaking part of belgium) sample size: 201 veterinarians n=201 intervention details: telephone survey and semi-structured face-to-face interviews study design: qualitative data analysis outcome studied: objective assessment of veterinary practitioners’ clinical decision making main findings (relevant to pico question): veterinary practitioners base their decision making on specialist opinion, first-opinion colleagues, laboratories, and on the internet, rather than scientific and peer-reviewed data. a lack of time is the key barrier to a wider adoption of ebvm. adequate information and tools are needed to optimise the time spent on query and assessment of scientific information. practitioners need to be trained in their use. limitations: based on a small population, findings may not apply outside the french speaking part of belgium mateus et al (2014) population: veterinarians sample size: 21 veterinarians from seven veterinary first opinion practices n=21 intervention details: semi-structured interviews study design: qualitative data analysis: thematic analysis using qualitative data analysis software (nvivo) outcome studied: criteria used for selecting antimicrobials influences by colleagues influences by clients pet characteristics sources of knowledge awareness of guidelines and protocols implemented in practice by veterinarians that may affect antimicrobial usage main findings (relevant to pico question): veterinarians make their decisions on antimicrobial use mainly based on individual preference of substance and previous experience. clinical and scientific evidence is not taken into account. the cost of therapy was only found to be a factor in lower socioeconomic areas. three out of 21 participants had a strong perception of the veterinary service as business. they took ‘meeting client expectations’ into their decision making. there was a perceived risk of losing clients to other practices. limitations: very small sample size faulkner (2014) population: na sample size: na intervention details: na study design: ideas, editorials, expert opinion outcome studied: delivering sustainable practice through four outcomes: clinical resolution client satisfaction financial resolution harmony and happiness main findings (relevant to pico question): an evidence-based consultation, using evidence-based diagnostics and treatment is seen as the ideal way of practicing. this may not be attained for practical or technical reasons, or because of lacking client buy in. clients can be dissatisfied with the best evidence-based advice if it does not ‘fit’ with their assumptions and beliefs about their pet’s condition and what should be done about it. limitations: ideas and expert opinion. topics not empirically tested viner (2010) population: na sample size: na intervention details: na study design: ideas, editorials, expert opinion outcome studied: clinical governance provides a framework to help improve standards of care main findings (relevant to pico question): clinical governance provides a framework for organisations to continually improve the quality of service and safeguard the high standards of care. clinical guidelines can assist in applying evidence-based veterinary medicine uniformly but need to be used flexibly with the needs of the individual patient in mind. limitations: ideas and expert opinion. topics not empirically tested kronfeld (2005) population: na sample size: na intervention details: na study design: series of commentaries on evidence-based medicine in equine medicine outcome studied: objective assessment of the factors influencing good clinical decision making. main findings (relevant to pico question): clinical decision making depends on 3 kinds of specific evidence:clinical, experimental, and economic,and 3 general factors:aesthetic, ethical, and social. business success is relevant to clinical decision making. it should be used as an ‘evidence factor’ because it integrates the effectiveness of veterinary services and the whole enterprise. limitations: ideas and expert opinion. topics not empirically tested gibbons (2009) population: na sample size: na intervention details: na study design: ideas, editorials, expert opinion outcome studied: description of how problem-oriented veterinary medicine can help veterinarians refine case information into a diagnosis, satisfy the concerns of their clients, and provide the best possible quality of life for their exotic companion animal patients. main findings (relevant to pico question): problem oriented veterinary medicine (povm), which forms the basis of evidence-based decision making, is a four step cyclical process which includes: (1) gathering case information, (2) identifying problems and assessing evidence, (3) making diagnostic, treatment and client education plans, (4) following up and evaluating progress. by practicing povm, the veterinarian has a guide to achieve the ultimate goals of every case, which are to satisfy the concerns of the client and provide the best possible quality of life for the patient. because in exotic animal practice few diseases and treatments have been researched, the approach is particularly beneficial to exotic animal practice. limitations: the author suggests that a problem oriented approach is good for veterinary business, but does not base this on evidence. holmes and ramey (2007) population: na sample size: na intervention details: na study design: ideas, editorials, expert opinion outcome studied: ebvm is the conscientious, explicit, and judicious use of the current best evidence in making decisions about the care of individual patients main findings (relevant to pico question): the decision-making process in ebvm: the optimal outcome depends on the clinical situation, best evidence, and wishes of the client (and patient). veterinary clinical expertise is required for all aspects of the decision-making process. a practice of adopting ebvm examines common procedures on a regular basis to establish that practice policy is backed up by the current best evidence. applying evidence-based approaches to veterinary care benefits all who participate in the veterinarian-client-patient interaction. limitations: topics not empirically tested ramey (2008) population: na sample size: na intervention details: na study design: ideas, editorials, expert opinion outcome studied: evidence-based veterinary medicine holds the promise of providing the best standard of care for animal patients main findings (relevant to pico question): when making clinical decisions a veterinarian takes into account: (1) their skills as a clinician, (2) a client’s ability and willingness to pay and, (3) their knowledge about a particular medical condition. clinical information not based on evidence can be dangerous to patient health. there is a need to make ebvm information wider available, and veterinarians need to be able to read and interpret study results. cost of treatment is a factor that needs to be included in clinical decision making limitations: topics not empirically tested. there is no direct link between ebvm and commercial benefits to veterinarians, but the paper does highlight that each client’s ability to pay is factored into a veterinarian’s decision making kochevar and fajit (2006) population: na sample size: na intervention details: na study design: ideas, editorials, expert opinion outcome studied: the process of implementing ebvm in small animal practice main findings (relevant to pico question): clinicians must be able to frame relevant answerable clinical questions and they must be able to understand statistical evidence, study design and application of clinical trials the therapeutic approach should be selected by integrating the critical appraisal with clinical expertise and an understanding of the unique circumstances of individual patients and clients. it is important to assess the decision-making process and outcomes continually for effectiveness and efficiency so as to improve future appraisals and outcomes. limitations: na appraisal, application and reflection little research exists on the commercial benefits of ebvm. while the clinical benefits have been fairly well documented, the business aspect of evidence-based veterinary medicine has not. two types of papers were included in this knowledge summary. firstly, non-empirical papers highlighting the perceived connection between ebvm and better business performance. secondly, empirical research that assesses veterinary practitioners’ decision making with regards to commercial benefits of ebvm. despite the specificity of the search terms, the search strategy was dominated by results that focused on specific clinical benefits of ebvm and did not touch on any financial or other commercial benefits.  this knowledge summary specifically focuses on financial, commercial and business impacts of ebvm on the individual business. while financial benefits only include monetary aspects such as profit and loss of a practice, business and commercial benefits include a wider spectrum of benefits such as client satisfaction, client retention and reputation. these benefits are often intangible and difficult to measure but can have a major impact on the success of a business. wider economic benefits, that include potential impacts on the entire economy, such as a decrease in disease outbreaks due to better veterinary practice, are outside the scope of this study. the methodologies used to research veterinary practitioners’ decision making include inductive approaches whereby conclusions were drawn from thematic coding of face-to-face interviews and telephone surveys (vandeweerd et al 2012; mateus et al 2014). some of the published research also consists of literature reviews, published commentaries and expert opinion on the topic and therefore offer opportunities for further exploration, rather than definitive conclusions based on empirical research. while these papers are not based on empirical research, they highlight an existing awareness of the potential business benefits of ebvm, thus these papers were included in this knowledge summary. while many authors (holmes and ramey, 2007; ramey, 2008; gibbons, 2009; faulkner, 2014) describe the application of ebvm in practice and mention the potential commercial benefits to be derived, they do not present any data or key performance indicators that show how the advent of ebvm has improved practice performance via commercial benefits. the aforementioned authors merely present ideas based on improvements to client engagement and possible improvements to business due to better clinical outcomes. studies investigating decision making in veterinarians found that often the business aspect does not feature in a veterinarian’s decision-making process and that ebvm is seen as one of many options to make clinical decisions (vandeweerd et al 2012; mateus et al 2014). a limitation of this study is the use of the two databases (cab abstracts and pubmed), which did not yield some of the grey literature available on ebvm. a further limitation is the very small number of papers published on the topic. this has led to the inclusion of opinion pieces, which are very low down the evidence pyramid and do not provide any empirical evidence on the topic. the reason for their inclusion was to demonstrate that there is recognition of the need for a commercial approach to ebvm.  to conclude, currently no papers provide evidence of any commercial benefits of ebvm. as such, the question relating to whether or not adoption of ebvm by veterinary practitioners leads to commercial benefits, cannot be answered by a review of the literature. while there are many papers suggesting a link between the practice of ebvm and better commercial benefits such as client satisfaction, client retention and lower production costs, a business case to clearly demonstrate the commercial benefits of ebvm is yet to be produced. methodology section search strategy databases searched and dates covered: cab abstracts on the cab direct interface, date range: 1973 2016 and pubmed accessed via the ncbi interface, date range: 1971 2016 search terms: (veterinar* and (business* or practice or practices or management or organisation* or organization* or company or companies)) and ("evidence-based" or "evidence* based" or ebm or ebvm or ebp or ebhc) and ((client* or owner* or consumer* or customer*) and (satisf* or benefit*)).or ("business case*" or economic* or monetary or financ*) or ((business* or commercial*) adj5 (benefi* or gain* or value* or potential* or advantag* or viable or viabilit*)) dates searches performed: february 19th 2016 exclusion / inclusion criteria exclusion: no link between ebvm and business, commercial or financial benefits. business benefits were defined as benefits to the veterinary business, excluded were farming and epidemiological outcomes. non english-language. inclusion: any link between evidence based practice and non-clinical benefits to veterinarians. search outcome database number of results excluded – does not answer pico question excluded – study design excluded – duplicates total relevant papers ncbi pubmed 51 47 1 0 3 cab abstracts 71 57 2 6 6 total relevant papers when duplicates removed 9 conflict of interest the authors declare no conflicts of interest. references faulkner, b. (2014) the colourful consultation: better for owners, pets and staff. european journal of companion animal practice, 24 (4), pp. 46-54. gibbons, p. m. (2009) problem-oriented exotic companion animal practice. journal of exotic pet medicine, 18 (3), pp. 181-186. http://dx.doi.org/10.1053/j.jepm.2009.06.012 holmes, m. a. and ramey, d. w. (2007) an introduction to evidence-based veterinary medicine. veterinary clinics of north america: equine practice, 23 (2), pp. 191-200. http://dx.doi.org/10.1016/j.cveq.2007.03.001 kochevar, d. t. and fajt, v. (2006) evidence-based decision making in small animal therapeutics. veterinary clinics of north america: small animal practice, 36 (5), pp. 943-959. http://dx.doi.org/10.1016/j.cvsm.2006.06.001 kronfeld, d. (2005) case series, owner assessment, and better business. journal of equine veterinary science, 25 (8), pp. 356-359. http://dx.doi.org/10.1016/j.jevs.2005.07.008 mateus, a. l. p. et al. (2014) qualitative study of factors associated with antimicrobial usage in seven small animal veterinary practices in the uk. preventive veterinary medicine, 117 (1), pp. 68-78. http://dx.doi.org/10.1016/j.prevetmed.2014.05.007 ramey, d. w. (2008) an introduction to evidence-based veterinary medicine. proceedings of the 30th bain fallon memorial lectures: dermatology, reproduction, dentistry and evidence-based medicine, cairns, queensland, australia, 14-18 july 2008, pp. 166-175. vandeweerd, j. m. et al. (2012) understanding veterinary practitioners' decision-making process: implications for veterinary medical education. journal of veterinary medical education, 39 (2), pp. 142-151. http://dx.doi.org/10.3138/jvme.0911.098r1 viner, b. (2010) clinical effectiveness: what does it mean for practitioners and cats? journal of feline medicine and surgery, 12 (7), pp. 561-568. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. do inhaled or oral glucocorticoids more effectively control feline asthma? a knowledge summary by savannah clare williams bvmedsci (hons) bvm bvs pgdip(vcp) mrcvs 1* 1university of bristol, langford vets, langford, somerset, bs40 5du *corresponding author (savannah_williams@hotmail.com) vol 7, issue 4 (2022) submitted: 06 dec 2021 published: 07 dec 2022 next review: 10 apr 2024 doi: 10.18849/ve.v7i4.560 pico question in cats with chronic bronchospasm and airway hypersensitivity (asthma) do oral glucocorticoids or inhaled glucocorticoids more effectively control the clinical signs?   clinical bottom line category of research question treatment. the number and type of study designs reviewed three prospective randomised clinical trials were appraised. two of the studies followed a crossover design and had a control group, whilst the third study described an interrupted time series. strength of evidence weak. outcomes reported the available studies deemed a reduction in eosinophilia on bronchoalveolar lavage fluid analysis, and a reduction in airway resistance as markers of treatment efficacy. conclusion there is weak evidence to suggest equal treatment efficacy of oral and inhaled glucocorticoid therapy for management of feline asthma. higher powered studies would be required before a definitive recommendation can be made.   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are presented with a 4 year old cat with a 5 month history of intermittent coughing alongside periods of acute wheezing and respiratory difficulty. clinical examination of the cat is unremarkable. investigations inclusive of bloodwork, thoracic radiography and a bronchoalveolar lavage reveal an eosinophilia, bronchial pattern, and eosinophilic infiltrate, respectively. a faecal baermann test was negative for lungworm larvae. a diagnosis of feline asthma is made. you wish to start the cat on glucocorticoids however, you are unsure whether oral therapy or inhalant therapy is more effective at controlling clinical signs. the evidence database searches identified three papers offering evidence to answer the pico question (verschoor-kirss et al., 2021; leemans et al., 2012; and reinero et al., 2005) once duplicates had been removed. all studies were prospective in nature with two of them following a crossover design (leemans et al., 2012; and reinero et al., 2005). none of the studies were directly comparable due to differences in study population type and differing drug regimens, although the outcomes measured were similar. summary of the evidence verschoor-kirss et al. (2021) population: naturally asthmatic cats that had not received treatment previously. sample size: nine cats. intervention details: cats were randomised into two study groups: four cats received 5 mg oral prednisolone bid for 2 weeks, then sid for 6 weeks; five cats received 5 mg oral prednisolone sid and110 ug of inhaled fluticasone bid for 1 week then 110ug of inhaled fluticasone bid exclusively for 7 weeks. study design: prospective non-blinded randomised clinical pilot trial. outcome studied: changes on thoracic radiography. lung function testing (airway resistance). total nucleated cell count and percentage of eosinophil count from blind bronchoalveolar lavage (bal) samples. serum fructosamine and serum allergy testing were assessed before (baseline) and after (8 weeks post) treatment. main findings (relevant to pico question): after 8 weeks of treatment both groups were absent of clinical signs of asthma as perceived by their owners and clinicians. there was no significant difference between pre and post-treatment thoracic radiographs, as assessed by a semi-quantitative scoring system. airway eosinophilia decreased significantly in all cats (p = 0.003) regardless of treatment modality. 3/4 (75%) cats (on oral therapy reached the therapeutic target point for airway eosinophilia compared to 2/5 (40%) cats treated with inhalant therapy. improvement in airway resistance was more notable in cats treated with oral glucocorticoids although baseline resistance was higher in this group. there was no relationship (r = 0.27) between the percentage of eosinophils in bal fluid and airway resistance. despite therapy, airway eosinophilia and increased airway resistance remained in several cats, even though they appeared clinically normal. both oral and inhalant glucocorticoid therapy improved lung function and airway eosinophilia. limitations: small study population. underpowered study. no placebo group. the cat population underwent lung function testing having not been aerosol challenged, therefore it may not be representative of an asthmatic cat. leemans et al. (2012) population: cats with experimentally induced asthma sensitised to ascaris suum allergen. sample size: six cats. intervention details: feline asthma was induced via two intramuscular injections of ascaris suum allergen, 2 weeks apart, and again 2–4 weeks later followed by a 5 minute long inhalation challenge with 0.01% aerosolised ascaris suum allergen. all cats received each treatment modality with a 4 week recovery interval between each round of treatment. then in a crossover design, the following treatments were administered for 4 days: oral prednisolone (1 mg/kg bid). fluticasone propionate (500 ug bid) via a metered dose inhaler. combination of inhaled fluticasone propionate and salmeterol (500 ug/50 ug) bid. untreated. on day 2 of the treatment course each cat underwent a single 5 minute challenge with 0.01% aerosolised ascaris suum allergen. study design: prospective randomised crossover clinical trial. outcome studied: thoracic radiological assessment via a semi-quantitative scoring system. lung function and airway responsiveness (by barometric whole-body plethysmography [bwbp]). this was assessed immediately prior to airway sensitisation and then at: 5 min, 15 min, 1 hour and 2 hours after challenge, and subsequently every 2h until 8h post challenge. haematology and matrix metalloproteinase (mmp) analysis. bronchoscopic findings. bronchoalveolar lavage (bal) fluid assessment: differential cell counts including percentage eosinophils, total protein content, 8-iso-pgf2a concentration, mmp analysis. main findings (relevant to pico question): there was no significant difference in bwbp between treatment groups. all medications caused a reduction in bal fluid eosinophil percentage, with the oral and combined treatments causing a significant reduction. fluticasone given as monotherapy was less effective than oral prednisolone at reducing the severity of airway eosinophilia. radiological score and bronchoscopic score did not differ between treatment groups (data not shown). limitations: small cohort. lack of crossover evaluation of untreated cats. experimentally induced asthmatic cats may not actively reflect the changes of natural asthmatic cats. cats were not sedated for thoracic radiography and only ventrodorsal and right lateral views were taken which may have affected scoring. reinero et al. (2005) population: cats sensitised to bermuda grass allergen (bga). sample size: six cats. intervention details: feline asthma was induced via subcutaneous administration of bga and sensitisation was confirmed via intradermal skin testing and aerosol challenge. cats were then exposed to each treatment for 2 weeks: prednisone 5 mg po q 12h. flunisolide 250 ug inhaled using a metered dose inhaler q 12h. lt-receptor antagonist (zafirlukast) 10 mg po q 12h. antiserotonergic (cyproheptadine) 2 mg po q 12h. control substance. a 4 week wash out period was maintained in between each treatment and subsequent challenge. study design: prospective randomised placebo controlled crossover. outcome studied: airway resistance. percentage of eosinophils in bal fluid. blood lymphocyte phenotype. serum content of allergen specific immunoglobulin e (ige). serum and bal fluid content of allergen specific immunoglobulin g (igg) and immunoglobulin a (iga). main findings (relevant to pico question): airway resistance was not consistently reduced by any of the drugs in the study. cats that received oral prednisolone or inhaled flunisolide treatments had a significantly reduced mean percentage of eosinophils detected in balf compared to control. inhaled flunisonide did not significantly decrease airway hyperresponsiveness in all cats. limitations: small cohort. disease model may not reflect all facets of natural asthma. appraisal, application and reflection all three studies used a reduction in airway resistance and reduction in airway eosinophilia as measures of treatment success (verschoor-kirss et al. 2021; leemans et al. 2012; and reinero et al. 2005). pulmonary function testing of asthmatic cats offers a non-invasive means of assessing response to therapy, and in the study by (leemans et al. 2012) barometric whole-body plethysmography was used in unrestrained conscious cats to assess changes in airway resistance. in contrast, reinero et al. (2005) and verschoor-kirss (2021), anaesthetised cats before airway challenge commenced and the airway’s response was assessed. leemans et al. (2012) and reinero et al. (2005) did not find a significant difference in the reduction of airway resistance among treatment groups. meanwhile verschoor-kirss (2021) found that there was a greater reduction in airway resistance with oral glucocorticoid treatment compared to baseline than with inhaled therapy. although this study does highlight that cats in the inhaled treatment group started with higher baseline resistance than those in the oral group. regardless of the study design all studies found that when an oral or inhaled therapy was used, treatment resulted in a reduction in airway eosinophilia. however, only leemans et al. (2012) found the decrease in bal fluid eosinophil percentage to be more significant with oral therapy compared to inhaled therapy alone. interestingly, when salbutamol was used concurrently with the inhaled therapy in this study, they found a significant decrease in bal fluid eosinophil percentage also (leemans et al. 2012). an additional method that was used to evaluate treatment response in the asthmatic cat cohorts, was the change in radiographic appearance of the lungs (determined by a clinical score). verschoor-kirss (2021) and leemans et al. (2012) used changes in the radiographic appearance of the lung as a study outcome. thoracic radiographs were assessed before and after treatment administration and assigned a score. however, no significant difference was detected between scores before or after oral or inhaled treatment in either study. two of the three papers chose to assess fluticasone propionate as the inhaled glucocorticoid and prednisolone as the oral glucocorticoid (verschoor-kirss et al. 2021; and leemans et al. 2012) whilst reinero et al. (2005) assessed flunisolide and prednisone. despite two of the studies using the same medications, they were not cross comparable as the doses of the drugs, and length of time for which cats received the oral and / or inhaled glucocorticoid treatment varied greatly. treatment duration varied from 4 days (leemans et al. 2012) to 8 weeks (verschoor-kirss et al. 2021). future studies could consider using varying concentrations of each treatment on the same study population to determine the minimum effective dose to control clinical signs associated with asthma. verschoor-kirss et al. (2021) was the only study that assessed a population of naturally asthmatic cats. clinically their response to treatment is more likely to reflect that of owned asthmatic cats. the treatment protocol in this study differed from the other studies; oral glucocorticoid treatment was given concurrently with the inhalant therapy for 1 week before inhalant therapy was continued exclusively. whilst this makes it more difficult to determine the efficacy of fluticasone as a sole therapy, this treatment protocol is more likely to be reflective of a feline asthma treatment protocol prescribed in general practice. all the clinical studies had low numbers of feline participants and study duration was short. the small cohort numbers reduce the statistical power of each paper’s results and consequently make it difficult to draw confident conclusions. power analysis would be beneficial before performing further prospective, randomised, blinded studies. overall, there is a weak pool of evidence available to determine if oral or inhaled glucocorticoid treatment is more effective at managing the airway inflammation associated with feline asthma. methodology section search strategy databases searched and dates covered: cab abstracts 1973 to 2021 week 46 (via the ovid platform) ovid medline® 1946 to present (via the ovid platform) search strategy: the same search was used for both databases: (cat or cats or feline*).mp. or exp cats/   (asthma* or wheez* or respiratory hypersensitiv* or airway hyper responsiveness or airway hyper-responsiveness or bronchospasm* or bronchial spasm*).mp. or exp asthma/ (glucocorticoid* or glucocorticosteroid*).mp. or exp glucocorticoids/ 1 and 2 and 3 dates searches performed: 10 apr 2022 exclusion / inclusion criteria exclusion: articles where the full text was not available in english; articles not relevant to the pico question; articles listed as: a single case report, conference proceedings, book chapter, or review article. inclusion: articles written in english; relevant to pico question; more than one animal; studies that used an inhaled and oral glucocorticoid as the only treatment. search outcome database number of results excluded – not relevant to the pico question excluded – not available in english excluded – book chapter / conference proceeding / single case report / review article total relevant papers cab abstracts 33 17 5 10 1 ovid medline® 55 50 1 1 3 total relevant papers when duplicates removed 3 orcid savannah clare williams: https://orcid.org/0000-0001-8341-9074 conflict of interest the author declares no conflicts of interest. references leemans, j., kirschvink, n., clercx, c., snaps, f. & gustin, p. (2012). effect of short-term oral and inhaled corticosteroids on airway inflammation and responsiveness in a feline acute asthma model. the veterinary journal. 192(1), 41–48. doi: https://doi.org/10.1016/j.tvjl.2011.01.020 reinero, c. r., decile, k. c., byerly, j. r., berghaus, r. d., walby, w. f., berghaus, l. j., hyde, d. m., schelegle, e. s. & gershwin, l. j. (2005). effects of drug treatment on inflammation and hyperreactivity of airways and on immune variables in cats with experimentally induced asthma. american journal of veterinary research. 66(7), 1121–1127. doi: https://doi.org/10.2460/ajvr.2005.66.1121 verschoor-kirss, m., rozanski, e. a., sharp, c. r., oura, t. j., egan, a., bain, p. & knoll, j. (2021). treatment of naturally occurring asthma with inhaled fluticasone or oral prednisolone: a randomized pilot trial. the canadian journal of veterinary research. 85(1), 61–67. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. does trazodone reduce anaesthetic agent requirement in dogs? a knowledge summary by gemma stewart bsc (hons), rvn 1* 1the royal (dick) school of veterinary studies, easter bush campus, midlothian eh25 9rg *corresponding author (gstewartrvn@hotmail.com) vol 7, issue 3 (2022) published: 03 aug 2022 reviewed by: louise clark (bvms certva dipecvaa msc [clinical management of pain] frcvs) and jodie hughes (bvsc certavp[va] fhea dip.ecvaa mrcvs) next review date: 12 dec 2023 doi: https://doi.org/10.18849/ve.v7i3.530 pico question in dogs undergoing anaesthesia, does the use of oral trazodone given 2 hours before induction of anaesthesia reduce injectable or inhalant anaesthetic agent requirements?   clinical bottom line category of research question treatment the number and type of study designs reviewed two randomised controlled trials were critically appraised strength of evidence moderate outcomes reported trazodone was shown to have a significant isoflurane minimum alveolar concentration (mac) sparing effect for isoflurane. there is also evidence to suggest trazodone has a similar effect on the cardiovascular system as acepromazine conclusion trazodone should be considered as part of a multimodal approach to anaesthesia in dogs to reduce the injectable and inhalant anaesthetic agent requirements   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario patients undergoing anaesthesia require handling, restraint and often painful procedures ahead of anaesthesia in veterinary practice, and many patients display signs of stress and anxiety in response. trazodone is a recognised anxiolytic (gilbert-gregory et al., 2016) that is frequently being used preoperatively in dogs. the purpose of this knowledge summary is to analyse the evidence behind the potential benefits of the use of trazodone ahead of general anaesthesia. trazodone is not licensed for use in dogs in the uk, therefore great consideration must be taken ahead of its administration as the veterinary medicines directorate (gov.uk., 2022) cascade must be followed when using trazodone. the evidence two relevant studies were found that addressed the pico question. one study on research dogs comparing the difference between the administration of trazodone and no premedication on minimum alveolar concentration (mac) (hoffman et al., 2018) and one based in clinical practice comparing trazodone to acepromazine as a premedicant for orthopaedic surgery (murphy et al., 2017). there is evidence that the use of trazodone provides a small reduction in volatile anaesthetic agent requirement but a lack of evidence to support any reduction in injectable induction agent requirements. there is a requirement for further research to directly study trazodone in a wider population of dog breeds and ages with fewer confounding factors and larger study sizes. summary of the evidence hoffman et al. (2018) population: adult healthy hound dogs <1 yrs old, 50% male 50% female. sample size: six dogs. intervention details: randomised into two blinded observer groups: 8 mg/kg trazodone administered orally 2 hours prior to induction of anaesthesia (n = 3). no premedication (n = 3). anaesthesia was induced with 6 mg/kg propofol as an intravenous bolus, the trachea was intubated with a cuffed endotracheal tube and anaesthesia was maintained with isoflurane in oxygen >95%. volume controlled ventilation was used at a rate of 10 breaths per minute, to achieve a tidal volume of 10–15 ml/kg to maintain normocapnia (pe’co2 30–45 mmhg). the same monitoring and active heating devices were used for each participant to maintain body temperature between 37.0–39.0°c. invasive blood pressure monitoring was used throughout the procedure. there was a 60 minute calibration period to allow the elimination of the induction agent propofol prior to minimum alveolar concentration (mac) determination. mac was determined using an iterative bracketing technique where repeated electrical stimulation was administered via two 24 gauge 10 mm insulated needle electrodes, inserted 2 cm apart in the buccal mucosa at 50 v 5 hz over a minute. if gross purposeful movement was made (objective assessment of gross purposeful movement, defined as lifting of the head and / or repeated limb movements, by a single observer), stimulation was ceased immediately. if gross purposeful movement was detected, the concentration of isoflurane was increased until the end expired isoflurane concentration (feiso) was 10% higher, the animal was then given 15 minutes to equilibrate before proceeding to repeat the stimulus. if gross purposeful movement was not detected, isoflurane concentration was reduced until a 20% decrease in feiso was achieved, the animal was then given 15 minutes to equilibrate before proceeding to repeat the stimulus. mac was recorded as the mean feiso between when gross purposeful movement occurred and when it did not in response to electrical stimulation. mac was determined twice per anaesthetic and a third time if the results were not within 10% of each other. there was a 7 day washout period between protocols. study design: randomised controlled trial, crossover design. outcome studied: mac of isoflurane in dogs. haemodynamic variables of dogs following the administration of trazodone. main findings (relevant to pico question): participants who received 8 mg/kg trazodone orally 2 hours prior to induction of anaesthesia had a mac concentration of isoflurane 0.85 ±17% compared with participants who did not receive a premedicant 1.02 ± 0.11% (p = 0.01, 95% confidence interval -0.25–-0.05). no significant differences were found in heart rate, invasive blood pressure or the time to extubation between interventions. limitations: low sample size of the same breed, all under a year in age, may alter the mac of isoflurane. large variation in results. no measurement of trazodone plasma concentration, oral bioavailability may have varied. baseline mac of isoflurane reported in this study is lower than others (barletta et al., 2016). mac of isoflurane is dependent on the frequency of the electrical stimulation, whilst identical to that used in other studies, may not be representative of mac with a greater noxious stimuli such as in invasive surgical procedures. the frequency of the stimulus used may not have been supramaximal leading to animals being at too light a plane of anaesthesia and therefore more close to an approximation of mac awake. murphy et al. (2017) population: systemically healthy, client-owned dogs presenting for cruciate surgery. exclusion criteria were a seizure history or treatment with other medications within five times the half-life of a given product. sample size: 30 dogs. intervention details: participants randomised into two groups: acepromazine 0.01–0.03 mg/kg intramuscularly 30 minutes before induction of anaesthesia (n = 15). trazodone 5 mg/kg if >10 kg or 7 mg/kg if ≤10 kg orally 2 hours prior to induction of anaesthesia (to the nearest quarter of a 50 mg tablet) (n = 15). both groups received: 1 mg/kg morphine sulphate intramuscularly 30 minutes prior to induction. 4–6 mg/kg propofol was administered to effect, intravenously, over 20–30 seconds, to induce anaesthesia. jaw tone, palpebral reflex and reaction to the laryngoscope touching the tongue were assessed by an independent clinician who was not aware that propofol was being studied, until a sufficient plane of anaesthesia was achieved to enable orotracheal intubation. participants had their heart and respiratory rates, mucous membrane colour and capillary refill time, pulse oximetry, end tidal side stream capnography, electrocardiogram (ecg) output, temperature anaesthetic depth and oscillometric non-invasive blood pressure monitored throughout the procedure. when in the operating theatre, participants had an arterial catheter placed to enable direct blood pressure monitoring. participants underwent either a tibial plateau levelling osteotomy (tplo) (n=22) or a tibial tuberosity advancement (tta) (n=8) including pre and postoperative radiography and a preoperative epidural of 0.1 mg/kg preservative free morphine and 0.5 mg/kg bupivacaine. anaesthesia was maintained using isoflurane or sevoflurane, manual ventilation was commenced if indicated based on capnography. blood pressure was initially monitored at 5 minute intervals using a non-invasive oscillometric device until an arterial catheter could be called following induction to enable direct arterial blood pressure monitoring throughout the procedure. intraoperative hypotension was managed with fluid boluses or medication. adjustments were made in the delivery of inhalant in response to hypotension and / or inadequate depth of anaesthesia. concurrent bradycardia and hypotension were treated with glycopyrrolate 0.005 mg/kg. additional analgesia was provided with nitrous oxide or constant rate infusion administration if required. study design: randomised controlled trial. outcome studied: volume of propofol required to induce anaesthesia was recorded by an observer. haemodynamic variables. main findings (relevant to pico question): no significant difference in propofol dose for induction of anaesthesia between groups (p = 0.33). no significant difference in isoflurane vapouriser setting during anaesthesia between groups (p = 0.50). no significant difference in cardiovascular variables between groups for dogs that received inotropic agents heart rate (p = 0.78), mean arterial pressure (p = 0.60), systolic arterial pressure (p = 0.24) or diastolic arterial pressure (p = 0.96). limitations: varying degrees of disease requiring variation in procedure performed and pain can cause differences in anaesthetic agent requirements. dose of acepromazine was selected based on anaesthetist’s preference and demeanour of dog, those receiving higher doses may have required less induction or inhalant anaesthetic agents. trazodone plasma levels were not measured and oral bioavailability may have varied. intraoperative medications varied between participants, affecting the inhalant anaesthetic agent being administered and therefore cardiovascular parameters. morphine dose administered as premedication may have caused enough sedation and propofol sparing to make the differences between the two groups negligible. rapid induction may have resulted in a greater volume of propofol being administered than actually required. drugs and procedures were performed by multiple members of staff at varying levels of qualification including students under supervision causing variations in technique and efficacy of treatments. fraction of expired inhalation agent was not measured in all participants so results are based on a vapouriser setting that may not accurately represent what was delivered to the participant. use of different inhalation anaesthetic agents reduced the number of participants analysed. varying success of epidural anaesthesia adjunct, the use of a consistent highly trained person may have reduced the variation but ultimately when designing the study a more standardised or less invasive procedure may have provided more reliable results. appraisal, application and reflection the randomised controlled trials appraised are designed appropriately to address the pico question (ebvm network, 2021). hoffman et al. (2018) used no treatment as a comparator and murphy et al. (2017) used a recognised premedication acepromazine as a comparator. the level of evidence appraised is level two based on the oxford centre for evidence-based medicine levels of evidence (cebm, 2009) which provides fairly robust evidence towards answering the pico question. there is no higher level of evidence published that was suitable to answer the pico question. both studies are based on objective assessments. randomly allocating the treatment group reduces potential bias from allocation and with the observer. the evidence appraised demonstrates trazodone provides an isoflurane minimum alveolar concentration (mac) sparing effect in anaesthetised dogs (hoffman et al., 2018) and has similar cardiovascular effects to acepromazine in anaesthetised, healthy dogs (murphy et al., 2017). hoffman et al. (2018) provides supporting evidence that trazodone does reduce the mac of isoflurane reported as 1.02 ± 0.11% reducing to 0.85 ± 0.17% with the addition of trazodone to the protocol (p = 0.01, 95% confidence interval -0.25–-0.05). murphy et al. (2017) could find no significant differences between trazodone and acepromazine, a strong comparator which has been shown independently to have a mac sparing effect (monteiro et al., 2016). however, there were multiple confounding factors which may have influenced the results. primarily, this study reported on the reduction in propofol dose required for induction of anaesthesia. no difference was found between the acepromazine and trazodone groups of patients. acepromazine has been shown to reduce the propofol dose required for the induction of anaesthesia (dantino et al., 2021), therefore trazodone may have a similar effect, although difficult to determine due to confounding factors of varied acepromazine doses and rate of propofol administration. acepromazine is known to have a reducing effect on blood pressure in dogs (grasso et al., 2015), therefore by having no significant difference in cardiovascular variables, trazodone may also have an impact on blood pressure. results demonstrated by hoffman et al. (2018) show that blood pressure and heart rate were similar in cases that had received trazodone or higher levels of isoflurane, which would suggest trazodone could have cardiovascular effects. both papers accounted for all of the animals included in the trial in the conclusion. hoffman et al. (2018) report results from all of the animals included in the trial. murphy et al. (2017) state some of the participants in their trial were excluded from the results, mostly because a standardised protocol was not used throughout the procedure, for example the use of isoflurane (n = 28) versus sevoflurane (n = 2). hoffman et al. (2018) used a crossover design to the study, enabling a direct comparison between interventions in all participants. other than the intervention and the comparator, the groups were treated equally in both studies appraised. there are limitations to the research available. inclusion and exclusion factors are well defined in both papers, but participants are not fully representative of all patients undergoing the multitude of procedures performed in practice. whilst they are of the correct species, the evidence focuses solely on systemically healthy dogs. potential candidates with concurrent disease were excluded from both studies, limiting the application of the research in clinical practice where many of the patients suffer with concurrent disease, highlighting an area for further research. there are weaknesses in the murphy et al. (2017) study design, despite being a randomised control trial, that limit the conclusions drawn from the research. no control was used for comparison meaning it cannot be determined whether or not trazodone reduced the quantity of propofol required for the induction of anaesthesia. the comparator, acepromazine, had a 200% variation in dose at the discretion of the anaesthetist, affecting the validity of the results obtained by comparison. further research would be desirable to improve the external validity of the evidence presented. the multiple variables that could be influencing the results in the murphy et al. (2017) study’s conclusion that there are no significant differences between acepromazine and trazodone are concerning and affect the level of reliability of the results. hoffman et al. (2018) do provide reliable results although on a small scale with a narrower population demographic. all of the evidence appraised is based on a single dose of orally administered trazodone 2 hours before the induction of anaesthesia, administered in the clinical setting. as an anxiolytic drug, if administered ahead of the stressor that is travelling and visiting a veterinary practice the effects may be improved and provide a more practical approach to the administration of trazodone as part of a pre-anaesthetic protocol. hoffman et al. (2018) used an 8 mg/kg dose 2 hours before the induction of anaesthesia and murphy et al. (2017) used a 5–7 mg/kg dose depending on body weight. the bsava formulary stated dose for use in dogs to treat chronic anxiety is ‘5–10 kg, 25 mg p.o. q24h; 11–20 kg, 50 mg p.o. q24h; >21 kg, 100 mg p.o. q24h’ (ramsey, 2017). jay et al. (2013) report the time to maximum plasma concentration following oral administration as 445 minutes ± 271 minutes which would mean the 2 hours allowed prior to induction would be inadequate. this could also be problematic when considering adding trazodone as part of premedication as to reach maximum plasma concentration, it would need to be administered 7.5 hours before induction. beneficial effects of the treatment were identified and no significant adverse effects were noted with the administration of trazodone when compared with no intervention or acepromazine. murphy et al. (2017) reported one dog experienced priaprism 24 hours post administration of trazodone which was resolved with treatment, this is a rare side effect also noted in humans (abber et al., 1987). trazodone has been shown to reduce stress in postoperative patients (gruen et al., 2014). this could be extrapolated to patients confined ahead of anaesthesia, who may therefore require less anaesthetic agents to induce and maintain a suitable depth of anaesthesia. there could be an argument for combining it as part of a multimodal approach to the pre-anaesthetic protocol, however, the reported mac reduction of trazodone is less than other agents such as alpha-2-agonists (sinclair, 2003) or opioids (credie et al., 2010). in conclusion, there is some strong evidence to support the intervention of trazodone to reduce the dose of inhalant anaesthetic agent administered. consideration must be taken regarding the use of the cascade due to lack of licensing and the potential for only a modest reduction in mac. administration orally 2 hours before the induction of anaesthesia, may be an inadequate time to reach maximum effect. further research would be beneficial to establish a stronger argument for the inclusion of trazodone in a multimodal anaesthetic protocol. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform 1973–december week 49 2021 medline on ovid platform 1946–december week 49 2021 pubmed 1900–december 2021 web of science 1970–2021 vetmed resource 1972–2021 search strategy: cab abstracts: (cani* or dog*) (anaesthe* or anesthe* or surgery or volatile agent) (trazodone) 1 and 2 and 3   medline: (cani* or dog*) (anaesthe* or anesthe*or surgery or volatile agent) (trazodone) 1 and 2 and 3   pubmed: ((cani* or dog*) and (anesthe* or anaesthe* or surgery or volatile agent)) and (trazodone)   web of science: topic: (cani* or dog*) and topic: (anaesthe* or anesthe* or surgery or volatile agent) and topic: (trazodone)   vetmed resource: (cani* or dog*) and (anaesthe* or anesthe* or surgery or volatile agent) and (trazodone) dates searches performed: 12 dec 2021 exclusion / inclusion criteria exclusion: articles not relevant to pico based on title and abstract, single case reports, duplicate articles and author responses. inclusion: articles written in english which were relevant to the pico based on title and abstract involving multiple animals. search outcome database number of results excluded – not relevant to pico excluded – single case report excluded – duplicate article excluded – author response total relevant papers cab abstracts 10 6 1 1 0 2 medline 7 5 0 2 0 0 pubmed 12 9 0 2 0 0 web of science 10 8 0 2 0 0 vetmed resource 10 6 1 3 0 0 total relevant papers when duplicates removed 2 conflict of interest the author declares no conflicts of interest. references abber, j.c., lue, t.f., luo, j.a., juenemann, k.p. & tanagho, e.a. (1987). priapism induced by chlorpromazine and trazodone: mechanism of action. the journal of urology. 137(5), 1039–1042. doi: https://doi.org/10.1016/s0022-5347(17)44355-2 barletta, m., quandt, j. & hofmeister, e. (2016). determination of minimum alveolar concentration of isoflurane in dogs and cats using the up-and-down method. a preliminary study. research in veterinary science. 106, 81–83. doi: https://doi.org/10.1016/j.rvsc.2016.03.011 centre for evidence-based medicine (cebm). (2009). oxford centre for evidence-based medicine—levels of evidence (march 2009). [online] available at: https://www.cebm.ox.ac.uk/resources/levels-of-evidence/oxford-centre-for-evidence-based-medicine-levels-of-evidence-march-2009 [accessed 28 jan 2021]. credie, r.g., teixeira neto, f.j., ferreira, t.h., aguiar, a.j., restitutti, f.c. & corrente, j.e. (2010). effects of methadone on the minimum alveolar concentration of isoflurane in dogs. veterinary anaesthesia and analgesia. 37(3), 240–249. doi: https://doi.org/10.1111/j.1467-2995.2010.00528.x dantino, s., kleine, s., smith, c., smith, s., zhu, x. & seddighi, r. (2021). evaluation of the effects of intravenous acepromazine and butorphanol on propofol induction dose in healthy dogs. veterinary anaesthesia and analgesia. 48(6), 986–s987. doi: https://doi.org/10.1016/j.vaa.2021.08.012 gilbert-gregory, s.e., stull, j.w., rice, m.r. & herron, m.e. (2016). effects of trazodone on behavioral signs of stress in hospitalized dogs. journal of the american veterinary medical association. 249(11), 1281. doi: https://doi.org/10.2460/javma.249.11.1281 gov.uk. (2022). the cascade: prescribing unauthorised medicines. [online] available at: https://www.gov.uk/guidance/the-cascade-prescribing-unauthorised-medicines [accessed 21 jul 2022]. grasso, ko, j.c., weil, a.b., paranjape, v. & constable, p.d. (2015). hemodynamic influence of acepromazine or dexmedetomidine premedication in isoflurane-anesthetized dogs. journal of the american veterinary medical association. 246(7), 754–764. doi: https://doi.org/10.2460/javma.246.7.754 gruen, m.e., roe, s.c., griffith, e., hamilton, a. & sherman, b.l. (2014). use of trazodone to facilitate postsurgical confinement in dogs. journal of the american veterinary medical association. 245(3), 296–301. doi: https://doi.org/10.2460/javma.245.3.296 hoffman, e.a., aarnes, t.k., ricco pereira, c.h., lerche, p., bednarski, r.m. & mcloughlin, m.a. (2018). effect of oral trazodone on the minimum alveolar concentration of isoflurane in dogs. veterinary anaesthesia and analgesia. 45(6), 754–759. doi: https://doi.org/10.1016/j.vaa.2018.08.002 jay, a.r., krotscheck, u., parsley, e., benson, l., kravitz, a., mulligan, a., silva, j., mohammed, h. & schwark, w.s. (2013). pharmacokinetics, bioavailability, and hemodynamic effects of trazodone after intravenous and oral administration of a single dose to dogs. american journal of veterinary research. 74(11), 1450–1456. doi: https://doi.org/10.2460/ajvr.74.11.1450 monteiro, e.r., coelho, k., bressan, t.f., simões, c.r. & monteiro, b.s. (2016). effects of acepromazine–morphine and acepromazine–methadone premedication on the minimum alveolar concentration of isoflurane in dogs. veterinary anaesthesia and analgesia. 43(1), 27–34. doi: https://doi.org/10.1111/vaa.12265 murphy, l.a., barletta, m., graham, l.f., reichl, l.j., duxbury, m.m. & quandt, j.e. (2017). effects of acepromazine and trazodone on anesthetic induction dose of propofol and cardiovascular variables in dogs undergoing general anesthesia for orthopedic surgery. journal of the american veterinary medical association. 250(4), 408–416. doi: https://doi.org/10.2460/javma.250.4.408 ramsey, i. (2017). bsava small animal formulary: part a: canine and feline / editor-in-chief, ian ramsey. ninth edition. gloucester: british small animal veterinary association. rcvs knowledge (2021). ebvm learning tutorial. [online] available at: http://www.ebvmlearning.org/  [accessed 20 jan 2021]. sinclair, m.d. (2003). a review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice. canadian veterinary journal. 44 (11), 885–897. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. does the use of topical honey result in a faster rate of second intention wound healing in dogs? a knowledge summary by louisa marcombes ma vetmb afhea mrcvs 1* 1university of liverpool, leahurst campus, neston, ch64 7te *corresponding author (louisa.marcombes@gmail.com) vol 5, issue 4 (2020) published: 25 nov 2020 reviewed by: louise anne buckley (phd, rvn) and tim charlesworth (ma vetmb certsas dsas (soft tissue) mrcvs) next review date: 13 feb 2022 doi: 10.18849/ve.v5i4.308 editorial notice: upon conducting the literature search for this knowledge summary the author discovered that the same paper had been published in two separate journals and that a third paper by the same author appeared to have used data from the same experimental subjects as the duplicate publication, despite reporting different methodology. the duplicate publications have been appraised by the author as one paper. the editorial office alerted the journals in question which resulted in the article that appeared in the iranian journal of veterinary surgery (jalali, f.s. s., tajik, h., saifzaideh, s and fartash, b. (2007b) topical application of natural urmia honey on experimental burn wounds in the dog: clinical and microbiological studies. iranian journal of veterinary surgery. 2(2), 13–21) being retracted: http://www.ivsajournals.com/article_114759.html. see our own policy on duplicate publication for more information. pico question in healthy dogs undergoing open wound management, does the topical application of honey, when compared to wounds treated with daily saline washes only, reduce the time to complete wound healing?   clinical bottom line category of research question treatment the number and type of study designs reviewed two studies satisfied the inclusion criteria for answering the pico; both were prospective randomised controlled trials strength of evidence weak outcomes reported the studies demonstrated a possible effect size of clinical importance of the use of honey in the treatment of canine wounds in terms of time to complete wound healing and antibacterial effect. however, the strength of the evidence provided by both studies is severely weakened by flaws in trial design, implementation and reporting, and the possible risk of pseudo replication between the two trials reported conclusion the use of topical honey in canine open wound management may reduce time to complete wound healing. however, the evidence for this is weak. at present, the evidence that use of topical honey in canine wounds reduces time to healing is insufficient to warrant a change in clinical practice   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a 7-year-old, male neutered standard poodle acquired an open wound to the left lateral thorax after having been accidentally scalded with boiling water. the initial dimensions of the wound were approximately 4 cm x 2 cm. the wound was irrigated daily with sterile saline solution and dressed with a non-adhesive dressing. the wound was considered fully healed, defined as fully epithelialised with no eschar or scabbing, 28 days after the accident. would the topical application of honey have resulted in a shorter time to wound healing in this patient? the evidence a systematic literature search found three papers relevant to the pico (jalali et al., 2007a; jalali et al., 2007b; and jalali et al., 2007c). however, two papers (jalali et al., 2007a; and jalali et al., 2007b) were confirmed to be the same paper published in two separate journals and have been designated a duplicated publication. consequently, two papers in total have been critically reviewed for this knowledge summary. it was also noted that jalali et al. (2007a/b) and jalali et al. (2007c) appear to have used data from the same experimental subjects, despite reporting different methodology. both the studies by jalali et al. (2007a/b; and 2007c) were prospective randomised controlled trials using experimentally induced burn wounds in dogs. they both reported that honey decreased the time to wound healing in dogs when compared to the saline-treated control. objective outcomes measured by jalili et al. (2007a/b) and jalali et al. (2007c) included observation of macroscopic wound changes during healing and qualitative and quantitative microbial assessment of the wounds at days 0 and/or 1, 3, 7, 14 and 21 and compared with a saline control. in addition, jalali et al. (2007a/b) measured the reduction of the wound area over time and jalali et al. (2007c) compared the microscopic appearance of honey-treated and control wounds at day 21. neither study provided a definition for complete wound healing nor had a clearly stated endpoint and both appear to have concluded before wound healing was complete (jalali et al., 2007a/b; and jalali et al. 2007c).  as a result, ‘time to wound healing‘, considered a fundamental outcome measure for the pico was not reported, despite the authors claiming it was a primary objective. furthermore, the results relied heavily on subjective descriptive narrative, were profoundly exposed to the influence of bias and often overstated. consequently, the confidence that the effect reported resembles the actual effect of honey on wounds is low, the evidence cannot be used to answer the pico reliably and, by extension, inform a change in clinical practice. summary of the evidence jalali et al. (2007a and 2007b) population: healthy, adult (4.5 ± 0.5 years old), medium sized (20 ± 4.25 kg) ‘mongrel‘ dogs of both sexes sample size: 10 wounds (10 dogs) intervention details: healthy dogs were selected on the basis of a physical examination and blood test (‘cbc’ and serum biochemistry). animals were kept in individual cages and had access to food and water ad libitum. honey samples, from targarvar bee keeping corporations, urmia, were filtered with a sterile mesh and stored at 2–8 ⁰c until used. five dogs were randomly assigned to either a control (cg) or honey treatment (htg) group and then anaesthetised (anaesthetic protocol provided) and a single experimental burn wound on the dorsum (hoekstra model brans et al., 1994), resulting in a wound area of 2 cm x 3 cm. in the experimental group, 10 ml of undiluted urmia honey was applied once daily. in the cg, the burns were treated with normal saline. after daily treatment, all wounds were covered with a non-adhesive dressing. all wounds were observed for evidence of infection, exudation or leakage until healing. on days 0, 7, 14 and 21, quantitative and qualitative microbiological assessments were carried out for each wound. digital photographs of each wound were taken on days 0, 7, 14 and 21. photographs were scanned and wound areas measured using digital scanning software (sigmascan pro 5.0 software). study design: non-blinded, prospective randomised controlled study outcome studied: primary outcomes: description of macroscopic changes during wound healing including degree of exudation, oedema, formation of granulation tissue and presence of epithelialisation (subjective). wound area in mm2 and % decrease in wound area on days 0, 7, 14, 21 (objective). secondary outcomes: qualitative description of microbial population on days 0 (methods) and/or 1 (abstract), 7, 14, 21 (objective). quantitative estimation of bacterial numbers (x 105 cm-1) day 0 (methods) and/or 1 (abstract), 7, 14, 21 (objective). statistical analysis:  an unpaired student’s t-test was used to compare the two groups for bacterial count and wound area size. a p < 0.05 was used to indicate significance. main findings (relevant to pico question): description of macroscopic changes (subjective, generalised commentary comparing all wounds across both groups): day 1 and 2: no gross difference in wound appearance between the treatment groups (htg and cg); inflammation and exudation observed. day 7: crusting of htg wounds with evidence of epithelialisation. cg wounds still inflamed and exudative. day 14: htg wounds reduced considerably in size and recognised as healed, the wounds of the cg were still crusting. day 21: the wounds of the htg were approximately closed; the wounds of the cg were still crusting. these results indicate a possible treatment effect of honey, although it is impossible to determine its magnitude.   comparison mean wound area reduction (mm2): day 0: htg (n = 5) 688.60 mm2, standard deviation (sd) = 42.22 mm2. cg (n= 5) 644.18 mm2, sd = 64.86 mm2. no significant difference between the groups at day 0. day 7: htg (n = 5) 364.40 mm2, sd = 16.26 mm2. cg (n = 5) 486.60 mm2, sd = 44.82 mm2. the mean wound size of the htg at day 7 is significantly smaller (p < 0.05. day 14: htg (n = 5) 62.24 mm2, sd = 24.44 mm2. cg (n = 5) 206.86 mm2, sd = 48.26 mm2. the mean wound size of the htg is significantly smaller than the cg at day 14 (p < 0.05. day 21: htg (n=5) 10.64 mm2, sd = 8.64 mm2.   cg (n = 5) 89.58 mm2, sd = 12.84 mm2. the mean wound size of the htg at day 21 is significantly smaller than the cg (p < 0.05.   qualitative description of microbial population: ‘before commencement of the study [sic]’; escherichia coli, staphylococcus aureus, streptococcus pyogenes and candida albicans were isolated from the skin of dogs in both groups. day 1, 3 and 7; s. aureus and e. coli were isolated from wounds of the htg. e. coli, s. aureus, s. pyogenes and candida albicans were isolated from the wounds of the cg dogs. day 14; s. aureus and e. coli were isolated from the wounds of the htg. s. aureus and e. coli from the cg. day 21; s. aureus was isolated from the htg and the cg. the spectrum of microbial colonisation is comparable to those of burn wounds in studies elsewhere.   quantitative estimation of mean (assumed) microbial count (cm-2): ‘before commencement of the study’: htg = 9.00 x 105 cm-2, sd = 0.50 x 105 cm-2. cg = 2.00 x 10 4 cm-2, sd = 0.60 x 104 cm-2. the bacterial count of the htg is significantly higher than the cg at day 0 of the study (p < 0.05, calculated by l marcombes). day 1: htg = 5.00 x 105 cm-2, sd = 0.60 x 105 cm-2. cg = 3.00 x 104 cm-2, sd = 0.60 x 104 cm-2. the bacterial count is significantly higher in the htg on day 1 (p < 0.05, calculated by l marcombes). day 7: htg = 1.00 x 106 cm-2, sd = 0.6 x 106 cm-2. cg = 7.00 x 105 cm-2 sd = 0.6 x 105 cm-2. on day 7 there is not significant difference in mean microbial count between the htg and cg. day 21: htg = 3.00 x 104 cm-2, sd = 0.30 x 104 cm-2. cg = 3.00 x 105 cm-2, sd = 0.50 x 105 cm-2. at day 21 the mean bacterial count of the cg is significantly higher than the htg (p < 0.05. limitations: the randomisation process was not adequately described. there was a lack of blinding for the evaluation of outcomes. the start and end point of the study was poorly defined. the duration of the study was stated to be 28 days; however, data was only collected up to day 21. this loss of data is unexplained. the end point (21 days) was not justified. the sample size was very small and not justified by a power calculation. no null hypothesis was provided for statistical testing. time taken to wound healing for each wound was stated as a measured outcome, however this was not reported. a definition of complete wound healing was not given. it was not stated whether or not there were any losses from the study. the methodology for quantitative and qualitative microbiological data collection was not adequately described. the described methods were not consistent with reported results; it was stated microbiological assessment was done on days 0, 7, 14 and 21. however, microbiology data of both groups was reported for day 1 and 3 instead of day 0. no reason was given for this discrepancy. the collection of microbial data on day 3 was not mentioned in the methods section. there is an inconsistency in naming timepoints (e.g. “day 0” and “before commencement of the study”), they are used interchangeably and without justification. for the gross macroscopic changes, quantitative and qualitative microbial data, it is not clear if the results given are of individual wounds or an overall trend in the study group. the treatment group had a significantly higher microbiological count prior to the study, an indication the two groups were not from the equivalent populations prior to the study. the authors fail to discuss why microbial count increased in the htc during the first 7 days when they claimed their results showed an antimicrobial effect. there was no discussion of study limitations and an overall tendency to overstate findings; the phrase “potent topical agent” is used to describe honey in the abstract. the standard used for the method of burn injury was based on a porcine model, the suitability of this standardisation for canine skin is an assumption. the results of a stated outcome measure (time to wound healing) were inadequately reported. the identical paper appears to have been published in two separate journals, which constitutes a potential violation of the ethics of academic publication, a possible infringement of copyright law, and pads the evidence-base with redundant material. the paper reports almost identical results to another publication (jalali et al., 2007c), despite discrepancies and omissions between the methods of the two studies, which calls into question the authenticity of the results. data missing for quantitative microbial count on day 3 and day 14. a significantly higher bacterial count in the htg at day 0 suggests this study was not adequately controlled. conflicts of interest (or absence of) not declared. jalali et al. (2007c) population: adult (4–5 years old), medium sized (21 ± 4.24 kg), ‘mongrel‘ dogs of both sexes sample size: 15 wounds (15 dogs), five wounds per study group intervention details: the animals were kept in individual cages. the dogs were randomly divided into three study groups: control (cg = 5); honey treatment (htg = 5); and silver sulphasalazine treatment (ssd = 5). all animals were anaesthetised (anaesthetic protocol given) and an experimental 2 cm x 3 cm burn was created using a standardised technique (hoekstra model) over the dorsal thoracolumbar area. honey was sourced from beehives in urmia, filtered with a sterile mesh and stored at 2–8 ⁰ the samples were collected and prepared by one investigator while experiments were performed blindly by the others. the groups had received the following treatment: control: daily washing with saline. honey-treated: wounds were washed daily with normal saline then 5 ml of honey was administered topically. ssd-treated wounds: 5 ml of 1% ssd ointment applied. all wounds were covered with non-adhesive dressing after daily treatment. study design: prospective blinded randomised controlled trial outcome studied: primary outcomes: time taken to complete wound healing description of macroscopic changes during wound healing including degree of exudation, oedema, formation of granulation tissue and presence of epithelialisation (subjective). description of microscopic features of wound healing at day 21 (subjective). secondary outcomes: qualitative description of microbial population on days 1, 7, 14, 21 (objective). quantitative estimation of bacterial numbers (x 105 cm-1) day 1, 7, 14, 21 (objective). statistical analysis: the time taken to healing and total bacterial count of the three groups were compared for significant difference using a one-way analysis of variances (anova). a p < 0.05 was considered significant. main findings (relevant to pico question): (data set for ssd treatment group has been omitted as not relevant to the pico question)    time taken to complete wound healing: htg: all wounds considered fully healed on day 21. cg: not reported; however, not fully healed by day 21.   observation of gross wound healing: day 1, 2: no difference in appearance (necrosis and inflammation) between htc and cg. day 7: htg wounds showed signs of epithelialisation, whereas the cg wounds retained an inflammatory appearance. day 14: the htg wounds were at a more advanced stage of healing than the cg. day 21: hcg were almost completely healed, whereas wounds of the cg were still significantly ulcerated.   observation of microscopic wound healing: day 21: htg had microscopic features of more mature granulation tissue and reduced inflammatory cells population when compared to the control group.   qualitative microbial assessment: day 1, 3, 7: candida albicans, s. pyogenes, s. aureus and e. coli were isolated from cg, and s. aureus and e. coli isolated from the htg. day 14: s. aureus and e. coli were isolated from cg and the htg. day 21: s. aureus was the only isolate found in the control and treatment groups.   quantitative estimation of mean (assumed by the author of this knowledge summary) microbial count (cm-2): ‘before the use of preparations’: htg = 9.00 x 105 cm-2, cg = 2.00 x 104 cm-2. mean values only provided, so unable to calculate the significance of the difference between the two groups. day 21: htg = 3.00 x 104 cm-2 cg = 3.00 x 105 cm-2 microbial count in htg group is significantly lower at day 21 (p <0.05). limitations: the process of randomisation was not adequately described. the process of blinding was not adequately described, particularly as it is a challenge to use honey in blinded trials due to its appearance and odour. the start and end point of the study was poorly defined. a definition of wound healing was not given. experimental subjects were not adequately screened for co-morbid disease and generally very limited information was provided about their environment during the study. the end point (21 days) was not justified. a small study population was used and there was no power calculation to justify this. no null hypothesis given for statistical testing the methodology for quantitative and qualitative microbiological data collection was not adequately described. qualitative and quantitative microbial data provided for “day 3”, despite this not being mention in abstract or methods. the authors fail to discuss why microbial count increased in the htg during the first 7 days when they claimed their results showed an antimicrobial effect. the standard used for the method of burn injury was based on a porcine model, the suitability of this standardisation for canine skin is an assumption. it is not stated if any animals/wounds were lost to the study.   time to healing for the cg is not given. most of the results were given over to a generalised narrative of macroscopic and microscopic features of healing in the three groups, which is highly subjective and impossible for the reader to draw any meaningful conclusion. microbial outcomes are identical to data published elsewhere (jalali et al., 2007a/2007b) which suggests the same experimental data set has been used, despite having been subjected to different methodology. incomplete reporting of statistical analysis. for the gross macroscopic and microscopic changes, and quantitative and qualitative microbial data, it is not clear if the results given are of individual wounds or an overall trend in the study group. there is an inconsistency in naming timepoints (e.g. ‘day 0’ and ‘before commencement of the study’), they are used interchangeably and without justification. quantitative microbial data not adequately reported. conflicts of interest (or absence of) not declared appraisal, application and reflection numerous clinical properties have been attributed to honey, including antimicrobial activity, a debriding action, anti-inflammatory effect, antioxidant activity, stimulation of wound granulation and epithelialisation (van hengel et al., 2013). this has prompted a degree of research activity in the veterinary and human medicine fields to determine if these properties have a clinical application in wound healing. this knowledge summary seeks to appraise the evidence for the effect of topically applied honey on the healing rate in canine wounds when compared to a saline control. a literature search initially found three papers that met the search criteria (jalali et al., 2007a; 2007b; and 2007c). two papers (jalali et al., 2007a; and 2007b) were found to be an identical manuscript in two different journals and therefore have been treated as a single publication in this summary. furthermore, the third study by this group, (jalali et al., 2007c), is strongly suspected of having derived data from the same experimental procedure, despite there being a disparity in the methods used and outcomes measured, which  degrades  the evidence. the measurement of wound healing of the skin is a visual process and therefore, one would intuit, relatively easy to implement in the experimental setting. however, care must be taken to ensure that appropriate end points are used and to minimise the risk of bias in measurements (gottrup et al., 2010). a further challenge to experiments involving topical wound treatments is the difficulty of implementing an effective blinding protocol. this is particularly tricky in the case of honey, with its distinct colour and odour.  both papers (jalali et al., 2007a/b; and jalali et al., 2007c) used an unjustified end point of 21 days, and jalali et al. (2007c) claimed that their trial was blinded, although the method of blinding was not reported. it was not stated by jalali et al. (2007 a/b) whether or not blinding was used. the experimental variable most relevant to the pico is time to complete wound healing. both studies (jalali et al., 2007a/b; and jalali et al., 2007c) claimed to have measured this, despite having failed to define complete wound healing. in addition, both used an end point which appeared to be set before wound healing was complete in the control groups. overall, the results provided were ambiguous, with opaque, sweeping statements such as ‘on day 21, the wounds gaps of treatment group [sic] were approximately closed‘ (jalali et al., 2007 a/b). as it is apparent that the trials were concluded before the wounds were fully healed, they cannot provide the evidence most pertinent to the pico. jalali et al. (2007a/b) instead recorded the wound healing rate by measuring the reduction of wound area over time. this has been shown to be a useful comparator between treatment groups in human studies (gotrupp et al., 2010). the method for measuring wound area, however, needs to be carefully standardised as measurements can be subject to over-estimation of up to 44% due to irregular wound shape (schutz et al., 2005) and therefore risk of under-estimation of the rate of healing. jalili et al. (2007 a/b) measured this outcome using computer-assisted analysis of digital photographs. the software used, sigmascan pro 5.0 (spss science, chicago, il), has been shown to have an accuracy  within 4.7% (95% ci 3.4% – 5.9%) (molnar et al., 2009) and so there is confidence that measurements taken using this method should yield reliable results, which here have demonstrated that the mean honey treated wound area was significantly smaller than the control at days 7, 14 and 21 (p < 0.05). both papers (jalili et al., 2007a/b; and jalali et al., 2007c) used qualitative and quantitative microbiological data as evidence that honey possesses antibacterial properties. the qualitative data consisted simply of a list of the micro-organisms isolated from each group at days 0 (jalali et al., 2007 a/b), 1 (jalali et al, 2007c), 3, 7, 14 and 21 days. the spectrum of isolates over time was similar for both groups, and the authors did not comment further on this, except to state the range organisms isolated were similar to those of a historical human study (lawrence, 1994) therefore the relevance of this variable to the pico remains poorly elaborated and its evidential value doubtful. the quantitative bacterial results (jalili et al., 2007a/b; and jalali et al., 2007c) showed bacterial counts from the honey-treated wounds were  significantly lower at day 21 (p < 0.05) and the authors claimed that this demonstrated an antimicrobial effect.  however, the data also showed a higher bacterial count in the honey-treated group up to day 14, which appears to contradict this claim, and this anomaly was not discussed. the discrepancy was, however, mitigated by the fact that wounds in the treatment group appeared to have had a significantly higher bacterial count at day 0. but then this would suggest the control and treatment groups were not equivalent and that the trial was not adequately controlled. a systematic review has shown of human burns studies has shown that high wound bacterial counts may predict worse clinical outcomes (halstead et al., 2018). they also found that wound swabs are relatively insensitive in discriminating clinically significant wound infection from incidental wound contamination, and that serial tissue culture, via biopsy, is a superior technique for quantifying bacterial load of wounds. consequently, the quantitative microbial data derived from wound swabs by jalali et al. (2007a/b; and 2007c) is unlikely to be reliable, and so this variable cannot be used to answer the pico. it was also noted that the microbiological data reported by both papers were identical, suggesting it was derived from the same experimental procedure, despite differing methodology. a recent cochrane review of the use of honey in human wound healing (jull et al., 2015) reported there was some good quality evidence that honey heals partial thickness burns more quickly than conventional dressings, and that honey is more effective than antiseptic for healing infected post-surgical wounds. however, the authors were ultimately obliged to downgrade most of the evidence derived from the 26 studies found, due to high risk of bias and problems of study design. which are issues similar to those identified in the papers that have been appraised for this knowledge summary. an early draft of the pico had specified manuka honey as the treatment intervention. honey from different flower sources vary in their biological properties, and monofloral manuka honey is considered to possess antibiotic and antioxidant properties superior to those of honey derived from other sources (alvarez-suarez et al., 2014). it is the medical-grade form of manuka honey that is used most widely and it was considered that studies using manuka honey would be most relevant to clinical practice. somewhat surprisingly, no studies using manuka honey on canine wounds were found, and the pico had to be expanded to encompass all forms of honey. jalili et al. (2007a/b) and jalali et al. (2007c) used urmia honey, which was not medically graded and therefore likely to limit relevance to clinical veterinary practice. a couple of studies were found that tested manuka honey in experimental wounds in other species. a randomised, controlled study in equine patients (bischofberger et al., 2013), of moderate evidential quality, supported the hypothesis that honey reduces time to complete wound healing, here defined as ‘when granulation tissue was no longer visible‘. in addition, haryanto et al. (2012) have shown that manuka honey accelerates the formulation of granulation tissue during wound healing in mice. honey is purported to possess properties that provide favourable healing conditions for every stage of the healing pathway (inflammatory, debridement, granulation, contraction/epithelialisation). however, this is in contrast to the general convention in veterinary clinical practice of limiting the use of honey to the inflammatory and debridement stages only (van hengel et al., 2013). nakajima et al. (2013) observed that japanese honey appeared to retard the granulation and contraction phases of wound healing in a murine model. furthermore, haryanto et al. (2012) demonstrated, also in a murine model, that manuka honey might delay the wound-contraction phase. this highlights the need for future studies that adopt a study design which discriminates between the healing phases, as this may allow a more substantial treatment effect of honey to be demonstrated. this knowledge summary has found that there is weak evidence (jalali et al., 2007a/b; and jalali et al., 2007c) that topical honey may have reduced the healing time from 28 days in the clinical scenario case. however, this evidence is of such low quality due to the high risk of bias, problems with the study design, and ambiguous results of the two papers appraised, that it cannot be used to justify a change in clinical practice. although, supported by the better-quality evidence found elsewhere, it does justify further research effort into the effect of topical honey on wound healing rate. adequately powered, randomised and blinded trials, using medical grade manuka honey, and scrutinising each healing stage may be powerful enough to reveal a treatment effect that has been diluted in studies to date. the confirmed antibiotic effect of honey in the clinical setting would be of particular interest as a means of reducing the use of systemic antibiotics in canine wound care. methodology section search strategy databases searched and dates covered: cab abstracts on ovid interface (1973–2020 week 05) pubmed on the ncbi interface (1960–2020 week 05) search strategy: cab abstracts: (dog or dogs or canine* or canis or bitch* or puppy or puppies or pup or pups).mp. or exp dogs/ or exp bitches/ or exp puppies/ or exp canidae/ or exp canis/ (wound* or lesion* or burn* or abrasion* or ulcer* or 'infected wound' or 'open wound' or 'wound breakdown').mp. or exp wounds/ (honey* or manuka or inhibines or apipharmacothera*).mp. or exp honey/ (heal* or improv* or regenerat* or epitheli* or harm* or advers* or toxic* or efficac* or safe* or effect* or hyperaem* or angiogen* or granulat* or contract* or antimicrob* or anti-microb* or 'anti microb' or antibacter* or anti-bacter* or 'anti bacter*' or 'secondary intention').mp. or exp antibacterial agents/ 1 and 2 and 3 and 4 pubmed: dog or dogs or canine or canis or bitch or bitches or puppy or puppies or pup or pups wound or lesion or burn or abrasion or ulcer or infected wound or open wound or wound breakdown  honey* or manuka or inhibines or apipharmacothera* 1 and 2 and 3 dates searches performed: 13 feb 2020 exclusion / inclusion criteria exclusion: conference proceedings, single case reports, case series, non-systematic reviews, articles not relevant to the pico, articles that were not accessible and chapters from textbooks. any language not in the english or french language. studies that used honey mixed with another substance. inclusion: studies that used dogs as subjects, studies that involved more than one animal, or controlled trials. the studies were required to examine the effect of topical honey on canine wounds. search outcome database number of results excluded – proceedings, single case reports, etc. excluded – not relevant to the pico excluded – in a language other than english or french excluded – duplicated publication excluded – not accessible total relevant papers cab abstracts 79 17 57 2 1 0 2 pubmed 23 1 22 0 0 0 0 total relevant papers when duplicates removed 2 conflict of interest the author declares no conflicts of interest. references alvarez-suarez, j. m., gasparrini, m., forbes-hernández, t. y., mazzoni, m. and giampieri, f. (2014). the composition and biological activity of honey: a focus on manuka honey. foods, 3(3): 420–432. doi: https://doi.org/10.3390/foods3030420 brans, t. a., dutrieux r. p., hoekstra, m. j., kreis, r. w. and du pont, j. s. (1994). histopathological evaluation of scalds and contact burns in the pig model. burns 20(1): s48–s51. doi: https://doi.org/10.1016/0305-4179(94)90090-6 bischofberger, a. s., dart, c. m., perkins, m. r., kelly, a., jeffcott, l. and dart, a. j. (2013). the effect of shortand long-term treatment with manuka honey on second intention healing of contaminated wounds and noncontaminated wounds on the distal aspect of the forelimb in horses. veterinary surgery, 42(2): 154–160. doi: https://doi.org/10.1111/j.1532-950x.2012.01083.x gottrup, f., apelquist, j. and price, p. 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(1994). burn bacteriology during the last 50 years. burns 18: 23–29. molnar, j. a., lew, w. k., rapp, d. a., gordon, e. s., voignier, d., rushing, s. and willner, w. (2009). use of standardised, quantitative digital photography in a multicenter web-based study. eplastyi, 9(e4). nakajima, y., nakano, y., fuwano, s., hayashi, n., hiratoko, y., kinoshita, a., miyahara, m.,  mochizuki, t., nishino, k., tsuruhara, y., yokokawa, y., iuchi, t., kon, y., mukai, k., kitayama, y.,  murakado, m., okuwa, m. and nakatani, t. (2013). effects of three types of japanese honey on full-thickness wound in mice. evidence based complementary and alternative medicine, volume 2013: 1–11. doi: https://doi.org/10.1155/2013/504537 schultz, g., mozingo, d., romanelli, m. and klaxton, k. (2005). wound healing and time; new concepts and scientific applications. wound repair and regeneration, 13(4): s1–s11. doi: https://doi.org/10.1111/j.1067-1927.2005.1304s1.x van hengel, t., ter haar, g. and kirpensteijn, j. (2013). chapter 2: wound management: a new protocol for dogs and cats in reconstructive surgery and wound management in the dog and cat eds kirpensteijn, j and ter haar, g. london: manson publishing ltd, 21–48. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. does soybean intravenous lipid emulsion therapy reduce time to recovery faster than clinoleic therapy in cats with permethrin toxicosis? a knowledge summary by shadira gordon dvm mpvm 1* 1university of california, davis, one shields ave, davis, ca 95616 *corresponding author (dsgordon@ucdavis.edu) vol 6, issue 4 (2021) published: 04 nov 2021 reviewed by: jacqueline renee cole (bsc bvetmed mrcvs) and merran govendir (bvsc phd med manzcvsc fherdsa) next review date: 10 oct 2023 doi: 10.18849/ve.v6i4.469 pico question is soybean oil-based intravenous lipid emulsion (ivle) therapy more effective than olive oil-based (clinoleic ivle therapy) for reducing time to recovery in cats with permethrin toxicosis?   clinical bottom line category of research question treatment the number and type of study designs reviewed five case reports and one randomised clinical trial strength of evidence weak outcomes reported soybean oil-based and clinoleic ivle therapies can be used safely as adjuvant treatments to reduce time to recovery in cats with permethrin intoxication. however, the evidence collected suggests that soybean oil-based ivle therapy is faster than clinoleic to reduce time to recovery after permethrin toxicosis conclusion the overall findings showed that the average recovery time after soybean oil-based ivle therapy between patients with permethrin intoxication was 8.5 hours and the average time to recovery after olive oil-based emulsions (clinoleic therapy) was 39 hours. this may suggest that soybean oil-based formulations are a better option for reducing the recovery time in cats after permethrin toxicity. dermal decontamination, supportive care, muscle relaxers, and anticonvulsant drugs are examples of recommended treatments before the administration of any intralipid therapies and must be used based on the clinical signs of each patient   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a 4 year old spayed female domestic short-haired cat presents to your emergency room with seizures and hypersalivation. the owners described the first episode of seizures occurring almost 3 hours after applying a permethrin spot-on (pso) product with a formulation higher than ≈ 45% directly on their cat's coat. this scenario is common in emergency rooms, as owners do not know that permethrin-based products intended to control ectoparasites in dogs should not be used in cats1-5. these highly concentrated formulations may cause severe clinical signs or death, even by secondary exposure (e.g., licking, grooming, or having close contact with recently treated dogs)6. the owners are concerned about their cat's welfare and the associated costs of treatment. you discuss with them two novel intralipid therapies useful for reducing hospitalisation times (soybean oil-based therapy and clinoleic therapy). the evidence five case reports (pelizzola et al., 2018; ceccherini et al., 2015; haworth et al., 2012; brückner et al., 2012; and kuo et al., 2013) and one randomised clinical trial (peacock et al., 2015) were evaluated because of their relevance to the pico question. the pelizzola et al. (2018) study evaluated three young cats treated with soybean oil-based ivle therapy. the outcome measured in this study was the time to recovery after ivle therapy administration and all the cases showed neurological improvement with an average time to recovery of 10 hours. the ceccherini et al. (2015) study evaluated four cats between 2–14 years old. this case-report showed a mean time to recovery of 5 hours after soybean oil-based ivle therapy. haworth et al. (2012) provided evidence on three adult cats in which all showed neurological improvement after soybean oil-based ivle therapy after an average time to recovery of 8.3 hours. the brückner et al. (2012) study was the only one in which two patients were treated with the clinoleic ivle therapy. the average recovery time after the olive oil-based intralipid therapy was 39 hours. kuo et al. (2013) evaluated the time to recovery of two cats with permethrin toxicosis treated with soybean oil-based ivle therapy. in this study, both cats showed neurological improvement within an average period of 14 hours. the randomised clinical trial by peacock et al. (2015) evaluated the progression of clinical signs of cats with permethrin intoxication before and after treatment with soybean oil-based ivle therapy compared to cats treated with saline solution control. the outcomes measured in this study were based on the differences around a clinical staging system designed by the authors, which ranged from stage a for cats that had no abnormalities detected to stage f for cats with grand mal seizures. there was a statistically significant difference in the distribution of relative frequencies of clinical stages over time between control cats and ivle treated cats, where cats treated with soybean oil-based ivle therapy showed lower clinical stages earlier. however, there were no significant differences between control and ivle treated cats in the hospitalisation times, which can be explained by other factors, such as the availability of owners to collect their cats after recovery. summary of the evidence pelizzola et al. (2018)6 population: young cats with permethrin toxicosis sample size: three cats intervention details: low-dose soybean oil-based ivle infusion (intralipid 20%, fresenius kabi). initially a 1.5 ml/kg bolus of ivle was given over 30 minutes, then a second bolus of 0.25 ml/kg/minute over 3 minutes, followed by a constant rate infusion (cri) of 0.025 ml/kg/minute. study design: case report outcome studied: time of recovery after soybean oil-based ivle therapy. main findings (relevant to pico question): case 1 showed neurological improvement 6 hours after low-dose soybean oil based ivle administration, while cases 2 and 3 after 12 hours. the mean time was 10 hours. limitations: low sample size (three patients). different initial treatments for each case (alfaxalone, dexmedetomidine, and diazepam for case 1, diazepam and propofol for case 2, and propofol and midazolam for case 3). ceccherini et al. (2015)7 population: adult cats with permethrin toxicosis sample size: four cats intervention details: case 1: ivle bolus at 2 ml/kg in 3 minutes, followed by a cri at 4 ml/kg/h for 5 hours. case 2: ivle bolus was administered at a dosage of 1 ml/kg in 5 min, followed by cri at 5 ml/kg/h for 3 hours. ivle therapy was reduced at 2 ml/kg/h and administered for 6 hours. case 3: a bolus of ivle at 2 ml/kg in 5 min followed by a cri of 4 ml/kg/h for 3 hours. case 4: a bolus of ivle at 2 ml/kg in 5 min followed by a cri of 2 ml/kg/h for 4 hours. study design: case report outcome studied: time of recovery after soybean-oil based ivle therapy. main findings (relevant to pico question): case 1 showed neurological improvement 5 hours after ivle administration, cases 2 and 3 after 6 hours, and case 4 after 4 hours. on average all cases showed neurological improvement within 5 hours from low-dose soybean oil-based ivle administration. limitations: low sample size (four patients). cases 2, 3, and 4 were referred after initial treatment in other hospital. authors used different doses and rate of bolus and cri of ivle therapy. different supportive treatments for each case (propofol plus dexmedetomidine for case 1, phenobarbital for case 2, diazepam, propofol, midazolam and dexmedetomidine for case 3, and dexmedetomidine for case 4). peacock et al. (2015)8 population: adult cats with permethrin toxicosis sample size: thirty-four cats intervention details: all cats in the clinical trial were randomised to receive 15 ml/kg of either intravenous 0.9% saline (control) or 20% soybean oil-based ivle therapy over 60 minutes. 14 cats received the control treatment and 20 cats received the soybean oil based ivle treatment. for each cat, a clinical stage was recorded at set time points before and after the randomised treatment was administered. the distribution of clinical stage stratified overtime was compared across treatment groups. study design: randomised clinical trial outcome studied: time of recovery after soybean oil-based ivle therapy. a clinical staging system was designed based on abnormalities found on physical examination of cats with permethrin toxicosis. the clinical staging system had 6 stages, ranging from stage a for cats with no abnormalities to stage f for cats with grand mal seizures. for each cat, a clinical stage was recorded at set time points before and after the randomised treatment (soybean oil-based ivle therapy was administered). the distribution of clinical stage stratified overtime was compared across treatment groups. main findings (relevant to pico question): there was a statistically significant difference in the distribution of clinical stages over time (p < 0.001) and from presentation stage to stage b (p = 0.006), with ivle treated cats (n = 20) having lower clinical stages earlier than control cats (n = 14). clinical stages of permethrin toxicosis in ivle treated cats improved earlier compared to control cats. limitations: veterinarians were not blinded to the treatment. a failure to blind them may result in detection bias (the outcome assessments may be systematically influenced by practitioners). external factors make it difficult to measure the difference in hospitalisation times between the control and ivle treated cats, so we can only conclude a difference in the time in which a patient reached a point to be considered stable but not regarding their hospitalisation discharge. confounding effects due to the timing and different drug administration between groups for neuroexcitatory signs control (alfaxalone, butorphanol, midazolam, acepromazine, medetomidine, phenobarbitone and propofol). haworth et al. (2012)9 population: adult cats with permethrin toxicosis sample size: three cats intervention details: case 1: 20% ivle therapy at a dose of 1.5 ml/kg over 30 minutes followed by a cri of 0.25 ml/kg/min for 45 minutes (total of 48.5 ml). case 2: 20% ivle therapy at a dose of 1.5 ml/kg over 90 minutes and an additional dose of 0.25 ml/kg/min over 30 minutes (total of 36 ml). case 3: 20% ivle therapy at a dose of 0.25 ml/kg/min over an hour (total of 90 ml). study design: case report outcome studied: time of discharge after 20% soybean oil-based ivle therapy. main findings (relevant to pico question): cases 1 and 2 were discharged 9 hours after 20% ivle therapy administration, while case 3, after 7 hours (mean time 8.3 hours). limitations: low sample size (three patients). case 1 had a second exposure to permethrin, which may have influenced its recovery time. also, this case received 20% ivle therapy 72 hours after initial exposure. authors used different doses and rates of bolus and cri of 20% ivle therapy. brückner et al. (2012)10 population: young cats with permethrin toxicosis sample size: two cats intervention details: bolus of 2 ml/kg of a 20% soybean oil-based and 80% olive oil emulsion (clinoleic 20%, baxter, uk) followed by a cri of 4 ml/kg/h for 4 hours. in case 1, it was repeated at the same dosage the following day. study design: case report outcome studied: time of recovery after clinoleic therapy. main findings (relevant to pico question): case 1 showed clinical improvement 48 hours after clinoleic iv administration. case 2 showed clinical improvement 30 hours after clinoleic iv administration. limitations: low sample size (two patients). differences between time of administration of clinoleic iv after initial exposure (24 hours for case 1 and 9 hours for case 2). kuo et al. (2013)11 population: adult cats with permethrin toxicosis sample size: two cats intervention details: case 1: a bolus of soybean oil-based ivle (2.5 ml/kg) was administered over 5 minutes, followed by an ivle infusion of 1 ml/min (0.33 ml/kg/min) for 30 minutes. ivle therapy was reduced at 1 ml/min for other 30 minutes. an additional dose of ivle was administered at day 2, with a total volume of 226 ml (61 ml/kg) given over 17 hours. case 2: a bolus of soybean oil-based ivle (2.2 ml/kg) was administered, followed by an ivle infusion of 1 ml/min (0.27 ml/kg/min) for a total of 75 minutes. the same ivle therapy was repeated 9 hours after presentation. study design: case report outcome studied: time of recovery after soybean oil-based ivle therapy. main findings (relevant to pico question): case 1 showed neurological improvement 12 hours after ivle administration, while case 2, 17 hours after ivle administration (mean time 14 hours). limitations: low sample size (two patients). both cases required additional ivle doses and authors used different doses and rates of bolus and cri of ivle therapy. appraisal, application and reflection most of the information available evaluated the use of soybean oil-based intravenous lipid emulsion (ivle) therapy to manage permethrin toxicosis in cats. the outcome of interest for this knowledge summary was the recovery time and time for discharge among cats with permethrin toxicosis treated with soybean oil-based ivle therapy or clinoleic ivle therapy. studies that provided information on any other outcomes were excluded because they were not relevant to answer the pico question. any ivle therapy, as described by (gwaltney-brant et al., 2018), should be used ‘in addition to, not instead of, standard symptomatic and supportive care because it is still an experimental procedure.’ all the case reports evaluated in this study suggest that cats with permethrin intoxication had an improvement in clinical signs after the administration of soybean oil-based or olive oil-based ivle (clinoleic) therapies, however, differences in recovery time were found. in the first case study evaluated (pelizzola et al., 2018) it was shown that three patients had neurological improvement after being treated with soybean oil-based ivle therapy. the average time to recovery with this therapy was 10 hours. one of the most important limitations is that each patient had different treatment protocols and the study design did not quantify the intrinsic effect of ivle therapy or in combination with other medications (injectable anaesthetics, anticonvulsants). also, it is worth mentioning that, as reported by pelizzola et al. (2018), there were differences between each permethrin product concentration among the cases evaluated. however, as described by boland et al. (2010) there is no reported correlation between the amount of permethrin exposure and the severity of clinical signs induced, so this may not lead to significant differences in the time to recovery. in the second case study evaluated (ceccherini et al., 2015), it was found that four patients had neurological improvement within an average of 5 hours after low-dose soybean oil-based ivle administration. an important aspect to consider is that three patients were treated in another clinic before arriving at the hospital, so information about any previous treatment was not available. another limitation of this study is that different dosages and cri were used for each patient, which in combination with a low sample number, can make it difficult to establish a dosing protocol for this treatment. in the third case study evaluated (haworth et al., 2012) three patients showed a clinical improvement after soybean oil-based ivle therapy administration with a mean time to recovery of 8.3 hours. one of the key limitations of this study is that one case received the ivle therapy 72 hours after the exposure and had a second permethrin exposure once discharged from the hospital, which influenced the overall recovery time. the remaining cases received ivle therapy 16 hours after exposure. the fourth case study evaluated (brückner et al., 2012) was the only one that evaluated the time to recovery after clinoleic ivle therapy administration. the most important limitation of this study is the sample size (two patients). both cats showed clinical improvement within 30 and 48 hours, with an average time to recovery of 39 hours. however, it is important to notice that there were differences in administration of clinoleic ivle therapy after initial exposure (24 hours for case 1 and 9 hours for case 2), which can influence the time to recovery between both cases. none of the patients showed any adverse reaction and both patients showed neurological improvement after the clinoleic ivle therapy but with a higher average time to recovery compared to those patients treated with soybean oil-based ivle therapy. the fifth case study evaluated (kuo et al., 2013) found that soybean oil-based ivle therapy was an effective adjuvant treatment to decrease the recovery time in patients with permethrin toxicosis, with an average time to recovery of 14 hours. the most important limitation was the sample size (two cases) and that both cases required additional ivle doses, which makes it difficult to establish a dosage protocol. as stated by the authors, this ivle therapy was well tolerated in both cases and no adverse effects were detected. finally, the sixth study evaluated (peacock et al., 2015) was a randomised clinical trial and the strongest evidence available. a statistically significant difference in recovery time (p = <0.006) was found among patients treated with soybean oil-based ivle therapy compared to control patients. the mean time to recovery was 5.5 hours (95% ci 1.6–9.5 hours) in soybean oil-based ivle treated patients and 16.2 hours (95% ci 9.1–23.3 hours) in control patients. this interim statistical analysis result gave rise to prematurely stop the trial and administer the soybean oil-based ivle therapy to the control patients. this study also used other medications in combination with ivle therapy, but no statistically significant differences were found among control and treated patients. another limitation of this study is that it was not blinded, which can lead to detection bias. however, the clinical staging system designed by the authors showed almost perfect agreement in a cochran-mantel-haenszel test for intra-viewer variability (consistent results by the same viewer), and interviewer variability (consistent results by different viewers), which increases the reproducibility, and reduces the variability and risk of bias in the outcome measurement. it is also worth noting that external factors, such as owners availability to pick up each patient, make it difficult to measure the difference in hospitalisation times between the control and ivle treated cats, so we can only conclude a difference in the time in which a patient reached a point to be considered stable but not regarding their hospitalisation discharge. all the studies appraised used different dosage protocols of intravenous boluses or continuous rate infusion of lipids. currently, there is no consensus among guidelines or protocols for ivle therapy dosage in feline patients with permethrin intoxication but on average, the dosage protocols used for both ivle therapies ranged from an initial bolus of 1–2.5 ml/kg and a cri of 4–5 ml/kg/h. overall, the clinical effectiveness of clinoleic ivle therapy in reducing time to recovery after permethrin intoxication in cats is still unclear and further research on this relevance, as well as robust clinical trials comparing both intralipid therapies should be conducted. the studies gathered for this review suggest that soybean oil-based ivle therapy is the preferable treatment and the most studied for permethrin toxicity among feline patients. it is important to recognise that supportive treatment11,12, dermal decontamination7,11,12, muscle relaxers12,13 anaesthetics12, and anticonvulsants12,13 are examples of recognised first-choice treatments and any intralipid therapy must be used as part of an adjuvant protocol. considering that ivle therapy is still an experimental procedure, it is important to assess for any adverse reaction that could arise (i.e., hyperlipidaemia, pancreatitis, haemolysis, phlebitis, vomiting)14-16. it is recommended to follow the dosage protocols reviewed in this knowledge summary to reduce complications and adverse effects. previous authors14,17 have recommended checking for visual evidence of gross lipaemia (i.e., milky plasma or serum) through a peripheral blood sample  before administrating additional ivle therapy doses or every 2 hours, and discontinue ivle therapy if no improvement is noted after three doses (bolus and cri). methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform: 1973 – 2020 pubmed database: 1973/01/01 – 2020/12/31 web of science core collection: 1973/01/01 – 2020/12/31 scopus advanced document search: 1973/01/01 – 2020/12/31 search strategy: cab abstracts: ((((cat* or feline* or felid* or adult cat) and (intralipid or intralipid therapy or ivle or intralipid infusion or intravenous lipid emulsion)) or (refined olive oil or clinoleic or refined soybean oil or mixture of refined olive oil)) and (recovery* or recuperation* or improvement* or treatment)) and (permethrin or permethrin intoxication).   pubmed: ((((cats* or feline* or felid* or “adult cat”) and (“intralipid” or “intralipid therapy” or “ivle” or “intralipid infusion” or “intravenous lipid emulsion”)) or (“refined olive oil” or “clinoleic” or “refined soybean oil” or “mixture of refined olive oil”)) and (recovery* or recuperation* or improvement* or treatment) and (permethrin* or intoxication*))   web of science: (((((((cats* or feline* or felid* or “adult cat”) and (“intralipid” or “intralipid therapy” or “ivle” or “intralipid infusion” or “intravenous lipid emulsion”)) or (“refined olive oil” or “clinoleic” or “refined soybean oil” or “mixture of refined olive oil”)) and (recovery* or recuperation* or improvement* or treatment) and (permethrin* or intoxication*)))))   scopus: all ( cat*  or  feline*  or felid* or  “adult cat” )  and  ( “intralipid”  or  “intralipid therapy”  or  “ivle”  or  “intralipid infusion”  or  “intravenous lipid emulsion” )  and  ( “refined olive oil”  or  “clinoleic”  or  “refined soybean oil”  or  “mixture of refined olive oil” )  and  ( recovery*  or  recuperation*  or  improvement*  or  treatment )  and  ( permethrin*  or  intoxication* ) dates searches performed: 10 dec 2021 exclusion / inclusion criteria exclusion: articles in languages different to english; non-peer reviewed literature such as technical reports and web-based guidelines; the paper fail to provide succinct evidence on the outcome of interest (time to recovery); single-subject case studies. inclusion: articles published between years 1973–2020; the patients in the study must be cats diagnosed with permethrin intoxication; patients treated with soybean oil-based ivle therapy or clinoleic ivle therapy. search outcome database number of results excluded – irrelevant to pico question excluded – non-peer reviewed literature excluded – sample size < 2 excluded – irrelevant to outcome of interest total relevant papers cab abstracts 10 2 1 2 0 5 pubmed 13 5 0 2 2 4 web of science 15 6 0 1 0 8 scopus 15 11 0 0 4 0 total relevant papers when duplicates removed 6 conflict of interest the author declares no conflicts of interest. references richardson, j.a. (2000), permethrin spot-on toxicoses in cats. journal of veterinary emergency and critical care, 10: 103-106. doi: https://doi.org/10.1111/j.1476-4431.2000 kwiatkowska, m., hoppe, s., pomianowski, a. & tipold, a. (2019). reactive seizures in cats: a retrospective study of 64 cases. veterinary journal. 244, 1–6. doi: https://doi.org/10.1016/j.tvjl.2018.11.009 merola, v. (2006). the 10 most common toxicosis in cats. veterinary medicine. 101(6), 339–42. available at: https://www.aspcapro.org/sites/default/files/zl-vetm0606_339-342.pdf [accessed on 25 nov 2020]. sutton, n., bates, n. & campbell, a. (2007). clinical effects and outcome of feline permethrin spot-on poisonings reported to the veterinary poisons information service (vpis), london. journal of feline medicine and surgery. 9(4), 335–339. doi: https://doi.org/10.1016%2fj.jfms.2007.05.003 sparkes, a. & bessant, c. (2010). permethrin and cats don't mix – call for action. journal of feline medicine and surgery. 12(1), 2–3. doi: https://doi.org/10.1016/j.jfms.2009.12.001 pelizzola, m., mattavelli, c., troìa, r., murgia, e. & giunti, m. (2018). low-dose intravenous lipid emulsion as a safe treatment for lipophilic intoxications in five cats. veterinary record case reports. 6(4). doi: https://doi.org/10.1136/vetreccr-2018-000663 ceccherini, g., perondi, f., lippi, i., grazia g. & marchetti, v. (2015). intravenous lipid emulsion and dexmedetomidine for treatment of feline permethrin intoxication: a report from 4 cases. open veterinary journal. 5(2), 113–121. available at: https://www.openveterinaryjournal.com/ceccheriniabstovj051.html [accessed on 25 nov 2020]. peacock, r.e., hosgood, g., swindells, k.l. & smart, l. (2015). a randomized, controlled clinical trial of intravenous lipid emulsion as an adjunctive treatment for permethrin toxicosis in cats. journal of veterinary emergency and critical care. 25(5), 597–605. doi: https://doi.org/1111/vec.12322 haworth, m., smart, l.(2012). use of intravenous lipid therapy in three cases of feline permethrin toxicosis. journal of veterinary emergency and critical care. 22(6): 697–702. doi: https://doi.org/10.1111/vec.12322 brückner, m. & schwedes, c. (2012). successful treatment of permethrin toxicosis in two cats with an intravenous lipid administration. tierärztliche praxis ausgabe k kleintiere / heimtiere. 40(2), 129–34. doi: http://dx.doi.org/10.1055/s-0038-1623631 kuo, k. & odunayo, a. (2013). adjunctive therapy with intravenous lipid emulsion and methocarbamol for permethrin toxicity in 2 cats. journal of veterinary emergency and critical care. 23(4), 436–441. doi: https://doi.org/10.1111/vec.12070 boland l. & angles j. (2010). feline permethrin toxicity: retrospective study of 42 cases. journal of feline medicine and surgery.12(2), 61–71. doi: https://doi.org/10.1016%2fj.jfms.2009.09.018 wismer, t. (2016). chapter 79 – feline toxins: recognition, diagnosis, treatment. august’s consultations in feline internal medicine. volume 7, 791–798. doi: https://doi.org/10.1016/b978-0-323-22652-3.00079-7 richardson, j.a. (2007). permethrin spot-on toxicosis in cats. journal of veterinary emergency and critical care. 10(2), 103–106. doi: https://doi.org/10.1111/j.1476-4431.2000.tb00006.x gwaltney-brant, s. & meadows, i. (2012). use of intravenous lipid emulsions for treating certain poisoning cases in small animals. veterinary clinics of north america: small animal practice. 42(2), 251–262. doi: https://doi.org/10.1016/j.cvsm.2011.12.001 yuh, e. & keir, i. (2018). hypertriglyceridemia and transient corneal lipidosis in a cat following intravenous lipid therapy for permethrin toxicosis. the canadian veterinary journal. 59(2), 155–158. seitz, m. & burkitt-creedon, j.m. (2016). persistent gross lipemia and suspected corneal lipidosis following intravenous lipid therapy in a cat with permethrin toxicosis. journal of veterinary emergency and critical care. 26(6), 804–808. doi: https://doi.org/10.1111/vec.12440 plumb, d.c. (2018). plumb’s veterinary drug handbook. intralipid, intravenous lipid emulsion, ile, ife, ivle. parenteral nutritional agent; antidote (systemic drug). 9th ed: john wiley & sons. stockholm, wi. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. ‘don’t pee on that!’ comparing environmental modification and medical management in cats with fic a knowledge summary by amelia poole dipavn dipfb certvn(ecc) certisfm(fn) rvn 1* 1harper adams university, edgemond, newport, tf10 8nb *corresponding author (amelia@rcvsknowledge.org) vol 6, issue 1 (2020) published: 11 mar 2021 reviewed by: jacqueline renee cole (bsc bvetmed mrcvs) and eva spada (dmv phd) next review date: 03 jun 2022 doi: 10.18849/ve.v6i1.337 pico question in cats with feline idiopathic cystitis (fic) is environmental modification superior than medical management in preventing reoccurrence?   clinical bottom line category of research question treatment the number and type of study designs reviewed 16 papers were critically reviewed; 14 randomised trials and two case studies strength of evidence critical appraisal of the selected papers meeting the inclusion criteria collectively provide weak evidence in terms of their experimental design and implementation outcomes reported there is weak evidence that any medication or environmental modification is successful in reducing the reoccurrence of fic when compared to a placebo. short-term use of amitriptyline can contribute to an increase in occurrence of fic conclusion in view of the strength of evidence and the outcomes from the studies the following conclusion is made; in cats with feline idiopathic cystitis there is weak evidence that environmental modification or medication are effective at preventing reoccurrence. further research is required into the cause of fic before comparisons on treatment options can be made, however, with the exception of short-term use of amitriptyline, environmental modification and systemic treatment of clinical signs did not contribute to an increase in occurrence of fic   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a 4-year-old, male neutered cat is being presented for the third time for cystitis. after a thorough work up, a diagnosis of idiopathic cystitis has been made. the patient is already on a gastrointestinal prescription diet, and the owner does not want to change this. the owner asks if other treatments are available to reduce the occurrence of his clinical signs. the evidence the literature searches uncovered 13 papers that addressed pharmaceutical treatment for cats with feline idiopathic cystitis (fic) and three papers addressing environmental modification as a treatment. pharmaceutical treatments included oral preparations of non-steriodal anti-inflammotory drugs (nsaids) (dorsch et al., 2016), steroids (osbourne et al., 1996), tricyclic antidepressants (chew et al., 1998; kruger et al., 2003; and kraijer et al., 2003), glucosamine (gunn-moore and shenoy, 2004) and prazosin (reineke et al., 2017). parenteral treatments include intravesical glycosaminoglycan (gags) (bradley et al., 2013), pentosan polysulphate and lidocaine (zezza et al., 2012) and subcutaneous pentosan polysulphate (wallius et al., 2009). of these studies, only one paper (chew et al., 1998) found that long-term (12 months) use of amitriptyline successfully decreased clinical signs of recurrent cystitis in 9/15 cats treated, however this improvement was only apparent in the last 6 months. three studies included environmental modification as a treatment option, which included the use of feline facial pheromones (ffps) (gunn-moore and cameron, 2004). the use of ffps did not have a statistical difference in reoccurrence of signs when compared to the placebo, however there was a clinical difference shown, with those exposed to ffp having a reduced occurrence and reduced severity of fic. a case study by seawright et al. (2008) followed a case with environmental modification for an extended period of time, which showed that episodes of cystitis only occurred during extraordinary stressful situations such as building works. a study into multimodal environmental modification (buffington et al., 2006) showed a resolution in signs for 75% for 10 months. each study into environmental modifications had a number of uncontrollable variables due to each cat’s condition and environment, so further studies are required to confirm any success. summary of the evidence osborne et al. (1996) population: male and female cats with idiopathic cystitis sample size: 12 cats intervention details: cats split in two groups group 1 (n=6) received oral prednisolone 1 mg/kg twice daily for 10 days (two female, four male) group 2 (n=6) received placebo with the same dosing schedule for 10 days (two female, four male) hospitalised for 10 days study design: double blinded clinical study outcome studied: for first 10 days urine analysis was completed daily 4 and 18 days after discontinuation of therapy urinalysis and bacterial urine cultures were performed daily observation of clinical signs for first 10 days to look for a reduction is dysuria, haematuria and struvite presence in urine main findings (relevant to pico question): dysuria subsided after a mean of 1.5 days in both groups haematuria reduced after a mean of 3.2 days in prednisolone treated cats and 3.5 days in placebo treated cats a 10 day course of prednisolone had no clinical benefit over the placebo limitations: patients were hospitalised throughout, potentially increasing stress and exacerbating any clinical signs act of collecting urine daily and medicating everyday has potential to increase stress and exacerbate clinical signs. study had a small sample size and was performed over a short period of time chew et al. (1998) population: cats with idiopathic cystitis that failed to respond to other treatments sample size: 15 cats intervention details: cats received 10 mg of amitriptyline per os (po), every (q)24 hours in the evening for 12 months, or until signs reoccurred study design: prospective study outcome studied: urinalysis, complete blood count, serum biochemical analysis, urine bacteriologic culture and cystoscopy were performed initially and after 6 and 12 months owner-observed severity scores of lower urinary tract signs were recorded main findings (relevant to pico question): during first 6 months 11/15 cats had no owner observed signs in the last 6 months 9/15 cats had no owner observed signs. cystoscopic abnormalities persisted in all cats haematuria and proteinuria were decreased in all cats at 12 month evaluation treatment with amitriptyline decreased signs and occurrence of fic in 9/15 patients over the 12 month period urinary calculi presented in 4/15 cats in the first 6 months limitations: owner evaluation can be inaccurate not a controlled study so external factors could have contributed small sample size paper did not include any cl or p-values kruger et al. (2003) population: cats with acute, non-obstructive idiopathic lower urinary tract disease sample size: 31 male and female cats intervention details: split into two groups group 1 (n=16) treated with 5 mg amitriptyline daily for 7 days – two cats then excluded from this group due to acquired urinary tract infection group 2 (n=15) given placebo for 7 days re-examined after 1 month of treatment owners interviewed by telephone 6, 12 and 24 months of treatment study design: randomised controlled trial outcome studied: incidence of pollakiuria and haematuria main findings (relevant to pico question): group 1 – pollakiuria and haematuria resolved by day 8 in cats treated with amitriptyline group 2 – pollakiuria and haematuria resolved by day 10 in cats treated with placebo pollakiuria and haematuria recurred faster and more frequently in amitriptyline treated cats results suggested that short-term amitriptyline treatment has no benefit in terms of resolution of pollakiuria and haematuria in cats with idiopathic lower urinary tract disease and may be associated with an increased risk of reoccurrence limitations: small sample size owner evaluation can be inaccurate external factors could have contributed potential for wide number of variables in each cat’s environment no p-value available kraijer et al. (2003) population: cats with idiopathic cystitis in the netherlands sample size: 24 cats intervention details: treatment group (n=11) amitriptyline 10 mg/cat given orally once daily in the evening for 7 days control group (n=13) received a placebo tablet with the same dosing schedule 10 mg/kg amoxicillin trihydrate orally twice daily given to all cats study design: double blind, placebo controlled study outcome studied: severity of symptoms marked by a practitioner on a visual analogue scale at days 0, 7 and 14 owners monitored urination frequency, duration and volume, level of activity and general attitude of the patient main findings (relevant to pico question): no statistical differences between the treatment group and placebo group by practitioner (p=0.2) or owner (p=0.5) the treatment was associated with a change in general attitude and decreased level of activity (p=0.02) treatment group experienced a reduction in microscopic haematuria and proteinuria after 5 days placebo group experienced a reduction in proteinuria after day 2 limitations: environment not controlled, so cats had other variables that could have affected results owner evaluation of signs can be inaccurate no p-values for the reduction in microscopic haematuria or reduction in proteinuria gunn-moore & cameron (2004) population: cats with a recent history of dysuria pollakiuria and haematuria; at least two episodes in 6 months. referred to the feline clinic of the university of edinburgh small animal hospital sample size: 12 cats (male neutered n=6; female neutered n=6) intervention details: group 1 (n=6) – six cats exposed to feline facial pheromone (ffp) for 2 months, then placebo for 2 months group 2 (n=6) – six cats exposed to placebo for 2 months, then ffp for 2 months one depression of spray 10 cm away from any object that protruded into areas where the cats walked the spray was applied daily in households with one or two cats, and twice daily in households with three or more cats study design: randomised double blinded, placebo controlled crossover study outcome studied: using linear visual analogue scales, the owners were asked to daily define the severity of the cat’s clinical signs: increased frequency of urination straining while urinating crying out while urinating blood in urine urination outside of litter box increased grooming around perineum a further visual analogue scale was used to assess whether the cats behaviour had changed. this was used on a weekly basis: increase or decrease in negative behaviours increase or decrease in positive behaviours increase or decrease in spraying in the house increase or decrease in eating main findings (relevant to pico question): no statistical differences between the two treatment groups (p=0.5). however, a clinical difference showing a trend for the six cats exposed to ffp to have less severe episodes and fewer recurrences of fic ffp total, mean ± standard deviation: ffp – 30, 4.3 ± 6.7 placebo – 69, 9.9 ± 19.1 limitations: three cats did not complete the study, and data for two cats were lost by the owners, so the sample size was small those recruited to the study were dedicated owners who had opted for referral, so not a representative sample owner evaluation can be inaccurate gunn-moore & shenoy (2004) population: cats with recurrent cystitis due to fic recruited from the referral cases of the feline clinic of the university of edinburgh small animal hospital between feb 2001 and may 2002 sample size: 40 cats intervention details: treatment group (n=20) – cats received 125 mg of n-acetyl glucosamine po once daily (uid) for 6 months placebo group (n=20) – cats received a placebo po uid study design: randomised, doubleblinded, placebo controlled outcome studied: owners asked to grade the severity of their cats’ signs at both start and end of study using a health score scale of 0 (very severe cystitis) to 5 (normal cat). owners also kept a cystitis diary every day (for 6 months), recording the following signs: increased frequency of urination straining while urinating crying while urinating blood in urine urination outside litter tray increased grooming around perineum altered behaviour mean urine specific gravity after 1 month was compared with the initial urine sample main findings (relevant to pico question): owner assessment suggested that those treated with glucosamine achieved a slightly greater improvement, however there was no significant difference (p>0.5) the majority of cats in both groups improved significantly (p<0.001, mean health score of each group at the start was 0.5 ± sd 0.5, compared to glucosamine 4.4 ± 0.7 and placebo 3.9 ± 1.6 at the end), however this was believed to have occurred due to the concurrent introduction of wet food the urine specific gravity at the start was significantly higher (mean 1.050 + sd 1.007) than when reassessed after 1 month (1.036 + 1.010 p<0.01) limitations: small sample size oral medication could increase stress owner evaluation can be inaccurate number of variables in different home environments. owners concurrently increased cats water intake during study potential placebo effect and reduction in stress due to owners increased understanding of condition buffington et al. (2006) population: cats with obstructive idiopathic cystitis sample size: 46 client owned indoor housed cats with idiopathic cystitis, specifically suffering from at least two bouts in the previous 10 months male (n=24) and female (n=22) from single (n=12) and multicat (n=34) households aged between 2 and 5-years-old intervention details: cases were offered recommendations for multimodal environmental modification (memo) based on a detailed environmental history memo included: not punishing the cat, increasing water intake, changing to an unscented clumping litter, improved litter box management, vertical enrichment, increased interaction, resolution of multicat conflicts and audit and video sensory stimulation study design: prospective observational study outcome studied: client reported reoccurrence of lower urinary tract signs, and any other signs main findings (relevant to pico question): after 10 months, no lower urinary tract signs (luts) were observed in 70–75% of the cats (p<0.0001) of those that did suffer from recurrent episodes, clients reported they resolved spontaneously without veterinary intervention reductions in fearfulness (p<0.0002), nervousness (p<0.002) and upper respiratory signs were seen (p<0.03) trends towards reductions in aggressiveness (p<0.09) and lower intestinal tract signs (p<0.20) were also reported limitations: owner evaluation can be inaccurate number of different variables changing for each cat no concurrent control groups seawright et al. (2008) population: 5-year-old male, neutered domestic short haired (dsh) with fic sample size: one cat intervention details: treatment with meloxicam, prazosin, dantrolene and gag supplementation for 3 weeks wet diet introduced as well as a water fountain patient given a core area with easy access to resources, increased number of hiding places and 3-dimensional space visual access to outside blocked cat followed up for 15 months study design: case-control study outcome studied: reoccurrence of urethral blockage or signs of fic behavioural assessment main findings (relevant to pico question): no recurrence of clinical signs for 6 months one stressful event (owner confined all cats household cats in close proximity) 2 days prior to recurrence of signs no recurrence of clinical signs for another 6 months limitations: number of variables including environment, medication and diet change owner evaluation can be inaccurate statistical analysis not available wallius et al. (2009) population: cats with clinical signs of cystitis, absence of positive urine culture for bacteria, absence of urethral obstruction sample size: 18 neutered male (n=9) and female (n=9) cats intervention details: treatment group (n=9) – cats were treated with subcutaneous injections of 3 mg/kg pentosan polysulphate on days 1, 2, 5 and 10 placebo group (n=9) – isotonic saline solution on days 1, 2, 5 and 10 cats examined at the time of injections and owners interviewed regarding urination habits telephone interview at 2 weeks, 2 months, 6 months and 1 year following treatment study design: double blinded, randomised, placebo controlled outcome studied: recurrence of lower urinary tract signs main findings (relevant to pico question): two cats left the study due to euthanasia no statistical differences between the two groups during treatment or at revaluation for clinical signs those that did show clinical signs, had been exposed to stressful events before clinical signs, which was found to be significant (p=0.0023) limitations: small sample size high number of variables owner evaluation can be inaccurate no reported confidence interval zezza et al. (2012) population: cats with obstructive idiopathic lower urinary tract disease (lutd), median of 5-years-old, median of 5.5 kg sample size: 26 cats – male neutered (n=25) male entire (n=1) intervention details: case group (n= 12) – treated with 0.2 ml/kg lidocaine (2%) and 0.06 ml/kg sodium bicarbonate (8.4%) intravesical uid for 3 days control group (n=14) – treated with placebo of 0.2 ml/kg saline solution and 0.06 ml/kg sodium bicarbonate (8.4%) intravesical uid for 3 days cats monitored every 2 hours for 2 days amoxicillin-clavulanic acid (20 mg/kg po q12hr) or amoxicillin (20 mg/kg po q12hr) started concurrently and continued in cats that did not re-obstruct immediately study design: randomised placebo controlled prospective clinical trial outcome studied: recurrence rate and amelioration scores of clinical signs were assessed and compared questionnaire follow-up at 2 weeks, 1 month and 2 months. questionnaire was composed of 8 visual analog scales, with values ranging from 0 (normal cat) to 10 (very severe clinical signs) owners asked to look for 8 signs: increased frequency of urination straining while urinating crying out while urinating presence of blood in the urine (macroscopic hematuria) urination outside the litter box increased grooming around the perineum altered behaviour (increased aggression, fear, or nervousness) gastrointestinal symptoms (e.g., vomiting, diarrhea) main findings (relevant to pico question): reoccurrence of urethral obstruction was 7/12 (58%) in the case group and 8/14 (57%) in the control group amelioration scores were similar between the two groups no clinical benefit to adding lidocaine amelioration of straining after 2 weeks was noted (p=0.01) limitations: small sample size high number of variables sample restricted to cats with urethral obstruction no reported confidence interval owner observation could be biased or inaccurate bradley et al. (2013) population: veterinary referred male cats with urethral obstruction from suspected fic sample size: 14 cats intervention details: all cats received bladder lavage and received fluid therapy treatment group (n=7) received intravesical gags at the time of urinary catheter placement and again 12 and 24 hours later placebo group (n=7) received intravesical saline at the time of urinary catheter placement and again 12 and 24 hours later three of the cats in the placebo group suffered obstruction within 7 days, and two were then crossed over to the treatment group patients were monitored for 7 days, including urinalysis at 0, 3 and 7 days, urine culture at 0 and 7 days, daily pain scoring and re-check at 3 and 7 days study design: randomised, blind placebo controlled clinical trial outcome studied: repeat urethral obstruction urine specific gravity pain score aerobic bacterial urine culture main findings (relevant to pico question): repeat obstruction rates were 3/7 (42.9%) placebo group cats and 0/9 (0%) treatment group cats (p= 0.06) mean urine protein content of the treatment group was 2.9 vs 1.6 for the placebo group (p=0.03) mean urine specific gravity of the treatment group was 1.028 vs 1.043 for the placebo group (p=0.02) limitations: study limited to males with urethral obstruction, not confirmed fic study size relatively small controlled hospital study can increase stress in cats which can lead to urethral blockage delille et al. (2016) population: cats obstructive fic sample size: 35 cats intervention details: all cats received intravenous fluids and buprenorphine once clinically stable an indwelling urinary catheter was placed and the bladder drained and flushed with warm sterile solution of sodium chloride until the urine appeared macroscopically clear treatment group (n= 18) received 30 mg pentosan polysulfate in 10 mls of saline. this was instilled into the bladder via urinary catheter, and the urinary catheter clamped for 30 minutes before connection to a closed system collection set placebo group (n= 17) only had saline instilled into the bladder all cats were treated with 0.01 mg/kg buprenorphine q8hours for day 1 to 5, 0.5 mg phenoxybenzamine q24 hours from day 3 to 14 and 0.05 mg of acepromazine q8–12hours for day 1 and 2 study design: prospective, randomised, placebo controlled, double-blinded study outcome studied: daily physical examinations and urinalyses were compared patients monitored for repeat urinary obstruction main findings (relevant to pico question): no statistical differences between the treatment group and placebo group on physical exam (p=0.99) no statistical differences between the treatment group and placebo group for repeat urethral obstruction (p=1.00) treatment group experienced a reduction in microscopic haematuria and proteinuria after 5 days (p<0.05) placebo group experienced a reduction in dipstick haematuria on day 5 (p<0.05) and reduction in proteinuria after day 2 (p<0.05) and day 3 (p<0.01) limitations: limited to those with obstructive idiopathic cystitis cats were hospitalised, potential for external stressors to affect results no reported confidence interval dorsch et al. (2016) population: cats with obstructive idiopathic cystitis sample size: 37 cats intervention details: cats received supportive treatment and an indwelling urinary catheter for 48 hours, concurrent to intervention treatments group 1 (n=18) received meloxicam orally at 0.1 mg/kg on day one, then 0.05 mg/kg on days 2–5 group 2 (n=19) received placebo alongside same schedule sent home after able to urinate for 24 hours by self study design: double blinded controlled clinical study outcome studied: physical exams and urinalysis repeated daily for 5 days, then owner reported demeanor for 5 days and repeat telephone interview after 3 months parameters for evaluation were occurrence of urethral obstruction, results of physical exams and demeanour main findings (relevant to pico question): recurrent urethral obstruction occurred after 5 days in 4/18 (22%) of cats in meloxicam group and 5/19 (26%) in group 2 (p=1.00) general abdominal pain and demeanour improved significantly during hospitalisation for both groups (p=<0.001) general demeanour, food intake and voiding behaviour were no different in both groups during the 3 months no significant different between groups at different time points limitations: patients receiving supportive treatment concurrently to meloxicam and placebo. this could affect results as you cannot credit any success to one treatment alone owner questionnaire was with a visual analog scale which can be inaccurate depending on owner interpretation and understanding study was performed on fic cats with only obstructive fic with the measured outcome being repeat obstruction. some cats show other signs before obstructing, with others not obstructing at all, so this study may not show any relevance to them cats were then observed at home, which although is a more natural environment, has uncontrollable external factors that will affect results reineke et al. (2017) population: male cats with urethral obstruction with urinary calculi >2 mm in diameter sample size: 47 cats intervention details: cats (n=27) were chosen at random to receive prazosin 0.25 mg/cat po q12hours for 1 month following obstruction remaining cats (n=20) received a placebo for 1 month owners reported signs at 1, 2, 3 and 4 weeks follow-up periods, and again at 6 months study design: double blinded, prospective, interventional study outcome studied: cats were monitored for: repeat urethral obstruction (ruo) severity of lower urinary tract signs main findings (relevant to pico question): no different in the ruo rate with prazosin or placebo prior to hospital discharge: (2/26 (7%) vs 1/19 (5%), p=1.00) no different in the ruo rate with prazosin or placebo during the 1 month medication period: (4/26 (15%) vs 3/18 (17%), p=0.776) no different in the ruo rate with prazosin or placebo at 6 months following treatment: (7/19 (37%) vs 4/13 (31%), p=0.811) following randomisation two cats (one from each group) were withdrawn limitations: study limited to males with urethral obstruction, not confirmed fic study size relatively small owner evaluation can be inaccurate nivy et al. (2019) population: male cats with fic associated urethral obstruction sample size: 51 cats intervention details: group 1 (n=24) – cats after hospitalisation were treated with phenoxybenzamine, alprazolam and meloxicam (0.025 mg/kg/day) for 2 weeks group 2 (n= 27) – cats after hospitalisation were treated with phenoxybenzamine and alprazolam for 2 weeks study design: prospective, randomised clinical trial outcome studied: recurrent urethral obstruction main findings (relevant to pico question): cumulative number of cats with recurrent urethral obstruction at: 10 days = 1 (2%) 1 month = 2 (4%) 2 months = 4 (8%) 6 months = 8 (16%) overall 12 cats: eight cats with added meloxicam and four cats without no clinical benefit of adding low-dose meloxicam was detected (p=0.70) limitations: small sample size number of variables in the environment owner evaluation can be inaccurate study limited to those with urethral obstruction sofyan et al. (2019) population: 8-month-old, male neutered domestic short haired (dsh) cat, weighing 4.5 kg, with fic sample size: one cat intervention details: doxycycline, diazepam and neurotropic vitamins for 5 days probiotic with lactobacillus casei, l. rhamnosus, l. acidophilus and bulgaricus and bifidobacterium infantis and breve and streptococcus thermophiuls dry food prescription for urinary disease study design: case report outcome studied: ability to urinate post catheterisation main findings (relevant to pico question): cat was able to urinate once treatments given limitations: patient was on a number of treatments study contributes success to probiotic combination treatment. however, no measurements or scales to analyse this does not state how long patient was monitored for appraisal, application and reflection a number of studies were identified due to the wide variables involved with searching for medication. however, each study focused on a different treatment, allowing for a wide range of results. there was no study that compared medical treatment alone to environmental treatment. only one study, chew et al. (1998), identified medication as having an effect on reducing the occurrence of fic. this was if the patients were treated with amitriptyline 10 mg/cat sid po long-term. the study showed that the medication decreased the occurrence in 9/15 (60%) cats, and reduced haematuria and proteinuria in 100% of cats at the 12 month evaluation. however, the sample size of this study was small (n=15) and could have been impacted by a number of variables within the cat’s environment. the cessation of haematuria and proteinuria is a positive outcome for the treatment; however, it is not made clear if these patients were tested within the same time period. fic being a self-limiting disease may indicate that the cats could have been asymptomatic at the time regardless of the treatment. 5 years later, kruger et al. (2003) found that short-term administration (7 days) of amitriptyline had no statistical benefit over the reduction in pollakiuria and haematuria. additionally, cats treated with amitriptyline had a faster recurrence rate when compared to the placebo. much like the study by chew et al. (1998) there were uncontrollable variables within the cat’s environment that could have contributed to these results. six of the studies focused specifically on cats with fic that caused urethral obstruction and the reoccurrence of symptoms if treatment was given at the time of obstruction. dorsch et al. (2016) identified that there was no significant difference between patients having meloxicam and a placebo for 5 days post obstruction, however due to the nature of the treatment for a urethral obstruction, this was given concurrently with a urinary catheter and fluid therapy, so credit of success cannot be given to one treatment alone. this study does not identify the cause of the obstruction, and whether patients had high amounts of urinary sediment, or inflammation. the measured outcome was a repeat urethral obstruction and does not record whether cats suffered with other generalised symptoms of fic before becoming obstructed. this was a similar finding to nivy et al. (2019) with the administration of phenoxybenzamine and alprazolam (n=51) with the addition of meloxicam (n=24). this study had the largest sample size, but no placebo control group, so the results cannot be contributed to any success. reineke et al. (2017) completed a longer-term study with the administration of prazosin (n=27) for 1 month following urethral obstruction. follow-ups for 6 months post-treatment identified no statistical difference between the prazosin and placebo for a repeat urethral obstruction, or a reduction in the severity of clinical signs. like the previous studies that test oral medication, the variables in the environment cannot be controlled, and may have contributed to the recurrence of clinical signs, alternatively the stress of giving medication on a daily basis could have also contributed to clinical signs. three studies focused on the administration of medication through intravesical means, one with intravesical gags (bradley et al., 2013), pentosan polysulphate (delille et al., 2016) and the other with intravesical sodium bicarbonate ± lidocaine (zezza et al., 2012). bradley et al. (2013) found that those treated with gags had a reduced recurrence of obstruction when compared to the placebo group (p=0.06), however the study size was small (n=14) and performed within a hospital environment with concurrent treatment of fluid therapy. when given intravesical pentosan polysulphate (delille et al., 2016), obstructed cats suffered with repeat obstruction at the same rate as those with a placebo (p=1.00). zezza et al. (2012) found no clinical benefit to the addition of lidocaine, however although the sample size was larger than bradley et al. (2013), it was again restricted to hospitalised patients (n=26) with concurrent treatments of amoxicillin-clavulanic acid for 2 days before discharge. wallius et al. (2009) combined owner interviews with clinical examination for treatment with subcutaneous injections of pentosan polysulphate, treatment used in human interstitial cystitis. the sample size was small (n=18) and was made smaller due to two cats being euthanised due to their clinical signs during the study. no statistical difference was found between the treatment and the placebo, despite the differing variables within the cat’s environment. giving other treatment concurrently to medication was common in these studies. those owners that participated in the studies were obviously keen to treat their cats, so tried all forms of treatment to alleviate symptoms. although beneficial for the patient, is not helpful in regard to studies as any results cannot be related directly to the medication. this was the case with gunn-moore & shenoy (2004) and grading the severity of fic signs alongside the administration of n-acetylglucosamine (n=40). participants for the study were recruited from those referred directly to the university so had an invested interest in the cat’s success. although owner assessment suggested that those treated had a greater improvement, there was no significant difference, and it was identified that owners had concurrently increased the water intake of the cats during the study, probably leading to the improvement seen. controlled studies within the hospital took place with the administration of prednisolone uid for 10 days (osbourne et al., 1996). although this allows for variables to be controlled, it also introduces the variable of the patient being stressed in an unnatural environment, thus potentially increasing the chance of stress related signs. osbourne showed that steroid treatment had no benefit for reducing the clinical signs of fic (n=12), however the sample size was small and was only concentrating on the cessation of signs and not the rate of recurrence. one study concentrated on environmental modification as a treatment (buffington et al., 2006), with indoor cats (n=46). a change in environment showed a reduction in the reoccurrence of lower urinary tract signs (p<0.0001) and a general improvement in fearfulness (p<0.0002) and nervousness (p<0.0002). however, the environmental modification for each cat was varied, with a number of options being given to the owner. with a number of different variables, it cannot be identified if one was more successful than the other, or if a variety is required for success. there were also no concurrent control groups. seawright et al. (2008) reported on a single case control study of a patient treated with a range of medications for 3 weeks and environmental treatment long-term. the patient was assessed for 15 months and showed only one period of fic signs, occurring due to a stressful event in the environment. this episode was self-resolving. this study indicates the effect the environment has on one cat suffering from fic; however, it is only one case with a number of variables in place and cannot be taken as a treatment option for a larger population. feline facial pheromones were used in adjunction to environmental therapy for 12 cats for a duration of 6 months. owners were asked to score their cats on a number of scales to identify not only signs of cystitis, but also signs of stress. owners were given visual analogue scales and daily diaries to record, and although there was no statistical difference between the treatment period and the placebo period, there was a clinical difference, with reports showing a reduced severity and occurrence of fic; however, those cats that were to experience stressful situations (such as building or moving house) were removed from the study so it is not known if this is an effective treatment during signs of stress. there was one paper that tested alternative methods of treating fic, a mix of medication, vitamins and a probiotic (sofyan et al., 2019). the case report by sofyan attributed the success of the cat being able to urinate post urethral obstruction to the probiotic. however, this was given concurrently with muscle relaxants and antibiotics. with no control study taking place, the evidence to support the probiotics success in this case is weak. there is limited evidence in this research area, with treatments focusing on reducing inflammation or stress to reduce the clinical effects of fic. this makes any research difficult, as to control variables cats have to be hospitalised, which increases the stress they experience. if not in the hospital, cats are then in their own home environment, where variables cannot be controlled, reducing the efficacy of the research by allowing other variables, meaning any success cannot be contributed to one treatment. two of the randomised control studies showed a statistical difference between the treatment group and the placebo, these being memo and long-term amitriptyline, with the trial involving ffp not showing a statistical difference but a clinical difference. two of the case reports based on environmental modification showed patient improvement, however their level of evidence is weak as they both have uncontrolled variables and cannot be repeated under the same conditions. it is clear from the variety of medical treatment options, that the true cause of fic has not been identified. further research is required to identify the true cause, to then make true comparisons. methodology section search strategy databases searched and dates covered: cab abstracts on ovid interface (1973 – 2020 week 21) pubmed accessed via the ncbi website (1910 – june 2020) search strategy: cab abstracts: cat or cats or feline or felines or exp cats/ or exp felis/ cystitis or 'feline interstitial cystitis' or 'feline idiopathic cystitis' or fic or 'feline lower urinary tract disease' or flutd environment* or behaviour or behavior or enrich* or exp environment/ or exp animal behaviour/ drug* or medicat* or medicin* or pharmaceutical* or opioid* or nsaid or nsaids or 'non-steroidal anti-inflammatory' or 'non-steroidal anti inflammatories' or 'non-steroidal anti-inflammatory' or 'non-steroidal anti-inflammatories' or ‘nonsteroidal anti-inflammatory' or 'nonsteroidal anti inflammatories' or 'nonsteroidal anti-inflammatory' or 'nonsteroidal anti-inflammatories' or exp anti-inflammatory agents/ or exp non-steroidal anti-inflammatory agents/ or exp opioids/ 1 and 2 and (3 or 4) manag* or treat* or therap* or prevent* 5 and 6 pubmed: cat or cats or feline or felines cystitis or “feline interstitial cystitis” or “feline idiopathic cystitis” or fic or “feline lower urinary tract disease” or flutd environment or environmental or behaviour or behavior or enrichment drug or medication or medicine or pharmaceutical or opioid or nsaid or nsaids or “non steroidal anti inflammatory” or “non steroidal anti inflammatories” 1 and 2 and (3 or 4) manage or management or treat or treatment or therapy or therapeutic or prevent or prevention 5 and 6 dates searches performed: 03 jun 2020 exclusion / inclusion criteria exclusion: no relevance to pico question (e.g. co-morbidities, cause for urine infection) non-english paper, duplicates, diet inclusion: any study which involved cats with idiopathic cystitis and medication or environmental treatment. this included obstructed idiopathic cystitis if this was mentioned search outcome database number of results excluded – not relevant to pico question excluded – non-english language excluded – conference abstract excluded – duplicate excluded – diet total relevant papers cab abstracts 189 146 21 10 1 2 9 pubmed 315 292 3 1 9 3 7 total relevant papers when duplicates removed 16 conflict of interest i work for rcvs knowledge as a project officer: quality improvement and vets now as an ecc rvn. student at harper adams university references bradley, a.m. & lappin, m.r. (2013). intravesical glycosaminoglycans for obstructive feline idiopathic cystitis: a pilot study. journal of feline medicine and surgery. 16(6): 504–6. doi: https://doi.org/10.1177/1098612x13510918 buffington, c.t., westropp, j.l., chew. d.j. & bolus, r.r. (2006). clinical evaluation of multimodal environmental modification (memo) in the management of cats with idiopathic cystitis. journal of feline medicine and surgery. 8(4): 261–8. doi:https://doi.org/10.1016/j.jfms.2006.02.002 chew, d.j., buffington, c.a., kendall, m.s., dibartola, s.p. & woodworth, b.e. (1998). amitriptyline treatment for severe recurrent idiopathic cystitis in cats. journal of the american veterinary medical association. 213(9): 1282–6. delille, m., fröhlich, l., muller, r.s., hartmann, k. & dorsch, r. (2016). efficacy of intravesical pentosan polysulphate sodium in cats with obstructive feline idiopathic cystitis. journal of feline medicine and surgery. 18(6): 492–500. doi: https://doi.org/10.1177/1098612x15588934 dorsch, r., zellner, f., schulz, b., sauter-louis, c. & hartmann, k. (2016). evaluation of meloxicam for the treatment of obstructive feline idiopathic cystitis. journal of feline and medicine and surgery. 18(11): 925–933. doi: https://doi.org/10.1177/1098612x15621603 gunn-moore, d.a. & shenoy, c.m. (2004). oral glucosamine and the management of feline idiopathic cystitis. journal of feline and medicine and surgery. 6(4): 219–25. doi: https://doi.org/10.1016/j.jfms.2003.09.007 gunn-moore, d.a. & cameron, m.e. (2004). a pilot study using synthetic feline facial pheromone for the management of feline idiopathic cystitis. journal of feline and medicine and surgery. 6(3): 133–8. doi: https://doi.org/10.1016/j.jfms.2004.01.006 kraijer, m., fink-gremmels, j. & nickel, r.f. (2003). the short-term clinical efficacy of amitriptyline in the management of idiopathic feline lower urinary tract disease: a controlled clinical study. journal of feline and medicine and surgery. 5(3): 191–6. doi: https://doi.org/10.1016/s1098-612x(03)00004-4 kruger, j.m., conway, t.s., kaneene, j.b., perry, r.l., hagenlocker, e., golombek, a. & stuhler, j. (2003). randomized controlled trial of the efficacy of short-term amitriptyline administration for treatment of acute, nonobstructive, idiopathic lower urinary tract disease in cats. journal of the american veterinary medical association. 222(6): 749–58. doi: https://doi.org/10.2460/javma.2003.222.749 nivy, r., segev, g., rimer, d., bruchim, y., aroch, i. & mazaki-tovi, m. (2019). a prospective randomized study of efficacy of 2 treatment protocols in preventing recurrence of clinical signs in 51 male cats with obstructive idiopathic cystitis. journal of veterinary internal medicine. 33(5): 2117–2123. doi: https://doi.org/10.1111/jvim.15594 osbourne, c.a., kruger, j. m., lulich, j.p., johnston, g.r., polzin, d.j., ulrich, l.k. & sanna, j. (1996). prednisolone therapy of idiopathic feline lower urinary tract disease: a double-blind clinical study. the veterinary clinics of north america small animal practice. 26(3): 563–9. doi: https://doi.org/10.1016/s0195-5616(96)50085-9 reineke, e.l., thomas, e.k., syring, r.s., savini, j. & drobatz, k.j. (2017). the effect of prazosin on outcome in feline urethral obstruction. journal of veterinary emergency and critical care. 27(4): 387-96. doi: https://doi.org/10.1111/vec.12611 seawright, a., casey, r., kiddie, j., murray, j., gruffydd-jones, t., harvey, a., hibbert, a. & owen, l. (2008). a case of recurrent feline idiopathic cystitis: the control of clinical signs with behaviour therapy. journal of veterinary behaviour. 3(1): 32–38. doi: https://doi.org/10.1016/j.jveb.2007.09.008 sofyan, m., rosman, n., krisnu, b. & kamaludeen, j. (2019). management of feline idiopathic cystitis (fic) using probiotic combination treatment. the indian veterinary journal. 96(12): 20–22. wallius, b.m. & tidholm, a.e. (2009). use of pentosan polysulphate in cats with idiopathic, non-obstructive lower urinary tract disease: a double-blind, randomised, placebo-controlled trial. journal of feline medicine and surgery. 11(6): 409–12. doi: https://doi.org/10.1016/j.jfms.2008.09.003 zezza, l., reusch, c.e. & gerber, b. (2012). intravesical application of lidocaine and sodium bicarbonate in the treatment of obstructive idiopathic lower urinary tract disease in cats. journal of veterinary internal medicine. 26(3): 526–31. doi: https://doi.org/10.1111/j.1939-1676.2012.00911.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. borrelia burgdorferi exposure in coyotes: an indicator of b. burgdorferi levels in urban versus rural environments a knowledge summary by laura shultz bs ba lat mpvm dvmc (‘23) 1* erik fausak mslis ma rvt lvt rlat 2 1university of california, davis school of veterinary medicine, 1 garrod dr, davis, ca 95616 2university library, university of california, davis, 1 shields ave, davis, ca 95616 *corresponding author (lcshultz@ucdavis.edu) vol 7, issue 1 (2022) published: 16 feb 2022 reviewed by: conor o'halloran (bvsc msc phd mrcvs), maureen o'mara (phd mgis) and essa suleman (phd) next review date: 10 nov 2023 doi: 10.18849/ve.v7i1.444 pico question do wild coyotes in the us that are in an urban habitat compared to a rural habitat have a higher prevalence of borrelia burgdorferi seroconversion?   clinical bottom line category of research question prevalence the number and type of study designs reviewed two papers, both utilising a cross-sectional study design strength of evidence zero outcomes reported the relevant studies provide very limited to no evidence towards answering this pico question. in one, while the absolute percentage of borrelia-antibody-positive canines (including dogs in addition to coyotes) is higher in metropolitan areas, the effect was not found to be statistically significant, possibly due to their small sample sizes. in the second study, prevalence of antibodies against borrelia was compared between different rural habitats, but no urban coyotes were tested as a comparison and thus the pico question cannot be evaluated conclusion there is a knowledge gap concerning the prevalence of borrelia in coyotes and how it differs between urban and rural environments. wild coyotes could be used as a sentinel species of lyme disease activity and to assess potential for domestic pet and human infections, which would inform clinical differential diagnoses as well as testing and vaccination recommendations. more studies are needed before this pico question can be answered in a confident manner   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a dog presents with fever, painful/swollen joints, shifting lameness, lack of appetite, lethargy, and swollen lymph nodes. the patient is not up to date on parasite preventatives, and lyme disease is suspected. knowing the prevalence of borrelia burgdorferi in the area and whether the patient lives in an urban or rural environment could influence how likely that diagnosis is and if it should be given serious consideration. coyotes occupy urban, rural, and wilderness environments and can serve as a sentinel species to indicate borrelia disease levels and geographical trends to help inform diagnoses and vaccination recommendations. the evidence while cross-sectional studies provide a high level of evidence for prevalence questions assessing exposure to this pathogen, neither of the two studies evaluated here were directly investigating whether borrelia burgdorferi levels vary between urban and rural environments in wild coyotes of the united states. due to this, the evidence that they provide towards the pico question of interest is extremely limited. in the olson et al. study from 2000, seroprevalence was determined for canines including both dogs and coyotes in san diego county, ca, allowing an assessment of risk for human cases of borreliosis to be conducted. no statistical association was found between disease prevalence and lifestyle (rural vs urban vs indoors) of the canine host, but prevalence of b. burgdorferi antibodies was higher in metropolitan dogs, with the lowest prevalence being found in the most natural habitat; they postulated this could be due to importation of seropositive animals by high mobility owners or ‘brush-border habitat’ styles in urban landscaping supporting tick populations (olson et al., 2000). however, when looking solely at coyotes, the sample size is small (n = 83), and there was only one positive individual, which was from a rural environment (olson et al., 2000). five years later, foley et al. (2005) published a study that looked deeper at variation in b. burgdorferi seroprevalence by vegetation type and climate within ixodes pacificus­­-infested counties of california. while foley et al. (2005) did not directly classify the tested individuals as urban or rural, ‘urban’ was a habitat option and urban areas are included in mapped visualisations of the data; examining their maps, it appears no or few coyotes from urban habitats were tested. with no tested urban coyotes clearly identifiable, this study does not allow us to answer the target pico question but does explore variation within rural environments at a finer scale (foley et al., 2005). prevalence was higher in areas with higher rainfall as well as in blue oak woodland, montane hardwood, and redwood vegetation habitats, with seasonal peaks in june – july and november – april (foley et al., 2005). there were no papers that directly addressed this pico question, which identifies a gap in knowledge where further research is needed. summary of the evidence olson et al. (2000) population: canines: dogs (canis familiaris) and coyotes (canis latrans). sample size: 1000 canines (917 dogs, 83 coyotes). intervention details: canine sera were obtained from local veterinarians, trappers, animal shelters, and humane societies between march 1992 and march 1993. urban or rural ‘lifestyle’ designation was included in the data collected by the investigators. sera were tested by elisa for borrelia burgdorferi antibodies with results being validated via western blot test and/or indirect fluorescent antibody (ifa) tests at reference laboratories. criterion for positive elisa: spectrophotometrically three standard deviations above the mean optical density of samples from control animals. criterion for positive western blot test: presence of 5/10 most common antigen igg bands. criterion for positive ifa: >1:128 of the equivalent when correlating for interlaboratory variability. study design: cross-sectional study design. outcome studied: the objective of this study was to determine the seroprevalence of b. burgdorferi in san diego county as assessed in canines, who can serve as a sentinel for human risk of lyme disease cases. seroconversion was measured by elisa and confirmed via western blot test and/or ifa at a reference laboratory. main findings (relevant to pico question): for wild coyotes, no association with lifestyle (urban vs rural) was found (p = 1.0 for coyotes). only one coyote (rural) tested positive for lyme disease. while no significance of burgdorferi occurred in the coyote population, the domestic dog data showed some interesting outcomes: the location considered the wildest, camp pendleton, a us marine corps training area, had the lowest seroprevalence in dogs (0.5%). seroprevalence of dogs in the metropolitan sector was the highest (4.6%). the authors postulate this could be due to importation of seropositive animals by high mobility owners or ‘brush-border habitat’ styles in urban landscaping supporting tick populations. limitations: when considering only coyotes, the sample size is small (total n = 83, seropositive n = 1), especially given that borreliosis is rare. the low number of positives limited the power of subset analysis.    prevalence may be overinflated due to cross-reactivity of antibodies. the authors did not utilise a vaccine free population, though they state only three dogs in the study had received the vaccine. foley et al. (2005) population: coyotes in ixodes pacificus infested counties of california. sample size: 215 total coyotes. intervention details: 215 coyotes were trapped by usda wildlife services as part of a predator control program and convenience samples were taken from these animals for analysis. 170 were tested for borrelia burgdorferi, as blood from 45 coyotes from one county was not available when burgdorferi testing was performed. coyotes were split into several subsets including county, habitat, and month for analyses with varying sample sizes from 1 to 57. ‘urban’ was a habitat option and urban areas are included in mapped visualisations of the data; examining the maps, there are no urban coyotes easily identifiable. blood was either collected ante-mortem into ethylenediamine tetraacetic acid (edta) or heart clot blood was collected post-mortem. sera was tested via indirect fluorescent antibody (ifa) for burgdorferi, with positive-ifa sera verified with western blot testing. criterion for positive ifa: a positive cut off of 1:25 was used to indicate further testing by western blot test. criterion for positive western blot test: presence of three or more diagnostic igg bands. study design: cross-sectional study design. outcome studied: the aim of this study was to examine spatial and temporal relationships at a smaller-scale to understand ecological drivers of disease among anaplasma phagocytophilum and b. burgdorferi-exposed coyotes. prevalence of disease between different vegetation type and climate in ixodes pacificus infested counties of california was investigated. seroconversion for b. burgdorferi was tested via ifa and confirmed via western blot test. main findings (relevant to pico question): there was a 18.9% seroprevalence (n = 148) with no association for sex in the tested coyotes. b. burgdorferi occurred at higher levels in areas with higher rainfall and in blue oak woodland, montane hardwood, and redwood vegetation regions, and decreased in coastal sagebrush and cropland, providing a finer-scaled analysis within a rural category. b. burgdorferi seroprevalence peaked seasonally (june – july and november – april). limitations: while rural coyotes were sampled in this study, urban coyotes do not seem to be included in the study population. when split into subsets, sample sizes are smaller (n = 1–57). appraisal, application and reflection lyme disease in the united states is caused by the bacterium borrelia burgdorferi sensu stricto (s.s.) and is vectored by ixodes ticks, namely ixodes scapularis in the eastern united states and ixodes pacificus in the western united states that feed on many animal species including humans (steere et al., 2016). throughout the united states, lyme borreliosis is an important emerging disease causing approximately 30,000 new human cases annually (cdc, 2019). while the majority of cases are in the northeastern/mid-atlantic united states have occurred in all 50 states (cdc, 2019) and the highly diseased regions are expanding (steere et al., 2016). this is also driven by climate change, allowing ticks to expand their geographic ranges and increase in abundance in recent decades presenting new and increased health risks to humans and animals (sonenshine, 2018). while lyme disease is more debilitating in humans, dogs and other domestic animals can also contract borrelia infections (self et al., 2018). in fact, canines can act as sentinels of lyme disease; testing for exposure to b. burgdorferi in dogs can be done during annual wellness visit examinations by veterinarians (self et al., 2018). veterinarians can then act as stewards of public health by reporting seroprevalence and cases of lyme borreliosis to the local public health department, helping to effectively track the spread of ixodes ticks and b. burgdorferi as climate change advances. this serves not only additional animal patients that may present as cases in new areas, but also as a warning flag for human health; public health policy makers can make informed interventions if made aware of new or increasing cases of lyme disease. while useful, in private practice domestic animals as a sentinel may be limited because diagnostics is often limited by the permission and finances of pet owners. coyotes (or other wild canids) are another sentinel species that can be sampled via convenience through animal control agencies, rehab facilities, and roadkill to add to the field’s understanding or borreliosis risk. while a convenience sample (use of easily available samples or samples on hand) is non-probabilistic and thus does have limitations on the amount it can inform the epidemiologic understanding of a disease, it is a good starting method that limits the challenges of wild species monitoring such as sampling effort and cost of the monitoring efforts. despite these inherent challenges that exist in monitoring wildlife such as varying population densities and smaller sample sizes, using coyotes as a sentinel is an established practice for other pathogens such as anaplasma phagocytophilum or yersinia pestis, which are both zoonotic vector-borne diseases (foley et al., 2005; and brown et al., 2011). testing coyotes can allow us to characterise disease levels in many different environments because coyotes will utilise and have successfully adapted to not only wilderness and rural but also urban environments (crooks, 2002). because coyotes utilise multiple environments and have large home ranges (gehrt et al., 2009), they could also serve as conduits to take borrelia-infected ticks between habitats or into new areas. by characterising the exposure and role of borrelia in coyotes, there is potential that daily clinical decisions of veterinarians can be informed. if veterinarians are aware of the prevalence of borrelia in surrounding wildlife and the risk posed to their patients, it can hold an appropriate place on their differential list for clinically affected patients and can be utilised to inform testing and vaccination decisions. at the time of this writing, there is a paucity of information concerning how prevalence varies between urban and rural environments and if this can inform clinical decisions of veterinarians; more research is needed in order to determine if wild coyotes have a higher prevalence of b. burgdorferi seroconversion in an urban habitat compared to a rural habitat, and if wild coyotes are indeed a good sentinel species for b. burgdorferi in urban environments. methodology search strategy databases searched and dates covered: cab abstracts on cab direct platform 1973 – 2021 (included products: cab abstracts, vetmed resource, cabi full text, global health, animal health and production compendium (ahpc))   medline on pubmed 1902 – 2021 (included products: medline, in process citations, “ahead of print” citations, out-of-scope citations, journals indexing prior to medline inclusion, pre-1966 citations, pubmed central, author manuscripts nih funding, ncbi bookshelf )   scopus by elsevier 1976 – 2021 search strategy: cab abstracts: coyote* or “canis latrans” borrelia or “lyme disease” or “lyme disease” or “b. burgdorferi” or  “borrelia spp.” or “borrelia sp.” serology or seroconversion or antibodies or elisa #1 and #2 and #3   pubmed: (((serology or seroconversion or antibodies or elisa) and (borrelia or lyme disease or b. burgdorferi or borrelia spp. or borrelia sp.)) and (coyote or canis latrans)   scopus: ( title-abs-key ( serology  or  seroconversion  or  antibodies  or  elisa  or  "enzyme-linked immunosorbent assay" ) )  and  ( title-abs-key ( borrelia  or  lyme  or  lyme's  or  {b. burgdorferi} ) )  and  ( title-abs-key ( coyote  or  coyotes  or  "canis latrans"  or  {c. latrans } ) ) dates searches performed: 10 nov 2021 exclusion / inclusion criteria exclusion: not in english study area is outside the us borrelia burgdorferi not actually measured / not in coyotes urban / rural distinction not made for tested coyotes not peer-reviewed inclusion: english study area is within the us borrelia burgdorferi measured by authors in coyotes urban / rural distinction not made for tested coyotes peer-reviewed search outcome database number of results excluded – not in english excluded – study area is outside the usa excluded – does not measure borrelia burgdorferi in coyotes excluded – urban / rural data not included excluded – not peer-reviewed total relevant papers cab abstracts 9 0 2 0 6 0 1 pubmed 10 0 2 1 5 0 2 scopus 10 0 2 1 5 0 2 total relevant papers when duplicates removed 2 conflict of interest the authors declare no conflicts of interest. the authors would like to acknowledge andres mauricio lopez-perez for his mentorship of l. shultz and proof-reading this manuscript. additional acknowledgement goes to the 2020 mpm208 class at university of california, davis through which this project was undertaken. references brown, h. e., levy, c. e., enscore, r. e., schriefer, m. e., deliberto, t. j., gage, k. l. & eisen, r. j. (2011). annual seroprevalence of yersinia pestis in coyotes as predictors of interannual variation in reports of human plague cases in arizona, united states. vector-borne and zoonotic diseases. 11(11), 1439–1446. doi: https://doi.org/10.1089/vbz.2010.0196 centers for disease control and prevention (cdc). (2019). lyme disease data and surveillance. [online] available from: https://www.cdc.gov/lyme/datasurveillance/index.html [accessed 10 dec 2020]. crooks, k. r. (2002). relative sensitivities of mammalian carnivores to habitat fragmentation. conservation biology. 16(2), 488–502. doi: https://doi.org/10.1046/j.1523-1739.2002.00386.x foley, j. e., queen, e. v, sacks, b. & foley, p. (2005). gis-facilitated spatial epidemiology of tick-borne diseases in coyotes (canis  latrans) in northern and coastal california. comparative immunology, microbiology and infectious diseases. 28(3), 197–212. doi: https://doi.org/10.1016/j.cimid.2005.01.006 gehrt, s. d., anchor, c. & white, l. a. (2009). home range and landscape use of coyotes in a metropolitan landscape: conflict or coexistence? journal of mammalogy. 90(5), 1045–1057. doi: https://doi.org/10.1644/08-mamm-a-277.1 olson, p. e., kallen, a. j., bjorneby, j. m. & creek, j. g. (2000). canines as sentinels for lyme disease in san diego county, california. journal of veterinary diagnostic investigation. 12(2), 126–129. doi: https://doi.org/10.1177/104063870001200204 self, s. c., mcmahan, c. s., brown, d. a., lund, r. b., gettings, j. r. & yabsley, m. j. (2018). a large-scale spatio-temporal binomial regression model for estimating seroprevalence trends. environmetrics. 29(8). doi: https://doi.org/10.1002/env.2538 steere, a. c., strle, f., wormser, g. p., hu, l. t., branda, j. a., hovius, j. w., li, x. & mead, p. s. (2016). lyme borreliosis. nature reviews. disease primers. 2, 16090. doi: https://doi.org/10.1038/nrdp.2016.90 sonenshine, d. e. (2018). range expansion of tick disease vectors in north america: implications for spread of tick-borne disease. international journal of environmental research and public health. 15(3), 478. doi: https://doi.org/10.3390/ijerph15030478 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. development of a database for study data in registration applications for veterinary medicinal products anke finnah1* sabine klee1 inga ruddat2 bettina schneider2 lothar kreienbrock2 1federal office for consumer protection and food safety (bvl), berlin, germany 2department of biometry, epidemiology and information processing, who collaborating centre for research and training in veterinary public health, university of veterinary medicine, hannover, germany *corresponding author (anke.finnah@bvl.bund.de) vol 2, issue 1 (2017) published: 09 feb 2017 reviewed by: laura urdes (phd, dvm, pgdip, certaqv) and peter rodgers doi: 10.18849/ve.v2i1.49 section index:    abstract | introduction | methods | results and discussion | conflict of interest | references | supplementary files abstract objective: in the present study, the feasibility of a systematic record of clinical study data from marketing authorisation applications for veterinary medicinal products (vmp) and benefits of the selected approach were investigated. background: drug registration dossiers for veterinary medicinal products contain extensive data from drug studies, which are not easily accessible to assessors. evidentiary value: fast access to these data including specific search tools could facilitate a meaningful use of the data and allow assessors for comparison of test and studies from different dossiers. methods: first, pivotal test parameters and their mutual relationships were identified. second, a data model was developed and implemented in a relational database management system, including a data entry form and various reports for database searches. compilation of study data in the database was demonstrated using all available clinical studies involving vmps containing the anthelmintic drug praziquantel. by means of descriptive data analysis possibilities of data evaluation including graphical presentation were shown. suitability of the database to support the performance of meta-analyses was tentatively validated. results: the data model was designed to cover the specific requirements arising from study data. a total of 308 clinical studies related to 95 vmps containing praziquantel (single agent and combination drugs) was selected for prototype testing. the relevant data extracted from these studies were appropriately structured and shown to be basically suitable for descriptive data analyses as well as for meta-analyses. conclusion: the database-supported collection of study data would provide users with easy access to the continuously increasing pool of scientific information held by competent authorities. it enables specific data analyses. database design allows expanding the data model to all types of studies and classes of drugs registered in veterinary medicine. the needs for detailed data recording and versatility of the data model must be carefully balanced. application: the database will be used by regulatory authorities. introduction medicinal products for human or veterinary use need to have suitable properties in terms of quality, safety and efficacy, which must be shown by scientific studies and other scientific literature. the supporting documents are compiled in registration dossiers, which are the primary source of information for evaluating medicinal products by regulatory authorities. in germany, veterinary medicinal products (vmps) are authorised by the federal office for consumer protection and food safety (bundesamt für verbraucherschutz und lebensmittelsicherheit, bvl). this authority keeps a large amount of scientific documentation related to vmps. registration dossiers usually consist of four parts, of which part iii safety and part iv efficacy contain the necessary information including study reports on pharmacology, toxicology, safety, and efficacy of the product or active compound. table 1 gives an overview of the main studies, which must be submitted along with the application for authorisation. table 1: relevant studies to demonstrate efficacy and safety of a vmp (european commission, 2015) the authority has archived all applications for authorisation including the supporting dossiers in electronic or in paper form. administrative product data are managed in a central database (arzneimittel-informationssystem, amis), which contains the relevant administrative product data (including summary of product characteristics, spcs) and is used for management purposes and to provide (non-confidential data) information to the public. scientific data from registration dossiers have not been stored in a database so far. therefore, if assessors need to make use of study data, they have to extract them from the paper or electronic dossiers. in human medicine, various databases for the registration of clinical studies on the efficacy of pharmaceuticals have been established in recent years (isrctn registry, 2016; clinicaltrials.gov, 2015; german clinical trials register, 2014). based on the declaration of helsinki on ethical principles in medical research in humans (world medical association, 2013), clinical trials must be registered in publicly available databases and the results of these trials must be published, irrespective of their outcome. in the field of regulation of human medicinal products, the european medicines agency established a european clinical trials database (eudract, 2016). eudract is used by national regulatory authorities to support the supervision of clinical trials. it was established as a confidential database, in accordance with article 11 of directive 2001/20/ec. some of the information held in the eudract database has also become publicly available (eu clinical trials register, 2016). in veterinary medicine no similar database systems for clinical studies have been established so far. in 2015 an international consortium started the vetalltrials initiative, dedicated to the development of one or more veterinary clinical trial registries (vetalltrials, 2015). some attempts at collecting study data in veterinary medicine with limited focus and user groups have been made (e.g. homvetcr: clinical research on veterinary homeopathy, 2011; coordination staff for veterinary clinical studies, n.d.). in the absence of databases for systematic collection of data from studies in veterinary medicine, up to now only publication databases like medline or veterinary science database have been able to be used. in accordance with the approach in practice for studies on human medicinal products, also for registration studies on veterinary medicinal products, a database for authority use should be established. decisions whether parts of it may become publicly available should be reached at a later time. nowadays the majority of marketing authorisations for vmps in the european union are granted by way of decentralised (dcp) or mutual recognition procedure (mrp) involving more than one member state (ms). this is closely followed by an increasing exchange of information between competent authorities (ca) in order to come to a consensual decision. moreover, new scientific findings, new safety risks and other issues may trigger a union referral procedure as laid down in articles 33, 34, 35, and 78 of directive 2001/82/ec, article 45 of regulation (ec) no. 728/2004 or article 13 of commission regulation (ec) no. 1234/2008. in these referrals, an assessment is made by the network and an opinion given on the questions raised. normally, the assessment is based on answers provided by concerned marketing authorization holders (mahs), supported by data from the original registration dossiers. thereby, known studies are re-evaluated in consideration of the new aspects. it is obvious that a common database, which includes all studies submitted to european cas, would be a useful tool to smoothen all these procedures within the network. the objective of this feasibility study was to develop a database for recording data from drug registration studies. the pivotal steps of this study included the construction of a relational data model, the implementation of the data model in a database, and the testing of functions and application options of the database. finally, application examples from an authority perspective were presented. methods data source the dossiers for registration applications for vmps submitted to bvl between 1974 and 2010 served as the data source. from the total number of dossiers a subset of 95 was selected encompassing all applications for vmps containing the anthelminthic agent praziquantel as either the only or one of several active substance(s). data from part i and part iv of the dossiers, i.e. data concerning the drugs and data on clinical efficacy studies were included in this feasibility study. within this publication, no confidential data are disclosed. data model design and implementation in a prototype database (ms access) data modelling was based on the entity-relationship method (chen, 1976). first, the dossiers were screened and the main product data and relevant study data were identified. entities, attributes and their relationships were determined as the key components of a relational data model. rules of normalisation were applied to the entire study and product data. to this end, all tables were split to remove any data redundancy and to resolve dependencies between non-key fields (klug, 2008). the data model was constructed of data tables, assignment tables and lookup tables. each table contained an attribute which served as a primary key that uniquely identified a data set. primary keys were labelled with the suffix “id” (e. g. study_id, result_id). each data table represented an entity including its attributes. lookup tables provided selection lists of terms to the user (e. g. list of species or active substances). some of these lists were based on internationally agreed terminology in the field of drug registration and pharmacovigilance (atcvet, 2016; edqm standard terms, 2016). tables were linked by 1:n relationship and the primary key of the reference table served as foreign key in the associated tables (bildner, 2008). the relational data model was implemented in a prototype database using ms access 2003. statistical evaluation following transfer of the data from access to sas (version 9.1.3, statistical analysis system, sas institute, cary, nc, usa) descriptive data analyses were performed. if applicable, significance testing was applied using the mann-whitney u test and the kruskal-wallis test (clauß and ebner, 1989). the null hypothesis of no differences between groups under observation was rejected if the p-value was below 5%. results and discussion data source: choice of compound and study types in veterinary medicine, the most frequently used medicinal products are indicated for the treatment of parasitic and bacterial infections and the majority of authorised vmps in germany as well as in the european union are antiparasitics and antibiotics (ifah annual report, 2013). compounds considered suitable for the purpose of this feasibility study should already have been on the market in germany for a long time (since the intention was to include product and study data from the early days of german drug law until the deadline in 12/2010). the products should have been approved for use in food-producing animal species and pet animal species. they should have been authorised by national, decentralised / mutual recognition or centralised procedure to cover the different data requirements involved. these criteria were best met by the antheminthic compound praziquantel. this agent is used in dogs, cats, horses and sheep to treat infestations with flatworms (plathelminthes) like tapeworms and trematoda. it is available as single agent vmp or combination vmp, i.e. in combination with other anthelminthic agents. three subtypes of clinical studies on the efficacy of praziquantel were identified in the dossiers, namely dose determination/dose titration studies, dose confirmation studies, and clinical evaluation/field studies. all studies meeting the criteria listed in table 2 were included in the database prototype and subsequently used for data analysis. table 2: summary of inclusion and exclusion criteria data model design the relational data model was based on the two pillars product data, i.e. administrative data and product characteristics, illustrated by the central entity data_product and data from clinical studies illustrated by the central entity data_studyadmindata. product data and study data were linked through an n:m relationship to ensure multiple possibilities of interaction between both. an assignment table (zuord_studyadmindata_product) was placed between these central entities in order to break down their relationship into two 1:n relationships. the following sections give a brief description of the entities, their attributes and relationships resulting from the requirements analysis and implemented in the data model. an overview of the complete relational data model is given in figure 1. terms referring to those used in the data model are printed in italics. product data product data were mapped in the data model by the central entity data_product. this entity contains attributes that are commonly used in the daily work of regulatory authorities and the pharmaceutical industry. these are: (1) name of the drug (vmp); (2) submission number (enr) which is a unique seven-digit number allocated to each vmp for which registration application has ever been submitted; (3) authorisation number (authornumb) which is a unique number allocated to approved products; (4) dosage form (dosform) such as tablet, solution, ointment; (5) atcvet code (atccode) based on the atc index for the classification of drugs (atcvet, 2016); and (6) the authorisation procedure (procedure) which is either national, decentralised or centralised depending on the european member states involved. four other entities were connected with the central entity. they provide selection lists (prf) of active substances, dosage forms, atcvet codes, and application procedures (prf_substance; prf_dosageform; prf_atc; prf_procedure). from these, the entity prf_substance was linked via assignment table (zuord_product_substance) to the central entity since vmps may be composed of more than one active substance and each active substance can be used in several products. study data figure 1: implementation of the entity-relationship model in ms access, 1:n relations are shown as 1:∞ relations the other part of the data model illustrates the relevant study-related data and the relationships thereof. data_studyadmindata which encompasses attributes of purely administrative nature and attributes which focus on the study design constitutes the central entity. these attributes are: (1) the type of the study (studysubcat) as shown in table 1; (2) the study identification number (studyno) which was allocated by the sponsor; (3) name of the study (studytitle); (4) beginning and end of the study (studyyear1, studyyear2); (5) place of study (studycountry1, studycountry2 etc.); (6) (10) randomisation of the test animals; blinding of the assessors; compliance with good clinical practice (vich gl 9, 2000); compliance with good laboratory practice (directive 2004/9/ec, directive 2004/10/ec); and the inclusion of a control group. combo boxes (yes/no/unknown) were added for the attributes (6) to (10). data entries of the attribute study type and place of study were made by means of look-up tables. text fields were added for (11) the description of the study design (studydesign); (12) object of the study (targetparam); (13) methods used (measmeth); (14) inclusion and exclusion criteria (criteriaforinclusion); and the description of the results (resultsdescript). lastly, (15) the total number of animals (totnumbanim) was included in the central entity. another important entity which is linked through a 1:n relationship with the entity data_studyadmindata compiles the quantitative study results (data_result). irrespective of the type of study, all types share the central entity and the entity data_result. two specific entities were added with data typical for clinical studies: the entity data_animal_clinicalstudies contains attributes related to the test and control animals, such as number of male and female individuals (numbmale, numbfemale), species and breed. the other entity data_dosage_clinicalstudies presents pivotal data on treatment regimen, such as number of animals per dosage group (numbanim) and information on drug(s) and dosage (dosage_med, dosage_n, dosage_u_id_fk). if the data model is made applicable to other types of studies (non-clinical studies) it is easy to achieve by adding further entities to the basic structure. thus, extensions can be made without the need for modifications to the original data model. implementation in ms access microsoft access 2003 was used to implement the data model (figure 1). additional features were implemented to allow for convenient input of study data and also for database queries with data outputs in a comprehensive and clear format. the main functions for database users are data entry and search functions. convenient access to these functionalities was provided by a top menu (figure 2), which leads to data entry on the one hand and to queries on the other hand. the items printed in bold have already been realised in the prototype; these may be supplemented in an extended version. for data entry, a form which automatically fills the data tables and includes drop down lists for contents of lookup tables, was created. besides ease of use, this helps to avoid errors in data entry as data sets in all related tables are generated automatically. four queries were implemented which exemplify ad-hoc searches on study data. these queries aim to identify those studies available per product, per active substance and per atcvet code. main study data are given as tabular outputs. complete details of study reports can be requested with the fourth query on study details. these basic search functions may be extended by the addition of filters in further database versions. in reports a) to c) filters for study year, target species or study quality (randomisation, blinding, and number of animals included) would produce more specific results, provided that a sufficient number of studies are in the database. the use of filters should be optional. users are able to obtain an overview of the available studies and then select an appropriate subset of studies. figure 2: top menu to open forms for data input and queries descriptive data analysis of selected studies descriptive statistical analyses of study data demonstrate what additional information can be obtained if all clinical studies archived in the bvl are available in a database system. due to the feasibility nature of the study, results shown below may serve as examples only and do not allow conclusions to be drawn concerning the entire amount of clinical studies submitted to bvl. as only a small subset of the available study data was included in the database prototype, results should not be interpreted regarding their contents but rather the possibilities for data usage thereof. data from 308 clinical studies derived from registration dossiers of 95 veterinary drugs containing praziquantel (from which 33 were single agent products and 62 combination products) met the inclusion criteria (table 2). data from these clinical studies were largely similar and could be recorded in a structured manner and were therefore suitable to be included in the database. the dossiers of 33 products (=35%) contained bibliographical data or were referenced to other authorised drugs. therefore, no clinical studies were presented in the dossiers of these products. seventy-five percent of the dossiers contained between 0 and 8 studies, with 35% containing no studies and 40% containing between 1 and 8 studies. the remaining dossiers had between 9 and 100 studies. the maximum of 100 studies was found in one dossier from 1993. as most of these studies were not conducted and presented according to current guidelines, with very small numbers of animals per study, they would not be counted as full-value studies nowadays. see figure 3. stratification of number of studies per 5-year period gives information on distribution of years studies were conducted, which has to be considered when assessing changes of certain parameters over time. up to 1975, already 69 studies on the single agent products had been conducted; further studies on different combinations of praziquantel with other substances have been conducted in recent years. as in all periods studies were carried out, study evaluation and time series analysis with regard to quality-related parameters is possible (see table 3). figure 3: number of studies per drug, comparison of mono-preparations and combination drugs table 3: number of studies stratified for 5-year periods when studies were conducted the analysis of the distribution of the number of studies per authorisation procedure gives an impression of the amount of knowledge gained in different kinds of procedures. the mean number of studies per drug is largest for centralised procedures as these are used for new and innovative agents or combinations (table 4). several other analyses were performed, looking at the number of studies used in one or several marketing authorisation applications (figure 4) or vice versa on the number of studies per dossier, which gives information on the re-use of studies for more than one drug and on the amount of clinical data per dossier. re-using studies in more than one dossier is possible if a company applies for or is granted more than one marketing authorisation for the same or a similar product. table 4: distribution of studies per authorisation procedure figure 4: number of studies used in one or several applications for approval the total number of animals included in a clinical study is an important criterion for the power of the study and herewith its quality. in the selected subset of studies, study size was between one (only in very old and pilot studies) and 539 animals per study (median 20 animals). based on the limited amount of studies included further stratifications were performed for study size in different kinds of authorisation procedures. further stratifications would be interesting to look at in larger numbers of clinical studies, e.g. per species or study subtype. some parameters associated with quality of studies were analysed for variation over time. this may be interpreted against the background of changes in legislation and adoption of guidelines for conducting clinical studies. whereas the study size, measured as numbers of animals per study, did not significantly increase, the proportion of studies with blinding, randomisation, gcp and/or glp compliance clearly increased over time (figure 5). for a larger amount of studies, this analysis should be performed not for time intervals but for single years to see if implementation of guidelines have led to greater changes in study quality. figure 5: proportion of blinded, randomised, gcp/glp compliant studies per interval related to all studies conducted evaluation of the data model and critical assessment of study data quality the data model developed in this feasibility study has proved to be suitable for presenting clinical study data from registration dossiers. it contains the most relevant information on veterinary medicinal products and their active substances. for the study data, a modular approach has been chosen, consisting of more general data relevant for all study types (administrative data, e.g. study number, date, title, results) and of data with specific information applicable for one study type only. information from clinical studies has been used as an example here, but tables for other study types can be added without any need for changes to the already existing structure. no major flaws were noticed during practical testing. however, it became evident that some minor changes to the data model would clearly improve performance and usability of the database. a second data field for study numbers should be added. besides the study number assigned by the principal investigator, some studies were allocated further numbers by other parties involved. when searching on the basis of the study number (query study details) both data fields should be accessed. a duplicate check should be established in order to avoid repeated entry of identical studies. a duplicate check may be achieved by extended query functions (e.g. for total number of animals, totnumbanim, and for year(s) of study conduct, studyyear_1/studyyear2). in the currently implemented version, up to three countries per study can be recorded, which was not sufficient for the dataset used for testing. more veterinary drugs are going to be developed for small patient cohorts, and the animal patients used in the registration studies need to be recruited from all over the world. the current limit of three countries should be changed by introducing a further allocation table linking data table data_studyadmindata and check table prf_studycountry. all active substances included in test and reference products should be searchable in the database. in the current version active substances are related to the test product only. other products that are administered in a clinical study and the active ingredients of these products are not covered by the current search functions of the database. a more precise mapping of data from study reports containing different products could be realised by adding an allocation table to link the lookup tables prf_substance to the data table data_dosage_clincalstudies. this would allow for recording of all active substances administered in compliance with the first normal form and for searches on test product basis. in the set of studies used for testing the data model, some studies integrate more than one study type within one study, e.g. a prevalence study and an efficacy study. as these include study aims and study details, which differ from one another, they were not fully presentable as one study within the prototype data model. this issue was not addressed in our feasibility study but may be covered by hierarchical sets of study type specific substudies. in one aspect the data model should even undergo some simplification: data table data_dosage_clinicalstudies contains information on the parasite species a drug is effective against, which is applicable for products for antiparasitic use only. knowledge gained on the current study population showed that parasite species were the same among tested dosage groups. thus, combining dosage group and parasite species is considered unnecessary. as the data model should also be suitable for clinical studies on other kinds of drugs, the demands of detailed recording of data should be balanced with the need for versatility of the data model. therefore, information concerning the parasite species should be integrated in the more general target parameter data field (data field targetparam in table data_studyadmindata). otherwise, inclusion of different data tables for different classes of drugs would lead to an unreasonably more complex data model. for use of a study database in live operation, constant updating of product data would be necessary. therefore, an interface between study database and product database would have to be implemented. as shown in the descriptive data analysis, the quality of studies, as well as the quality of study reports have improved in more recent clinical studies. in the set of studies used for testing, problems in data recording due to insufficient or missing data were found in older studies only. examples of problems in data recording due to shortcomings in data quality and presentation of data are missing study numbers or inconsistencies regarding contents such as differences in numbers of parasites under consideration between study plans and final study reports. as only indications based on endpoints predetermined in study plans would be accepted, this may have an impact on the outcome of authorisation procedures. missing values were found concerning numbers of animals per treatment group. also, in some older studies, only summary reports were available with missing information on aspects like inclusion or exclusion criteria. in any case, entry of data should be combined with a check of data quality and it may be useful to have a text field in the administrative part of the data mentioning problems in data quality. outlook tabulated study reports in this feasibility study, complete study reports were browsed for those data considered important to be stored in the database prototype. this time-consuming work would be reduced significantly for further studies if these particular data were made available in an easy-to-view format. as already available for toxicological studies, also for clinical studies uniform templates are considered useful to provide a quick overview of studies regarding protocoland results-related information. it would also avoid burdensome extraction of data from study reports and facilitate the process of data entry into a study database. the authors therefore suggest that all studies in application documents of veterinary medicinal products should provide tabulated study reports containing the parameters used in the database prototype. based on this initial proposal, involved stakeholders, the pharmaceutical industry and regulatory authorities would need to further discuss and agree on a set of relevant parameters to be included in a template for tabulated study reports. an appropriate template should become part of the “notice to applicants” documents. potential uses and benefits of a study database the majority of studies submitted to bvl are in support of drug registration applications. these studies are assessed within the application process. for post-authorisation surveillance of safety or efficacy, assessors might seek to gain further information from studies conducted with similar products. moreover, the exchange of scientific information has attained greater importance due to cooperation within the network of european regulatory authorities. summaries of study reports are commonly requested from the national authorities that granted the first marketing authorisation of a medicinal product in a european member state. in addition, for streamlining products by means of harmonisation procedure (e.g. indications or withdrawal periods) compilations of available study data are needed. a study database may be used to gain an overview of all available study data on for example one specific substance, either to have a summary of the current level of knowledge or to conduct meta-analysis to acquire a common estimate for the endpoint of interest. at present, it is cumbersome to select the relevant studies from individual dossiers. doubtlessly, this would be accelerated by saving all incoming studies in a database. such a knowledge database would serve for secondary use of data by providing elaborated search functions in combination with direct access to study data. considerations regarding a study database would have to address retrospective inclusion of study data. this feasibility study revealed large differences in the quality of clinical studies and of study reports, with clear tendency towards higher quality in more recent clinical studies, while early studies often failed to meet present-day requirements. thus, the cost-benefit-ratio for including older studies might not be balanced and the authors would recommend limiting data collection to studies from a given cut-off point onwards. a reasonable starting point could be the year 2001, when the relevant legislation (directive 2001/82/ec of the european parliament and of the council of 6 november 2001 on the community code relating to veterinary medicinal products) came into effect. alternatively, starting points could be set for groups of drugs or active substances dependent on the date the relevant guideline documents on conducting studies came into effect. further perspectives in the long term, it would be reasonable to establish a system for direct transmission of electronic study-related data into suitable databases accessible to regulatory authorities. for this purpose, technical standards concerning data format and structure of data need to be developed. it lies within legislation to pave the way forward. conflict of interest acknowledgments: the authors would like to thank stephan steuber for his helpful contribution to the sighting of vmps for this research project. competing interests: none to declare. the manuscript, or parts of it, have not been and will not be submitted elsewhere for publication. none of the authors have any financial or personal relationships that could inappropriately influence or bias the content of the paper. references atcvet (2016) collaboration center for drug statistics 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[accessed 26 jan 2017]. world medical association (2013). declaration of helsinki – ethical principles for medical research involving human subjects. jama, 310 (20), p. 2191. doi http://dx.doi.org/10.1001/jama.2013.281053. supplementary files, images & tables intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. personal health and nutrition information-seeking attitudes and behaviours of first year canadian and united states veterinary students shelby a. nielson bsc (hons) msc phd student1* may k. kamleh bsc (hons) phd2 peter d. conlon dvm phd med3 jennifer e. mcwhirter bsc phd1 elizabeth a. stone dvm ms mpp dacvs4, 5 deep k. khosa bsc bvms manzcvs (small animal medicine) phd1, 6 1department of population medicine, ontario veterinary college, university of guelph, 50 stone rd e, guelph, on, n1g 2w1 canada 2harris county public health, 2223 w loop south, houston, tx, 77018 usa 3department of biomedical sciences, ontario veterinary college, university of guelph, 50 stone rd e, guelph, on, n1g 2w1 canada 4department of clinical studies, ontario veterinary college, university of guelph, 50 stone rd e, guelph, on, n1g 2w1 canada 5college of veterinary medicine, north carolina state university, raleigh, nc 27607 usa 6hill’s pet nutrition primary healthcare centre, university of guelph, 48 smith lane, guelph, on, n1g 4s7 canada *corresponding author (snielson@uoguelph.ca) vol 7, issue 2 (2022) published: 13 apr 2022 reviewed by: maureen o'mara (phd mgis) and najat yahia (phd ms rd ld) doi: 10.18849/ve.v7i2.543 section index:    abstract | introduction | methods | results | discussion | conflict of interest | references abstract objective: to identify the primary sources of information first year canadian and us veterinary students relied on for their personal health and nutrition information, and to explore their attitudes towards, and perceptions of, health information resources. background: though the animal health information-seeking behaviours (hisb) of veterinary students have been explored, research regarding personal hisb of this professional student population is limited. evidentiary value: participants were first year veterinary students (n=322) at the five canadian veterinary schools and five randomly selected us veterinary schools. an online questionnaire was used to gather students’ demographic information, sources of health and nutrition information, and information-seeking attitudes and perceptions. this study may impact practice at the institutional level for veterinary educators. methods: stata 15.1© was used for quantitative analysis; involving multivariate logistic regression models, univariate analyses, and measures of frequency. results: results indicated high reliance on the internet for personal health 213/322 (66%) and nutrition 196/322 (61%) information. while respondents revealed high trust levels in dietary recommendations from family doctors, 132/322 (41%) of students revealed their doctor did not provide any information on healthy diets. students who reported the use of peer-reviewed journal articles for personal nutrition information were at greater odds of having confidence in knowing where to find nutrition information (odds ratio [or] = 6.61, p<0.001). conclusion: participating students reported a high reliance on the internet search engine google, and a general lack of guidance from medical professionals regarding general health needs. application: veterinary schools should consider this information to enhance student information literacy skills, particularly to facilitate personal hisb, and consequently help in management of personal health throughout the growing demands of the programme.   introduction modern technological advances have provided wide access to health and nutrition information for the general population. this may be especially true for university students who have frequent access to the internet and rely on it throughout their education. research suggests that the use of the internet may influence health information-seeking behaviours (hisb) (chen et al., 2018), which is recognised as the process of gathering information about health (mukherjee & bawden, 2012). such information-seeking behaviours have been shown to inform decision-making and encounters with health professionals as well as personal health behaviours (chen et al., 2018; and mckinley & wright, 2014). given its fundamental role and influence on overall health and well-being, nutrition is an important component of hisb (lichtenstein et al., 2006). understanding where and how individuals seek health-related information can subsequently advise targeted initiatives to promote individual and population health (mukherjee & bawden, 2012). the hisb of post-secondary students (those enrolled in education beyond high school) have been somewhat explored, and results have demonstrated a trend towards greater reliance on the internet for health information over time. a 2005 study noted that less than half of college students reported they had frequently searched the internet for health information (escoffery et al., 2005). although in a 2011 study, percheski & hargittai found that 831/1060 (78%) of first year undergraduate students indicated the internet as a health information resource, more traditional health information resources such as family and friends and health professionals remained highly ranked. more recently, results by basch et al. (2018) indicated that 191/258 (74%) of college students were most likely to often or always use the internet for health information, and reported more reliance on this source than on medical professionals and family and friends. these results were consistent with those of rennis et al. (2015), who found that the internet was the most consulted health information source by college students. further, research focusing on students in advanced healthcare programmes such as medicine and dentistry have also revealed a high use of the internet to support their learning (o’carroll et al., 2015; and schleyer et al., 2012). though some researchers have examined the hisb of veterinary students specifically, most existing literature has focused on the information search habits in regard to animal health information. results of those studies have similarly identified a reliance on the internet (dale et al., 2011; weiner et al., 2011; and lai et al., 2019). while online sources may be a convenient way for students to access information related to animal health, students may also access unreliable information, thereby potentially affecting student learning. previous research has identified inconsistencies in the accuracy and completeness of online animal health information, including focused topic areas such as canine cruciate ligament disease, canine osteoarthritis, and canine anaesthesia (taggart et al., 2010; jehn et al., 2003; and hofmeister et al., 2008). similar trends of unreliability have been identified in online human health information, where authors concluded that websites provided incomplete or inaccurate information despite the overall quality of such websites ranking as fair (reynolds et al., 2018). given that research studying first semester veterinary students revealed that students used few criteria to evaluate the quality of websites and provided information prior to use (weiner et al., 2011), it is important to explore what resources veterinary students are using to learn about their own health and nutrition. in a highly demanding programme such as veterinary medicine, it is critical for students to make beneficial nutrition decisions and stay healthy to best support themselves as the requirements of the programme intensify. presently, however, little is known about how and why veterinary students make health and nutrition decisions. this study aims to help address gaps in this knowledge. as an exploratory study, the objectives were to: identify the sources used by first year veterinary students to learn about their health and nutrition; and explore students’ attitudes and perceptions of health and nutrition information sources during their first year of veterinary school. outcomes from this study may inform future research and intervention strategies to promote veterinary student information literacy skills, including personal hisb, upon entering the programme in order to make progressive decisions to best support personal health and well-being, and accomplish educational and professional goals.   methods study design students commencing their first year of veterinary medicine studies (dvm or its equivalent) at the five canadian veterinary schools and five randomly selected us veterinary schools were recruited in this multi-centre cross-sectional study. they were invited to complete an online questionnaire between september 2016 and november 2016. since the veterinary schools were randomly selected, the authors of this paper have chosen to omit the names of the individual veterinary schools. this study received university of guelph’s research ethics board approval (reb # 16ja039), and ethics approval from all participating schools.   questionnaire design a review of the existing literature and focus group discussions with pre-veterinary (undergraduate students with interest in attending veterinary school) and veterinary students (n=84) were used to develop a questionnaire. it included questions about demographics, sources of health and nutrition information, and health and nutrition information-seeking attitudes and perceptions. for the purposes of this study, health information was defined as the seeking of information regarding health status, health-promotive activities, or social or personal sense of health overall. nutrition information for the purposes of this study referred to all aspects of nutrition-related health inquiries. questions were in multiple-choice or 5-point likert scale formats. in the case of multiple-choice questions, respondents had the opportunity to select more than one response and further specify their response using an ‘other’ category. the survey questions were distributed to participants as part of a larger research study (kamleh et al., 2020b).   demographics using multiple-choice questions, first year veterinary students were asked their age, gender, previous programme of study, if they were a domestic or international student, and their future career plans.   sources of health and nutrition information using multiple-choice questions, respondents were asked to identify primary information sources relied on for both their personal health, as well as their personal nutrition needs (e.g. personal healthcare provider, books / magazines, the search engine google, family member). google was the only internet search engine offered in these response options.   health and nutrition information-seeking attitudes and perceptions respondents were asked to use 5-point likert scales to rate how much knowledge they believed to exist on human nutrition (1 = none, 5 = very high amount) and their confidence in knowing where to find information about their own nutrition (1 = very difficult, 5 = very easy). students were additionally asked to rate their levels of trust in various nutrition information sources (e.g. messages the media portrays with regards to nutrition, online sources for nutrition, family doctors recommending certain diets) using a 5-point likert scale (1 = none at all, 5 = a great deal). finally, respondents’ views on the quality / quantity of information provided to them about healthy eating by their doctor was explored using a 5-point likert scale (1 = my doctor does not provide information about healthy diets, 5 = information is more than i need).   questionnaire distribution the survey was initially piloted in english at the home research department with six veterinary students during the second semester of their programme. the feedback received from pilot testing was used to further refine the survey questions and establish content validity. internal consistency of the questionnaire instrument was satisfactory (cronbach’s alpha = 0.76). a translator was used to develop a french version of the survey. the final questionnaire was uniformly distributed via qualtrics© (provo, utah) by email invitation from each school’s student affairs office. a cover letter was included within the questionnaire to ensure that uniform information was provided to all participants, including a statement that described the general risks of managing data over internet transit. students were required to read the cover letter and provide consent to participate in the survey. the questionnaire was provided in english to all the schools and additionally in french to the french-language canadian veterinary school. the survey was anonymous, and students were provided with an external link to enter a separate, optional prize draw upon submission of the questionnaire.   questionnaire data analysis questionnaire data were numerically coded and entered into an excel spreadsheet for quantitative analysis using stata 15.1© (2017, college station, texas). the initial univariate analysis involved verifying distributions. the decision to dichotomise variables that were measured on a 5-point likert scale was made prior to analysis to support interpretability of results. for ‘the amount of information to exist on human nutrition’, categories 1, 2 and 3 (none, small amount, unsure) were combined, as were categories 4 and 5 (moderate amount, very high amount) to create a dichotomous variable (0 = small amount, 1 = large amount). ‘confidence in finding personal nutrition information’ was dichotomised, where categories 1, 2 and 3 (strongly unconfident, moderately unconfident, neither confident nor unconfident) were combined, as were categories 4 and 5 (moderately confident, strongly confident) to create a dichotomous variable (0 = unconfident, 1 = confident). ‘trust in different nutrition information sources’ was dichotomised, so that categories 1, 2, and 3 (none at all, a little, a moderate amount) and categories 4 and 5 (a lot, a great deal) were combined to create a dichotomous variable (0 = not trusted, 1 = trusted). categories 1, 2 and 3 (my doctor does not provide information about healthy diets, information and advice is insufficient, information is neither excessive nor insufficient) for the question about the ‘quality / quantity of information provided about healthy diets by a family doctor’ were combined, as were categories 4 and 5 (information and advice is sufficient, information is more than i need) were combined to create a dichotomous variable (0 = information is insufficient, 1 = information is sufficient). the variable ‘age’ was reduced from six to three categories where categories 1 and 2 (<20 and 20–22), 3 and 4 (23–25 and 25–27 [sic]), and 5 and 6 (28–30 and >30) were combined to create three overall categories (1 = ≤ 22, 2 = 23–27, 3 = ≥ 28). predictor variables were pre-screened using a liberal p-value (£ 0.2) for inclusion in the respective model. to screen for any pairwise correlations between the independent categorical variables, a spearman’s correlation analysis was performed. a likelihood ratio test was completed prior to removing any categorical variables that did not yield statistical significance (p-value ≤ 0.05) for inclusion in the respective final multivariable logistic regression model. univariate analyses were used to examine the effect of different nutrition sources on perceived amount of information to exist on human nutrition, and two logistic regression models were constructed to evaluate the effect of predictor variables on confidence in nutrition information-seeking abilities, and trust in family doctors recommending certain diets. measures of frequency were evaluated for: primary sources of nutrition information; primary sources of general health information; amount of information students think exist on human nutrition; perceived confidence in knowing where to find personal nutrition information; perceived difficulty in finding personal nutrition information; amount of trust placed in different nutrition information sources; and perceived quality / quantity of information regarding healthy diets received from family doctor. the non-parametric mann-whitney rank sum test was performed to check for significant differences between information sources used for personal nutrition and health information. significance was considered at p ≤ 0.05.   results response rate and demographics of the 942 students who received the questionnaire, 322 completed it yielding a 34% response rate. most (150/322 [47%]) of the respondents were ≤22 years old, with 45% (145/322) between 23–27 and only 8% (27/322) were ≥28. the majority (285/322 [89%]) of students identified as female, with only 11% of respondents identifying as male (37/322). canadian respondents were slightly more represented (160/322, 50%) than american respondents (156/322, 48%), with the remaining students either identifying as an international resident (4/322 [1%]) or preferring not to declare their area of residence (2/322 [1%]). animal biology (142/322 [44%]) was the most common previous programme of study. the majority of respondents planned to pursue a career in a companion animal exclusive practice (105/322 [33%]) or rural community practice (82/322 [25%]) (table 1). table 1. previous programme of study and career plans upon graduation of first year canadian and us veterinary students who completed questionnaire on nutrition attitudes and behaviours (n=322).   sources of health and nutrition information as shown in figure 1, 93% (298/322) of students reported the use of a personal healthcare provider (php) as a primary information source for their general health, but only 41% (133/322) of students relied on their php as a primary resource for their personal nutrition information. more than half of respondents reported using the internet search engine google as a primary information source for their personal health (214/322 [66%]) and personal nutrition (197/322 [61%]) needs. family members and university lectures were also reported as primary information sources by over 50% of students, with family members relied upon by 53% (172/322) for general health information and 52% (168/322) for nutrition information, and university lectures relied upon by 59% (191/322) and 51% (165/322) for general health and nutrition information, respectively. there were significant differences in the reported use of books / magazines, internet blogs, nurses, peer-reviewed journal articles, and phps for personal health versus nutrition needs. additionally, there was a significant difference in students who preferred not to answer with regards to their primary information sources for personal health versus nutrition needs (p <0.05). a complete comparison of information sources utilised by first year veterinary students for their general health and nutrition is shown in figure 1. figure 1. primary sources of information utilised for general health and personal nutrition needs by first year canadian and us veterinary students (n=322) retrieved from questionnaire that assessed health attitudes and behaviours. students could select more than one response option for these questions (*p <0.05, derived from mann-whitney rank sum test).   health and nutrition information-seeking attitudes and perceptions when asked how much information students perceived to exist on human nutrition, most believed a very high (186/322 [58%]) or moderate (99/322 [31%]) amount existed. 2% (5/322) of respondents believed that only a small amount of information existed on human nutrition, and less than 1% (1/322) of students believed that no information existed on this topic. there were 6% (18/322) of respondents who indicated that they were unsure of how much information exists on human nutrition. table 2 highlights the results of univariate analyses of personal nutrition information sources associated with students’ perceived amount of human nutrition information to exist. university lectures was the only nutrition information source significantly associated with students’ perceived amount of information to exist on human nutrition, with students who reported using this source for their own nutrition needs being more likely (or = 4.37, p = 0.049) to perceive a large amount of information to exist on human nutrition. table 2. univariate analyses results of primary nutrition information sources influencing first year canadian and us veterinary students’ self-reported perceived amount of information to exist on human nutrition showing variables, odds ratio, 95% confidence intervals, and significance values (n=322).   students were asked how easy it is to find information about their own nutrition. the majority (138/322 [43%]) of respondents thought this task to be moderately easy, with 16% (50/322) believing it to be very easy. 11% (37/322) of students thought finding information about their own nutrition to be moderately difficult, and very few (5/322 [2%]) thought it to be very difficult. one quarter (79/322) of respondents were unsure how easy they perceived finding information about their own nutrition to be. using a series of subscale question statements, students were asked to rate their level of trust with respect to regulatory standards, dietary recommendations by health professionals, messages portrayed by the media, and online information sources (table 3). advice from a registered dietician for personal nutrition ranked relatively high in trust by respondents, with most trusting them either ‘a lot’ (116/322 [36%]) or ‘a great deal’ (122/322 [38%]). messages that the media portrays and advice from a health professional who is sponsored by a certain food company were only trusted ‘a little’ by almost half of respondents (135/322 [42%]). students indicated a general trust towards diet recommendations from family doctors, with 34% (108/322) and 33% (106/322) trusting this information ‘a lot’ or ‘a moderate amount’, respectfully. the age of first year veterinary students was significantly associated with having trust in family doctors recommending certain diets (table 4). younger students were more likely to trust this information, with those aged ≤ 22 three times as likely (p <0.02), to trust dietary recommendations from family doctors than those aged ³ 28. there was no significant difference in trust between respondents aged ≤ 22 and 23–27. students who indicated their php as a primary source for their own nutrition information were also more likely to trust family doctors recommending certain diets (or = 2.02, p <0.03). table 3. amount of trust placed in different information sources as self-reported by first year canadian and us veterinary students as part of questionnaire on health and nutrition attitudes and behaviours (n=322).   table 4. reduced* multivariable logistic regression results of variables influencing first year canadian and us veterinary students’ self-reported trust in family doctors recommending certain diets showing significant variables, odds ratios, 95% confidence intervals, and significance values (n=322).   when asked about the quality and quantity of information regarding healthy diets first year students received from their family doctor, almost half of respondents (134/322 [42%]) indicated that their doctor did not provide any information about healthy diets. figure 2 presents a complete breakdown of students’ views on the nutrition information provided to them by their family doctor. figure 2. first year canadian and us veterinary students’ response to the question, ‘what is your view on the quality / quantity of information provided about healthy diets by your family doctor?’ on a questionnaire that assessed health and nutrition attitudes and behaviours (n=322).   almost half (157/322 [49%]) of respondents acknowledged that they were moderately confident in knowing where to find information relating to their nutrition, with 18% (57/322) of respondents being strongly confident. 19% (62/322) of students were neither confident nor unconfident in knowing where to find information about their own nutrition, 8% (27/322) were moderately unconfident, and only 2% (6/322) of students indicated that they were strongly unconfident in this ability. results of significant variables associated with students’ confidence in their nutrition information-seeking abilities is presented in table 5. of note, reliance on peer-reviewed journal articles as a primary information source significantly influenced students’ confidence in their own nutrition information-seeking abilities (or = 6.61, p <0.001). students who perceive a large amount of information to exist on human nutrition were also more likely to have confidence in their information-seeking abilities with regards to their own nutrition (or = 5.25, p <0.001). table 5. reduced* multivariable logistic regression results of variables influencing first year canadian and us veterinary students’ self-reported confidence in personal nutrition information-seeking abilities showing significant variables, odds ratios, 95% confidence intervals, and significance values (n=322).   discussion sources of health and nutrition information findings of this study offer an understanding of first year veterinary students’ attitudes and behaviours regarding their personal health and nutrition information-seeking habits. though phps were the most commonly reported primary information source by students for general health information, the internet search engine google was the next-most reported source and was the highest-ranked primary information source for students’ personal nutrition needs. research indicates that young, highly educated, healthy females may be especially active in online hisb in the us population, and these predictors have remained consistent over time (percheski & hargittai, 2011; rice, 2006; and song & oh, 2015). these demographic identities align well with our study population, with a distinct female gender bias (285/322 [89%]). this may be one reason why online information sources were highlighted in our findings and reflects the gender composition at other veterinary colleges (royal et al., 2018). moreover, high reliance on the internet is consistent with existing literature investigating health and nutrition information-seeking behaviours amongst diverse student populations (basch et al., 2018; o’carroll et al., 2015; and schleyer et al., 2012), and in the animal health information-seeking habits of veterinary students (weiner et al., 2011; lai et al., 2019; and kamleh et al., 2021).   information-seeking attitudes and perceptions the internet may be an advantageous resource for students seeking health information by being easily accessible, discrete, and acting as a host to various communities to facilitate supportive interactions (rennis et al., 2015; giles & newbold, 2013; ho et al., 2014; and lagoe & atkin, 2015). despite such benefits, use of internet search engines, such as google, can produce an overwhelming amount of results which may lead to unreliable information and feelings of frustration (chen et al., 2018; and lai et al., 2019). while data was collected on the use of other online resources, such as specific health websites and peer-reviewed journal articles, further information regarding specific sources retrieved from the internet search engine google by students were not collected. in general, students in our study believed a very high amount of information to exist on human nutrition, and while they thought this information to be generally easy to find, most students were only moderately confident in knowing where to find such information. these perceptions surrounding mass information availability that is easy to find, yet a shared lack of confidence in an ability to do so, may be a reflection of students’ reliance on the internet search engine google to acquire this information in our study. students who primarily relied on books or magazines, or peer-reviewed journal articles had improved odds of having self-confidence in their nutrition information-seeking abilities. however, only 99/322 (31%) of students reported the use of these resources for their personal nutrition needs. like the internet, literature sources such as books and magazines can vary significantly in reputability of published information, and may contain advertisements which inadvertently promote an unhealthy lifestyle (hassan et al., 2007). as such, students should be better educated surrounding the selection of these resources to most effectively influence their personal health and nutrition needs. lack of confidence in knowing where or how to find information may introduce additional consequences to students’ personal health and well-being. 34/322 (10%) of first year veterinary students indicated a lack of knowledge about healthy eating as a significant barrier to changing their eating habits, and the perceived lack of knowledge significantly associated with reduced odds of perceiving their diet as healthy (nielson et al., 2021). though almost all first year veterinary students indicated their php as a primary information source for their own general health information, less than half identified their php as a key resource for their own nutrition information, resulting in a dichotomy in reliance on this source. the essential role of nutrition in the prevention and treatment of various diseases is well known (lichtenstein et al., 2006). yet, 134/322 (41%) of first year veterinary students revealed their doctor did not provide any information on healthy diets, and another 45 (14%) claimed the information they did receive to be insufficient. previous research investigating online hisbs have identified a significant association between unmet needs of patients, including information provided by the physician, and reliance on the internet (tustin, 2010). although first year veterinary students in this study indicated a general trust towards dietary recommendations from family doctors, their perceived lack of guidance from medical professionals may be hindering the opportunity physicians have to correct potential misconceptions that students could develop from using the internet, which may influence personal health and nutrition behaviours. in a previous study by the authors, physician recommendations were considered to be a motivating factor to changing personal eating habits by nearly half of first year veterinary students (nielson et al., 2021). given first year veterinary students who reported the dietary information and advice received from their doctor to be sufficient were significantly more likely to be confident in knowing where to find personal nutrition information, it is important for the php to regularly address nutrition during appointments. such practices can support students’ confidence in knowing where to access reliable information and ensure the dietary needs of these patients are being met. moreover, considering younger students in our study had improved odds of having trust in family doctors recommending certain diets in comparison to older students, specifically those aged 28 or older, it is especially critical for these younger students to have already established a sufficient nutrition-related dialogue with their family doctor in an effort to maintain these trust levels throughout adulthood. students who reported a reliance on their php as a primary information source for personal nutrition needs were also associated with greater odds of trusting dietary recommendations from their family doctor. results by van weel (2003) suggest that physicians should approach nutritional counselling with their patients using consistent, short discussions, which can be accommodated in the time constraints of regular appointments. research investigating pet owners’ attitudes and intentions towards nutritional guidance received from veterinarians reveals a parallel to the outcomes of our study; though pet owners revealed general trust in veterinary advice, owners perceive a need for more frequent nutritional counselling from their veterinarians (kamleh et al., 2020a). encouraging first year veterinary students to express interest in regularly discussing their nutritional needs with their php would not only support them to experience the personal benefits of this credible resource, but could also serve as a professional example to these future professionals to frequently address nutritional concerns with pet owners (walsh et al., 2002; and kamleh et al., 2020b). while advice from a registered dietician was ranked as highly trusted by first year veterinary students, these health professionals were reported as a primary source for personal nutrition information by less than a quarter of respondents. information was not collected regarding the accessibility of such services to students, although many post-secondary institutions in canada and the us offer dietician-run programmes and appointments through their student health services. the 2007 canadian national physician survey reported that 52% of family physicians collaborated with dieticians or nutritionists, and 42% offered nutritional counseling within their practice (family physicians and nutrition counseling, 2010). these statistics increased from previously conducted surveys, and at the time of that survey, over 81% of second-year family medicine students indicated they had collaborated with dietitians or nutritionists as part of their training (family physicians and nutrition counseling, 2010). this information points towards developing accessibility to specialised nutritional services through family physicians, yet such support was not reflected in the results of our study. while 134/322 (41%) of first year veterinary students revealed their php as a primary information source for personal nutrition needs, and most revealed trust in family doctors recommending certain diets, the quantity and quality of information received was generally perceived to be insufficient. these results indicate that while students may generally trust and rely on nutrition and dietary information from their doctor, they may not be receiving this type of information in the capacity that they need. further research investigating students’ accessibility to, and perceptions of, registered dieticians, as well as phps for personal nutrition information is needed to better understand the hisb of this population. information provided to students by veterinary educators may influence student learning beyond the context of veterinary medicine; over half of first year veterinary students in our study reported university lectures as a primary information source for both personal health (191/322 [59%]) and nutrition (165/322 [51%]) needs. the high demands of veterinary medical curricula are well understood, and research in other veterinary student populations have reported information overload as a significant source of stress in these individuals (mclennan & sutton, 2005). first year veterinary students who reported university lectures as a primary nutrition information source had improved odds of believing a very high amount of nutrition information to exist. thus, students may already feel overwhelmed by the amount of extensive health and nutrition information they are acquiring through the veterinary curriculum. as veterinary schools develop student wellness initiatives, they may want to consider providing personal health and nutrition information that complements concurrent lectures on animal health and nutrition. similarly, such information could be incorporated into a well-being stream in the curriculum. these approaches could benefit students by reinforcing health and nutrition concepts valuable to their studies, while promoting personal applications to well-being. another approach could consider results by dale et al. (2011) who suggested that online communities using web 2.0 tools (web applications that facilitate individuals to create, share, collaborate and communicate) are largely advantageous for veterinary professionals and play an important role in continuing education. as reliance on technology continues to grow, extending such online communities to support veterinary students and professionals with personal health and well-being needs could be an accessible opportunity to guide this population in retrieving credible information from an online source (dale et al., 2011). information-seeking literacy skills are essential for identifying and evaluating reputable information resources. guiding students to reputable information sources such as peer-reviewed journal articles and trusted books or magazines is one component, as is helping them assess internet websites for accuracy and reliability. the goal is improved self-confidence in hisb. veterinary schools should work to ensure students have the necessary skills and resources to effectively navigate health information to endorse good hisb both academically and personally. the literature suggests that poor health literacy can hinder the ability to effectively find, comprehend, and use information to manage personal health conditions (world health organization, 2021; ferguson & pawlak, 2011). such skills are especially important for veterinary students who are responsible for managing their own health and eventually, the health of their patients. online, in-person, and blended approaches have been shown to be equally effective for recalling information literacy skills (anderson & may, 2010). assisting veterinary students to develop sound hisb will not only support them in making well-informed decisions for their personal health and nutrition but encourage future client counselling habits that align with these objectives as professionals. there are some limitations to this study. first, given the small pilot sample of the survey and limits in language translation and generalisation, the potential challenge of item development cross-linguistically, cross-culturally, and across universities sampled should be acknowledged. results from this study provide useful insights, however standard questionnaire biases should be considered, including social desirability, acquiescence, and item order. further, the power of the predictive models of this data may be impacted by such biases, given the potential interaction effects of questionnaire biases with result variance. though it was stressed to students that our questionnaire was anonymous and efforts to maintain confidentiality of personal identifying data were outlined, there was a significant difference in respondents who preferred not to disclose their primary information sources for general health versus nutrition needs. personal nutrition may be perceived as highly personal and is a potentially sensitive topic for individuals, including health professionals. such sensitivities have the potential to result in non-response and social desirability biases. furthermore, we did not collect information regarding students’ health status, which could influence information-seeking habits. thus, these aspects should be considered both in interpreting our results, and in future research and initiative efforts. our findings present the primary personal health and nutrition information sources relied upon by first year canadian and us veterinary students, and their held attitudes and behaviours of related resources. results illustrate a high reliance on internet search engines, and a general lack of guidance from medical professionals regarding students’ personal nutrition needs. this information should encourage veterinary schools to further guide their students in developing and applying sound hisb, in order to effectively support students with personal health and nutrition decisions and behaviours, and thrive as veterinary students and future health professionals.   conflict of interest the authors declare no conflicts of interest.   references anderson, k. & may, f.a. 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(2011). information-seeking behaviors of first-semester veterinary students: a preliminary report. journal of veterinary medical education. 38(1), 21–32. doi: https://doi.org/10.3138/jvme.38.1.21 intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. is inhaled immunotherapy more effective than environmental management when treating equine asthma? a knowledge summary by amy leather bvsc pgdip (clinical veterinary practice) mrcvs 1* sarah smith ma vetmb mvetmed dacvim mrcvs 1 1university of bristol, langford house, langford, bristol, bs40 5du *corresponding author (al14572@bristol.ac.uk) vol 6, issue 1 (2021) published: 25 mar 2021 reviewed by: rachel conwell (bvetmed dipeceim certem(intmed) mrcvs) and adele williams (bvsc mrcvs dipeceim phd) next review date: 22 jun 2022 doi: 10.18849/ve.v6i1.391 pico question in horses with severe equine asthma syndrome, is inhaled immunotherapy compared to environmental reduction of allergen exposure more effective in disease modification?   clinical bottom line category of research question treatment the number and type of study designs reviewed 12 papers were critically reviewed. nine clinical trials; one crossover study; one split-plot design study; and one cross-sectional study strength of evidence low outcomes reported four studies found inhaled immunotherapy to improve the clinical signs associated with equine asthma and the lung function of horses with asthma. three papers found environmental modification improved lung function and the clinical signs associated with equine asthma but two studies provide moderate evidence that environmental management alone is insufficient to permanently cure asthma conclusion there is a low level of evidence to support the use of inhaled immunotherapy as a treatment for equine asthma   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you have recently diagnosed a 10-year-old pony with severe equine asthma syndrome. the owner would like to know more about inhaled immunotherapy as an option for treating equine asthma and if inhaled immunotherapy will result in better disease modification compared to environmental management alone for the pony. summary of the evidence the papers appraised include a number of different terms previously used for severe equine asthma. the original terms used in the paper can be found in the population section of each individual appraisal, otherwise the term equine asthma is used.   abbreviations: aado2 alveolar-arterial oxygen gradient bal bronchoalveolar lavage balf bronchoalveolar lavage fluid cbc complete blood count cpg cytosine-phosphate-guanosine cpg-odn cytosine-phosphate-guanosine oligodeoxynucleotides gnp gelatin nanoparticle hpw highly purified water hpw-gnp highly purified water bound to gelatin nanoparticle ifn-γ interferon gamma il interleukin mmp matrix metalloproteinase paco2 arterial partial pressure of carbon dioxide pao2 arterial partial pressure of oxygen timp tissue inhibitor of matrix metalloproteinase   klier et al. (2019) population: adult horses with equine asthma case selection: resting respiratory rate (rr) (>16/min) on contact to dusty hay and straw increased abdominal breathing effort abnormal thoracic auscultation increased neutrophilic granulocyte percentage in balf (>25%) reduced partial oxygen pressure at rest (<90 mmhg) increased interpleural pressure (>15 cmh2o) no concurrent respiratory disease no medication in the 8 weeks prior to/during study sample size: 29 horses intervention details: horses assigned into treatment groups considering age, housing management and breed treatment groups, each received a total of 10 inhalations: cpg single dose, 187.5 μg cpg‐odn (n= 11): one inhalation q 48 h for 20 days cpg double dose, 375 μg cpg‐odn (n= 9): one inhalation q 48 h for 20 days beclomethasone, 1600 µg (n=9): one inhalation q 24 h for 10 days technique: standardised horses were assessed at the following time points: time point i: before treatment time point ii: immediately after treatment period time point iii: 8 weeks after final inhalation study design: double-blinded clinical field trial outcome studied: subjective assessments: hoarsi: standardised horse owner assessed respiratory signs index (time points i and iii) bronchoscopy: evaluation of mucus, redness or swelling of nasal mucosal membranes (time points i, ii and iii) objective assessments: clinical examination scores (time points i, ii and iii) lung function testing (time points i, ii and iii) bal for cytokine assay and immunalysis (time points i, ii and iii) blood sample: cbc and fibrinogen (time points i, ii and iii) horses were also clinically observed daily main findings (relevant to pico question): single dose cpg: improvement in resting rr (clinical examination score) at time points ii and iii improvement of 82% clinical parameters at time point ii improvement in 100% clinical parameters at time point iii beclomethasone: no improvement in resting rr improvement in 72% clinical parameters measured at time point ii improvement in 50% clinical parameters measured at time point iii double dose cpg: did not result in improvement compared to single dose cpg single dose cpg vs beclomethasone: cpg single dose improved hoarsi scores at time point iii compared to beclomethasone group no difference in cytokine analysis at time points ii or iii no difference in cd4+ lymphocyte analysis  no adverse effects of cpg treatment were noted limitations: environment and management were not standardised which may have influenced horses’ response to treatment no placebo group small sample size owner bias klier et al. (2015) population: adult horses with severe equine asthma (chronic recurrent airway obstruction (rao)) case selection: increased resting rr on contact to dusty hay/straw increased abdominal breathing effort abnormal thoracic auscultation increased neutrophil percentage in balf (>25%) reduced partial oxygen pressure at rest (<90 mmhg) increased interpleural pressure (>15 cmh2o) no additional medication for 2 months prior to/during study sample size: 24 horses intervention details: inhaled cpg or placebo treatment groups, one inhalation q48 hours for 10 days: cpg group (n=16) – 187.5 μg cpg‐odn placebo group (n=8) – hpw-gnp technique: standardised horses were assessed at the following time points: time point i: before treatment time point ii: immediately after treatment period time point iii: 4 weeks after final inhalation study design: randomised, double-blinded, placebo-controlled clinical trial outcome studied: subjective assessments: bronchoscopy (time points i, ii and iii) objective assessments: clinical examination scores (time points i, ii and iii) lung function testing (time points i, ii and iii) bal and cytology (time points i, ii and iii) horses were also clinically observed daily main findings (relevant to pico question): cpg: improvement between time points i and ii in: breathing pattern lung auscultation partial oxygen pressure aado2 neutrophil percentage nasal discharge tracheal secretion quantity and viscosity improvement between time points i and iii in: breathing pattern lung auscultation aado2 nasal discharge tracheal secretion quantity and viscosity cpg vs placebo: improvement in rr after cpg compared to placebo placebo resulted in no improvement of any parameters measured cpg inhalation improved 70% of clinical, endoscopic and cytological variables evaluated between time points i and iii no adverse effects to cpg inhalation were detected during the study limitations: the environment and management of horses in study was not standardised small sample size klier et al. (2012) population: adult horses with equine asthma (moderate rao) and healthy adult horses sample size: 12 horses intervention details: healthy – placebo or cpg rao – cpg treatment groups: rao group (n=4) – 5 μg cpg‐odn: one inhalation q 48 hours for 10 days compatibility group (n=4) – 5 μg cpg‐odn: one1 inhalation q 48 hours for 6 days placebo group (n=4) – hpw-gnp: one inhalation q 48 hours for 6 days all horses were assessed at: time point i: before treatment time point ii: after third inhalation the rao group were also assessed at: time point iii: after five inhalations technique: inhalations were administered with the same nebuliser equipment study design: placebo-controlled clinical trial outcome studied: subjective assessment: bronchoscopy objective assessment: rr blood gas analysis and pao2 balf cytology and cytokine analysis horses were also clinically observed daily main findings (relevant to pico question): cpg inhalation in rao horses: increased il-10 and ifn-γ in balf between time points i and iii increased pao2 between time points i and iii decreased rr between time points i and iii decreased balf neutrophil percentage between time points i and iii no difference in balf neutrophil percentage between rao group after treatment and healthy horses after placebo no adverse effects of treatment with cpg were detected limitations: rr was the only clinical examination parameter measured small sample size the assessors were not blinded to the treatment protocols management and environmental conditions are unspecified signalments of horses is not divulged klier et al. (2017) population: adult horses with equine asthma case selection: increased resting rr (>16/min) increased abdominal breathing effort abnormal thoracic auscultation increased neutrophilic granulocyte percentage in balf (>25%) reduced partial oxygen pressure at rest (<90 mmhg) increased interpleural pressure (>15 cmh2o) no additional medication in the 8 weeks prior to study or during study sample size: 20 horses intervention details: inhaled cpg or cpg with specific allergen treatment groups: cpg inhalation, 5 μg cpg‐odn (n=9): one inhalation q48 hours for 14 days cpg + two individually selected allergens (n=11): one inhalation q48 hours for 14 days allergen selection: functional in vitro test on whole blood was carried out on horses and two allergens were selected for each horse based on geographical location, seasonality of clinical signs and results of blood test technique: all inhalations were administered with the same nebuliser equipment all horses were assessed at the following time points: time point i: prior to treatment time point ii: immediately after last inhalation time point iii: 6 weeks after inhalational therapy study design: prospective, randomised clinical trial outcome studied: objective assessments: arterial blood gas measurements: pao2 and paco2 aado2 maximum interpleural pressure differences cytology of tracheobronchial secretion: neutrophil percentage subjective assessments: clinical examination scores endoscopy horses were also clinically observed daily main findings (relevant to pico question): cpg only vs allergen group: no difference was found at any time point, of any parameter or cytokine measured, between the groups in both groups there were significant improvements between time point i and iii in: resting rr breathing type score pao2 nasal discharge score lung auscultation score tracheal mucous and viscosity tracheal wash (tw) and serum il-4 limitations: environmental and management conditions of horses were not standardised no control group small sample size assessors were not blinded to the treatment interventions barton et al. (2019) (follow on paper from klier et al. 2017) population: adult horses with equine asthma sample size: 20 horses intervention details: inhaled cpg or cpg with specific allergen treatment groups: cpg inhalation, 5 μg cpg‐odn (n=9): one inhalation q48 hours for 14 days cpg + two individually selected allergens (n=11): one inhalation q48 hours for 14 days allergen selection: functional in vitro test on whole blood was carried out on horses and two allergens were selected for each horse based on geographical location, seasonality of clinical signs and results of blood test technique: all inhalations were administered with the same nebuliser equipment all horses were assessed at the following time points: time point i: prior to treatment time point ii: immediately after last inhalation time point iii: 6 weeks after inhalational therapy study design: randomised clinical trial outcome studied: objective assessments: ifn and il enzyme-linked immunosorbent assay (elisa): serum and tracheal wash (tw) fluid mmp and timp elisa from bal main findings (relevant to pico question): higher tw concentrations of mmp-2, mmp-9, timp-1 and timp-2 in horses with severe asthma vs mild asthma both groups – mmp-2 and timp-2 reduced at time point ii and iii in both groups, mmp-9 and timp-1 were reduced at time point iii in both groups tw il-4 was reduced at time point ii no adverse effects of inhalational therapy detected limitations: environmental and management conditions were not standardised no control group small sample size couëtil et al. (2005) population: adult horses with equine asthma (rao) case selection: history of chronic respiratory disease >2 years increased respiratory effort when fed hay management unchanged for 6 months prior to the study horses were grouped as mild, moderate or severe asthma horses in each group were then randomly assigned to a treatment group sample size: 28 horses intervention details: inhaled or oral corticosteroid treatment or inhaled placebo treatment groups: inhaled fluticasone (n=10): 9 puffs (1980 μg) q12 hours for 2 weeks, then 5 puffs (1100 μg) q24 hours for 1 week, then 5 puffs (1100 μg) q48 hours for 1 week oral prednisone (n=9): 500 mg q12 hours for 2 weeks, then 200 mg q24 hours for 1 week, then 200 mg q48 hours for 1 week inhaled placebo (n=9): nine puffs q12 hours for 2 weeks, five puffs q24 hours for 1 week, five puffs q48 hours for 1 week all horses managed outdoors with a completely pelleted diet for duration of study. half the horses were managed by their owners at home during the study. technique: inhaled substances were delivered using the same inhaler prednisone crushed and delivered directly by dosing syringe horses were assessed: prior to treatment (day 0) after 2 weeks of treatment (day 14) after 4 weeks of treatment (day 28) study design: double-blinded, controlled clinical trial outcome studied: objective assessments: pulmonary function tests clinical examination score balf cytology main findings (relevant to pico question): clinical examination: clinical examination score of all horses improved during the study, independent of treatment lung function tests: severely classed horses treated with fluticasone had improved pulmonary function and pulmonary resistance after 2 weeks no difference in lung function between the oral prednisone and the control group improvement of all forced expiration values regardless of treatment group at 4 weeks bal cytology no improvement for any variable measured in any treatment group limitations: half the horses were managed by their owners at home during the study. treatment may have been incorrectly administered and environment may have differed small sample size short study time vandenput et al. (2010) population: adult horses with asthma (chronic obstructive pulmonary disease (copd)) and healthy adult horses case selection: asthma horses: clinical history of asthma, positive response to hay and straw challenge with clinical signs reversible by administration of atropine (0.02 mg/kg iv) healthy controls: no history of respiratory disease, no respiratory abnormalities on clinical exam or pulmonary function tests, no response to hay and straw challenge sample size: 12 horses intervention details: changing environment environments for asthma group (n=6): at pasture, no access to barn or hay (period a – 2 months) in barn, wood shavings and grass silage (period b – 6 weeks) in barn, straw and grass silage (period c – 6 weeks) in barn, straw and dry hay (period d – <6 weeks) control horses (n=6): kept in period d environment for 6 weeks management: frequency and time of mucking out was standardised horses were fed twice daily at the same times horses were exercised for 30 minutes every morning copd horses were assessed at the end of: period a, b and c after they developed clinical signs of copd during period d control group were assessed: after 6 weeks in period d environment study design: prospective, controlled clinical trial outcome studied: objective assessments: lung function tests rr arterial blood gas horses were also clinically observed each day main findings (relevant to pico question): asthma horses – no clinical signs of asthma until period d after period d, the asthma group had increased pulmonary resistance, maximum change in pleural pressure and significantly decreased dynamic compliance and pao2 no difference in rr between the control group and the asthma group in period d limitations: small sample size hay exposure without straw should also have been assessed to determine if the development of asthma clinical signs was due to dry hay contact leclere et al. (2011) population: adult horses with asthma (heaves) age-matched healthy control horses case selection of asthma horses (n=6): 3–10 year history of asthma reversible airway obstruction when exposed to hay otherwise healthy based on clinical exam, cbc and biochemistry selection of controls (n=5): age-matched clinically normal horses sample size: 11 horses intervention details: all horses were maintained at pasture for > 3 months prior to the start of the study horses were then stabled with hay for the duration of the study each horse was examined at three time points: time point i: prior to stabling time point ii: day 1 of stabling time point iii: day 30 of stabling study design: prospective clinical trial outcome studied: objective assessments: pulmonary function endobronchial and peripheral lung biopsy histology and morphometric analysis/ airway smooth muscle mass measurements balf cytology main findings (relevant to pico question): prior to stabling there was no significant difference in pulmonary function between the asthma and control groups significant decrease in pulmonary function in the asthma group after 30 days compared to the control group significant increase in neutrophil percentage of balf in asthma group after 1 and 30 days mean airway smooth muscle mass was significantly increased in asthma horses compared to controls at all time points limitations: assessors were not blinded small sample size leclere et al. (2012) population: adult horses with chronic heaves (asthma) selection criteria: history of heaves for >4 years signs of airway obstruction and inflammation on hay exposure no other health concerns based on clinical exam, cbc and biochemistry sample size: 11 horses intervention details: all horses housed indoors and exposed to hay until clinical signs of heaves induced at beginning of study treatment groups: antigen avoidance group (n=5): 24 hour turnout, no access to hay inhaled corticosteroids group (n=6): fed hay indoors and treated with inhaled corticosteroids for 6 months then turned out with no hay access and treated with inhaled corticosteroids 2,000 µg q12 hours for 1 month, then 2,000–3,000 µg q12–24 hours as required to control clinical signs for the duration of the study each horse was examined at: baseline (after clinical signs of heaves induced) 6 months of treatment 12 months of treatment additional data collected after 1 and 7 months study design: prospective clinical trial outcome studied: objective assessments: pulmonary function endobronchial and peripheral lung biopsy histology and morphometric analysis/airway smooth muscle mass measurements balf cytology and polymerase chain reaction (pcr) main findings (relevant to pico question): pulmonary function improved in both treatment groups with no significant difference between them airway smooth muscle mass significantly decreased with both treatments corticosteroids resulted in a quicker improvement in both pulmonary function and muscle mass neutrophil percentage of balf returned to normal after exposure to antigen had ceased in both treatment groups il-8 was significantly decreased in both treatment groups limitations: no control group small sample size assessors were not blinded to treatment groups jackson et al. (2010) population: adult horses with asthma (inducible airway obstruction) case selection: asthma induced by straw and moldy hay atropine was administered (0.02 mg/kg iv), lung function was remeasured to test reversibility of airway obstruction horses were rested for at least 30 days prior to the study sample size: 12 horses intervention details: treatment groups: environmental: pine shavings and complete pelleted feed environmental + prednisone: pine shavings and complete pelleted feed and oral prednisone once a day (2.2 mg/kg) horses were assessed for both treatments at: day 0 day 3, 7 and 14 day 44 (after 30 day wash-out) timeline of study: horses randomly allocated to first treatment group heaves induced with management until airway obstruction resulted in maximal change in pleural pressure (>25 cmh2o) lung function and bal test at day 0, 3, 7, 14 treatment maintained for 14 days followed by a 30 day wash-out period crossover of treatment groups after washout period study design: prospective, crossover clinical trial outcome studied: objective assessments: lung function tests bal cytology main findings (relevant to pico question): environment modification only: improvement of lung function by day 3 no effect on balf cytology by day 14 environment + prednisone: improvement of lung function by day 3 improved balf neutrophil percentage by day 3, no further improvement at day 14 wash-out period: best improvement in pulmonary resistance, interpleural pressure, total cell numbers and percentage neutrophils were seen in both groups at day 44 (after 30 day wash-out) limitations: assessors were not blinded to the treatment group small sample size long-term effect not assessed miskovic et al. (2008) population: adult horses with asthma (rao) age-matched healthy control horses case selection of asthma horses (n=24): maximum transpulmonary pressure >15 cm h2o >25% neutrophils in balf cytology reversible airway obstruction after modifying environment maximum of 5–6 years since diagnosis no treatment except in times of acute asthma crisis turned out for 24 hours a day with no access to hay no medications in the 6 months prior to the study selection of controls (n=24): age-matched clinically normal horses normal clinical exam no history of respiratory clinical signs no signs of respiratory disease when housed and fed hay sample size: 48 horses intervention details: asthma horses were grouped based on number of years of environmental management since diagnosis: group i: 1 year (n=9) group ii: 2–3 years (n=7) group iii: 5–6 years (n=8) management of asthma horses during study: 24 hour turnout, no access to hay management of controls: 24 hour turnout with access to a three sided stable shelter and hay each horse was examined once during the study study design: cross-sectional study outcome studied: objective assessments: lung function forced expiratory manoeuvres balf cytology subjective assessments: clinical examination score main findings (relevant to pico question): asthma group ii had higher clinical exam scores than the control group there was no difference in the standard lung function tests between the asthma and control groups forced expiratory flow (fef, mean between 75–95% of the exhaled vital capacity) was lower in the asthma groups than control group no difference in balf total nucleated cell count between the asthma and control groups limitations: clinical examination assessors were not blinded small sample number in each group auger & moore-colyer (2017) population: stable design (n= 8 barns/blocks with 32 stables): american barns: open windows, roof ventilation, main doors open single stable complexes: half doors, windows, vents sample size: 128 air samples intervention details: management regimes (two barns and two stable blocks/regime): steamed hay and shavings (regime 1) dry hay and shavings (regime 2) haylage and straw (regime 3) dry hay and straw (regime 4) stables sampled once a day when the yard was quiet, horses were present in the stables and free to move around two samples per stable (breathing zone (bz) as horses ate and stable zone (sz)) study design: split-plot design study outcome studied: objective assessments: airborne respirable dust concentration (ard, particles <5 μm) main findings (relevant to pico question): steamed hay and shavings – lowest ard (sz and bz) dry hay and straw – highest ard limitations: factors including wind, temperature and humidity varied feeding system varied – mangers/hay nets/from the ground horses movements in stables may have affected samples samples were only collected at quiet times; sampling at busiest times would have shown peak variability in regimes only four regimes were used appraisal, application and reflection there are currently no studies directly comparing inhaled immunotherapy with environmental modification for the management of equine asthma, and only limited studies exploring the use of inhaled immunotherapy. papers that directly investigated the effect of inhaled immunotherapy on clinical signs of asthma in horses were included. five papers were found that investigated the use of inhaled cpg. comparators used included placebos, inhaled corticosteroid or varying doses of cpg. there are no reports of adverse effects to cpg inhalation. due to the incomplete understanding of the pathophysiology of equine asthma (couëtil et al., 2016) it is difficult to assess the effect of specific interventions on disease modification. the different studies measured a variety of outcomes. bronchoscopy and bal fluid analysis, clinical exam scoring, and arterial blood gas analysis were used in all 5 studies. other outcomes investigated included pulmonary function tests, immunologic analysis of tracheal washes and serum, and owner questionnaires. the length of these studies ranged; the longest being klier et al. (2019) which assessed the horses 8 weeks after the treatment period. therefore, none of these studies is able to determine the long-term effect of inhaled immunotherapy on disease modification. four studies found inhaled cpg to improve the clinical signs associated with equine asthma (klier et al., 2019; klier et al., 2017; klier et al., 2015; and klier et al., 2012). a significant improvement in clinical score was found following treatment with cpg compared to beclomethasone inhalation in the one study that assessed this (klier et al., 2019). allergen-specific inhaled immunotherapy was found to be of no significant benefit over inhaled cpg (klier et al., 2017). two studies investigated the effects of cpg inhalation on immunomodulation. cpg inhalation was found to significantly increase il-10 and ifnγ (klier et al., 2012) although the clinical benefits of this are yet to be assessed. cpg inhalation significantly reduced the expression of mmp-2, mmp-9, timp-1 and timp-2 and il-4 in tracheal wash fluid (barton et al., 2019). the authors suggest this indicates cpg may be able to prevent the formation of pulmonary fibrosis and be effective in modifying the disease course of equine asthma. the five studies investigating the effects of immunotherapy together provide mild evidence supporting the use of inhaled immunotherapy as a treatment for equine asthma. due to the lack of papers with a direct comparison relevant to the pico, papers comparing environmental modification with an alternative treatment for equine asthma were included in this knowledge summary. seven papers were identified that investigated the effect of environmental management on horses with asthma. three papers found that environmental modification by outdoor turnout with no access to hay improved lung function and the clinical signs associated with equine asthma (jackson et al., 2010; couëtil et al., 2005; and leclere et al., 2012). there was no significant improvement in clinical scores of asthmatics or pulmonary function when inhaled fluticasone or oral prednisone were used alongside environmental modification (couëtil et al., 2005). leclere et al. (2012) found that inhaled corticosteroids improved pulmonary function of asthmatics more quickly than environmental modification alone, but after 6 months of either treatment there was no significant difference in pulmonary function between groups. leclere et al. (2010) found a significant negative impact of poor environmental management (stabled with access to hay for 30 days) on pulmonary function of asthmatic horses when compared to healthy horses. two papers investigated the effect of environmental management on airway smooth muscle mass (asm). it was found that horses with heaves had a significantly increased asm compared to healthy horses, both prior to antigen exposure and after 30 days of antigen exposure (leclere et al., 2011). leclere et al. (2012) found a significant decrease in asm of horses with heaves after 12 months of environmental management or inhalation of corticosteroids. there was no significant difference in asm between the groups, but inhaled corticosteroids resulted in a faster reduction of asm. auger and moore-coyler (2017) identified that dry hay and straw result in a higher concentration of airborne respirable dust (ard) and showed that by modifying the stable environment, concentrations of ard can be significantly reduced. miskovic et al. (2008) found that after 6 years of outdoor environmental management with no access to hay, horses with rao had a significantly lower forced expiratory flow than age-matched healthy horses. vandeput et al. (1998) found that contact with dry hay can bring horses with copd out of remission and result in development of clinical signs. these studies provide moderate evidence that environmental management alone is insufficient to permanently cure rao. the papers reviewed in this knowledge summary all had major limitations. firstly, the management of horses was heterogenous within studies, horses were kept in their normal environments, with different types and quality of bedding and forage material used, as well as different stable designs and levels of ventilation. this makes it difficult to assess the effect of treatment as the environments of individual horses will also have affected the clinical study results. all of the studies had low study populations and no details were given about power calculations, decreasing the statistical power of results. other major limitations are the lack of controls in some studies which is likely to affect the clinical significance of each study. the immunotherapy papers share many of the same authors, and there are no publications available from a separate research group, which may create author bias. alternative treatments for asthma, that can be used alongside environmental management, are needed. there is the potential for poor owner compliance in maintaining appropriate environmental modifications (simoes et al., 2020) and in horses with underlying or a history of endocrinopathy, systemic corticosteroid use may be unsuitable (cornelisse & robinson, 2011). recent research has identified inhaled ciclesonide as an effective treatment for equine asthma without affecting serum cortisol (lavoie et al., 2019), however further research is needed to compare the effect of inhaled ciclesonide with environmental management for equine asthma. in conclusion, there is low level evidence to support the use of inhaled immunotherapy, alongside environmental modification, as a treatment for equine asthma. the long-term effect of immunotherapy is yet to be assessed, but these papers find it to be effective for up to 8 weeks following a treatment period. there is also the need for further research into the effect of immunotherapy when environmental factors including housing, bedding and forage are controlled, in order to determine if immunotherapy can be recommended as a sole treatment for equine asthma. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform [1973–week 26 2020] pubmed via ncbi website [1910–week 26 2020] search strategy: cab abstracts: (equine* or horse* or pony or ponies or equid or exp equidae/ or exp horses/) ("allergic asthma" or copd or "chronic obstructive pulmonary disease" or rao or "recurrent airway obstruction" or "allergic airway disease" or "equine asthma syndrome" or eas or asthma or heaves or hypersensitivity or "summer pasture-associated obstructive pulmonary disease" or spaopd) (immunotherapy or “allergen specific immunotherapy” or asit or “intra-dermal testing” or cpg or immunomodulation) ((stable or stables or hous* or exp stables/) and (manage* or design or ventilat*)) (environment* and (modi* or manage*)) (1 and 2 and (3 or 4 or 5))   pubmed: (equine or horse or pony or ponies or equid) and (allergic asthma or copd or chronic obstructive pulmonary disease or rao or recurrent airway obstruction or allergic airway disease or equine asthma syndrome or eas or asthma or heaves or hypersensitivity or summer pasture associated obstructive pulmonary disease or spaopd) and ((immune modulation or immune therapy or immunotherapy or immunomodulatory or immunomodulation or allergen specific immunotherapy or asit or intra dermal testing or cpg) or (((stable or stables or house or housing) and (manage or management or design or ventilated or ventilation)) or ((environment or environmental) and (modify or modification or manage or management)))) filter: veterinary science dates searches performed: 22 jun 2020 exclusion / inclusion criteria exclusion: articles not relevant to the pico question: species other than equine diseases other than equine asthma (and terms formerly known as) articles not including one of the treatment methods in the pico unpublished papers papers unavailable in english literature reviews, knowledge summaries, discussions and reviews inclusion: all research papers relevant to the pico: equine asthma immunotherapy or environmental management search outcome database number of results excluded – irrelevant to pico excluded – relevant but not in english excluded – irrelevant, not in english excluded – not clinical trials excluded – wrong species total relevant papers cab abstracts 110 59 5 9 29 1 7 pubmed 249 112 0 26 26 74 11 total relevant papers when duplicates removed 12 conflict of interest the authors declare no conflicts of interest. if you would like to make any acknowledgements, please state them in this section. thank you to clare boulton, head of library and knowledge services at rcvs knowledge for her guidance and assistance with literature searching.   references auger, e. & moore-colyer, m. (2017). the effect of management regime on airborne respirable dust concentrations in two different types of horse stable design. journal of equine veterinary science. 51, 105–109. doi: https://doi.org/10.1016/j.jevs.2016.12.007 barton, a., shety, t., klier, j., geis, s., einspanier, r. & gehlen, h. (2019). metalloproteinases and their inhibitors under the course of immunostimulation by cpg-odn and specific antigen inhalation in equine asthma. mediators of inflammation. 2019, 1–7. doi: https://doi.org/10.1155/2019/7845623 beech, j. & merryman, g. (1986). immunotherapy for equine respiratory disease. journal of equine veterinary science. 6(1), 6–10. doi: https://doi.org/10.1016/s0737-0806(86)80072-7 cornelisse, c. & robinson, n. (2011). glucocorticoid therapy and the risk of equine laminitis. equine veterinary education. 25(1), 39–46. doi: https://doi.org/10.1111/j.2042-3292.2011.00320.x couëtil, l., cardwell, j., gerber, v., lavoie, j., léguillette, r. & richard, e. (2016). inflammatory airway disease of horses-revised consensus statement. journal of veterinary internal medicine. 30(2), 503–515. doi: https://doi.org/10.1111/jvim.13824 couëtil, l., chilcoat, c., denicola, d., clark, s., glickman, n. & glickman, l. (2005). randomized, controlled study of inhaled fluticasone propionate, oral administration of prednisone, and environmental management of horses with recurrent airway obstruction. american journal of veterinary research. 66(10), 1665­–1674. doi: https://doi.org/10.2460/ajvr.2005.66.1665 jackson, c., berney, c., jefcoat, a. & robinson, n. (2010). environment and prednisone interactions in the treatment of recurrent airway obstruction (heaves). equine veterinary journal. 32(5), 432–438. doi: https://doi.org/10.2746/042516400777591165 klier, j., bartl, c., geuder, s., geh, k., reese, s., goehring, l., winter, g. & gehlen, h. (2019). immunomodulatory asthma therapy in the equine animal model: a dose‐response study and evaluation of a long‐term effect. immunity, inflammation and disease. 7(3), 130–149. doi: https://doi.org/10.1002/iid3.252 klier, j., fuchs, s., may, a., schillinger, u., plank, c., winter, g., gehlen, h. & coester, c. (2012). a nebulized gelatin nanoparticle-based cpg formulation is effective in immunotherapy of allergic horses. pharmaceutical research. 29(6), 1650–1657. doi: https://doi.org/10.1007/s11095-012-0686-8 klier, j., geis, s., steuer, j., geh, k., reese, s., fuchs, s., mueller, r., winter, g. & gehlen, h. (2017). a comparison of nanoparticulate cpg immunotherapy with and without allergens in spontaneously equine asthma‐affected horses, an animal model. immunity, inflammation and disease. 6(1), 81–96. doi: https://doi.org/10.1002/iid3.198 klier, j., lehmann, b., fuchs, s., reese, s., hirschmann, a., coester, c., winter, g. & gehlen, h. (2015). nanoparticulate cpg immunotherapy in rao-affected horses: phase i and iia study. journal of veterinary internal medicine. 29(1), 286–293. doi: https://doi.org/10.1111/jvim.12524 lavoie, j.‐p., bullone, m., rodrigues, n., germim, p., albrecht, b. & von salis‐soglio, m. (2019). effect of different doses of inhaled ciclesonide on lung function, clinical signs related to airflow limitation and serum cortisol levels in horses with experimentally induced mild to severe airway obstruction. equine veterinary journal. 51(6), 779–786. doi: https://doi.org/10.1111/evj.13093 leclere, m., lavoie-lamoureux, a., gélinas-lymburner, e., david, f., martin, j.g. & lavoie, j.p. (2011). effect of antigenic exposure on airway smooth muscle remodeling in an equine model of chronic asthma. american journal of respiratory cell and molecular biology. 45(1), 181–187. doi: https://doi.org/10.1165/rcmb.2010-0300oc leclere, m., lavoie-lamoureux, a., joubert, p., relave, f., setlakwe, e.l., beauchamp, g., couture, c., martin, j.g. & lavoie, j.p. (2012). corticosteroids and antigen avoidance decrease airway smooth muscle mass in an equine asthma model. american journal of respiratory cell and molecular biology. 47(5), 589–96. doi: https://doi.org/10.1165/rcmb.2011-0363oc miskovic, m., couëtil, l. & thompson, c. (2008). lung function and airway cytologic profiles in horses with recurrent airway obstruction maintained in low-dust environments. journal of veterinary internal medicine. 21(5), 1060–1066. doi: https://doi.org/10.1111/j.1939-1676.2007.tb03065.x simões, j., sales luís, j. & tilley, p. (2020). owner compliance to an environmental management protocol for severe equine asthma syndrome. journal of equine veterinary science. 87, 102937. doi: https://doi.org/10.1016/j.jevs.2020.102937 vandenput, s., duvivier, d., votion, d., art, t. & lekeux, p. (2010). environmental control to maintain stabled copd horses in clinical remission: effects on pulmonary function. equine veterinary journal. 30(2), 93–96. doi: https://doi.org/10.1111/j.2042-3306.1998.tb04466.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. can sedation be used for equine lameness investigation? a knowledge summary by helene termansen dvm pgdip vcp (equine) mrcvs 1* lucinda meehan bvsc msc cert avp (vdi) dipecvdi mrcvs 2 1langford vets, university of bristol, langford, bs40 5du 2st john’s innovation centre, cowley rd, cambridge, cb4 0ws *corresponding author (termansen94@gmail.com) vol 6, issue 2 (2021) published: 18 jun 2021 reviewed by: michael de cozar (bsc (hons) bvetmed mrcvs) and josh slater (phd dip eceim) next review date: 19 jun 2022 doi: 10.18849/ve.v6i2.373 pico question in horses undergoing lameness investigation, does sedation with a2-adrenergic agonists alone versus sedation with a2-adrenergic agonists in combination with butorphanol tartrate effect the degree of lameness?   clinical bottom line category of research question diagnosis the number and type of study designs reviewed six papers were critically reviewed. there were three crossover clinical studies, two crossover controlled clinical studies and a randomised controlled clinical study strength of evidence moderate outcomes reported there was limited evidence to suggest that xylazine and romifidine in combination with butorphanol has an effect on forelimb lameness and that detomidine has an effect on hindlimb lameness. most evidence suggests that xylazine alone or in combination with butorphanol has no effect on the lameness conclusion in general, sedating a horse with an a2-adrenergic agonist alone or in combination with butorphanol tartrate does not change the baseline degree of lameness. due to the large variation in the measurements, the small magnitude of few significant effects and the inconsistency of these significant findings, there is insufficient evidence to recommend avoiding the use of sedation in cases where it would increase the safety of those involved. however, regardless of protocol used, clinicians must appreciate the possibility of individual horse variation   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario when physical restraint is not sufficient to ensure safe and correct injection of diagnostic analgesia, sedation may be required. many veterinary clinicians remain concerned about the effect sedation could have on the locomotory pattern and degree of lameness. is there evidence to suggest cause for concern and which sedation protocol should one choose if needed? the evidence six papers have been published on the use of a2-agonists for lameness investigation. most of the studies were controlled clinical trials, however two were crossover trials only. the level of evidence of these papers was therefore moderate. summary of the evidence morgan et al. (2020) population: six adult horses with a lameness of grade 1/5 or less on a subjective lameness scale previously described by ross (2011) (aaep lameness scale): three mares, three geldings three thoroughbreds, three standardbreds sample size: six horses intervention details: n = 6 grade 3–4/5 aaep lameness grade unilateral forelimb lameness induced with set screws inserted into a custom-made shoe. each horse received six treatments with a minimum washout of 7 days between trials: xylazine hydrochloride at 0.1 or 0.2 mg/kg iv, acepromazine maleate at 0.02 or 0.04 mg/kg iv, 1 ml saline iv, local analgesia (abaxial nerve block – 4 ml 2% mepivacaine hydrochloride). 10 ml blood was collected by direct venipuncture for quantification of xylazine, acepromazine and mepivacaine at each time point. study design: randomised placebo controlled crossover trial outcome studied: lameness was assessed subjectively using digital video recordings and objectively by using an objective lameness assessment system – difference in minimum head position (hdmin), difference in maximum head position (hdmax), head movement asymmetry (vs) and stride rate were measured. each assessment was categorised as sedated, somewhat sedated or not sedated and ataxic, equivocally ataxic or not ataxic. the horses were assessed at time 0 (immediately after lameness induction) and 10, 30, 45 and 60 minutes post-treatment. intra and interobserver agreement of subjective lameness grade. main findings (relevant to pico question): acepromazine (0.02 and 0.04 mg/kg) and xylazine (0.2 mg/kg) did not result in significant differences in objective lameness parameters at any time point. xylazine (0.1 mg/kg) did not result in significant differences in hdmin or vs. observers consistently (435/438 observations) selected the limb with the set screw as the lame limb for the saline, xylazine and acepromazine treated groups. stride rate was decreased in the acepromazine groups at all time points compared to baseline. neither xylazine nor acepromazine were associated with significant change in average subjective lameness grade however acepromazine induced variation between individuals which may complicate subjective lameness evaluation for some observers. large interindividual variation in measurements recorded regardless of sedation and time post administration. limitations: small sample size. only studied forelimb lameness. video lameness assessment may be less sensitive than direct observation. high grade lameness was induced (grade 3–4/5). this questions whether the results of this study would be repeatable when investigating more subtle lameness. the dose of xylazine used in this study reflects the datasheet (noah compendium) dose and the dose commonly used in practice. the doses of acepromazine given are at the low end of the recommended datasheet dose and lower than the dose commonly used in practice. beck júnior et al. (2019) population: adult horses categorised as free of lameness by using objective lameness measurement: four geldings, 12 mares four brazilian warmblood horses and 12 crossbreeds sample size: 16 horses intervention details: metal clamps were placed on the hoof wall of either the right or the left hindlimb (random selection) and tightened until horses showed a 3–4/5 aaep lameness grade. each horse received three treatments: 1. xylazine hydrochloride 10% (0.3 mg/kg) 2. xylazine hydrochloride 10% (0.3 mg/kg) combined with butorphanol tartrate (0.01 mg/kg) 3. untreated control group between each treatment there was a washout period of at least 48hrs. study design: controlled crossover trial outcome studied: lameness was evaluated using an objective lameness assessment system (pelvic vertical movement asymmetry) before sedation (time 0), and at 20, 30, and 40 minutes post sedation. level of sedation was evaluated at the same times using a physical and behavioural scale (0–3) and by measuring the head height above ground. main findings (relevant to pico question): there was no difference in pelvic asymmetry between xylazine, xylazine with butorphanol and untreated control group at the different evaluation times. there was no correlation between head height above ground and lameness improvement. limitations: the sample size was small. only hindlimb lameness was studied. trotting speed and stride rate were not measured. the veterinarian evaluating the level of sedation was aware of which group the horse was in, allowing potential for bias. a 3–4/5 aaep lameness grade is a substantial lameness and questions whether the results are repeatable for more subtle lameness.  moorman et al. (2019) population: adult polo horses with naturally occurring forelimb and/or hindlimb lameness varying from grade 1–3 on the aaep lameness grading system: 13 mares, four geldings 10 thoroughbreds, one thoroughbred cross, two argentine thoroughbreds, one argentine polo pony, one crillo, one standardbred cross and one american quarter horse sample size: 17 horses intervention details: seven protocols were trialed with a washout period of at least 7 days between each. the protocols were: saline (0.09% nacl, 2 ml iv) xylazine hydrochloride (0.33 mg/kg iv) detomidine hydrochloride (0.007 mg/kg iv) romifidine hydrochloride (0.033 mg/kg iv) xylazine hydrochloride (0.33 mg/kg iv) and butorphanol tartrate (0.007 mg/kg iv) detomidine hydrochloride (0.007 mg/kg iv) and butorphanol tartrate (0.007 mg/kg iv) romifidine hydrochloride (0.033 mg/kg iv) and butorphanol tartrate (0.007 mg/kg iv). study design: placebo controlled crossover trial outcome studied: degree of sedation (subjective) 1–5, 1 being mild sedation and 5 being deep sedation. degree of sedation (objective): head-height to horse-height ratio. mechanical nociceptive threshold (mnt): pressure applied 1 cm proximal to the coronary band at a rate of approximately 5–10 kg/cm2/s until the horse displayed avoidance behaviour. subjective (modified aaep lameness scale) and objective lameness assessment. all outcomes were assessed prior to (time 0) and 10, 15, 20, 30, and 40 minutes post administration of each protocol. main findings (relevant to pico question): across all data points, there was a significant difference in head movement asymmetry (vsfl) from baseline for xylazine alone and the romifidine-butorphanol combination. when looking at pelvic movement asymmetry (vshl), there was a significant difference from baseline for detomidine hydrochloride alone across all data points. none of the measurements recorded after injection of any of the drugs were significantly different from the corresponding measurements recorded after injection of saline. apart from xylazine alone, mnt measurements were significantly higher than baseline and corresponding saline measurements for all time points. large interindividual variation in measurements recorded regardless of sedation and time postadministration. limitations: the initial lameness evaluation was performed 1 month prior to the study. the lameness degree could have changed in this time, regardless of sedation protocol. lameness may also have changed during the washout periods (naturally occurring lameness). small sample size. rettig et al. (2016) population: 44 horses of which four horses were sound and 40 were lame on a forelimb or hindlimb or both. sample size: 44 horses intervention details: the horses were divided into subgroups of sound, mildly lame and markedly lame and were then randomly split into treatment and control groups of approximately equal numbers. treatment group was treated with xylazine (0.3 mg/kg diluted with saline to 10 ml total iv) and the control group was treated with sterile saline (10 ml iv). study design: randomised, placebo controlled outcome studied: objective lameness evaluation (head/pelvic movement asymmetry) was carried out using an objective lameness assessment system prior to (time 0) and 20, and 60 minutes post-treatment. the number of horses staying the same, improving and worsening in head or pelvic movement asymmetry were compared between the treatment and control group at each time point (0 vs. 20 and 0 vs. 60) head height above ground was used as an objective evaluation of degree of sedation and the horses were also evaluated subjectively for ataxia. stride rate was measured. main findings (relevant to pico question): the study found no statistically significant differences in head or pelvic movement asymmetry between the two groups. this suggests that the dose of xylazine used in this study does not mask lameness. however, some (4/9) horses with forelimb lameness showed a decreased lameness degree at 60 minutes post-treatment suggesting that caution should be used with mild forelimb lameness.  mean stride rate at 20 minutes decreased significantly more in the xylazine group than in the saline group. this was however probably not clinically significant as the lameness remained unchanged. large interindividual variation in measurements recorded regardless of sedation and time postadministration. limitations: some of the horses in the control group showed an increase in lameness through the course of the study. the lack of stability of the lameness questions the validity of the results. few horses had forelimb lameness which could have made detection of small, statistically significant differences, difficult. da silva azevedo et al. (2015) population: adult horses that had an aaep lameness grade of 1–3 on any limb – 16 crossbreeds sample size: 16 horses intervention details: all horses were evaluated for head and pelvic movement asymmetry using the lameness locator before treatment. eight horses were then treated with acepromazine 1% (0.025 mg/kg iv) and the other eight were treated with xylazine 10% (0.25 mg/kg iv). the horses were then re-evaluated 5 minutes later using the lameness locator. on the second day of the study the horses initially treated with acepromazine were treated with xylazine and vice versa. the same data collection protocol was used on day 2.  study design: crossover trial outcome studied: five minutes after treatment, lameness was reevaluated using the lameness locator the same data collection protocol was used on day 2.  main findings (relevant to pico question): there was no difference in foreand hindlimb asymmetry before and after treatment with xylazine or acepromazine. there was no difference between horses after xylazine or acepromazine. limitations: no control treatment group to account for changes in lameness through the course of the study. the study also had a small population size. the study only looked at the effects up to 5 minutes postsedation and so may have limited relevance to clinical lameness investigations where horses are evaluated over longer periods. buchner et al. (1999) population: 17 adult horses of which nine were sound and eight had a chronic, slight (degree 1–2/5) forelimb lameness: 10 geldings, three stallions, four mares sample size: 17 horses intervention details: on day 1 all horses were sedated with detomidine (10 µg/kg iv). on day 2 all horses received the same sedation which was then antagonised with atipamezole (100 µ/kg iv) after 15 minutes. study design: crossover trial outcome studied: the locomotion pattern was recorded while trotting at a constant speed of 3.9 m/s on a treadmill. level of sedation was evaluated using measurements of head height above ground and pulse rate. objective lameness was evaluated using head acceleration asymmetry, stride and stance duration and stride length. measurements were collected at time 0 and 15, 25, 35, 45, and 60 minutes postsedation. on day 2 the same recording procedure was performed with antagonisation of the sedation immediately following the 15 minute recording. main findings (relevant to pico question): sedation with detomidine did not change the degree of lameness in the eight horses with chronic forelimb lameness but altered the general locomotion pattern (increase stride length, stride duration and stance duration). some of the increase in stride length and duration could be reversed using atipamezole. large interindividual variation in measurements recorded regardless of sedation and time postadministration. limitations: only looks at forelimb lameness. treadmill used to compare stride variables and the findings may therefore not be applicable in traditional lameness evaluations on ground. no control group to account for changes in lameness through the course of the study. appraisal, application and reflection equine lameness is a common reason for seeking veterinary attention (seitzinger et al., 2000). intrasynovial or perineural diagnostic analgesia is the most valuable tool for localising pain causing lameness (bassage & ross, 2011). however, these procedures can be difficult to perform on fractious, highly-strung or needle shy horses and therefore pose a significant occupational risk to the clinician and assistants. the use of chemical restraint to increase safety has therefore been researched. whilst sedation eases patient compliance, some clinicians avoid its use due to the possible analgesic effects of these drugs (pilsworth & dyson, 2015). a recent review found evidence to support the use of a2-agonists on their own for lameness investigation (de cozar, 2019). three clinical papers have since investigated the use of a2-agonists in combination with butorphanol (beck júnior et al., 2019; moorman et al., 2019; and morgan et al., 2020). of the a2-agonists, xylazine is the most frequently studied. when looking at hindlimb lameness, da silva azevedo et al. (2015) found no significant difference in lameness degree after 5 minutes when using xylazine alone. rettig et al. (2016), beck júnior et al. (2019) and moorman et al. (2019) found the same tendency up to 60, 40 and 40 minutes respectively. furthermore beck júnior et al. (2019) found no significant difference when using xylazine in combination with butorphanol while moorman et al. (2019) found a significant difference from baseline lameness at 4/5 time points but no difference from administration of saline at any time point. when using the objective measurement of head movement asymmetry, morgan et al. (2020) found no significant difference from baseline or saline treatment when using xylazine. however, moorman et al. (2019) found a significant difference across all data points when using xylazine alone in naturally-occurring lameness, and rettig et al. (2016) found a decrease in some forelimb lameness at 60 minutes but no overall significant effect. it was therefore suggested that caution should be taken when interpreting forelimb lameness following administration of xylazine. only one paper (moorman et al. (2019)) assessed the effect of xylazine in combination with butorphanol on head movement asymmetry. they found a significant difference from baseline lameness at 2/5 time points. this result is however based on data from a small sample and moorman et al. (2019) were unable to show statistical difference between any of the treated groups and the control group. the locomotory pattern after administration of xylazine was assessed in two papers (morgan et al., 2020; and rettig et al., 2016). these papers showed an inconsistent reduction of stride rate that was only significant at 45 and 20 minutes respectively. since the lameness remained unchanged, it is unlikely that these findings are of clinical relevance. there is therefore very little evidence to suggest that the xylazine, with or without the addition of butorphanol should change degree of lameness. the use of detomidine hydrochloride was studied by buchner et al. (1999) and moorman et al. (2019). buchner et al. (1999) found that the use of detomidine did not alter forelimb lameness degree but did alter the general locomotory pattern. likewise, the study by moorman et al. (2019) found no effect of detomidin on head movement asymmetry but did find a significant difference in pelvic movement asymmetry across all data points. they found no significant difference in head or pelvic movement asymmetry when using detomidine combined with butorphanol. the use of romifidine for lameness evaluations was only studied by moorman et al. (2019). their results showed a significant difference in head movement asymmetry when horses had received romifidine in combination with butorphanol but showed no difference in pelvic movement asymmetry. romifidine used on its own showed an inconsistently significant difference in head and pelvic movement asymmetry from baseline. of the papers reviewed, four were controlled clinical trials of which three were crossover trials and two were randomised trials. the remaining two papers were crossover trials without a control group. an attempt has therefore been made to limit bias and the level of evidence was deemed moderate. nevertheless, caution must be shown due to the small sample sizes used in these papers. only two of the studies compared objective and subjective lameness evaluation after sedation had been used, which questions whether there would be agreement between the two in a clinical setting. furthermore, 2/6 of the papers reviewed induced lameness experimentally whilst the remaining four evaluated the effect of sedation on naturally occurring lameness, which could have changed throughout the course of the studies. the degree of lameness assessed spanned from 1–4 on the aaep lameness scale and thus related well to cases seen in clinical practice. while the experimental design used in the papers reviewed is robust, there is a large variation between observations. this indicates that large sample sizes would be required to detect potential significant effects of different sedation protocols. in conclusion, there is limited evidence to suggest that using an a2-adrenergic agonist alone or in combination with butorphanol tartrate for lameness evaluation changes the baseline lameness in general. in the reviewed literature, there is large variation of the measurements recorded for different horses, the magnitude of the significant effects of using sedation is small and there is inconsistency in these significant effects both throughout a single study and between studies. there is therefore insufficient evidence to recommend avoiding the use of sedation in cases where it would increase the safety of those involved. the evidence regarding the use of xylazine, the most frequently studied sedative, indicates there is no clinically significant change in lameness. however, regardless of protocol used, clinicians must be aware of the possibility of individual horse variation. additional studies assessing the effect of a2-adrenergic agonists in combination with butorphanol tartrate on lameness degree are needed to ensure a more reliable conclusion. further investigation into how sedation affects subjective versus objective lameness evaluation is needed to establish whether all cases that require sedation for lameness investigation should be referred to a practice with equipment for objective lameness evaluation. methodology section search strategy databases searched and dates covered: cab abstracts via ovid interface 1973–week 23 2020 pubmed via ncib website 1973–june 2020 search strategy: cab abstracts: (horse or horses or equine or equines) (sedation or sedative or tranquilizer or tranquilisation) lameness or gait or blocking 1 and 2 and 3   pubmed: (((horse) or (horses) or (equine) or (equines)) and ((sedation) or (sedative) or (tranquilliser) or (tranquillisation)) and ((lameness) or (gait))) dates searches performed: 19 jun 2020 exclusion / inclusion criteria exclusion: sound horses only without lameness induction, non-english language, review or non-journal articles, not relevant to pico question inclusion: lame horses or lameness induced, relevant to pico question, clinical studies search outcome database number of results excluded – not english language excluded – irrelevant to pico question excluded – only sound horses included excluded – not journal article total relevant papers cab abstracts 47 6 29 6 1 5 pubmed 45 0 36 5 0 4 total relevant papers when duplicates removed 6 conflict of interest the authors declare no conflicts of interest. references bassage, l.h. & ross, m.w. (2010). diagnostic analgesia. in: diagnosis and management of lameness in the horse: second edition. 2nd ed. saint louis: w.b. saunders, 100–135. doi: https://doi.org/10.1016/b978-1-4160-6069-7.00010-9 beck júnior, a.a., de la côrte, f. d., brass, k.e., dau, s.l., silva, g.b. & camillo, m.de a.. (2019). effect of xylazine and butorphanol on experimental hind limb lameness in horses. journal of equine veterinary science. 73, 56–62. doi: https://doi.org/10.1016/j.jevs.2018.11.007 buchner, h.h., kübber, p., zohmann, e. & peham, c.h. (1999). sedation and antisedation as tools in equine lameness examination. equine veterinary journal. 30(s30), 227–230. doi: https://doi.org/10.1111/j.2042-3306.1999.tb05223.x de cozar, m.j. (2019). can i give alpha-2 agonists for blocking and accurately assess the horse’s lameness once blocked? equine veterinary education. 31(2), 111–112. doi: https://doi.org/10.1111/eve.12877 moorman, v.j., bass, l. & king, m.r. (2019). evaluation of the effects of commonly used α2-adrenergic receptor agonists alone and in combination with butorphanol tartrate on objective measurements of lameness in horses. american journal of veterinary research. 80(9), 868–877. doi: https://doi.org/10.2460/ajvr.80.9.868 morgan, j.m., ross, m.w., levine, d.g., stefanovski, d., you, y., robinson, m.a. & davidson, e.j. (2020). effects of acepromazine and xylazine on subjective and objective assessments of forelimb lameness. equine veterinary journal. 52(4), 593–600. doi: https://doi.org/10.1111/evj.13225 pilsworth, r. & dyson, s. (2015). where does it hurt? problems with interpretation of regional and intra-synovial diagnostic analgesia. equine veterinary education, 27(11), 595–603. doi: https://doi.org/10.1111/eve.12392 rettig, m.j., leelamankong, p., pungsri, p. & lischer, c.j. (2015). effect of sedation on foreand hindlimb lameness evaluation using body-mounted inertial sensors. equine veterinary journal. 48(5), 603–607. doi: https://doi.org/10.1111/evj.12463 ross, m.w. (2010). movement. in: diagnosis and management of lameness in the horse: second edition, 2nd ed. saint louis: w.b. saunders, 64–80. doi: https://doi.org/10.1016/b978-1-4160-6069-7.00007-9 seitzinger, a.h., traub-dargatz, j.l., kane, a.j., kopral, c.a., morley, p.s., garber, l.p., losinger, w.c. & hill, g.w. (2000). a comparison of the economic costs of equine lameness, colic and equine protozoal myelocencephalitis (epm). proceedings of the 9th international symposium on veterinary epidemiology and economics. da silva azevedo, m., de la côrte, f.d., brass, k.e., gallio, m., pozzobon, r., lopes, m.a.f. & lopes, l.f.d. (2015). the use of xylazine or acepromazine does not interfere in the lameness evaluation by inertial sensors. journal of equine veterinary science. 35(1), 27–30. doi: https://doi.org/10.1016/j.jevs.2014.10.007 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in cats undergoing midline ovariohysterectomy, is the use of local anaesthesia with bupivacaine associated with a reduction in postoperative pain score? | veterinary evidence skip to main content knowledge summary keywords: ovariohysterectomy; feline; bupivacaine; local anaesthesia; postoperative pain; perioperative analgesia; neutering; spay in cats undergoing midline ovariohysterectomy, is the use of local anaesthesia with bupivacaine associated with a reduction in postoperative pain score? tara freeman, bsc (hons) rvn1* amelia wisbey, fdsc rvn1 kate burroughs, bsc (hons) rvn1 samantha gentle, bsc (hons) rvn1 connie ellis, fdsc rvn1 sarah batt-williams, msc vet ed. fhea bsc (hons) rvn1 1 the royal veterinary college, hawkshead lane, hatfield, hertfordshire, al9 7ta, uk * corresponding author email: tfreeman18@rvc.ac.uk vol 8, issue 1 (2023) submitted 29 oct 2021; published: 22 feb 2023; next review: 09 sep 2024 doi: https://doi.org/10.18849/ve.v8i1.552 pico question in cats undergoing midline ovariohysterectomy, is the use of local anaesthesia with bupivacaine via intraperitoneal or subcutaneous injections, in comparison with the use of a control substance or other analgesic measure, associated with a reduction in postoperative pain score? clinical bottom line category of research treatment. number and type of study designs reviewed three studies were critically appraised in this knowledge summary. they included two prospective, blinded, randomised, controlled clinical trials and one prospective randomised, blinded clinical trial. strength of evidence weak. outcomes reported bupivacaine does not eliminate postoperative pain in cats undergoing ovariohysterectomies; minimal evidence was found to suggest that it was better at reducing postoperative pain scores in comparison to other analgesics. however, bupivacaine may provide analgesic benefits to cats when administered via intraperitoneal or subcutaneous injections as local anaesthesia and in combination with other analgesic agents. the need for postoperative rescue analgesia was minimised when bupivacaine was administered prior to or during the ovariohysterectomy. conclusion when compared to a control, pain scores for the participating cats were lower after administration of bupivacaine, however, statistical significance was only reached in one of the studies. additionally, other medications were found to lower the post operative pain score to a greater effect. however, bupivacaine administration is cheap and simple to perform, so it’s use as part of a multimodal analgesic protocol is supported. confounding factors within the studies may have altered the perceived effectiveness of the analgesic properties of bupivacaine though, so further investigation involving larger cohorts with standardised controls would be prudent. how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a client is considering an ovariohysterectomy for their cat. they notice a fee for a bupivacaine local anaesthetic block and question the necessity of this. you review the evidence for the use of bupivacaine as part of a multi-modal anaesthetic protocol in cats undergoing elective ovariohysterectomy via ventral midline coeliotomy. the evidence all three studies followed a reliable method, appropriate to the category of research.  each of the three studies consistently found that bupivacaine provided some level of analgesia in comparison to the saline / placebo measures. however, they were inconclusive in verifying bupivacaine’s superiority over other analgesics. unvalidated pain scales were used in all three studies which may have resulted in inaccurate representation of participant pain. although the study’s individual methods were appropriate, combined use of validated and unvalidated pain scales may have impacted results drawn from the studies. whilst statistical significance was only reached in one of the three studies, trend to lower pain scores in cats receiving bupivacaine was noted in all three. summary of the evidence benito et al. (2016a) population: client-owned, healthy mixed-breed female cats undergoing ventral midline incision for ovariohysterectomy. inclusion criteria: client owned cats. female. healthy, based on medical history and complete physical examination and haematology. exclusion criteria: aggression. cardiac arrhythmias. pregnancy. lactation. obesity (body condition score of >7 of scale 1–9). anaemia. clinical signs of disease. sample size: n = 45 cats. intervention details: intervention groups: the same volumes of bupivacaine or saline were administered via injection in each group: saline 0.9% intraperitoneal, negative control group (ng) (n = 15). saline 0.9% intraperitoneal and meloxicam subcutaneous, positive control group (pg) (n = 15). bupivacaine hydrochloride (hcl) 0.25% intraperitoneal, bupivacaine group (bg) (n = 15). group characteristics: pg: mean body condition score 5 (range 4–5). mean weight 3.1 (standard deviation [sd] 0.6). ng: mean body condition score 5 (range 4–5). mean weight 3.1 (sd 0.6). bg: mean body condition score 5 (range 4–7). mean weight 3.1 (sd 0.8). premedication: given intramuscularly acepromazine (0.05 mg/kg). buprenorphine (0.01 mg/kg). administration of local anaesthetic / saline: intraperitoneal injections. the solution was divided equally into three parts and administered into the right and left ovarian pedicles and the caudal uterus. injections given immediately before the ovariohysterectomy. pain scale used: dynamic and interactive visual analog scale (divas). unesp-botucatu multidimensional composite pain scale (mcps). statistical analysis: demographic data for each group was analysed using one-way anova or χ2 test. temporal changes within a treatment group were analysed using the cochran-mantel-haenszel test for ordinal scores followed by pairwise comparisons between groups. study design: prospective, blinded, randomised, controlled, clinical trial. outcome studied: requirement for rescue analgesia. pain scores of the patients (before, at 30 minutes, 1 hour and 1.5 hours after surgery). mean mechanical nociceptive thresholds (mnt) (before and at 2 hours after surgery. main findings (relevant to pico question): pain scoring:   postoperative pain scores increased compared to baseline (pre-operative) pain score in all treatment groups.   divas a statistically significant increase in postoperative pain score was found for all treatment groups when compared to baseline. pg at 0.5 hours (p = 0.002), 1 hour (p = 0.0008) and 2 hours (p = 0.0006). ng at 0.5 hours, 1 hour and 2 hours (p = <0.0001 at all intervals). bg at 1 hour and 2 hours (p = <0.0001 at all intervals).   however, there was no statistically significant difference between divas pain scores among treatment groups, suggesting that all treatments provided the same level of analgesia.   mcps a statistically significant increase in postoperative pain scores was found for all treatment groups when compared to baseline (pre-operative pain score). pg, ng and bg at 0.5 hours, 1 hour and 2 hours (p = <0.0001 for all intervals). however, there was no statistically significant difference between mcps pain scores among treatment groups, again suggesting that all treatments provided the same level of analgesia. lower divas and mcps scores were seen in the pg and bg groups compared to the ng group. no statistical significance was found though.   requirement of rescue analgesia:   18 cats required rescue analgesia (ng, n =12, 80%, pg, n =2, 13%, bg, n =4, 27%). there was a significant difference in need for rescue analgesia between ng and bg (p = 0.02). there was a significant difference in the need for rescue analgesia between ng and pg (p = 0.0004). there was no significance in need for rescue analgesia between the pg and bg (p = > 0.05). limitations: small sample size, possibly impacting generalisability of results and could lead to a type 2 error. the effects of sedation were not clear and may have affected the results. the divas pain scale was not a validated pain scale for cats so may not be accurate in identifying levels of pain. the study was conducted in a veterinary teaching hospital but the level of experience of the veterinary surgeon was not stated. inexperience could have led to sub-optimal technique and hindered the reliability of the results.   fudge et al. (2020) population: healthy female shelter cats undergoing ventral midline ovariohysterectomy. inclusion criteria:  healthy. female cats (from shelter). weighed >0.9 kg. age >2 months. exclusion criteria: pregnant. incomplete data available. sample size: n = 212 cats. intervention details: intervention groups:  the bupivacaine or saline were injected into the suspensory ligaments and vessels, uterine body and incisional subcutaneous tissues for the treatment and placebo groups. treatment (bupivacaine 0.5%, 2 mg/kg). placebo control (0.9% saline). sham control (observation only).   phase 1 36 cats (bupivacaine group n = 12, saline group n = 17, sham group n = 7). phase 2 176 cats (bupivacaine group n = 59, saline group n = 41, sham group n = 76).   premedication: buprenorphine (0.01 mg/kg) given intramuscularly.   induction: intramuscular injection of ketamine and dexmedetomidine at the doses of; 15 mg ketamine + 0.0075 mg dexmedetomidine (cats weighing 0.9–1.8 kg), 20 mg ketamine + 0.01 mg dexmedetomidine (cats weighing > 1.8 kg).   administration of local anaesthetic: bupivacaine (or saline) volume was equally divided into four. injections into right (1) and left (2) suspensory ligament of ovary, mesovarium, and pedicles of ovarian vessels, uterine body (3), and incisional subcutaneous tissue (4). administration occurred during ovariohysterectomy.   pain scale used: modified unesp-botucatu multidimensional composite pain scale (mcps) was used in the first phase. (subscale 3 including arterial blood pressure and appetite monitoring was removed). 0–10 numerical rating scale (nrs) used in both phases. modified colorado state university feline acute pain scale (mcsu) was used in the second phase (removed palpation of the surgical site).   statistical analysis: one-way anova was used to compare age, weight, and breed. one-way anova was used to determine potential differences between pain score averages. a holm-bonferroni post-hoc analysis was carried out to compare groups where a difference was found via anova. a correlation analysis was used to measure the strength of the relationship between evaluators scores. study design: prospective, randomised, double-blinded, placebo-controlled clinical trial. the study consisted of two phases. outcome studied: pain score of the patients, 1 hour post anaesthesia recovery and immediately before the same-day discharge (<7 hours post anaesthesia). requirement for rescue analgesia. main findings (relevant to pico question): after standardisation and comparison, bias in the agreement between the evaluators’ pain scores was found in the first phase (-0.15), with nrs scores higher than mcps. data gathered from phase one was disregarded, therefore, the below results are from phase two only (176 cats). bias was smaller in the second phase (0.02) and was deemed acceptable.   pain scores:   as participants were randomly allocated, there was natural variation leading to, significant differences in age and weight between the groups, so results were separated into different categories for each treatment group during data analysis, this was to help with interpretation.   weight group 0.9–1.5 kg and >1.5–2.7 kg: no significant difference in the pain scores among the three groups in this weight category. weight group >2.7 kg: pain scores for the bupivacaine group were significantly lower than in the control groups at 1 hour post-recovery (p = 0.008) and at discharge (p = 0.004). for all weight groups and drug groups, pain scores were significantly higher 1 hour post-recovery than at discharge.    requirement for rescue analgesia:   none of the cats required rescue analgesia. limitations: pain was quantified via a numerical rating scale (nrs); a unidimensional scale which does not consider the complexity of the pain experience. however, these scores were compared to a multidimensional scale mcsu which would have minimised interpretation issues. the pain scales used were not validated for use in cats and were modified by the researchers to suit the data they could collect. participants in the saline group were significantly older, this may have impacted their metabolism of the treatments, possibly altering postoperative pain scores. induction of anaesthesia with known analgesic drugs (ketamine and dexmedetomidine) did not account for the current weight of the animal (only dependent on more or less than 1.8 kg). so that heavier patients received quantitatively less systemic analgesics when reported to their body weight (or surface area) than lighter patients. this may have blunted pain scores and decreased differences between groups in the first two weight strata.   tobias et al. (2006) population: client-owned, healthy female cats undergoing midline ovariohysterectomy. inclusion criteria: healthy (asa1). intact females. weighing over 2.2 kg. unknown ages but estimated at least 6 months old. exclusion criteria: pregnant. sample size: n = 52 cats. intervention details: intervention groups: two cats were removed from the study after surgery because they had anemia due to accidental overdose of intravenous fluids, leaving the sample size at 50 cats, organised into the following groups. carprofen (2.2 mg/kg) po before sedation (n = 12). ketoprofen (2.2 mg/kg) sc after sedation (n = 14). butorphanol tartrate (0.44 mg/kg) im after sedation (n = 12). bupivacaine (1.1 mg/kg) sc before first surgical incision (n = 12). premedication: acepromazine (0.022 mg/kg) intramuscularly (im). ketamine (4.4 mg/kg) im. administration of local anaesthetic: injected subcutaneously over a 2.5 cm distance along the midline, midway between the umbilicus and pubis. pain scales used: visual analog scale (vas). interactive visual analog scale (ivas). statistical analysis: mixed model analysis of variance procedure to evaluate pain scores where cat was included in the model as a random factor. study design: prospective, randomised, blinded clinical trial. outcome studied: patient pain scores. taken with vas and ivas preoperatively and postoperatively (extubation and 1, 2, 4, 8, 12 and 24 hours after surgery). requirement for rescue analgesia. mean cortisol concentrations in blood plasma preoperatively and 1, 2, 4, 8, 12 and 24 hours postoperatively. mean plasma concentrations of the drug in the blood plasma preoperatively and 1, 2, 4, and 8 hours postoperatively. the results mentioned in points 3 and 4 are irrelevant to the pico question so there will be no further mention of them in this knowledge summary. main findings (relevant to pico question): pain scoring: all cats had vas and ivas scores of 0 before surgery (baseline). cats receiving bupivacaine had significantly higher vas and ivas pain scores at 1 and 2 hours post-surgery compared to baseline, as did those receiving carprofen and ketoprofen (p ≤ 0.0122). in all groups, cats’ vas and ivas scores were not significantly different to baseline at 4–24 hours after surgery. pain scores for cats receiving bupivacaine were significantly higher 1 hour post-surgery (p = 0.002) compared to those receiving butorphanol (p = 0.029). there was no significant difference in pain scores at any time between cats receiving carprofen, ketoprofen, or butorphanol.   rescue analgesia: rescue analgesia was administered 2 hours after surgery for one patient in the bupivacaine infusion block group and 1 hour after surgery in one patient in the ketoprofen group. limitations: one cat was given the wrong analgesic, so the groups were not evenly distributed, hindering comparison between groups. the varying sedative effects of the medications used was not accounted for in addition to other affects such as delayed onset of medications, this may have impacted the accuracy of pain scoring. it is unknown if the intravenous fluid therapy provided during surgery affected plasma concentrations of the medications, possibly impacting their effect on nociception. there was no mention of a sample size calculation and the sample size was small, hindering the generalisability of the study.   appraisal, application and reflection three studies were found to be appropriate for this knowledge summary. they were all published in peer-reviewed journals and used prospective, controlled clinical trials. benito et al. (2016a) and tobias et al. (2006) implemented a blinded randomised method and fudge et al. (2020) used a randomised double blinded placebo-controlled method. all three studies had approval from relevant bodies and the researchers ensured that all participants were provided additional rescue analgesia postoperatively, if required. the first study analysed was benito et al. (2016a), which included 45 client-owned cats of varying breeds. the use of client-owned participants increased the applicability of findings to general practice. the requirement for rescue analgesia was significantly higher in the group receiving saline only compared to the groups receiving saline and meloxicam (p = 0.0004) or bupivacaine (p = 0.02). of the saline group, 12/15 (80%) required further analgesia, compared to only 2/15 (13%) of the saline and meloxicam group, and 4/15 (27%) of the bupivacaine group. whilst this shows that bupivacaine reduced patients’ pain scores and the need for further postoperative analgesia compared to the control, there was no statistically significant difference between the effectiveness of saline and meloxicam and the bupivacaine groups, suggesting that either protocol is appropriate. fudge et al. (2020) studied 212 cats from a shelter. although a randomised study, the results were separated into different weight categories for each treatment group during data analysis to help with interpretation. all patients had an elevated pain score 1 hour postoperatively compared to discharge pain scores. cats which received bupivacaine showed reduced pain scores compared to the two control groups (saline and sham controls) in all the weight brackets, however, the only statistical significance was found in the group weighing over 2.7 kg. it was found that cats both in the higher weight category and the bupivacaine group had a significantly lower pain score compared to the control groups 1 hour postoperatively (p = 0.008) and at discharge (p = 0.004). this implies that the effectiveness of bupivacaine may not be generalisable to all individuals due to weight related drug variations. however, the drug dosages were not specific to the patients’ exact weight, only to their weight category. this may have altered the significance of any difference in pain scores between the lower weight categories, and therefore should be considered when interpreting the significant data. the third study, conducted by tobias et al. (2006), assessed 52 client-owned cats. no sample size calculation was undertaken, which should be noted when making generalised assumptions from this study. baseline pain scores were taken using both chosen pain-scoring methods, and then repeated at intervals postoperatively. participants who were given carprofen, ketoprofen, or bupivacaine had a significant increase in their pain scores, compared to the baselines (p ≤ 0.0122). these were recorded by both scoring methods at 1 and 2 hours postoperatively. comparatively, those participants who received butorphanol had no significant change in their visual analogue scale (vas) scores, only a significant difference in the interactive visual analogue scale (ivas) pain score 2 hours postoperatively (p = 0.0231). additionally, participants from the bupivacaine group had higher postoperative pain scores compared to the other groups. whilst this was only high enough in one participant to require rescue analgesia, it does suggest that there might be more beneficial analgesics to consider. in general, these three main studies concluded that bupivacaine may have a clinical effect as an analgesic drug to reduce postoperative pain scores, however, statistical significance was not found in every study. this suggests that there was a possibility of the correlation between a bupivacaine local anaesthetic block and a reduced pain score being due to chance and other medications may be equally or even more effective in controlling postoperative pain. despite the similar generalised conclusions in the three main studies, there were some discrepancies between their findings. this suggests that a definitive conclusion cannot be drawn from these studies alone, without further research. inconsistencies between methods, discussed below, may have contributed towards these differences in results. the location of the local anaesthetic block was noted as a key difference in methodology, varying between studies. benito et al. (2016a) and fudge et al. (2020) administered the local anaesthetic in specific intraperitoneal locations, whereas tobias et al. (2006) administered bupivacaine subcutaneously. this will have impacted the effect of the drugs and resulted in different nerves being blocked, hindering evaluation of the analgesic properties of bupivacaine. another variation to the methodologies was the chosen dose and dilution of bupivacaine. these variations may have indirectly resulted in the effectiveness of dose and dilution being evaluated, rather than the analgesic properties of bupivacaine. benito et al. (2016a) used the lowest dilution of bupivacaine out of the three studies analysed. this chosen dilution was supported by research conducted by benito et al. (2016b). whilst it was found to be safe, the difference in dilution may hinder accuracy of the comparison between the three studies. benito et al. (2016a) suggests that there is no difference between the analgesic properties of bupivacaine and their control medications, however, their findings may be reflective of the dilution rather than the analgesic properties of bupivacaine. therefore, this needs to be considered when evaluating the effect on resulting pain scores. additionally, the chosen premedications varied throughout the studies. the studies either used acepromazine or dexmedetomidine as their chosen sedative. the duration of action for these two drugs is up to 6 hours and 20–60 minutes respectively , according to ramsey, 2017. however, the duration of action of dexmedetomidine varies between sources, granholm et al. (2006) found that heart rate and respiratory rate were still affected by dexmedetomidine over 3 hours after administration, indicating prolonged effects. both acepromazine and dexmedetomidine had a risk of interfering with pain scores due to extended analgesic and sedative effects, possibly hindering the ability to infer analgesic properties of bupivicaine. the analgesic effects of buprenorphine and ketamine should also be considered. the duration of action of these two drugs is up to 6 hours (ramsey, 2017) and 20–40 minutes with a 1–4 hour recovery (noah, 2021). the duration of action of buprenorphine means it would have been active during most of the pain scores, the cats may also still have been recovering from the effects of ketamine. additionally, ketamine can cause abnormal behaviour during recovery (ramsey, 2017), which could hinder the process of pain evaluation. whilst it is important to recognise and understand the impact of premedication drugs, each study followed a standardised method throughout their data collection, therefore, producing valid results. furthermore, the use of an opioid combined with a sedative drug is a routinely used premedication protocol in general practice (murrell & ford-fennah, 2020). the premedications used are standard, applicable to a real-life setting and thus appropriate as administered in these studies. a fourth key difference affecting comparison between the methods of the studies were the pain scoring systems used (figure 1). benito et al. (2016a) used the dynamic and interactive visual analogue scale (divas) and unesp-botucatu multidimensional composite pain scale (mcps. fudge et al. (2020) started with the latter, however many of the participants were feral, reducing application to practice and the ability to fully complete the scale. they switched to the modified colorado state university feline acute pain scale (mcsu) and numerical rating scale (nrs). this change in pain scoring system reduced the palpation of the surgical site, and therefore the potential for staff injury. tobias et al. (2006) employed the visual analogue scale (vas) and interactive visual analogue scale (ivas), allowing for numerical and observational assessment. despite repeated use within the veterinary industry (bloor, 2017), most of the pain scales used are not validated for cats. this should be considered when evaluating the reliability of the results, as they may have led to an inaccurate representation of participant pain. issues with the reliability of pain scales were present in fudge et al (2020), where the first phase of the study was disregarded due to significant difference between nrs and mcps pain scores. nrs scores were higher than mcps scores. the differences in scores were deemed as bias and therefore produced unreliable data for the study. however, the second phase of fudge et al (2020)’s study replaced the validated mcps scale with the mcsu, an unvalidated scale for use in cats. therefore, the results are based on two unvalidated pain scales, and the results from phase one suggest they may have produced inaccurately high pain scores. the supposed bias should have been noted to highlight the possible inaccuracies of an unvalidated pain scale. these inaccuracies may also be reflected in the results of tobias et al (2006), as they also only used unvalidated pain scales during their study. the blinded nature of the study designs is expected to reduce bias, allowing for honest observations, without any preconceptions or opinions swaying the results (moustgaard et al., 2020). in addition, all assessors throughout the three studies were trained to conduct the pain scores, which may have improved interobserver agreement.   abbreviation pain scale validated for feline patients? method of assessment which studies used which scoring system? (divas) dynamic and interactive visual analogue scale no visualising pain using a 10cm line (each cm represents a score). 0–10 scale (0 = no pain, 10 = high pain).       benito et al. (2016a) &  fudge et al. (2020) started with mcps but altered their method (mcps) unesp-botucatu multidimensional composite pain scale yes emotional and physical effects of pain. multiple behavioural categories are scored, equaling an overall score. (mcsu) modified colorado state university feline acute pain scale no removed palpation of surgical site. multidimensional scale which uses behavioural cues to assess pain.       fudge et al. (2020) (nrs) numerical rating scale no the observer assigns a score of pain from 0–10 (0 = no pain, 10 = high pain). (vas) visual analogue scale no visualising pain using a 10 cm line (each cm represents a score). 0–10 scale (0 = no pain, 10 = high pain).       tobias et al. (2006) (ivas) interactive visual analogue scale no visualising pain using a 10 cm line (each cm represents a score). 0–10 scale.   figure 1. table showing the pain scales used in the studies.   the timing of pain scoring was the final methodology difference analysed. bupivacaine has an initial onset time of 2 and 5 minutes, with full block normally occurring between 5–10 minutes (grubb & lobprise, 2020). all postoperative pain scores were taken after this onset time and within bupivacaine’s duration of action. however, within the study by fudge et al. (2020), postoperative pain scores were taken 1 hour into recovery and at discharge. discharge times ranged from 1.7–7 hours post anaesthesia; therefore, some scores would have been taken close to the end of bupivacaine's duration of action, possibly reducing analgesic effects. this could have influenced the ability of pain scores to accurately assess the effect of bupivacaine at this timepoint. since evaluation of these three studies, fudge et al. (2021) has published further research, comparing the use of bupivacaine with other targeted intraoperative injections (bupivacaine-lidocaine-epinephrine, dexamethasone, meloxicam). they conducted a prospective, randomised, double-blinded clinical trial with 151 cats, all undergoing midline ovariohysterectomies. the research followed similar guidelines to fudge et al. (2020) but aimed to see if other drugs administered as targeted injections provided more effective analgesia than bupivacaine, like tobias et al. (2006). using the 0–10 numerical rating scale (nrs), they found no statistical significance in postoperative pain scores between any of the groups 1 hour post-anaesthesia. whilst meloxicam showed lower post-operative pain scores at 3 hours post-anaesthesia compared to all groups, it only gained statistically significant lower scores than the bupivacaine-lidocaine-epinephrine group (p = 0.018). fudge et al. (2021) concluded that all of the tested drugs performed similarly as part of multimodal analgesia for feline ovariohysterectomies, except for meloxicam which may lower pain scores more than the bupivacaine-lidocaine-epinephrine block. similarly, benito et al. (2019) conducted a study following benito et al. (2016a), aiming to determine if administering bupivacaine with dexmedetomidine would provide superior analgesia in comparison to bupivacaine alone, when given to cats via splash block during ovariohysterectomy. this time benito et al. (2019) used the unesp-botucatu composite pain scale to evaluate postoperative pain. they found that median pain scores in cats receiving just bupivacaine were significantly higher than those receiving bupivacaine and dexmedetomidine (p = 0.023) at 12 hours post-surgery, suggesting that administering bupivacaine along with another analgesic may reduce postoperative pain scores. prior to this study, benito et al. (2018) investigated the efficacy and pharmacokinetics of bupivacaine given in combination with epinephrine or dexmedetomidine to cats undergoing ovariohysterectomies. results found that both drug combinations provide similar analgesic effects.  although this study does not fit the pico question for this knowledge summary due to the absence of testing bupivacaine alone, its conclusions support the use of bupivacaine in conjunction with another drug. furthermore, there may also be other alternative forms of bupivacaine which could be more favourable. bupivicaine liposome injectable suspension is a longer lasting lipid based injectable that has a prolonged analgesic effect (gordon-evans et al., 2020). although it is not directly comparable to bupivacaine hydrochloride and is not yet available globally, it may be another option to explore in the future. generalised findings conclude that a bupivacaine local anaesthetic block may influence post-operative pain in cats undergoing ovariohysterectomies, reducing the need for rescue analgesia. the technique of administering bupivacaine requires minimal skill to perform and is cost effective (fudge et al., 2020).  however, further research is required to assess a range of other medication combinations, to ensure that the method is not only used because it is cheap and easy, but also effective and warranted. research suggests that use of bupivacaine in conjunction with other analgesics may be preferable, but this should be explored further. use of validated pain scales such as the glasgow composite measure pain scale (wsava, 2015) and the incorporation of an objective assessment method such as the mechanical nociceptive threshold probe used by benito et al. (2016a) could improve future research, although may be challenging with more aggressive patients. conducting prospective randomised double blinded placebo-controlled clinical trials on different analgesics and locations could fill an evidence gap currently present. methodology search strategy databases searched and dates covered: cab abstracts (2006–2022) pubmed (2006–2022) science direct (2006–2022) search strategy: cab abstracts: (cat or cats or feline or felines or queen or queens) (spay or spey or spaying or speying or ovariohysterectomy or neutering or neuter)  (block or blocking or  anaesthesia or  anaesthetic or anesthesia or anesthetic) (bupivacaine or bupivicaine) post-operative or postoperative or pain scoring or pain score or pain scale 1 and 2 and 3 and 4 and 5 pubmed: (feline or cat or cats or queen or queens or felines) and (spay or spey or spaying or neutering or neuter or ovariohysterectomy) and (local blocks or local blocking or local anaesthesia or local anaesthetic or local anesthesia or local anesthetic) and (bupivacaine or bupivicaine) and (post-operative pain score or pain score or pain scale) science direct: (feline) and (spay or ovariohysterectomy) and (local anaesthesia) and (bupivacaine) and (post-operative pain score) dates searches performed: 09 sep 2022   exclusion / inclusion criteria exclusion: studies including species other than feline.  studies evaluating the effect of bupivacaine and the percentage of volatile agent used. studies using ovariectomy or flank spay. studies using combination blocks. studies using a combination of local analgesic drugs. studies published before 2006. inclusion: studies involving feline midline ovariohysterectomy.  studies bupivacaine administration and control measures (placebo or other analgesia). peer-reviewed studies.   search outcome database number of results excluded – canine / dog excluded – ovariectomy excluded – before 2006 excluded – irrelevant to pico total relevant papers cab abstracts 13 0 0 0 10 3 pubmed 7 0 0 0 4 3 science direct 53 47 1 1 3 1 total relevant papers when duplicates removed 3   author contributions tara freeman: conceptualisation, investigation, resources, writing – original draft, writing – review & editing (lead). amelia wisby: conceptualisation, investigation, resources, writing – original draft. kate burroughs: conceptualisation, investigation, resources, writing – original draft. samantha gentle: conceptualisation, investigation, resources, writing – original draft. connie ellis: conceptualisation, investigation, resources, writing – original draft. sarah batt-williams: supervision. orcid tara freeman: https://orcid.org/0000-0002-5588-9623 kate burroughs: https://orcid.org/0000-0003-4062-2739 connie ellis: https://orcid.org/0000-0002-3305-6866 sarah batt-williams: https://orcid.org/0000-0001-8713-6944 conflict of interest the authors declare no conflicts of interest. references benito, j. evangelista, m.c., doodnaught, g.m., watanabe, r., beauchamp, g., monteiro, b.p. & steagall, p. 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(2016b). pharmacokinetics of bupivacaine after intraperitoneal administration to cats undergoing ovariohysterectomy. american journal of veterinary research. 77(6), 641–645. doi: https://doi.org/10.2460/ajvr.77.6.641 bloor, c. (2017). pain scoring systems in the canine and feline patient. the veterinary nurse. 8(5), 252–258. doi: https://doi.org/10.12968/vetn.2017.8.5.252 brondani, j.t., mama, k.r., luna, s.p.l, wright, b.d., niyom, s., ambrosio, j., vogel, p.r. & padovani, c.r. (2013). validation of the english version of the unesp-botucatu multidimensional composite pain scale for assessing operative pain in cats. bmc veterinary research. 9(1), 143. doi: https://doi.org/10.1186/1746-6148-9-143 fudge, j.m., page, b. & lee, i. 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(2015). feline composite pain scale. [online]. available from: https://wsava.org/wp-content/uploads/2020/01/feline-cmps-sf.pdf [accessed september 2022]. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use.   veterinary evidence is an rcvs knowledge initiative. issn: 2396-9776 first floor, 10 queen street place, london ec4r 1be resources student awards staff login policies privacy policy accessing information policy cookie declaration terms of use copyright notices stay connected podcasts twitter facebook instagram linkedin back to top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443. when treating medial patellar luxation in dogs is a block trochleoplasty superior over a wedge trochleoplasty? a knowledge summary by maria norell candetoft dvm 1* 1djursjukhuset anicura albano, rinkebyvägen 21a, 182 36 danderyd, sweden *corresponding author (maria.norell.candetoft@anicura.se) vol 7, issue 3 (2022) published: 15 jul 2022 reviewed by: andy morris (bsc[hons] bvsc certavp[gsas] mrcvs) and maureen o'mara (phd mgis) next review date: 22 nov 2023 doi: 10.18849/ve.v7i3.517 pico question as part of the surgical correction for medial patellar luxation in dogs, which procedure results in a better outcome for the patient: block or wedge recession trochleoplasty?   clinical bottom line category of research question treatment the number and type of study designs reviewed three studies satisfied the inclusion criteria for answering the pico; one cadaver study, one retrospective observational study and one clinical case series strength of evidence weak outcomes reported postoperative complications including reluxation rates. ex vivo: trochlear groove depth, patella articular contact, percentage of recessed trochlear surface area, resistance to medial patella luxation conclusion there is only weak evidence to support block recession trochleoplasty over wedge recession trochleoplasty as part of the surgical correction for medial patella luxation in dogs. both procedures are associated with a good clinical outcome. there are some proposed benefits to trochlear block recession made from an ex vivo study comparing the two procedures. these include an increased patellar volume under the trochlear ridges when the stifle is extended. the articular contact and recessed trochlear surface area were also increased in the trochlear block recession group when compared to trochlear wedge recession. however, the clinical relevance of these perceived benefits remains unproven. in practice, and until prospective randomised controlled trials are carried out, veterinary surgeon preference and previous experience remain relevant factors in choosing which procedure to perform   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you have been working for a long time in a large veterinary hospital and over the years performed many block recession trochleoplasties as part of the surgical treatment of medial patellar luxation, and you have been very satisfied with the postoperative results. now you have recently been employed by another veterinary hospital where all veterinary surgeons perform wedge recession trochleoplasty and they want you to switch your method since that they think that wedge recession is superior. you decide to read about the topic to learn more regarding the evidence between the two methods. to do a block or a wedge, that is the question. the evidence the literature search uncovered only three papers that addressed the pico question and fitted the inclusion and exclusion criteria applied. the three studies described the outcome of wedge recession trochleoplasty and block recession trochleoplasty; one study in cadavers (johnson et al., 2001), one retrospective observational study (rossanese et al., 2019) and one case series study (ballatori et al., 2005). the number of cases included in the cadaver study by johnson et al. (2001) was low, 12 cases with 24 stifles, and only four cases with eight stifles were included in the case series study. the latter study by ballatori et al. (2005), was included despite the fact that it had both lateral and medial patellar luxations, although only the results applying to the medial patellar luxation (two dogs) were included. the study that included most animals was rossanese et al. (2019) with 87 cases and a total of 100 stifles in the study by johnson et al. (2001) the difference in patellar depth, patellar articular contact, percentage of recessed trochlear surface area, and resistance to medial patellar luxation in stifles treated with trochlear block recession or trochlear wedge recession were described. in the specimens, the block technique was superior to the wedge technique as it had a deeper proximal patellar depth, a greater patellar articular contact in the extended stifle (p< 0.01), a larger percentage of recessed trochlear surface and a greater resistance to medial patellar luxation. since the study was performed on cadavers with specimens mounted in a position device, it is difficult to interpret the results in live animals. also, all dogs were large breed dogs, and it is unclear whether or not the results can be applied also to small breed dogs. in the study by rossanese et al. (2019) femoral trochleoplasty was performed in 90 stifles and included a trochlear wedge recession in 68 stifles (76%) and a trochlear block recession in 22 stifles (24%). results from this study showed no significant difference in complication rates between the trochlear wedge technique and the trochlear block technique. the type of trochleoplasty performed (block vs wedge) was not associated with the occurrence of postoperative complications. valid conclusions may not be drawn from the study by ballatori et al. (2005) as only four dogs and eight stifles were included, and two dogs had medial patellar luxation and two dogs had lateral patellar luxation. summary of the evidence johnson et al. (2001) population: normal, large-breed canine cadavers. the dogs were euthanised for reasons unrelated to the study and were determined to be free of stifle disease via orthopaedic examination and radiographs. mean weight was 31.9 kg (25.0–38.6 kg). sample size: 24 stifles from 12 dogs. intervention details: specimens consisting of femur, tibia and intact stifle joint were removed bilaterally from each cadaver. soft tissues were dissected free, leaving only the stifle joint capsule and ligaments intact. the quadriceps tendon of insertion on the patella was transected 1.5 cm proximal to the patella. bilateral pelvic limb specimens were mounted on two identical position devices so that the legs could be examined and tested in standardised methods. to simulate a shallow trochlea, the trochlear ridges of each specimen were reduced using a high-speed drill and burr. a plastic guiding template was used to make the trochlea ridges at the same (low) height on each specimen. the joint capsule was opened laterally (to mimic a stretched lateral joint capsule) and a mechanic arm applied 40° of internal tibial rotation in both flexion and extension. the medially internal rotation made all of the patellas to luxate medially within 40° of internal tibial rotation in each trial. trochlear block recession (tbr) and trochlear wedge recession (twr) was performed on opposite stifles of paired specimens, selection of right or left leg in each pair was managed by flipping a coin. depth and position of twr were standardised between specimens using a custom-made template that directed the saw blade in the same way in all the trochleas. the position of the tbr was also standardised between specimens based on anatomic landmarks. each specimen was evaluated before and after trochleoplasty (tbr or twr) with computed tomography (ct) and biomechanical testing with the stifle held in extension (148° to evaluate the patella within the proximal trochlea) and in flexion (113° to evaluate the patella within the central trochlea). the depth of the trochlea in the central and proximal portion was measured as well as the patellar coverage percent. the patellar articular contact with the recessed trochlea was also determined postoperatively. the percentage of recessed trochlear surface area was determined for each specimen. study design: in vitro ct and biomechanical evaluation using a cadaver model. outcome studied: to compare tbr to twr with regards to patellar depth (percentage of patellar volume under the trochlear ridges), patellar articular contact, percentage of recessed trochlear surface area, and resistance to patellar luxation. main findings (relevant to pico question): no significance in the depth of trochlear recession existed between groups. postoperative patellar depth in the extended stifle position was significantly greater in the tbr group compared with the twr group. in the extended stifle position, postoperative patellar articular contact was significantly greater in the tbr group compared with the twr group. postoperative recessed trochlear surface area was significantly greater in the tbr group (76.5%) compared with the twr group (49.9%). postoperatively patellar luxation did not occur in any specimen in the flexed stifle but in the extended stifle (with the leg held in 40° internal rotation) the patella luxated in 8% (1/12) after tbr and in 42% (5/12) after twr. the difference was not statistically significant (p = 0.06). limitations: although more versatile, ct is a less sensitive imaging modality for visualising articular cartilage compared with magnetic resonance imaging (mri). however, to investigate the groove depth of the trochleoplasty it is easier to make measurements from ct reconstruction / multiplanar image manipulation compared to mri. this was a cadaver study so we do not know how to correctly interpret the data in live animals. the authors did not attempt to approximate physiologic forces placed on the patella by the quadriceps muscle group. the model also does not account for tibial or femoral torsional deformities commonly seen in dogs with patellar luxation. the test was only performed in specimens from large breed dogs so we do not know if the results would be the same for small breed dogs. rossanese et al. (2019) population: dogs <20 kg surgically treated for medial patellar luxation between 2011–2016. the preoperative luxation grade was classified as grade i in one stifle grade ii in 51 stifles, grade iii in 42 stifles and grade iv in six stifles. median weight 8.2 kg (total range 1.2–20.00 kg). sample size: 87 dogs met the inclusion criteria and a total of 100 surgical procedures for medial patellar luxation were performed. intervention details: surgery was performed by an experienced surgeon in 70 cases and by a resident under supervision in 30 cases. no dogs in the study required corrective osteotomy techniques in the distal femur. all surgical procedures included lateral tibial tuberosity transposition (ttt). medial soft tissue release was performed in 41 stifles (41%). lateral imbrication was performed in 81 stifles (81%). femoral trochleoplasty was performed in 90 stifles (90%) and included a trochlear wedge recession in 68 stifles (76%) and a trochlear block recession in 22 stifles (24%). medial surgical time was 75 minutes (total range 25–195 minutes). study design: retrospective observational study. outcome studied: complications in dogs weighing <20 kg surgically treated for medial patellar luxation and to determine risk factors associated with these complications. main findings (relevant to pico question): 37 stifle joints developed postoperative complications. 12 were considered minor (patellar reluxation grade i, tibial tuberosity fracture, skin irritation), and 25 complications were considered major (patellar luxation grade ii, surgical site infection, wound dehiscence, removal of k-wires because of pin-fracture, pin-migration or seroma). results relevant to the pico question included four cases of grade i patellar luxation that did not require reoperation, and two cases of grade ii patella luxation that required revision surgery. results from the study showed no significant difference in complication rates between the trochlear wedge technique and the trochlear block technique. limitations: retrospective observational studies are considered to provide low-level scientific evidence. the data reported relies on the accuracy of the medical record entries. the article identified long-term complications by reviewing the referring veterinarian clinical records and it might be possible that some long-term complications were not noticed by the referring veterinarian. we do not know if the wedge trochleoplasty has a greater tendency to reluxate after several years, when the dog is older and has less muscle mass compared with the block trochleoplasty or vice versa, or if none of the techniques reluxates later on in life. the study did not address the progression of osteoarthritis. there were no standardised protocols to compare the different techniques. all of them performed transposition of the tibial tuberosity, but in some cases imbrication of the joint capsule and / or medial release of the joint capsule was also performed. since the article only reviewed dogs less than 20 kg of body weight, we do not know if either of the two different trochleoplasty techniques are more or less suitable for heavier dogs. as surgical procedures cannot be clearly differentiated from the surgeons performing them, we do not know whether or not we are investigating the surgeons or the procedures. ballatori et al. (2005) population: dogs with bilateral patellar luxation grade i–iv brought to the department with a complaint about secondary lameness, between the years 2002–2004. sample size: eight stifles in four dogs. two dogs had medial patellar luxation and two dogs had lateral patellar luxation. intervention details: radiographic examination was performed to exclude severe malformation of the femur and tibia. two types of surgeries were performed in the same dog: trochlear block recession (tbr) in the right stifle and trochlear wedge recession (twr) in the left stifle. both procedures were performed in the same operation. both of the dogs with medial patellar luxation also had tibial tubercle transposition (transposition of tibial tuberosity). the dogs had a postoperative period of physiotherapy with gradual return to normal activity in about 2 months. follow-up period: 10–15 days postoperatively, 2–3 months postoperative and one case 12 months postoperatively. study design: clinical case series. outcome studied: immediate postoperative computed tomography (ct): direct after the surgical procedure the stifles were examined with ct in ventrodorsal position with semi-flexed pelvic limbs. the ct images was used to estimate trochlear depth and patellar depth. a line between the trochlear ridges and the centre of the trochlear surface provided the measurement for the trochlear depth. the patellar depth was measured as the percentage of the entire patellar volume positioned under the trochlear ridges. clinical evaluation 10–15 days postoperative: 10–15 days postoperative the robert jones bandage was removed and clinical articular evaluation was assessed. clinical evaluation 2–3 months postoperative: 2–3 months after surgery the dogs were evaluated clinically regarding distribution of weight between the two hindlegs, tolerance during activity, muscular growth, patellar stability and pain. one dog was examined with ct 12 months after surgery. main findings (relevant to pico question): ct findings: the ct showed correct autograft positioning and an adequate patellar lodging into the trochlear groove in all cases, independently of surgical technique used. in the central trochlea both tbr and twr allowed the achievement of a good trochlear depth, but the patellar depth was greater in the knee with rectangular recession. the proximal trochlear sulcus was wider and deeper with tbr than with twr. the distal part of the subchondral wedge reached deeper in the caudal portion of the femoral trochlea but the proximal part of the autograft wedge is entirely excavated in the cranial portion of the trochlea. findings in the clinical evaluation: in the postoperative period no complications or relapses in any of the dogs were seen. 15 days after surgery the patients showed a fairly good ability to distribute weight on both operated limbs but there was more lameness and pain in articulations with tbr. the postoperative clinical picture 2–3 months after surgery was similar in both joints, with the difference that the patella was stable in the flexed position but in extended position a more lateromedial patellar instability was recognised in stifles treated with trochlear wedge recession. limitations: very small sample size. case series which is lower in evidence hierarchy. the group was not homogenous: the dogs with medial patellar luxation were of different age (18 months and 7 years), different breeds (pinscher and springer spaniel) the grade of patellar luxation was not the same (ranging from grade i–iv) and it was not the same grade between the legs in the same patient. no observer standardised clinical examination was described, introducing observer bias. it does not say if the patellas luxated postoperatively, only that the patella was more unstable in a lateromedial direction in the trochlear wedge technique. no description of inclusion or exclusion criteria (except for radiographic examination for malformation of femur / tibia). no long-term follow-up was available to examine if any surgical method acquired less degenerative joint disease. appraisal, application and reflection outcome as a measure of success might be difficult to objectively assess as it is influenced by many different factors. when surgically correcting a medial patellar luxation one seldom only corrects the trochlea but most often also amends the soft tissues (imbrication of the joint capsule, release incision of the retinaculum or desmotomi) in combination with longitudinal realignment of the tibial tuberosity relative to the trochlear groove, by performing a tibial tuberosity transposition (arthurs & langley-hobbs, 2006). thus, it is difficult to determine if a trochlear block recession is superior to a wedge recession technique as the two different surgical methods are not performed in isolation. only three studies were identified addressing the pico question; one biomechanical cadaver study, one retrospective observational study with 100 stifles and one case series including only two dogs. thus, the evidence base for answering the query if block recession trochleoplasty is superior to wedge recession trochleoplasty when treating medial patellar luxation is indeed very limited. of the three studies, the biomechanical cadaver study (johnson et al., 2001) has a more impressive implementation with ex vivo testing of a stifle model that mimics patellar luxation, objective interobserver assessment and distinct variable measurements obtained from the computed tomography. the main limitation with the cadaver study, when using it to answer the pico question, is that results might not be applicable to live animals. also, long-term effects cannot be evaluated. the retrospective observational study by rossanese et al. (2019) described complications following surgical correction of medial patellar luxation in dogs < 20 kg. in the study including 87 dogs and 100 stifles with different degree of patellar luxation, complications were recognised in 37 stifles; 12 minor and 25 major. the outcome relevant to the pico question showed no significant difference in complication rates between trochlear wedge resection and trochlear block resection. one of the main limitations with this study, apart from it being a retrospective study, is that it lacks long-term follow-up. we do not know if any of the trochleoplasty techniques had worse or more favourable outcome after several years. also, to use this article to answer the question whether or not one surgical method is superior to another is difficult because, there are no kinematics, no description of repeated clinical examinations, no owner questionnaires, or second-look arthroscopy.  however, a second look arthroscopy may not be of added value to the animal and thus not considered to be ethical. in addition, time records to perform each procedure are not published. it is therefore not possible to comment if one procedure is less time consuming. this would be an interesting factor to compare. generally, retrospective case series are regarded low on the hierarchy of the evidence scale. in the case series by ballatori et al. (2005), the number of dogs studied are by far too low to allow a meaningful comparison between the treatment methods as only two dogs had medial patellar luxation and also with different luxation degree in the individual hindleg. the difference between the two surgical methods judged by the use of computed tomography is a result of the geometry of the block and wedge. the articular width of the block and wedge are similar in the centre of the trochlea, but the block maintains the articular surface width along the entire length of the trochlea compared to the wedge, which tapers to a point proximally and distally. after trochlear wedge recession, as the stifle is extended and the patella moves proximally, the patella may articulate with the non-recessed proximal femoral trochlea instead of the recessed articular cartilage of the wedge, resulting in decreased patellar depth. the reduction in proximal patellar height could be essential in the clinical treatment of patellar luxation since the patella most often luxate in the proximal trochlea when the stifle is extended (talcott et al., 2000, and johnson et al., 2001). in dogs with medial patellar luxation, block trochlear recession results in a proximal deeper trochlear groove and a larger contact area between the proximal trochlea and patella, compared with the wedge trochlear recession. in the extended stifle, the patella lies deeper in the proximal part of the joint (johnson et al., 2001; and talcott et al., 2000). since no long-term studies comparing the amount of degenerative changes in the stifle joint and re-luxation rates between the two methods exist, and since the scientific information that actually compares the methods are very limited, no conclusion can be made from the existing evidence regarding whether or not a trochlear block recession is superior to trochlear wedge recession technique, when treating medial patellar luxation in dogs. since there are few reports comparing the two surgical methods, studies describing outcomes and complication rates with each technique might provide useful information when choosing between the two surgical methods: slocum et al. (1982) performed trochlear wedge surgery and showed excellent results in 13/17 stifles and good results in the remaining cases. the follow-up period in that study was 12–29 months. talcott et al. (2000) described 100 dogs after trochlear block surgery with positive short-term results: the joints were considered free of crepitus, limb function was improved and patellar stability achieved in the 6 week follow-up period. however, no long-term radiographic studies, histological analyses or second-look arthroscopy was performed in that study.  a retrospective case series by gallegos et al. (2016) described bilateral wedge trochleoplasty in 50 small breed dogs (100 stifle joints) with medial patellar luxation. in the study, 5/50 dogs (10%) had reluxation (grade i) none of the dogs showed clinical lameness postoperatively. the median follow-up time was 8 weeks. arthurs & langley-hobbs (2006) reported retrospectively the clinical outcome in 109 dogs undergoing surgery because of lateral or medial patellar luxation. in the study, 74/107 (69%) had trochlear wedge recession and 8/107 (7%) had trochlear block recession. however, no comparison was made between the methods. in another retrospective study by gibbons et al. (2006) trochlear wedge or trochlear block was performed to treat patellar luxation in 70 large breed dogs (>15 kg). as no comparisons were made between the two methods, no conclusions regarding the superiority of either method can be drawn. cashmore et al. (2014) reported a retrospective study regarding complications and risk factors associated with surgical correction of medial patellar luxation in 124 dogs. major complications (implant associated, patellar luxation and persisting lameness, patellar tendon rupture etc.) occurred in 24/124 (19%) of dogs. although no comparisons were made between methods, a case of trochlear wedge displacement was reported. in a pilot study (blackford-winders et al., 2021) of 10 dogs, where the trochlear block recession technique was performed, the block autograft fractured in three cases. in a case report by ellis & house (2021) the trochlear block migrated distally 7 days postoperatively. in another case report (chase & farrell, 2010) a fracture of the lateral trochlear ridge following trochlear block recession was described. one plausible reason for recurrent postoperative patellar luxation may, at least in part, be caused by inadequate appreciation of the underlying skeletal deformity and subsequent selection and application of corrective surgery. accurately measuring anatomic conformational abnormalities, for example identifying an extensive varus deformity or torsion in the distal femur, to better understand the deformities and subsequently better tailor corrective surgery by performing different kind of osteotomies than trochleoplasties, of the distal femur or proximal tibia, may result in lower frequency of reluxation. in conclusion, further studies are needed to evaluate both short-term and long-term clinical outcome in small breed dogs with medial patellar luxation undergoing either trochlear wedge recession or trochlear block recession. on one hand, the block technique might be considered to be more physiologically or anatomically appropriate creating a deeper trochlea proximally in the joint and a more profound femoropatellar contact. on the other hand, the wedge technique is less invasive and thus conceivably associated with lower risk of complications. whether or not the degree of subsequent osteoarthrosis might be influenced by the choice of surgical technique is of major importance for the individual dog. the preference and previous experiences of the veterinary surgeon are relevant issues when choosing which operation to perform until randomised and controlled trials in live animals and in comparable groups are performed. methodology section search strategy databases searched and dates covered: cab abstracts on the ovid interface 1973–2021 week 46 pubmed accessed via the ncbi website 1920–nov 2021 search strategy: cab abstracts: (dog or dogs or canine or canines or canis or bitch or bitches or puppy or puppies).mp. or exp dogs/ or exp bitches/ or exp puppies/ or exp canidae/ or exp canis/ (lux* or mpl or dislocat*).mp. or exp dislocation/ ((trochle* or sulcoplas*) and (wedge or block or recession)).mp. 1 and 2 and 3 pubmed: dog or canine or bitch or puppy luxation or mpl or dislocation (trochleoplasty or sulcoplasty or trochlear) and (wedge or block or recession) 1 and 2 and 3 dates searches performed: 22 nov 2021 exclusion / inclusion criteria exclusion: non-english language. inclusion: articles concerning canine stifles with medial patellar luxation that have undergone either trochlear block recession or trochlear wedge recession. search outcome database number of results excluded – wrong species excluded – not in english excluded – not relevant to the pico question total relevant papers cab abstracts 48 2 4 40 2 pubmed 20 1 0 18 1 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflicts of interest. references arthurs, g.i. & langley-hobbs, s.j. (2006). complications associated with corrective surgery for patellar luxation in 109 dogs. veterinary surgery. 35(6), 559–566. doi: https://doi.org/10.1111/j.1532-950x.2006.00189.x ballatori, c., modenato, m. & sbrana, s. (2005). comparison of trochlear block recession and trochlear wedge recession in four dogs with bilateral patellar luxation. annali della facolta di medicina veterinaria di pisa. 58, 295–303. [online]. available from: http://eprints.adm.unipi.it/209/1/295.pdf [accessed 26 may 2021]. blackford-winders, c. l., daubert, m., rendahl, a. k. & conzemius, m. g. (2021). comparison of semi-cylindrical recession trochleoplasty and trochlear block recession for the treatment of canine medial patellar luxation: a pilot study. veterinary and comparative orthopaedics and traumatology. 34(3), 183–190. doi: https://doi.org/10.1055/s-0040-1721107 cashmore, r. g., havlicek, m., perkins, n. r., james, d. r., fearnside, s. m., marchevsky, a. m. & black, a. p. (2014). major complications and risk factors associated with surgical correction of congenital medial patellar luxation in 124 dogs. veterinary and comparative orthopaedics and traumatology. 27(4), 263–270. doi: https://doi.org/10.3415/vcot-13-08-0100 chase, d. & farrell, m. (2010). fracture of the lateral trochlear ridge after surgical stabilisation of medial patellar luxation. veterinary and comparative orthopaedics and traumatology. 23(3), 203–208. doi: https://doi.org/10.3415/vcot-09-11-0117 ellis, l.f. & house, a.k. (2021). trochlear block recession sulcoplasty migration in a dog. journal of small animal practice. 62(9),823. doi: https://doi.org/10.1111/jsap.13340 gallegos, j., unis, m., roush, j. k. & agulian, l. (2016). postoperative complications and short-term outcome following single-session bilateral corrective surgery for medial patellar luxation in dogs weighing <15 kg: 50 cases (2009–2014). veterinary surgery. 45(7), 887–892.doi: https://doi.org/10.1111/vsu.12525 gibbons, s.e., macias, c., tonzing, m.a., pinchbeck, g.l. & mckee, w.m. (2006). patellar luxation in 70 large breed dogs. the journal of small animal practice. 47(1), 3–9. doi: https://doi.org/10.1111/j.1748-5827.2006.00004.x johnson, a.l., probst, c.w., decamp, c.e., rosenstein, d.s., hauptman, j.g., weaver, b.t. & kern, t.l. (2001). comparison of trochlear block recession and trochlear wedge recession for canine patellar luxation using a cadaver model. veterinary surgery. 30(2), 140–150. doi: https://doi.org/10.1053/jvet.2001.21391 talcott, k.w., goring, r.l. & de haan, j.j. (2000). rectangular recession trochleoplasty for treatment of patellar luxation in dogs and cats. veterinary and comparative orthopaedics and traumatology. 13(1), 39-43. doi: https://doi.org/10.1055/s-0038-1632628 slocum, b., slocum, d.b., devine, t. & boone, e. (1982). wedge recession for treatment of recurrent luxation of the patella: a preliminary report. clinic orthopaedics and related research. (164), 48–53. rossanese, m., german, a.j., comerford, e., pettitt, r., tomlinson, a. & de vicente, f. (2019). complications following surgical correction of medial patellar luxation in small-to-medium-size dogs. veterinary and comparative orthopaedics and traumatology. 32(4), 332–340. doi: https://doi.org/10.1055/s-0039-1683872 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. erratum to: are glucocorticoids or nsaids more effective in reducing idiopathic feline urinary tract disease signs than no treatment or placebo? lesca monica sofyan baavbs(honsii) mvs dvm1* 1orchard hills veterinary hospital, 49–63 wentworth rd, orchard hills nsw 2748, australia *corresponding author (lesca.sofyan.xx@hotmail.com) vol 6, issue 4 (2021) erratum published: 09 nov 2021 original paper published: 12 aug 2021 the original article was published in veterinary evidence vol 6, issue 3 (2021): https://doi.org/10.18849/ve.v6i3.439 doi: 10.18849/ve.v6i4.532 erratum the publishers apologise for their error in the original version of the title, which was published as: the title was changed from: are glucocorticoids or nsaids effective in idiopathic feline urinary tract disease signs than no treatment or placebo? this has been corrected to: are glucocorticoids or nsaids more effective in reducing idiopathic feline urinary tract disease signs than no treatment or placebo? this error was in the html and pdf. this has now been updated in both versions. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. does the use of lidocaine in dogs and cats reduce post-operative tracheitis? a knowledge summary by erik fausak mslis, ma, cvt, lvt, rlat1* kirsten soules1 1bel-rea institute of animal technology,1681 s dayton st, denver, co 80247, usa *corresponding author (efausak@gmail.com) vol 2, issue 1 (2017) published: 03 feb 2017 reviewed by: matyas liptovszky (dvm, msc, mrcvs) reviewed by: bruce smith (bvsc ms fanzcvs dacvs) next review date: 20 feb 2019 doi: 10.18849/ve.v2i1.61 clinical bottom line examination of a human systematic review and two veterinary prospective trials suggest topical application on the glottis, and placement of lidocaine on the endotracheal tube both seem to improve sore throat and laryngeal response in animals. choice of pre-medicants and induction agents appears to have an impact on the extent of lidocaine efficacy. consideration should be given in allowing enough time for lidocaine placement to have effect (around 60-90 seconds). limitations in more confident assertions of the efficacy of lidocaine being utilized to prevent tracheitis is that only the human systematic review had enough follow up time to examine the benefits of lidocaine on sore throat in intubation. question in dogs and cats, does the use of lidocaine lubricant on the endotracheal tube or placed on the glottis reduce tracheitis? clinical scenario at bel-rea institute of animal technology, shelter pets are routinely neutered and lidocaine lubricant is applied to the cuff and tip of endotracheal tubes to reduce post-operative sore throat or tracheitis. incidence of sore throat after surgery has not been evaluated at our institution. additionally, lidocaine is utilsed in feline intubation to reduce laryngospasm. the evidence a systematic review in human medicine and 2 prospective veterinary studies were utilised. summary of the evidence cassu (2004) population: 10 cats average weight 3kg (8 males, 2 females), healthy. sample size: 40 (crossover) intervention details: 10 cats underwent induction and intubation four times: group gti0 was thiopental and intubation, group gtio+lido was thiopental with 10% lidocaine sprayed on the glottis, group gprop was propofol and intubation, group gprop+lido had propofol and 10% lidocaine sprayed on the glottis. all lidocaine spraying occurred on the glottis and the intubator waited 60-90 seconds before intubating. 15 days elapsed between the four procedures. all animals were previously sedated with acepromazine. study design: prospective, non-blinded, controlled, crossover study outcome studied: respiratory, heart rate, pulse oximetry, number of intubation attempts, cough reflex, occurrence of laryngospasm, degree of relaxation of glottis, and need for additional induction agent. main findings (relevant to pico question): lidocaine spray groups worked better with thiopental but no real difference was seen between the propofol groups with lidocaine or without. limitations: no critical evaluation and lack of description of who induced and who intubated, which could have made this a blinded study. highly subjective criteria of cough reflex without interobserver reliability. no lidocaine lubricant was placed on tube. not enough follow-up time in post-extubation tracheitis. dyson (1988) population: 32 healthy cats scheduled for elective surgery. no additional information. sample size: 32 cats intervention details: cats were separated into 4 groups: group 1 lidocaine iv.  not specified. group 2 2% lidocaine applied to larynx, larynx was reviewed after induction.  use of tuberculin syringe, with a 20g catheter that had 25g holes and the end sealed by heat. group 3 10% lidocaine aerosol (one "squirt") to larynx, larynx was reviewed after induction. group 4 no lidocaine.  not specified intubation was attempted 90 seconds after groups 1-3 were given lidocaine. one clinician intubated all animals.  study design: prospective, non-blinded, controlled outcome studied: the following were evaluated by the intubating clinician: induction consideration        amount of thiopental used for intubation        amount of thiopental used for a smooth transfer to the inhalant laryngeal relaxation (only applied to groups 2 and 3) intubation consideration        response (laryngospasm)         # of attempts         # of coughs         tube size extubation influence         evidence of complications during extubation. main findings (relevant to pico question): less laryngospasm with topical lidocaine than iv or no treatment. fewer efforts were made with both topical lidocaine administrations. topical intubation allowed for larger endotracheal tubes. limitations: same intubator, less interobserver reliability with subjective evaluations. not blinded. lidocaine 2% administration was complicated with a modified catheter. no et tubes are lubricated not enough follow up time for sore throat evaluation tanaka (2015) population: adult humans undergoing intubation. sample size: 1940 adult humans undergoing endotracheal intubation. intervention details: systematic review, study inclusion criteria: randomised control trials involving adult humans with varying degree of lidocaine use in endotracheal intubation (iv, spray, on the tube, in the cuff). databases searched were: cochrane central register of controlled trials (central) medline, and embase measurements used: visual aanalogue scale (vas) of sore throat. follow up duration was 12-30 hours post-operative two authors independently evaluated studies, but were not blinded to authors and institutions. intervention types: -endotracheal cuff was inflated with lidocaine -lubrication of distal end of endotracheal tube with lidocaine -spraying the glottis with lidocaine -iv lidocaine administration study design: systematic review with meta-analysis including 19 randomised control trials. outcome studied: risk of sore throat 12-30 hours after intubation/surgery. severity of sore throat 12-30 hours after intubation/surgery. amount of negative results from lidocaine administration. main findings (relevant to pico question): all approaches with lidocaine appear to have been beneficial to prevent sore throat. no toxicities were reported in the use of lidocaine. limitations: didn't mention what portion of lidocaine lube administration included besides, "distal". relevant information would include if “distal” endotracheal tube includes application on the cuff. all studies had unclear risk of bias and received a lower grade (trial evaluation criteria) score. appraisal, application and reflection veterinary appreciation of lidocaine's effect on post-operative sore throats is limited due to communication barriers between humans and other animals. human research in some way provides greater advantage because patients could communicate the existence of sore throat after intubation, which occurs 30-70% of the time in tanaka et al.'s (2015) study. veterinary study limitations for sore throat did not have a significant follow up time, to evaluate post-extubation sore throat. future research should have better followup periods following lidocaine application. no veterinary study examines placement of lidocaine on the endotracheal tube. measurement of sore throat is another veterinary challenge because visual analogue scales will not reliably work in determining severity of animal sore throats. despite the limitations in the quality of human research and surrogate outcomes measured in veterinary research, lidocaine by any route does seem to improve sore throat or laryngeal response with minimal toxicity concerns. methodology section search strategy databases searched and dates covered: pubmed, vetmed resource, and cab abstracts search terms: pubmed sore throat and lidocaine and intubation cabi and vet med resource: lidocaine and intubation dates searches performed: 12 april 2016 exclusion / inclusion criteria exclusion: only systematic reviews and metanalysis were included from human medicine. inclusion: any relevant research with dogs, cats and systematic human reviews. search outcome database number of results excluded – human systematic reviews only excluded – relevance and species specific excluded – duplicates total relevant papers ncbi pubmed 158 157 0 0 1 thomson reuters web of science 36 0 31 0 5 cab direct 40 0 4 36 0 total relevant papers when duplicates removed 3 conflict of interest the authors declare no conflicts of interest. references cassu, r.n. et al (2004) effects of topical lidocaine in the endotracheal intubation in cats. ars veterinaria, 20 (1), pp. 28-34. dyson, d.h. (1988) efficacy of lidocaine hydrochloride for laryngeal desensitization: a clinical comparison of techniques in the cat. journal of the american veterinary medical association, 192 (9), pp. 1286–1288. tanaka, y. et al. (2015) lidocaine for preventing postoperative sore throat. the cochrane database of systematic reviews, 7, p.cd004081. intellectual property rights knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. does adipose-derived stromal cell adjuvant therapy for fragmented medial coronoid process in dogs influence outcome? a pilot project kristina m. kiefer dvm, phd, ccrp, dacvsmr1 katja lin dvm, dacvs2 noel fitzpatrick duniv mvb, certvr, dsao, acvsmr, mrcvs3 g. elizabeth pluhar dvm, phd, dacvs1 michael g. conzemius dvm, phd, dacvs1 1university of minnesota, college of veterinary medicine, 1365 gortner ave, st paul, mn 55108, united states 2las vegas veterinary specialty center, 650 w tropicana ave b-107, las vegas, nv 89147, united states 3fitzpatrick referrals, halfway lane, eashing, godalming, gu7 2qq, united kingdom *corresponding author (kief0048@umn.edu) vol 1, issue 4 (2016) published: 9 nov 2016 reviewed by: adam swallow (bvsc mrcvs) doi: 10.18849/ve.v1i4.45 section index:    abstract | introduction | methods | results | discussion | footnotes | conflict of interest | references | supplementary files abstract objective: the primary objective of this study was to identify adverse events associated with multiple intra-articular injections of adipose stromal cell (asc) therapy and secondarily to objectively assess the therapeutic effect of asc therapy for treatment of fragmented medial coronoid process (fmcp) in dogs when used as an adjuvant to standard of care (soc) treatment.  background: preliminary trials assessing autologous asc therapy to treat osteoarthritis indicate a positive impact on clinical signs, but assessment of donated, allogeneic asc therapy is lacking. evidentiary value: this prospective, randomised, controlled trial in dogs (n=30) provides objective evidence for clinical practitioners regarding asc therapy in a naturally occurring osteoarthritic disease model.  methods: dogs diagnosed with fmcp and osteoarthritis were enrolled. all dogs had arthroscopic fragment removal and proximal ulnar osteotomy (puo) and were assigned into three groups (n=10/group): 1) control group with no further treatment beyond the puo and fragment removal (soc), 2) puo + autologous ascs and 3) puo+ allogeneic ascs. each dog had force platform gait analysis, canine brief pain inventory (cbpi) questionnaires, and delayed gadolinium enhanced magnetic resonance imaging scores prior to and six months after therapeutic intervention. results: no serious adverse events were reported in any participant. 3/10 dogs in the control group, 3/10 autologous asc group and 7/10 allogeneic asc group participants were assessed as successful outcomes.  conclusion: this study provides preliminary safety data for the use of intra-articular allogeneic asc therapy to treat osteoarthritis, and justification for larger clinical studies. application: clinical practitioners considering asc therapy within their practice are provided with additional evidence of autologous asc therapy for osteoarthritis. researchers committed to developing and generating effective asc therapies are provided with safety information for allogeneic asc, as well as identified biases important for study design. introduction an estimated 1 in 5 dogs in the united states suffer from osteoarthritis affecting elbows, knees and hips1. once the disease process begins, it is a non-reversible, progressive disease. because current therapeutics do not cure this disease, a wide variety of therapeutic options are available, all of which have limitations and variable efficacy. since the outcome of this disease process significantly affects quality of life in many patients and concurrent disease and/or adverse events may limit the pharmaceutical options that can be used, alternative therapies that impact outcome have generated great interest. fragmentation of the medial coronoid process (fmcp) in the elbow of the dog often results in lameness and progressive osteoarthritis (oa), even after surgical management 2–5. adipose derived stromal cells (asc) have garnered interest for the treatment of osteoarthritic conditions in the dog, and following a small number of publications, have become a widespread therapy offered to owners 6–11. these studies reported patient improvement compared to placebo control groups based on visually assessed lameness scores and caregiver-reports on improved quality of life 6,7. other studies demonstrated an improvement in force plate analysis after administration of ascs 8–10. these studies assess small numbers of cases and various inconsistent cellular therapies. the asc therapy may consist of a stromal vascular fraction (svf), which includes all unspecified, nucleated cells extracted from an autologous adipose tissue sample 6,7, culture expanded ascs 11, or culture expanded ascs combined with platelet rich plasma (prp) 8–10. these factors make clinical decision making when evaluating the value of asc therapy challenging.   svf therapy provides a rapidly produced and safe product for therapy of patients, but is a heterogeneous product that is inconsistent from patient to patient. utilising a cultured and characterised preparation of asc provides a less heterogeneous product that can be defined and selected for a specific purpose. allogeneic cultured ascs generate a therapeutic option for patients that cannot tolerate an anesthetic episode and are an immediately accessible treatment, as opposed to waiting several weeks for autologous cell culture. one study assessed dogs treated with autologous cultured ascs in combination with prp and found improved limb function using force platform gait analysis,  indicating that cultured cells may still have a positive effect as a therapeutic 8–10. allogeneic cultured ascs may provide the same clinical advantages of autologous cultured cells, but are a donated cell source. allogeneic ascs have been reported to improve limb function in people with knee oa without increased adverse events when compared to a placebo treated group 12.  asc therapy in oa is expected to take advantage of the immunomodulatory capacity and trophic effects that mesenchymal stem cells (msc) provide 13–17. ascs in particular have a capacity to immunomodulate their environment, making them attractive as a therapy for active inflammatory conditions 6–8,10,13–16,18–22.  in addition to reducing inflammation and inflammatory responses, ascs have the capacity to recruit local host cells that can induce a response that may not otherwise be present 16,20. the capacity of ascs to immunomodulate is significant enough that allogeneic ascs are better tolerated than other grafts, being accepted and incorporated into the local environment. they have been widely investigated for other immune modulating disease processes, but neglected in osteoarthritis in canine medicine 23–25. the primary objective of this study was to identify adverse events associated with multiple intra-articular injections of asc therapy and secondarily to objectively assess the therapeutic effect of asc therapy for treatment of fmcp in dogs when used as an adjuvant to standard of care (soc) treatment.  additional objectives were to identify potential study biases and collect baseline outcome data to assist in future study designs and determine if a larger, more definitive randomised clinical trial was justified. finally, to the authors’ knowledge, this is the first reported use of delayed gadolinium enhanced magnetic resonance imaging (dgemric) in a clinical population of naturally occurring oa in canines to assess cartilage quality. methods case selection thirty client-owned dogs (greater than 8-months of age and 10-kg body weight) that presented to university of minnesota, college of veterinary medicine or fitzpatrick referrals, eashing, gadalming, surrey, uk, for evaluation of a forelimb lameness with identified elbow pain secondary to a fmcp (confirmed by mri and surgery) were included in this study. dogs could be of any breed, sexual status or age. informed owner consent for participation in the study with owner agreement to follow postoperative care guidelines and recheck examinations was required for participation in the study. dogs that had previous elbow surgery, intra-articular injectable drug therapy for arthritis within 30 days of treatment, other systemic illnesses, or had other, concurrent, related (elbow incongruency, osteochondritis dissecans) or unrelated orthopedic or neurologic disease processes were excluded. all study procedures were in accordance with a protocol approved by the university of minnesota institutional animal care and use committee (iacuc # 1203a11421). experimental groups treatment groups included soc (arthroscopic fragment removal and proximal ulnar osteotomy (puo), soc with autologous svf therapy, or soc with allogeneic asc therapy. all dogs that were to receive cell therapies were treated at the university site in an effort to standardise cell preparation techniques and limit cell viability issues that might be associated with parcel delivery. surgeons participating in the study standardised surgical technique so dogs would receive similar care regardless of treatment site. complete transection of the ulna for puo was confirmed at the time of surgery and with radiographic assessment post-operatively. at the university site, the first 15 enrolled dogs were randomly assigned to soc or soc+svf therapy and the final 10 dogs were assigned to soc+allogeneic asc (complication with cell availability after the onset of the study delayed availability of this treatment group). pre and post-operative care anesthetic protocols were individually selected and designed by staff board certified anesthesiologists at the university of minnesota. post-operative management included hydromorphonea 0.05mg/kg intramuscularly every six hours overnight, and beginning the following morning, oral tramadolb 2-4 mg/kg every eight hours for ten days and a non-steroidal anti-inflammatory of the surgeon’s choice administered per manufacturer’s directions for ten days. isolation of adipose-derived stromal vascular fraction immediately following elbow surgery, dogs assigned to soc with autologous svf therapy had a ventral mid-line abdominal incision of 4-8cm in length made between the xiphoid process and the umbilicus. the falciform adipose tissue was identified, exteriorised, and ligated with a circumferential 2-0 pds suture prior to transection. the falciform tissue, approximately 30 grams, was placed into a sterile, covered container and transferred to the laboratory for processing. falciform adipose tissue was harvested at the time of surgery and was processed according to previously reported protocols for isolation of the stromal vascular fraction overnight 6,7,39. the nucleated fraction was used to determine cell number, and aliquoted into 5x10^6 million nucleated cells/dose. svf cells were cryopreserved in liquid nitrogen after the first treatment 40. isolation of allogeneic adipose-derived stromal cells falciform adipose tissue was harvested at the time of surgery from ten healthy dogs admitted to the university of minnesota college of veterinary medicine for abdominal surgery unrelated to the study. dogs with neoplastic or septic disease were excluded. owner consent was obtained and all procedures were performed in accordance with the university of minnesota institutional care and use committee (iacuc # 1203a11421).  adipose tissue was processed according to previously reported protocols for isolation of the svf 6,7,41. the nucleated cell fraction was then placed into keratinocyte n acetyl-l-cysteine supplemented (knac) medium consisting of modified mcdb153 medium (keratinocyte-sfm)e, mcdb153 medium (keratinocyte-sfm)e, 2mm n-acetyl-l-cysteinef, 0.2mm l-ascorbic acid 2-phophatef 0.09mm calcium and human recombinant epidermal growth factor (5ng/ml)e, bovine pituitary extract (50ug/ml)e, insulin (5ug/ml)f,  hydrocortisonef (74ng/ml), 5% fetal bovine serumg, and 1% antibiotich 15,3915,39. this protocol was chosen from amongst the treatments assessed in a previous study, to maximise tri-lineage differentiation, particularly chondrogenesis, and retention of cd90, cd44 and mhci surface markers, as well as minimize pro-inflammatory mediators 41. cells were expanded to provide multiple doses per cell line, and harvested for therapy at passage three. cells were then aliquoted as 5 x 10^6 cells per dose and cryopreserved in liquid nitrogen until use 40. intra-articular injections dogs assigned to either cell treatment group were given 0.05mg/kg hydromorphonea and either 0.125mg/kg diazepamc or 0.002-0.004 mg/kg dexmedetomidine hydrochlorided intravenously the day after surgery, prior to cell administration. all cell preparations were rinsed three times with sterile saline to remove medium or digestive agents from the preparation prior to administration. a preparation of either 5x10^6 svf nucleated cells or 5x10^6 allogeneic ascs constituted in 0.5ml of sterile saline was injected intra-articularly into the operated elbow 24-hours after surgery. this protocol was repeated once, six weeks post-operatively. for the six-week injection and all allogeneic asc injections, cells were thawed at room temperature prior to rinsing. subjective outcome measures owners completed a canine brief pain inventory (cbpi) questionnaire prior to group assignment, and six months post-operatively. the cbpi is a validated means of assessing owner opinion of outcome regarding pain and activity in dogs with clinical symptoms secondary to osteoarthritis 42,43. radiographs were made prior to admission to study to confirm disease diagnosis. dogs had radiographs made immediately post-operatively, at six weeks and at six months post-operatively. each follow-up radiograph was evaluated for healing at the site of puo. osteotomy sites were classified as healed (site was bridged with osteosynthesis with little to no evidence of osteotomy site), not healed with osteogenic activity present, or not healed with no osteogenic activity. objective outcome measures force platform gait analysis was used to evaluate patient ground reaction forces (grf), peak vertical force (pvf; the maximal force applied by the foot in weight bearing, perpendicular the platform) and vertical impulse (vi; a calculation of the force and time a limb is weight bearing) 44–46. each dog was assessed prior to surgical intervention, and six months post-operatively. data was collected by acquiring five valid trials for each forelimb at a walk on a force platformi measuring 0.5m2 in the center of a 10 meter runway. velocity and acceleration were measured with the aid of five photoelectric cells coupled with a triggered timing mechanism and mounted 1 meter apart. a velocity range between 1-1.3 m/s, and an acceleration range of -0.5 to 0.5 m/s2 was used to consider a trial valid. data was collected at 1000 hz, and stored on a personal computer with softwarej designed to record values velocity, acceleration, peak vertical force (pvf) and peak vertical impulse (vi). to be considered valid the entire foot had to make contact with the platform, without striking an edge, and the ipsilateral hind limb needed to follow with the same criteria. all dogs were weighed prior to data collection and trials were normalised to patient body weight. the severity of oa was measured using delayed gadolinium enhanced magnetic resonance imaging (mri) of cartilage (dgemric) scores as previously described, utilising the methods and protocols (mri sequences, coils, landmarks and post-processing techniques) published 30. dgemric was performed just prior to surgery and six months after surgery. after induction of anesthesia, each patient was administered gadopentetate dimegluminek (0.1 mmol/kg) intravenously followed by ten minutes of passive range of motion of the affected elbow. mri was performed as previously described, with a 3t systeml 30.  scout images were evaluated, and two sagittal slices that included the medial coronoid process were selected for t1weighted fse inversion recovery sequences, to allow further processing with a data software programm, to generate a color map for each of the two images (dgemric image) 30. each dgemric image was evaluated and a roi was drawn to include articular cartilage of the medial coronoid process, the corresponding articular cartilage of the humerus, and the intra-articular space in between 30. the roi was selected by the same individual for all cases and the individual was blinded to treatment group. each image was evaluated three different times, with a new roi identified for each assessment. the image intensity scores generated by the program from the roi were averaged for the three images creating a single, average dgemric score for each assessment period. successful outcome definition since the arithmetic mean is a less reliable description of group central tendency in studies with low power and in an effort to generate clinically applicable information, we chose to define criteria within each outcome measure that would classify the intervention as successful: improved owner survey, near normal limb, and no progression of oa.  for a case to have a successful outcome, a case had to meet all three criteria:  1) at the six month recheck there had to be a minimum of a ten percent improvement in cbpi survey scores for quality of life and lameness, 2) ground reaction forces (peak vertical force and vertical impulse) in the affected limb had to reach a minimum of eighty-five percent of normal forces measured in contralateral limbs at the six-month recheck 47, 3) and there could not be a decrease in dgemric score over the course of the study.  adverse events adverse events (ae) were defined as an observation in an enrolled animal that was unfavourable and unintended, and occurred after use of a cell treatment (svf or allogeneic asc) or surgical intervention at any time during the study period. any abnormal clinical sign noted when the dog was in the hospital or reported by the owner was documented as an ae. adverse events were classified as non-serious or serious and the relationship to the cell treatment was categorised as unknown, unlikely, possible, or probable. statistical analysis statistical analysis was performed using sofa statistics softwaren. cbpi scores are reported as means of pain or function scores and were assessed using a wilcoxon signed rank sum test. grf are reported as percentage of body weight (100*n/n) and values are expressed as means of the five collected trials at each assessment. dgemric scores are reported as the mean of the all roi generated for each outcome measure time point. summary statistics are all reported as mean +/standard deviation (sd). differences between groups at the initial assessment, and at the 6-month recheck for grf and dgemric scores were evaluated using a one-way anova test. differences between initial exam and 6-month recheck for grf and dgemric scores were evaluated using a paired t-test. differences in frequency of a successful outcome were tested using a fisher’s exact test. values of p ≤ 0.05 were considered statistically significant. results thirty dogs (n=10/group) met the inclusion criteria and completed the study. body weights ranged from 12.5 kg to 64 kg, (31.82kg+/-9.12). there was no significant difference between treatment groups with respect to body weight throughout the study. patient age ranged from 0.66 years to 10 years (2.47years+/-2.43). the allogeneic asc treated group was significantly older (4.43years +/-3.18, p=0.03) than any of the other treatment groups, while no difference in age existed between the remaining two groups. subjective outcome measures no significant difference was found between groups for pain and function scores on the cpbi scores at the initial or 6 month assessments. all groups improved pain and function scores at the 6 month assessment compared to the initial assessment (figures 1 and 2). there was a significant decrease between initial pain score and 6 month recheck pain score in the soc (5.17+/-7.21, p<0.01) and autologous (1.8+/-2.44, p<0.02), but not allogeneic (5.87+/-4.23, p=0.06). there was a significant improvement between initial and 6 month function scores in function scores in the soc (3.7+/-7.6019, p<0.01) and autologous (3.0+/-4.05518, p<0.01), but not allogeneic (7.0+/-8.56, p=0.06). dogs that had improvement in overall scores had an average improvement of 90.4% (range: 47.2-100%). all dogs had radiographic evidence of osteosynthesis at the puo at 6-week recheck. 28/30 dogs were considered healed at the 6 week assessment. of the two remaining dogs, one was considered healed at the 6-month recheck, and the final one was considered healed at a one-year recheck. subjectively, all dogs had some shifting of the proximal ulna relative to the distal ulna on recheck radiographs, as compared to the post-operative radiographs. figure 1: comparison of pain scores between initial and follow-up assessments. average score of canine brief pain inventory questionnaire for each treatment group’s pain score is indicated at initial assessment (black), and at 6-month follow-up assessment (grey). the xaxis is each treatment group, and the y-axis is the average score of owner assessment of patient pain calculated by answering four questions. (0= no pain, 10= extreme pain) the highest (worst pain) possible score would be forty. treatments consisted of standard of care (soc), autologous (auto) or allogeneic (allo) cell therapies. letters above columns are to distinguish statistical significance. columns labeled with the same letter indicate no statistical significance between scores. columns that do not share a common alphabetic letter are p<0.05 and are considered statistically different. figure 2: comparison of function scores between initial and follow-up assessments. average score of canine brief pain inventory questionnaire for each treatment group’s function score at initial assessment (black), and at 6-month follow-up assessment (grey). the xaxis is each treatment group, and the y-axis is the averaged score of owner assessment of patient function calculated by answering six questions. (0= no interference, 10= completely interferes) the highest (worst) possible score would be sixty. treatments consisted of standard of care (soc), autologous (auto) or allogeneic (allo) cell therapies. letters above columns are to distinguish statistical significance. columns labeled with the same letter indicate no statistical significance between scores. columns that do not share a common alphabetic letter are p<0.05 and are considered statistically different.  objective outcome measures there were no significant differences in ground reaction forces (grfs) between any of the groups at the initial assessment (pvf p>0.06; vi p>0.09 for all groups) and at the 6-month assessment (pvf p>0.26; vi p>0.37). (figures 3 and 4) all groups had increased grfs between initial and 6-month recheck. there was no significant change in vi in any of the groups (p>0.06), but a statistically significant improvement was found in pvf of the svf group (p=0.006 and p=0.002, respectively). figure 3: comparison of peak vertical force between initial and follow-up assessments. average peak vertical force, corrected for body weight, depicted on the yaxis, with each treatment group depicted on the x-axis. initial assessment (black) and 6-month assessment (grey) are depicted side by side for each treatment group. treatments consisted of standard of care (soc), autologous (auto) or allogeneic (allo) cell therapies. letters above columns are to distinguish statistical significance. columns labeled with the same letter indicate no statistical significance between scores. columns that do not share a common alphabetic letter are p<0.05 and are considered statistically different. figure 4: comparison of peak vertical impulse between initial and follow-up assessments. average peak vertical impulse, corrected for body weight, depicted on the yaxis, with each treatment group depicted on the x-axis. initial assessment (black) and 6-month assessment (grey) are depicted side by side for each treatment group. treatments consisted of standard of care (soc), autologous (auto) or allogeneic (allo) cell therapies. letters above columns are to distinguish statistical significance. columns labeled with the same letter indicate no statistical significance between scores. columns that do not share a common alphabetic letter are p<0.05 and are considered statistically different. there was no significant difference in dgemric scores amongst groups at initial assessment (soc 306.93+/-62.14, svf 337.43+/-39.19, allsc 358.7+/-27.56, p>0.05), or at the 6-month assessment (359.15+/-53.88, 329.37+/50.49, 365.5+/-60.83, p>0.05). a significant difference was identified between the initial score and the 6-month score in the soc group, with the average 6-month score being higher. (figure 5) figure 5: comparison of dgemric scores between initial and follow-up assessments. averaged delayed gadolinium enhanced magnetic resonance imaging (mri) of cartilage (dgemric) score for each group depicted on the y-axis. each treatment group is depicted on the x-axis at initial assessment (black) and 6 month recheck (grey) side by side. treatments consisted of standard of care (soc), autologous (auto) or allogeneic (allo) cell therapies. letters above columns are to distinguish statistical significance. columns labeled with the same letter indicate no statistical significance between scores. columns that do not share a common alphabetic letter are p<0.05 and are considered statistically different. defining success using our defined criteria, thirty percent of cases (3 of 10) treated with proximal ulnar osteotomy (puo) alone or autologous stromal vascular fraction (svf) had successful outcomes. seventy percent of cases (7 of 10) treated with allogeneic asc met criteria to be considered successful. this difference was not statistically significant (p=0.18). adverse events one dog in each treatment group (soc, puo + autologous asc and puo + allogeneic asc) had a seroma develop at the surgical site of the puo, reported or identified between 7-42 days after surgery. one dog (soc+ allogeneic asc) developed a swelling at the puo site and was mildly febrile (39.3°c) 4 days after surgery. it was treated presumptively as an infection with 12.4mg/kg clavamoxo and resolved without further intervention. one dog (soc+svf) reportedly slipped, developed a worsening in lameness and was found to have a fissure at the puo site 9 days after surgery. lameness resolved with restricted activity. one dog (soc) had redness and swelling at the surgical site 8 days post-operatively that resolved with 3.7mg/kg firocoxibp. one dog (soc+ allogeneic asc) was found to be painful on palpation of the puo surgical site at 42 days post-operatively, and was determined to have delayed healing of the osteotomy site. radiographic healing was determined to be present at the 6-month recheck. two dogs (soc+svf, soc+ allogeneic asc) were reported to have diarrhea. one of those dogs (soc + allogeneic asc) developed it two days prior to the 42 day recheck, while the other (soc+ svf) developed it within 24 hours of the second injection (39 days). the first resolved with 13mg/kg metronidazoleq, and the second was self limiting, resolving within 24 hours. no local swelling or erythematous reactions were reported by owners of dogs who received cellular therapy. all adverse events were considered non-serious. discussion to date, there are no published studies evaluating the use of allogeneic asc to treat fmcp or oa in dogs, in spite of the many advantages they may provide over svf. this pilot clinical study generates initial safety and efficacy data. to provide consistency in our assessments (and since the number of dogs/groups were small), we elected to investigate a single disease process, fragmented coronoid process (fmcp), which inevitably results in osteoarthritis of the canine elbow 26. while this disease model involved surgery, the safety of use for multiple allogeneic intra-articular injections can be applied to any oa patient. the mean age of the dogs enrolled in the study is anticipated, given the disease process 26–28. the allogeneic asc group average age was significantly older than the other groups, and in particular included the two oldest dogs enrolled, at 8 and 10 years at time of enrollment. these two cases likely skewed the mean age of this group relative to the other three groups. this may also have skewed the outcome of this group, as the duration of the disease process may increase the severity of oa and limit the ability of a patient to improve 26–28. identifying a correlation between severity of oa, body weight and age in regards to outcome would be useful information but was not assessed in this study due to the small numbers. severity of preexisting oa may be an unidentified bias that influences response to therapy. all dogs had improved cbpi scores from initial assessment to six-month rechecks, which could be explained by true or perceived improvement. although owners could not choose group assignment, they were not blinded to the group they were assigned to, as it was apparent which groups had an abdominal incision. we did not feel it was ethically appropriate to perform surgical incisions in all dogs for the sole purpose of blinding the owners. likewise, dogs receiving an asc injection were sedated at the second injection, whereas the soc was not, making it apparent to owners which group they had been assigned to. this is important to note, as the care-giver placebo effect can be quite potent 29. the soc + allogeneic asc group had improvement of function based on scores, but pain scores at the 6-month recheck were higher compared to the soc and soc + svf group. this group started at a higher pain score compared to the other two groups, and comparatively had a similar degree of improvement. finally, owners were informed that allogeneic asc treatment was experimental in nature, so this may have influenced owner responses. radiographs were assessed in each group six weeks after surgery to ensure progression to healing. the only noted radiographic problems with puo were delayed healing in the oldest dog, and fissure following a traumatic incident. however, radiographic union did not appear to dramatically influence limb function as this dog achieved the clinical success guidelines at the 6-month time point. mean pvf and vi improved after intervention regardless of treatment group assignment.  dogs in the soc + svf group had the only statistically significantly difference in grfs. the grfs of these groups were lower at initial assessment, which may have allowed for a greater degree of improvement, and thus statistical significance. it cannot be ruled out that initial grfs are predictive of outcome regardless of therapy. progression of oa is difficult to assess in a clinical study. use of validated mri techniques (e.g. dgemric, t2-mapping) helps resolve this problem by providing an objective estimation of cartilage health 30. dgemric provides a measurement of glycosaminoglycan content and t2-mapping provides a measurement of water content in the region of interest (roi); in this study we used dgemric. since it has been reported that osteophytosis progresses even after surgical treatment of a fmcp, one would expect a decreased dgemric score over time 2–5. mean dgemric score decreased over time only in the soc+svf group. this change was not statistically significant and is not likely clinically relevant since it has been reported that, for the canine elbow, a change in dgemric needs to approach 30 ms before being considered a real change (wucherer, 2012). possible explanations for no change in dgemric over time include that a follow-up time of 6-months was too short and oa would have progressed if follow-up time were longer, or that glycosaminoglycan content in the medial compartment does not decrease short-term following the interventions studied even though subjective scoring of radiographic osteophytosis progresses. dogs in the soc group did have an increased dgemric score. this could be explained by the changed pathomechanics in the elbow following the puo 31 32. the dgemric procedure had good interand intra-observational consistency when evaluated in normal dog elbows. 30 while it has not been applied to abnormal dog elbows in a clinical situation prior to this study, it has been used to follow the progression of oa in people 33. since dogs with dysplastic elbows can have distorted anatomy (e.g. blunted coronoid processes, displaced coronoid) and that anatomy changes following coronoidectomy, it is possible that there is increased variability in the outcome measure in clinical patients because of inconsistent slice selection. however, throughout this study we noticed that the medial coronoid process was not particularly wide; and there were few choices where two slices (3-mm apart) could actually be selected during the mri scan. likewise, even if slice selection is consistent, coronoidectomy changes the anatomy that is evaluated and arguably increases average glycosaminoglycan in the roi. for example, the region of the fmcp likely has the greatest amount of diseased cartilage. after this diseased region is removed the remaining components of the medial compartment would have a higher average glycosaminoglycan content. if these factors are valid, one could argue that dgemric shortly after surgery should have been compared to the 6-month follow-up; that comparison may provide for a more accurate assessment of the response of the cartilage to the intervention over time.  standard of care therapy used in this study has conflicting reports regarding the efficacy it may provide 27,34–36.  we may have found greater improvement between groups if a group that received no surgical intervention was included. however, since the objective of this study was to investigate any additional risks or benefits of adding biologic therapy to soc we felt it more important to have soc consistent across groups.  all adverse events, save one report of diarrhea (soc +svf), were considered unrelated to cellular therapy. the episode of diarrhea cannot be clearly attributed to the svf injection versus the sedation drugs necessary to give the injection. there were no reactions to injections that would suggest a severe immune response. this provides no indication that even repeat intra-articular treatment with allogeneic ascs add risk to the patient. certainly, a systemically administered preparation (i.e. intravenous) could result in a different outcome. one major limitation of this study is the small numbers of dogs in each group. in this pilot project, statistical differences, or lack thereof, need to be cautiously interpreted because 1) they are subject to type i (incorrect rejection of null hypothesis) and type ii (incorrectly retaining null hypothesis)  error and, 2) they are conflicting. for example, the soc had the greatest improvement in dgemric score, the soc+svf had the greatest improvement in grfs, and the soc+allogeneic ascs had the most dogs with a successful outcome. as expected in a study with only ten dogs/group it is difficult to draw a strong conclusion regarding a treatment by group effect. however, fmcp is a complicated disease and not fully understood 26,27,37,38. we were able to identify study biases that will allow for improved study designs in the future. in this study population the greatest improvement in limb function came from the dogs with the greatest lameness. this is not surprising since they have the most room for improvement. the opposite may be true for the severity of oa; dogs with severe oa at the onset may be limited in how much they can improve. future studies should consider stratifying groups according to initial outcome measures to alleviate some of the bias that appeared within our groups. finally, it is possible that the frequency of assessments and duration of follow-up should be different than the 6-months used in this study. it may be argued that the therapeutic benefit of ascs could be shorter (needing more frequent observations) or much farther-reaching (needing longer duration of follow-up).  we identified no major contra-indications to repeat intra-articular injections of autologous or allogeneic asc therapy, and provided some evidence that there may be a therapeutic benefit. thus, we failed to reject our hypothesis that all treatments are well tolerated and safe for use. this study provides preliminary safety data for the use of allogeneic asc therapy, and justification for larger clinical studies with greater numbers of dogs, stratification of participants based on initial limb function and dgemric scores, and more observation periods and longer follow-up. it further adds objective outcome measures demonstrating some improvement in clinical signs for patients receiving autologous svf. it also demonstrates the possibility of using dgemric in naturally occurring osteoarthritis in dogs to assess oa progression. footnotes a west-ward, eatontown, nj, usab amneal pharmeceutical, ny, usa c orion corporation, ny, ny, usa d hospira, il, usa e gibco, life technologies, grand island, new york, usa f  sigma-aldrich, st. louis, mo, usa g hyclone, thermo fischer scientific, minneapolis, mn, usa h mediatech inc, corning, ny, usa i amti or 6-5 force platform, advanced mechanical technology, watertown, mass, usa j sharon software inc, dewitt, mi, usa k  bayer health care pharmaceuticals inc, nj, usa l ge sigma excite milwaukee, wi, usa m matlab, mathworks, natick, mass., usa n sofa, v1.3.4, patonsimpson & associates ltd, auckland, new zealand o zoetis, florham park, nj, usa p merial, duluth, ga, usa q heritage pharmaceuticals, 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(2014) the influence of culture medium type on cellular phenotype of canine adipose derived stem cells. open journal of regenerative medicine, 3 (1), pp. 28-37. http://dx.doi.org/10.4236/ojrm.2014.31004 brown, d.c. and farrar, j.t. (2010) development and psychometric testing of an instrument designed to measure chronic pain in dogs with osteoarthritis dorothy. journal of the american veterinary medicalassociation, 68 (6), pp. 631-637. brown, d.c. et al. (2007) development and psychometric testing of an instrument designed to measure chronic pain in dogs with osteoarthritis. american journal of veterinary research, 68 (6), pp. 631-637. horstman, c.l. et al. (2004) assessing the efficacy of perioperative oral carprofen after cranial cruciate surgery using noninvasive, objective pressure platform gait analysis. veterinary surgery, 33 (3), pp. 286-292. http://dx.doi.org/10.1111/j.1532-950x.2004.04042.x feldsien, j.d. et al. (2010) serum cortisol concentration and force plate analysis in the assessment of pain associated with sodium urate–induced acute synovitis in dogs. american journal of veterinary research. 71(8). moreau, m. et al. (2010) influence of changes in body weight on peak vertical force in osteoarthritic dogs: a possible bias in study outcome. veterinary surgery, 39 (1), pp. 43-47. http://dx.doi.org/10.1111/j.1532-950x.2009.00621.x rumph, p.f. et al. (1999) interday variation in vertical ground reaction force in clinically normal greyhounds at the trot. american journal of veterinary research, 60 (6), pp. 679-683. supplementary files, images & tables all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. literature searching for evidence-based veterinary medicine: coping with zero hits emma place1* 1subject librarian | university of bristol, school of veterinary sciences, university walk, bristol, bs8 1td *corresponding author (emma.place@bristol.ac.uk) vol 1, issue 4 (2016) published: 2 dec 2017 doi: 10.18849/ve.v1i4.77 emma place gives a talk on how it can be common to get zero or low numbers of hits for a veterinary pico search in bibliographic databases, particularly if results are screened for clinical trials... this is a podcast of emma place's talk at the veterinary evidence today conference, edinburgh november 3, 2016. find out more about emma. view presentation slides comments: preliminary evaluation of a practice-based ebvm skills development program ava firth bs dvm mvs manzcvs dacvecc mrcvs1 ian robertson bvsc, phd, macvsc2* 1vets now support office, penguin house, castle riggs, dunfermline, fife, ky11 8sg 2box hill, victoria 3128, australia *corresponding author (dr.i.j.robertson@gmail.com) vol 1, issue 4 (2016) published: 16 dec 2016 doi: 10.18849/ve.v1i4.81 whilst there is a small body of research that investigates the development of ebvm skills in veterinary undergraduates there is a paucity of research that aims to understand the development of ebvm skills in practice-based post-graduate veterinary surgeons. this talk on a paper is a small step in remedying that shortfall. in particular, the paper provides a progress report on an rcvs knowledge funded study that is evaluating a practice-based ebvm development program. this is a podcast of ava and ian's talk at the veterinary evidence today conference, edinburgh november 2, 2016. find out more about ava. view presentation slides comments: are novel allergen or hydrolysed diets an effective means of reducing the gastro-intestinal signs in dogs with inflammatory bowel disease when compared to oral prednisolone? a knowledge summary by adam swallow bvsc, afhea, mrcvs1* 1university of cambridge, the old schools, trinity ln, cambridge, cb2 1tn *corresponding author (adamswallow26@gmail.com) vol 2, issue 1 (2017) published: 20 mar 2017 reviewed by: constance white (dvm, phd) and nicola ackerman (bsc(hons) rvn certsan certecc vts(nutrition) a1 v1 c-sqp hons) next review date: 20 mar 2019 doi: 10.18849/ve.v2i1.56 clinical bottom line novel allergen or hydrolysed diets are a valid modality for the management of gastro-intestinal symptoms in dogs with chronic enteropathy, however bias in case selection in the literature means a direct comparison of dietary modification versus prednisolone was not able to be achieved. further prospective trials would be needed to better answer this pico. question in (dogs with chronic enteropathy) is the (use of either a novel allergen or a hydrolysed diet) as effective as the (use of prednisolone) in (controlling the gastro-intestinal signs)? clinical scenario you have just obtained some histopathology results regarding eric, a 4 year-old male neutered staffordshire bull terrier. he has a 4 month history of intermittent, bilious vomiting twice a day and small intestinal diarrhea approximately once every 2-3 days although his stool always seems a bit soft. however, he remains bright and well in himself. he is a healthy weight, and in good body condition score (bcs 5/9). after a course of fenbendazole failed to improve the situation you performed routine haematology, biochemistry and urinalysis (which were unremarkable, including serum tli, folate and cobalamin) in addition to abdominal ultrasonographic examination. you then elected to proceed to gastroduodenoscopy with mucosal biopsy. the biopsies documented the presence of a mild lymphoplasmacytic enteritis, confirming your suspicions of a chronic enteropathy. normally, you would lean towards prescribing prednisolone at this time however eric’s owner is not keen on him having steroids unless absolutely necessary, having read about their side effects on the internet. the practice’s new graduate recently said something about using hypoallergenic diets for cases like these and you are interested to know if this would be a suitable option for eric instead of prednisolone. summary of the evidence ibd: inflammatory bowel disease cibdai:canine inflammatory bowel disease activity index. score 0-3= clinically insignificant disease. 4-5= mild ibd. 6-8= moderate ibd. >9= severe ibd. ccecai= canine chronic enteropathy clinical activity index. score 0-3= clinically insignificant disease. 4-5= mild ibd. 6-8= moderate ibd. 9-11= severe ibd. >12= very severe ibd. allenspach (2007) population: dogs with signs of chronic enteropathy (vomiting or diarrhea 6+ weeks). sample size: 70 dogs (n=70). intervention details: follow up information was available for 3 years (monthly updates) with repeat examinations should symptoms worsen. all dogs had other causes of their symptoms eliminated and histological evidence of inflammatory intestinal infiltrates was documented. no dog received antibiotics or corticosteroids or antacids for 2 weeks prior to entering the trial. prior to referral, dogs received fenbendazole (50mg/kg sid 5 days) all dogs received haematology, biochemistry (inc. tli, folate and cobalamin), urinalysis, faecal analysis (smear, culture, zinc flotation), crp measurement and abdominal ultrasound. all dogs given a cibdai score. an endoscopy score was given to each dog for the duodenum and colon (0 being normal3 severe changes to mucosa/ difficulty insufflating).  5 biopsy specimens were examined and graded with mild (infiltrative cells but normal architecture) to severe (infiltrates with extensive architectural distortion and epithelial immaturity/areas of epithelial necrosis). dogs given elimination diet for 10 days; improvement = assigned “food responsive”. no improvement means assigned to “steroid-treatment group”.2mg/kg/d po for 210 days, tapered over 10 weeks.  dogs in food responsive group re-evaluated after 4 weeks with repeat cibdai score and endoscopy/ histopathology scores assigned.  the steroid responsive group was re-evaluated in the same way after 10 weeks. steroids had been stopped 2 weeks prior to this.  all dogs received elimination diet exclusively for 14 weeks.  dogs not responding to prednisolone underwent a second 10 week course. these dogs received ciclosporine 5mg/kg po for 10 weeks before repeat endoscopy.  study design: prospective clinical trial. outcome studied: to establish predictors of a negative outcome (euthanasia due to refractory symptoms).  main findings (relevant to pico question): 39 dogs were in the food responsive group.  21 dogs required prednisolone in addition to the elimination diet.  10 dogs classified as having protein-losing enteropathy (ple) as they had panhypoproteinaemia with severe hypoalbuminaemia (mean albumin 11.3g/l sd 3.19 range 10-18g/l ref 24-35g/l and ascites +/pleural effusion/peripheral oedema).  variety of breeds represented. no statistically significant difference in the sex distribution between groups. 34 females overall (22 spayed) and 36 males (15 neutered).  mean age 5.3yrs (range 6m13yrs). mean age of food responsive group 3.5yrs (range 0.6-7.6) which was significantly less than the steroid responsive group; mean age 6.52yrs, range 2.113yrs. only 1 dog died in the food responsive group in a 3 year follow up period.  on a provocation diet, 31/39 dogs did not re-develop clinical signs and remained symptom free. in the other 8 dogs signs did recur so food intolerence was suspected. 10 dogs in st group responded to the initial therapy and did not relapse for 3 years. a further 3 patients in the steroid group were euthanased after the steroid trial and the remaining 8 dogs received ciclosporine, which saved 2 dogs from euthanasia. dogs with large intestinal signs were more likely to be food responsive.  the cibdai was significantly lower in the food responsive group than in the steroid-responsive group. dogs in the food responsive group improved significantly more than the steroid responsive group. cibdai was median score 6.3, range 2-12 initially, which decreased to 1.2, range 0-7 afterwards. in the steroid group the median starting score was 8.3, range 2-15 versus 5.5, range 0-16 after intervention. limitations: only 10 days allowed for dogs to be food responsive (this can take 4 weeks). the data collected here was part of a larger trial with the university of bern.  small intestinal bacterial overgrowth was not excluded first.  the diet used was salmon and rice, not a hydrolysed diet and so it is possible that some dogs who did not respond favourably to this diet may have responded better to a hydrolysed protein diet. the overall severity of disease in a patient may have affected their likelihood of responding to dietary manipulation. craven (2004) population: dogs with idiopathic inflammatory bowel disease (histologically confirmed) between 1995 and 2002. sample size: 80 dogs (n=80). intervention details: case records were reviewed and owners contacted by telephone to complete a questionnaire over the phone.  referring vets were also contacted for additional information if required.  dogs were classed as being in either remission (complete control of signs for 6m+), intermittent signs (every 14 days or more) or uncontrolled disease (signs seen more frequently than every 14 days).  owner gave an assessment of quality of life. animals excluded if gastric mucosa inflammation present alone in presence of helicobacter. study design: retrospective observational study. outcome studied: control of clinical signs. main findings (relevant to pico question): median age 4.3yrs (range 6m-14yrs). 49 male dogs (11 neutered) and 31 female (23 neutered).  median duration of clinical signs prior to diagnosis was 9.5 months (range 0.5-78) intestinal biopsies were diagnostic in 70/77 dogs. 2 dogs found to have infiltration in the sub-mucosa.  prednisolone was the most commonly prescribed medication. 45/74 dogs receiving medication had this (61%).  13/20 dogs with upper intestinal disease received immunosuppressive therapy. 17/32 dogs with lower intestinal disease received immunosuppressive treatment as did 17/22 dogs with diffuse disease. there was no significant difference between treatment and outcome in these groups.  38 dogs received prescription diets. this was continued in 30 dogs and diet was not known for the remaining 6 dogs. diet type was not associated with outcome.  quality of life was available for 53/74 dogs at follow up. no dogs decreased in quality of life after treatment and quality of life was significantly associated with the outcome of treatment. 21/80 dogs were in remission at follow-up. of these, 19 were on no treatment and 2 received pulse therapy. median duration of remission was 14 months (range 6-55).  50% of dogs had “intermittent” signs for a median 17 months (range 7-64) and 26 dogs received treatment. 8 dogs received pulse therapy and 18 dogs received continuous treatment. median relapse frequency was 3 months, range 14 days-5 months.  3 dogs afterwards had uncontrolled ibd, of median duration 19 months (range 10-25 months).  10 dogs were euthanised due to refractory ibd. 6 dogs died due to unrelated reasons.  the duration of clinical signs was not correlated with outcome. there was no association between the outcome and the site, type or severity of disease, although hypoalbuminaemia was associated with a negative outcome more strongly. limitations: retrospective study has inherent limitations associated with it, including a higher risk of bias. dogs not re-examined, merely owner responses to telephone questionnaire.  no direct comparison between the use of prednisolone and a hydrolysed diet is possible. the authors merely state that a “prescription” diet was used. the exact details of the diet used are not known. kawano (2016) population: dogs diagnosed with chronic enteropathy (diagnosed by endoscopic biopsy), that did not respond to 2 weeks of antibiotics (metronidazole, ampicillin or fluoroquinolone) and did not receive any immunosuppressive agents in the 2 weeks prior to enrollment. endoparasites were ruled out by faecal smear and zinc sulphate flotation. sample size: n=32 intervention details: all dogs received the elimination diet for at least 10 days. the diet was selected based on the lymphocyte proliferation test (lpt). if a food resulted in a lymphocyte proliferation index >1.2% then the allergen was excluded in the diet trial.  a positive response to a diet trial (gastro-intestinal symptoms improved) meant they were classified as “food responsive” if the dog failed to improve on the elimination diet, then glucocorticoids were prescribed (prednisolone 0.5-2mg/kg/day). improvements meant they were classified as “steroid responsive”. serum albumin was measured in all cases, <20g/l defined hypoalbuminaemia.  study design: prospective clinical trial. outcome studied: improvement in the gastro-intestinal symptoms. main findings (relevant to pico question): average age of patients: 5.33 years (range 4 months-13 years) 31/32 cases displayed a positive lpt to 2+ allergens. 1 dog showed 0 response to lpt. after the elimination diet, 18/32 dogs were classified as food-responsive. the remaining 14 were steroid responsive. successful diets used included anallergenic (n=8), select protein (royal canin d&t; n=1), z/d ultra allergen-free (n=2) and w/d (n=1: hills), home-made diets (n=2) and d assist ko select protein (n=1: eukanuba).  histopathology documented 25 dogs suffered from lymphocytic-plasmacytic enteritis (13 dogs were in the steroid group, other 12 were food responsive), 3 dogs had eosinophilic enteritis and 4 dogs had “minimal change”. dogs who were steroid responsive had a higher ccecai score than dogs who were food responsive. 8.6 (mean; sd 3.3) versus mean 6.4 (sd 2.8) for food responsive. overall mean was 7.4; range 1-13. this difference was not statistically significant.  10 dogs had hypoalbuminaemia. 8 of these were steroid responsive and 2 food responsive. animals with minimal change are advised to undergo dietary management first.  limitations: no dietary provocation tests performed.  not all animals received a hydrolysed diet; some only received restricted antigen diet.  the lpt is not a definitive test and the presence of positive response to food allergens on immunology testing in dogs with suspected intolerances is controversial. it is often recommended to allow 4 weeks to see an effect from dietary trials; some dogs were only provided with the diet for 10 days. not all dogs will have been through the same protocols so standardisation is an issue with this study. this may have introduced a selection bias that favored dogs with milder disease. not a large amount of patients, and there was no long term follow-up.   mandigers (2010) population: dogs with chronic enteropathy. sample size: 26 dogs (n=26) intervention details: dogs were assigned to receive either a hydrolysed diet (18 dogs) or a highly digestible diet (8 dogs) after diagnosis of a chronic enteropathy (histologically confirmed).  dogs were re-evaluated 3 times: at 3, 6-12 and 36 months.  outcome measures included response of clinical signs (complete, partial or none), change in severity of signs (cibdai), change in body weight and need for further therapy.  only dogs with signs of small intestinal disease were enrolled. dogs were excluded if they had received corticosteroids in the preceding 3 weeks or if hypoproteinaemia was preset.  dogs not responding at the time of first follow up then other treatments added as needed. if a dog had responded then the dog was challenged with the previous diet for 7 days to see if it was an adverse food reaction.  at second follow up, repeat endoscopy was performed if the owner consented and other therapies offered if they had relapsed. other therapies were also available if relapse occurred at the final re-evaluation. complete response: all signs resolved/returned to normal for the animal. partial response meant signs were at least 50% improved, but not entirely normal.  study design: randomised, controlled clinical trial (non-blinded). outcome studied: to determine if a hydrolysed diet was superior in managing the symptoms of chronic enteropathy compared to a highly digestible diet. main findings (relevant to pico question): despite randomisation, the cibdai was higher in the test diet group.  most dogs responded at first evaluation, with no significant difference between groups. however, significantly more dogs remained asymptomatic at the 2nd and 3rd re-evaluation, with a significantly greater decrease in cibdai. there was no significant difference between groups in terms of duration of clinical signs or patient age/sex/breed/body weight.   at first re-evaluation 16/18 dogs had responded to a test diet. 12 complete, 4 partial. 7/8 dogs responded to a control diet; 6 fully 1 partially. cibdai decreased significantly in both groups, but the test diet group decreased significantly more. bodyweight increased significantly in the test diet group (median increase 4%; range 3-22%) with 13 dogs increasing, 1 dog decreasing and 4 dogs being stable. the control group bodyweight did not change significantly. (median 0%, range -9-17%. 4 dogs increased, 2 dogs decreased and 2 dogs were stable. body weight not significantly different between groups though.  4 of 6 dogs in the test diet group relapsed on dietary challenge and 4 of 6 of dogs on the control diet relapsed on challenge.  22/23 dogs came for 2nd evaluation (other dog died of unrelated causes).  13 dogs on test diet remained asymptomatic, other 2 dogs were partial responders. 2 of 7 control dogs remained asymptomatic, with a higher cibdai for this group. dogs in control diet group were offered alternative therapies. at the final follow up, 20/23 dogs were still on the trial. 14 were in the test group, 6 from the control group. 1 test group dog experienced occassional symptoms and 2 did so after dietary indiscretion. only 1 dog in the control group was still in remission. other dogs were given alternative therapy.  limitations: results were based on subjective interpretation of clinical signs; repeatability of results may be difficult to achieve. there was no group receiving prednisolone therapy in this trial so cannot compare the 2 modalities of treatment.  selection bias is present in that patients with potentially more severe disease were excluded from the trial. there is a potential conflict of interest with the authors many dogs had eosinophilic infiltrates on histopathology, which is different to the findings outlined in the pico. marks (2002) population: dogs with confirmed inflammatory bowel disease. all dogs had chronic vomiting and diarrhea of more than 3 months duration. sample size: 6 dogs (n=6) intervention details: dogs were fed purina ha hypoallergenic diet; enzymatically hydrolysed and defatted soy globulin diet. prior to starting the diet trial all dogs had a faecal flotation test that was negative for parasites, physical examination and endoscopic examination ruling out other gastro-intestinal pathology and histologically confirmed inflammation of the stomach or duodenum. owners completed a questionnaire every 2 weeks for 10 weeks and repeat endoscopic examination was performed at the end of 10 weeks. dogs were recruited over a 6 month period. all dogs were fed twice a day with the test diet according to their calculated energy requirement (132 x bwkg75) owners assessed faecal consistency daily, with an average figure collected every 2 weeks. “moderate improvement” represented a 50% improvement in faecal consistency or a 50% reduction in the frequency of vomiting. “complete resolution” was also an option. biopsies were examined in a blinded and randomised fashion by a single pathologist and a semi-quantitative score was assigned to the samples (0-3 as previously described). study design: non-randomised clinical trial. outcome studied: whether or not dogs improved after a hydrolysed diet and whether or not there was a histological improvement in the degree of mucosal inflammation. main findings (relevant to pico question): mean age was 3.3 years, range 1.59 years. duration of vomiting and diarrhea was a mean of 9months, range 318 months. 5 dogs had previously failed to respond to a variety of other medical therapies (excluding corticosteroids) including novel protein diets. faecal scores improved from a mean of 91.7 to 42.5 after dietary therapy. 4 dogs achieved an “adequate” level of clinical benefit in terms of faecal consistency and 2 of these 4 achieved complete resolution of the diarrhea within 3 days. the other 2 dogs experienced a marked improvement over 12 days. for one dog, a complete improvement was not made despite an improvement in faecal consistency and intermittent bouts of diarrhea persisted. 2 dogs required additional medical therapy, although 1 dog was subsequently diagnosed with inflammatory bowel disease with concurrent exocrine pancreatic insufficiency. another dog displayed a moderate improvement in the symptoms, which completely resolved after the addition of metoclopramide. limitations: there was no control diet used and no group receiving prednisolone to allow for direct comparison between the 2 treatment modalities. there was no long term follow-up information available. there was no mention of a trial of anti-parasitic medicine to definitively eliminate endoparasites. only 1 hydrolysed diet was used; sometimes multiple hypoallergenic diets are required so there is a chance that the non-responders may have responded to an alternative diet. only a small study population was used. appraisal, application and reflection the evidence available generally consisted of prospective clinical trials. these generally followed a similar set of inclusion criteria and diagnostic protocol, which allows for greater consistency in the results between papers. however no papers directly compared the use of a hydrolysed diet to the use of prednisolone; prednisolone was often used after dietary manipulation had failed and so it has not been possible to directly compare the 2 treatment modalities. there is a definite paucity in studies looking at long term follow up in dogs after a successful response to a hypoallergenic diet in the short term  and so this would be interesting to consider for the future. selection bias was probably the most significant issue with the studies appraised above. the inclusion criteria many authors used played a big role in determining which intervention an animal received and the method used meant that only animals who were seemingly more affected progressed onto prednisolone therapy. this is less ideal from an efficacy perspective as it would be ideal to know which intervention yielded a greater response when directly compared. this would also be worthy of consideration for the future. methodology section search strategy databases searched and dates covered: pubmed (1900 – 2017); cab abstracts (1983 – 2016) search terms: (dog or dogs or canine) (prednisolone or diet or food or hydrolysed or hydrolyzed or hypoallergenic) (inflammatory bowel disease or ibd or chronic enteropathy or food responsive enteropathy) dates searches performed: 30th august 2016 exclusion / inclusion criteria exclusion: articles that were not relevant to the pico, articles not available in the english language and articles where the full text was not available. review articles and case reports were also excluded. inclusion: original prospective or retrospective studies relevant to the pico where the full text was available to examine. search outcome database number of results excluded – not available in the english language excluded – case reports excluded – review article excluded – not relevant to the pico total relevant papers ncbi pubmed 140 2 4 15 114 5 cab direct 26 0 0 1 25 0 total relevant papers when duplicates removed 5 conflict of interest the author declares no conflicts of interest. references allenspach, k. wieland, b. grone, a. (2007) chronic enteropathies in dogs: evaluation of risk factors for negative outcome. journal of veterinary internal medicine, 21 (4), pp. 700-8. doi: http://dx.doi.org/10.1111/j.1939-1676.2007.tb03011.x craven, m. et al. (2004) canine inflammatory bowel disease: retrospective analysis of diagnosis and outcome in 80 cases (19952002). journal of small animal practice, 45 (7), pp. 336-42. doi: http://dx.doi.org/10.1111/j.1748-5827.2004.tb00245.x kawano, k. et al. (2016) prevalence of food-responsive enteropathy among dogs with chronic enteropathy in japan. journal of veterinary medical science, 78 (8), pp. 1377-1380. doi: http://dx.doi.org/10.1292/jvms.15-0457 mandigers, p.j. et al. (2010) a randomized, open-label, positively-controlled field trial of a hydrolyzed protein diet in dogs with chronic small bowel enteropathy. journal of veterinary internal medicine, 24 (6), pp. 1350-7. doi: http://dx.doi.org/10.1111/j.1939-1676.2010.0632.x marks, s.l. laflamme, d.p. mcalose, d. (2002) dietary trial using a commercial hypoallegenic diet containing hydrolyzed protein for dogs with inflammatory bowel disease. veterinary therapeutics, 3 (2), pp. 109-18. intellectual property rights knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. quality improvement: origins, purpose and the future for veterinary practice freya rooke bsc (hons) mres1* john burford ma vetmb phd certva certes(soft tissue) sfhea frcvs1 sarah freeman bvetmed phd certva certvr certes dipecvs fhea frcvs1 tim mair bvsc phd deim dests dipeceim assocecvdi frcvs2 jo suthers bvm&s mphil certes(soft tissue) dipecvs mrcvs3 marnie brennan bsc(vb) bvms phd pgche dipecvph(pm) fhea mrcvs1 1school of veterinary medicine and science, university of nottingham, college road, sutton bonington, loughborough, leicestershire, le12 5rd 2cvs ltd, bell equine veterinary clinic, mereworth, maidstone, kent, me18 5gs 3cvs ltd, b&w equine hospital, breadstone, berkeley, gloucestershire, gl13 9hg *corresponding author (freya.rooke@nottingham.ac.uk) vol 6, issue 2 (2021) published: 06 may 2021 reviewed by: peter cockcroft (ma vetmb msc dchp dvm&s dipecbhm mba mrcvs), catherine oxtoby (bvsc phd) and adam swallow (bvsc mrcvs) doi: 10.18849/ve.v6i2.358 section index:    introduction | what is quality care? | what is quality improvement and how has it been used? | qi within uk healthcare | barriers to qi implementation | which way forwards for qi in veterinary practice? | footnotes | conflict of interest | references introduction providing the highest quality veterinary care can often be a delicate balancing act: the client/owner’s wishes, financial parameters and emotional needs have to be considered, whilst also meeting the animal’s clinical needs. but what actually defines quality care? it is a term frequently used in both the human and veterinary healthcare literature, but often has little explanation or definition attached to it. ‘quality’ in relation to care delivered is not a static concept and will hold different meanings to different individuals within a healthcare service. john ruskin, a victorian writer and critic of art and society observed: ‘quality is never an accident; it is always the result of high intention, sincere effort, intelligent direction and skillful execution’ (1,2).   what is quality care? it is easiest to describe quality care within the context of human medicine, as it is in this sector where the majority of the literature is based. the institute of medicine (iom), a non-profit organisation that provides evidence-based research and recommendations for public health and science policy, currently defines quality care as, ‘the degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge’ (3). this definition, however, places quality care in a very one-dimensional space, with a heavy focus on the clinical outcomes of care which results in a limited explanation of quality care. categorising in this way solely on positive versus negative outcomes means that the iom definition falls short in describing a holistic all-encompassing quality care experience. the royal college of physicians (rcp), a british professional body dedicated to improving the practice of medicine chiefly through advocacy, education and research, takes a broader approach to defining and measuring quality care. the rcp describes quality care as involving five factors, ‘creating a delicate balance between health and wellbeing of the population, sustainable finance, environment and resources alongside providing the best possible care for the individual’ (4,5). this description is also more representative of the multidimensional nature of providing care as well as recognising the pressures exerted on the industry in the 21st century. there is an ongoing shift in the ideology of human healthcare providers, particularly within the national healthcare service (nhs), looking to create a model of care more akin to a business model (6,7). bowers (6) and singh (7) discussed the perception of quality and user-experience by the patients and clients, this experience presented itself as the key focus and core of the nhs strategy instead of the service providers. this was more akin to business models that measure the impact of company structure and service on customer ‘delight’ and behavioural intentions. in short this can be summarised as how the experience of the customer had impacted their future behaviour and likelihood to return as a customer (8). in order to develop strategies to achieve this goal within the nhs it is necessary to understand the cause, variations, definitions and drivers of quality care; it is not possible to effectively measure quality of care without defining what formulates a quality care experience (9,10). the transformation in attitude within the human healthcare sector is supported by changes in policy which encourages the widespread adoption of quality measuring and improvement methods. patient surveys have also been used to benchmark performance by measuring satisfaction with the care provided (7). defining quality care within veterinary services is complicated by the fact that the receiver of care, the animal, is not able to articulate their experience. instead it is a third party, often the owner, who employs the service and may pay the bill without personally receiving clinical care. reported client satisfaction or analysis of complaints made against practices and practitioners is the common focus when defining quality care within organisations (11–13). although this method does give some insight into the success and any potential problems with care being delivered, it will not provide a truly representative description on the quality of care delivered by a particular practice or practitioner. a much broader approach to quality monitoring and effective utilisation of a variety of quality improvement (qi) methods is required (13).   what is quality improvement and how has it been used? quality improvement methods comprise a series of generally iterative tests that are used to measure the quality of a current practice and to provide focus on any issues arising, as well as highlighting excellent practice to benchmark for others. these methods are successfully utilised in many different industries including aviation, education, manufacturing and healthcare (14–17). quality improvement in its most basic form hypothesises that the quality of goods and services is ultimately determined by the processes of design and delivery. due to this ethos, the key focus of any qi method is understanding, managing and improving work processes rather than correcting individual’s mistakes after the event (18,19). when the description of quality care is constructed in this manner the balance and association held between providing the best possible care for the individual and the five factors named by the rcp, namely the health and wellbeing of the population, sustainable finance, environment and resources can be identified. these can then be measured serially using a variety of methods in an approach collectively termed qi. there are multiple definitions of qi, and like quality care, it is not a static concept (20). within the manufacturing industry where the qi methodology was originally developed, there exists many terms used to describe the process of improving the quality of a product or service, for example, continuous quality improvement (cqi), quality management (qm) and total quality control (tqc) (21). despite the different names used, all of these methods follow the same basic principles: using a scientific, methodical and regulated series of actions to continually improve a work process, the end goal being to offer an improved standard of goods or services for the customer (22,23). the introduction of qi methods into the healthcare setting can be linked to a need to gather data and measure the quality of care being delivered to patients. within the medical healthcare sector, it was hoped that comparing performance amongst care providers and organisations would consequently encourage better performance and result in higher quality care for all patients (10). the healthcare quality improvement partnership (hqip) is an independent organisation led by the academy of medical royal colleges, the royal college of nursing, and national voices, an organisation which represents doctors, nurses and patients within the nhs. established in april 2008, its goal is to promote quality in the medical profession and increase the impact that qi has on healthcare (24). the hqip qi handbook identifies twelve key qi methods (table 1) best suited to utilisation within the healthcare setting.   table 1. list of the different qi methods recommended by the hqip in human healthcare (25). qi method used to clinical audit check that clinical care delivered meets quality standards plan do study act cycle (pdsa) introduce and test potential qi on a small scale and assess its impact, building upon the learning from previous cycles in a structured way before wholesale implementation model for improvement decide upon, test and re-define the qi method best suited to the system being improved lean / six sigma eliminate waste and redirect resources for qi ensuring upmost efficiency performance benchmarking drive qi though setting and achieving performance targets healthcare failure models and effect analysis systematically evaluate the entire healthcare process to identify areas that could benefit from qi process mapping map the patient journey to identify opportunities for improvement along the patients journey of care statistical percentage control measure and control process of care qualities against predetermined parameters root cause analysis systematically uncover the cause of events effecting quality to then be improved upon / eliminated communication tools improve quality of care through structured information exchange between practitioners / team members technological innovations automate processes and systems to ensure continuity of care to patients decision trees improve the quality and consistency of processes in healthcare through a systematic information organisation system   the hqip has produced clear guidance, information and training for qi which is evidence-based and utilises the findings of an international review of literature on the use of qi in healthcare to inform their recommendations. the list of methods is not exhaustive or prescriptive, however, it is one of the most comprehensive summaries of qi methods currently applicable to the medical field. the hqip has produced 20 publications dedicated to qi methods’ utilisation, however the rigid categorisation and definition could be detrimental to increasing uptake from staff. using technical and complex terms could potentially be viewed as jargon, leaving people unwilling to implement methodologies that seem intricate and lengthy (26). conversely, the rigid definition creates a solid base of training and information available to all. multiple investigations into what constitutes an effective qi intervention in the healthcare setting have found that success is often determined by the amount of ‘buy in’ and investment you can garner from the team carrying out the method (27–29). the reality of any qi method applied to healthcare is that by nature it needs to be flexible, adaptive and easy to carry out. additionally, attention needs to be paid to the particular features of the process or system being evaluated, whilst also considering the practitioner who will be using the qi methods (30). skill sets of the staff, work-load and data analysis requirements are all key aspects that affect the success of a method (4). the veterinary industry is complex and diverse, comprised of many sectors which in turn are organised into micro and meso systems of management with their own protocols and guidelines (31). the veterinary industry is behind the human healthcare sector as far as defining and adopting qi methods into everyday practice. examples of many, although not all, can also be found in published veterinary research literature and conference proceedings and include clinical audit (32), checklists (33), morbidity and mortality rounds (34), benchmarking (35), communication tools (36), six sigma (37) and significant event audit (38). interestingly, some of these qi methods evidenced in veterinary literature do not feature specifically in the hqip literature, for example checklists which are not clearly and singularly identified but instead their use is encouraged to ensure staff are correctly following each step of other qi methods identified. most qi methods are not an alien concept to the veterinary sector and its practitioners; however, more work needs to be done to improve uptake of terminology to ensure a unified approach like the nhs has achieved. these activities were not routinely recognised as qi but recently the charitable entity of the royal college of veterinary surgeons (rcvs), rcvs knowledge, has encouraged awareness and uptake of some aspects of the qi methods through practice guidelines and their information hub (39). in 2019 rcvs knowledge commissioned rand europe to investigate current use of qi methods within uk veterinary practice (39,40). the report published in january 2020 comprised of data gathered from a national survey, focus groups, interviews with animal caregivers and an in-depth literature review. a summarisation of the report stated that, ‘though the veterinary professions have made progress in establishing some form of clinical governance, full-cycle quality improvement (qi) is not yet embedded in day-to-day work across the sector’ (40). rand also made recommendations on how to firmly cement qi ideology within veterinary practice including the need for better definitions of qi terms that specifically relate to veterinary practice which would reduce the current confusion within the profession surrounding terminology. detailed interviews and/or focus groups with key workers within the veterinary industry was also suggested as these could help determine exactly how qi could be effectively utilised in practice and what allowances would need to be made to give professionals time to carry out qi activities. with time and support from relevant governing bodies the veterinary sector could look to achieve similar widespread adoption of qi as in the nhs.   qi within uk healthcare ever increasing demands on both funds and staff along with greater standards of care expected from patients and management have pushed forward the adaptation of several qi methods to meet the specific needs and challenges of healthcare work (41). these methods are both formally and informally being executed in multiple hospital trusts across the health service, and have frequently been used as a key component of healthcare legislation set forward by various governments over the past two decades (42,43). the rationale for measuring quality and the improvement of quality in healthcare is simple: good practice and in turn, good performance when measured and reported, encourages similar behaviours within the industry (26). by directly comparing the care provided to established guidelines and benchmarks, nhs trusts are provided with a baseline measure of performance and the ability to track progress in quality of care delivered forwards and backwards over time, through cycles of qi analysis. qi methods have now been recognised and utilised within the nhs for over two decades. they have been instigated to address a wide variety of issues, from resource management of facilities and equipment, financial management through to adaptations to the delivery of care and clinical innovations (43). the motivation behind the compulsory implementation of these methods was to establish a culture of self-reflective adjustment and continual improvement ultimately leading to improvements in the quality of care delivered to patients (44,45). overall, this end-goal of changing the culture of healthcare seems to have been achieved, and the care quality commission (cqc) has noted a gradual increase in the uptake of true qi programmes across the uk nhs trusts over the last decade (46–48). moreover, in a 2017 report from the cqc, the value of established programmes of qi methods was recognised, stating ‘it feels confident about the ‘long-term sustainability of the quality of care’ at those nhs trusts where it finds ‘an established qi culture’ across the organisation’ (48). reflective practice has become embedded within education and training programmes for both doctors and nurses who are training in the uk. this method is designed to aid practitioners to solve their daily problematic situations. participants are encouraged to use a continuous cycle of conscious thought processes to examine actions and experiences. through this they can develop their decision-making in practice and enhance clinical knowledge which can then be shared amongst colleagues (49,50). this reflective practice is essential when looking to improve the quality of care as it is a key aspect of proactive change to prevent errors and gives a better understanding of personal actions, which in return develops professional skills (51).   barriers to qi implementation despite a sustained commitment to continual improvement of quality of care delivered within the nhs over the past 25 years (52–54), reviews examining the use of qi in the healthcare sector as a whole often report mixed levels of success. ultimately the success or failure of qi models in published healthcare literature seems to be primarily based on a trial and error system to find the best improvement methods for the specific context of the problems identified (27). despite the recommended infrastructure needed for success laid out by numerous reviews and published papers, the level of organisation regarding implementation and subsequent accomplishment of qi has varied across trusts within the nhs (4). this in part could be due to the historically chaotic nature of the ever-changing structure of the governing bodies and organisations involved. in many ways the veterinary sector has an advantage over the nhs here; although the ‘supervisory structures’ and governing bodies are much more numerous within the veterinary sector, their powers are far more limited, which allows the scope for a much more individualised approach to qi implementation and wide-spread adoption. this is contrary and potentially more successful than the one size fits all approach taken by the nhs. two early reviews of qi in the nhs both raised concerns over the apparent deficiency in the sustainability of changes introduced through qi analysis to upper-level management practices (55,56). at the time the reviews took place however, there was a lack of published large-scale projects that may have contributed to this assertion. young and mcclean (57) conducted a wide-ranging review of the use of the ‘lean process’ in healthcare. their study identified, ‘the strong evidence of the activity of champions’, acknowledging the individuals within a department that consistently made the concerted effort to measure and improve the quality of service delivered. similar to findings in the two preceding reviews, significantly lower success rates were seen in larger scale, organisational level changes that were attempted (55,56). subsequent reviews across the last decade have suggested that lower–level changes made by an individual or a small group are sustainable and often successful (29,58–60). in contrast, bigger projects have less than a 30% success rate in either initial implementation or achieving sustained improvements across different services or nhs trusts (29,58–60). this deficiency in uptake and sustained change is often put down to one or more of the following factors: structural issues, human issues and environmental context. the nhs is a combination of several complex organisations all with different goals, ethea, occupational groups, patients and technological utilisation (57,61,62). the department of health’s report ‘the nhs plan’ delivered in 2000, aimed to improve quality of care through two strands of change: emphasising the use of a centralised command and control approach whereby the department of health will have the ultimate say over approach to reform through national standards, league tables, inspection and regulation; empowerment of frontline staff and organisations to give them ownership of their work and make them the driving force behind reform. this slightly confused and contradictory approach is retrospectively viewed as largely counterproductive in the development of qi methods within the nhs (63,64). by putting emphasis on accountability to a higher power whilst simultaneously trying to give the freedom to staff to direct and lead change resulted in policy taking precedence over innovation and left staff disempowered. the setting of national standards, targets and benchmarking as performance indicators has become a dominant paradigm applied to the nhs to address qi (65). the efficacy of implementing such measures is debated amongst academics and healthcare professionals alike. it is possible to find articles to both support and discourage the use of benchmarking and target achievement exercises from a higher governing power within the healthcare sector. one study went so far as to suggest that the regimented implementation and enforcement of rigorous national standards, targets and benchmarking was encouraging ‘systemic psychopathy’ at the highest levels of management within the nhs (66). the paper suggests the climate of fear, bullying and target-orientated management style was directly correlated to declining standards of patient care (66). undoubtably this is an extreme point of view on this subject; however, boddy et al. (66) is not alone in their concerns over the effect such measures have on patient care and employee wellbeing within healthcare (67,68). the specific challenges of benchmarking strategies utilised in healthcare systems include case-mix fallacy[1], under-reporting of figures, comparison of noncomparable hospitals, selection bias, and possible implementation of inappropriate strategies for the development of quality care from incorrect benchmarking analyses (67,69). an example of the large-scale benchmarking strategies utilised in human healthcare is the performance assessment framework (paf) in the nhs. the paf is a custom designed measuring and monitoring system employed by the department of health. it is designed to assist local nhs organisations keep track and maintain accountability for the service delivered by their trust whilst still meeting central government's long-term objectives and targets (70). this resulted in a paradigm being created where-by managers were attempting to conform to the social norms and expectations of the patients treated by their service, whilst simultaneously attempting to meet the imposed performance indicators, which were at times incompatible with each other (71). this provides another example where a one-size fits all approach was attempted and found to be insufficient to meet the variable nature of healthcare services. the performance assessment framework was however successfully used as a communication tool between central government and local trusts, as well as providing a strategic management mechanism to generate performance information and highlight areas for change or those examples of excellent practice. benchmarking within veterinary medicine is certainly not as established as in human medicine, and the same level of information about the pitfalls and successes is not available. the lack of overarching government policy that collects and collates the benchmarking data and produces league tables in the nhs could be a reason for this. many audit projects will occur internally within individual veterinary practices and corporate groups with the information not shared beyond those organisations. larger scale projects do exist within the industry, however nowhere near the scale that exists within the nhs. the royal veterinary college (rvc) operates a central database called ‘the vetcompass programme’ collecting anonymised clinical records from practices across the country for epidemiological research purposes (72). the university of liverpool runs a similar scheme called the small animal veterinary surveillance network (savsnet). originally this was run in partnership with the british small animal veterinary association (bsava), however now it is managed totally by the university. the aim of the project is to produce a system that could be utilised to improve companion animal disease surveillance at local, regional and national levels (73). this is achieved through using electronic health records (ehr) from veterinary practices and diagnostic laboratories across the uk that volunteer to submit their data. rcvs knowledge also run ‘vetaudit’, another anonymised central database, collecting data on small animal neutering, canine cruciate procedures and antimicrobial resistance, the latter in collaboration with savsnet, which allows practices to assess their current standards with those reported by others (74). there is evidence in veterinary practice that there is good engagement in these projects when data are intended to be used for overall surveillance such as the4 savsnet database. when the data could potentially be used, to influence client decisions about where to have their pet treated, however, the desire to share data may be reduced as competition for clients is likely to be high between practices and corporations. ultimately the decision on whether to share data, particularly regarding clinical outcomes, is based on the final intended use of that data. it can be very easy to draw incorrect conclusions from a set of benchmarks without context, and for this reason benchmarking needs to be used carefully. that is not to assume that benchmarking cannot be successfully utilised in veterinary systems; benchmarking has been used successfully to encourage better performance within teams, and subsequently a higher quality of care or product delivered to patients (75).   which way forwards for qi in veterinary practice? as described for human healthcare, qi in veterinary care with its multifaceted work systems incorporating multiple actors such as: veterinary staff, veterinary paraprofessionals including physios’, dentists, hydrotherapist’s, owners and trainers, requires the systematic application of scientific evidence and knowledge, and a wide variety of tools and methods applied in a personalised approach to each task (76). there are undoubtably lessons to be learned and tools to be utilised from the experiences of implementing qi into the nhs. parallels can be drawn from the human healthcare literature, however there are notable differences identified between the two sectors. for this reason, it would undoubtably benefit the veterinary industry to have all available research collated into one place as the hqip and other organisations have done for the nhs. rcvs knowledge has taken steps to produce this central database of information regarding qi methods (39); however, more qi specific research needs to be conducted. this gap in research has perhaps slowed the uptake of qi within the veterinary sector, for example confusion around the terminology used (77) and not recognising aspects of their current practices as fitting within the definition of qi (78,79). conducting more research studies would provide comparable evidence of implementation and execution of a variety of qi methods in veterinary practice which would help to identify methods that will be the most beneficial. when utilised correctly, qi methods can assist to bridge the gap between practice and research by providing the implementation of evidence-based medicine into clinical practice. this assists veterinary practices to maintain and improve the standards of care delivered to their patients. empowerment of frontline staff in the nhs has been suggested to be a key aspect regarding the success or failure of a qi intervention. for this to happen, staff need to have received training and be given time to undertake these activities. furthermore, there needs to be acceptance that qi processes may be best implemented by veterinary nurses or the client care team rather than solely by veterinary surgeons. encouragement should be given for individuals to utilise these methods within all job roles across the practice to be able to generate benefits for patients and clients.   footnotes observational studies evaluating healthcare services or interventions that compare groups or populations within a healthcare system often undergo a ‘case-mix adjustment’ which accounts for any imbalances between the groups being compared. studies examining this adjustment have, however, shown that case-mix adjustment can make any present bias worse. the belief that this case-mix adjustment has to be made is referred to as a case-mix fallacy (26,69,80).   conflict of interest freya rooke’s phd is funded by the university of nottingham’s school of veterinary medicine and science and cvs equine   references ruskin, j. & rosenberg, j.d. 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(2007). case-mix adjustment in non-randomised observational evaluations: the constant risk fallacy. journal of epidemiology community health. 61(11):1010–3. doi: http://dx.doi.org/10.1136/jech.2007.061747 intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. diagnostic accuracy of cytology for canine osteosarcoma compared to histopathology a knowledge summary by ioannis l. oikonomidis dvm phd afhea mrcvs 1* theodora k. tsouloufi dvm phd afhea mrcvs 1 1the royal (dick) school of veterinary studies, university of edinburgh, eh25 9rg, uk *corresponding author (ioannis.oikonomidis@ed.ac.uk) vol 6, issue 2 (2021) published: 16 apr 2021 reviewed by: panayiotis loukopoulos (dvm pgdipvst phd) and chris thomson (dvm) next review date: 11 jun 2022 doi: 10.18849/ve.v6i2.399 pico question what is the sensitivity and specificity of cytology as a test for canine osteosarcoma when compared to histopathology as a gold standard?   clinical bottom line category of research question diagnosis the number and type of study designs reviewed overall, four diagnostic validity studies (two prospective and two retrospective) were critically appraised strength of evidence weak to moderate outcomes reported there is evidence of moderate strength to support that cytology is highly sensitive and specific for diagnosing histologically confirmed osteosarcomas as mesenchymal malignant neoplasms (cytological diagnosis of sarcoma). evidence of weak strength suggests that the sensitivity and specificity of cytology for identifying the exact histotype (cytological diagnosis of osteosarcoma) are low and high, respectively. finally, there is currently evidence of weak strength indicating that the sensitivity and specificity of cytology are comparable to that of preoperative histopathology after incisional biopsy for the diagnosis of canine osteosarcoma conclusion based on the available evidence, the diagnostic accuracy of cytology in diagnosing histologically confirmed osteosarcomas as sarcomas is high, whereas a confident conclusion cannot be drawn regarding the diagnostic accuracy of cytology for the identification of the exact histotype (cytological diagnosis of osteosarcoma). there is currently scant evidence suggesting that cytology has comparable diagnostic accuracy to preoperative histopathology (i.e. after incisional biopsy) for the diagnosis of canine osteosarcomas, however, more studies are warranted to confirm these results   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. the evidence the available evidence consists of two prospective studies, one retrospective study in which the cytological and histopathological samples were retrieved and re-examined, and one retrospective study in which the initial cytological and histopathological diagnoses were utilised. only the two retrospective studies investigated the diagnostic accuracy of cytology for providing a specific diagnosis of osteosarcoma and overall the sensitivity was low, while the specificity (reported only in one of the studies) was high; therefore, the evidence might be considered of weak strength and thus, clear recommendations cannot be made at this stage. on the other hand, cytology appears to be highly sensitive and specific for identifying malignancy (i.e. a generic cytological diagnosis of sarcoma); however, the current evidence should be considered of moderate strength, mostly due to the reported high prevalence of osteosarcoma that has probably induced a positive bias for the specificity. importantly, the sensitivity and specificity of cytology was comparable to that of preoperative histopathology after incisional biopsy; however, the current evidence is based on a single study and should therefore, be considered weak overall. summary of the evidence loukopoulos et al. (2005) population: dogs with histologically confirmed osteosarcomas sample size: 27 dogs intervention details: preoperative cytological examination was performed, but no further details for the procedure are available. histopathological examination was performed, but no further information is available regarding the procedure. study design: diagnostic validity retrospective study outcome studied: sensitivity of cytology for the diagnosis of canine osteosarcoma using histopathology as a gold standard main findings (relevant to pico question): in 3/27 (11.1%) cases, the cytological diagnosis was not specific or was inconclusive. in 6/27 (22.2%) cases, the cytological diagnosis was in full agreement with the histopathology. in 13/27 (48.1%) cases, the cytological diagnosis was in partial agreement with the histopathology (cytological diagnosis of malignant neoplasia). in 5/27 (18.5%) cases, the cytological diagnosis was not in agreement with the histopathology. therefore, the sensitivity of cytology for identifying the malignancy was 70.3%, while for determining the exact histotype was 22.2%. after excluding the non-diagnostic specimens from the analysis, the sensitivity of cytology for diagnosing the malignancy and exact histotype was 79.2% and 25.0%, respectively. limitations: the authors retrospectively identified the cases to be included, but they did not retrieve the samples to re-examine them. they relied on the initial cytological and histopathological diagnoses made by different pathologists. specificity was not reported and it could not be calculated based on the available data. the authors did not mention if the histopathological diagnoses were based on post-mortem/surgical biopsies or preoperative incisional biopsies. britt et al. (2007) population: dogs with aggressive appendicular bone lesions sample size: 36 dogs intervention details: fine needle aspiration (fna) cytological examination was performed using a 20 gauge needle and a 12 ml syringe. the smears were stained with wright-giemsa. histopathological examination was performed after preoperative incisional or surgical excisional biopsy. study design: diagnostic validity prospective study outcome studied: sensitivity and specificity of fna cytology for the diagnosis of canine osteosarcoma using histopathology as a gold standard main findings (relevant to pico question): 4/36 (11.1%) specimens were non-diagnostic. 30/32 diagnostic sample cases were diagnosed as osteosarcomas histologically. 2/32 samples were diagnosed as reactive bone histologically. cytology classified 29/30 histologically confirmed osteosarcomas as sarcomas. one of them was diagnosed as reactive bone. further classification into a specific histotype was not possible. the sensitivity of cytology for identifying osteosarcomas as sarcomas was 85.3% or 96.7%, after excluding the non-diagnostic specimens from the analysis. the specificity was 100%. limitations: the prevalence of osteosarcoma was very high in this study, inducing inevitably a positive bias in the calculation of specificity. the authors provided a diagnosis of sarcoma cytologically without attempting to specify the exact histotype. neihaus et al. (2011) population: dogs with lytic and/or proliferative bone lesions sample size: 27 dogs intervention details: fna cytological examination was performed using a 22 gauge needle and a 6 ml syringe. the smears were stained with wright-giemsa. core aspirate (ca) cytological examination was performed using a 16 gauge bone marrow biopsy needle. the smears were stained with wright-giemsa. histopathological examination was performed after an incisional biopsy using jamshidi™ needle. the sections were stained with haematoxylin and eosin. study design: diagnostic validity prospective study outcome studied: sensitivity and specificity of fna and ca cytology for the diagnosis of osteosarcoma using histopathology as a gold standard main findings (relevant to pico question): 20/27 cases were diagnosed as osteosarcomas histologically. fna cytology identified 17/20 histologically confirmed osteosarcomas as sarcomas. ca cytology identified 19/20 histologically confirmed osteosarcomas as sarcomas. all missed cases (3/20 using fna cytology and 1/20 using ca cytology) were diagnosed as reactive bone. the sensitivity of fna and ca cytology for identifying osteosarcomas as sarcomas was 85.0% and 95.0%, respectively. fna and ca cytology specificity was 100%. limitations: the prevalence of osteosarcoma was very high in this study, inducing inevitably a positive bias in the calculation of specificity. the authors provided a diagnosis of sarcoma cytologically without attempting to specify the exact histotype. sabattini et al. (2017) population: dogs with bone lesions sample size: 68 dogs with bone lesions, 40 dogs with osteosarcomas intervention details: fna cytological examination was performed using 21–22 gauge needle and 2.5–5.0 ml syringe. the smears were stained with may-grünwald-giemsa. histopathological examination was performed after preoperative incisional biopsy using 8–11 gauge jamshidi™ needle. the sections were stained with haematoxylin and eosin. histopathological examination was performed after surgical excisional biopsy or post-mortem examination. the sections were stained with haematoxylin and eosin. study design: diagnostic validity retrospective study outcome studied: sensitivity and specificity of fna cytology and preoperative histopathology for the diagnosis of osteosarcoma using surgical or post-mortem histopathology as a gold standard main findings (relevant to pico question): in 5/40 histologically confirmed osteosarcomas, cytological examination was not performed. fna cytology identified correctly 15/35 (42.9%) osteosarcomas. fna cytology identified 13/35 (37.1%) osteosarcomas as sarcomas (10 generic sarcoma, two chondrosarcoma, one giant cell tumour of the bone), while 7/35 (20.0%) specimens were non-diagnostic. the sensitivity of fna cytology for providing a diagnosis of sarcoma was 80.0% (28/35). the sensitivity for identifying the histotype was 42.9% (15/35). the calculated sensitivity of fna cytology is 53.6% (15/28) for identifying the histotype and 100% for providing a generic diagnosis of sarcoma, when the non-diagnostic specimens are excluded. fna cytology diagnosed osteosarcoma incorrectly in 2/18 (11.1%) of non-osteosarcoma lesions (one poorly differentiated sarcoma and one chondrosarcoma). the specificity of cytology is 88.9% (16/18) for the histotype and 100% (18/18) for providing a generic diagnosis of sarcoma. preoperative histopathological examination identified correctly 5/11 (45.5%) osteosarcomas. in 3/11 (27.3%) malignancy was correctly identified by preoperative histopathology. the sensitivity of preoperative histopathology was 45.5% (5/11) for the histotype and 72.8% (8/11) for malignancy. the specificity of preoperative histopathology was 100%. limitations: this was a retrospective study and only a few non-neoplastic lesions were included as bone lesions are more likely to have a surgical or post-mortem histopathological examination when a neoplasm is suspected. therefore, a positive bias in the calculation of specificity may have been induced. the number of cases with both fna cytology and preoperative histopathology was limited, precluding the comparison of the diagnostic accuracy of the two techniques for the same lesion. appraisal, application and reflection moderately strong evidence indicates that cytology is highly sensitive and specific for diagnosing histologically-confirmed osteosarcomas as sarcomas. there is weak evidence suggesting that the sensitivity and specificity of cytology for identifying the exact histotype (i.e. osteosarcoma) are low and high, respectively. finally, weak evidence suggests that the sensitivity and specificity of cytology and preoperative histopathology after incisional biopsy are comparable for the diagnosis of canine osteosarcoma. malignant bone tumours are relatively common in dogs. specifically, according to two studies performed in the usa, they account for 2–7% of all malignant neoplasias in dogs,1,2 while in one epidemiological european study, the incidence rate of malignant bone tumours was 5.5 cases per 10,000 dog-years at risk.3 osteosarcoma is by far the most common malignant bone neoplasm, accounting for up to 85% of primary skeletal malignant neoplasms.4 the clinicians often rely on signalment, history, clinical findings, and radiographical abnormalities to make a presumptive diagnosis of a malignant bone tumour. however, benign disorders (e.g. osteomyelitis) may exhibit similar clinical and radiographical features with malignancies, thus complicating the differential diagnosis. moreover, the surgical approach, the prognosis and further post-surgery therapeutic interventions might differ substantially between the different types of primary bone malignancies. specifically, osteosarcoma is considered a highly malignant neoplasm with a low median survival time and high metastatic potential, while adjuvant chemotherapy may also be required to prolong the survival time in these cases.5 incisional biopsy and histopathological examination is often recommended prior to surgery and is considered the gold standard for the diagnosis of primary bone lesions. however, several technique related complications, such as pathological fractures, haematomas, or even local seeding of neoplastic cells have been reported with bone biopsy.6 moreover, the procedure requires the induction of general anaesthesia and is reportedly associated with enhanced patient pain.6 fine needle aspiration (fna) cytology is a cost-effective and less invasive alternative to preoperative histopathology, which is typically associated with minimal complications, and is characterised by a very short turnaround time.7 overall, four studies met the inclusion criteria for critical appraisal. the sensitivity of cytology for diagnosing histologically-confirmed osteosarcomas as sarcomas was high, ranging from 79.2% to 95.0%, and its specificity was 100% in three out of four studies.4,8–10 the sensitivity of cytology in identifying the exact histotype (i.e. providing a specific diagnosis of osteosarcoma rather than a generic diagnosis of sarcoma) was investigated only by loukopoulos et al. (2005) and sabattini et al. (2017), and it was found to be lower (25.0% and 42.9%, respectively).4,11 conversely, the specificity was only reported by sabattini et al. (2017) and found to be quite high (88.9%).4 interestingly, sabattini et al. (2017) compared the diagnostic accuracy of fna cytology and preoperative histopathology after incisional biopsy with that of histopathology after surgical excisional biopsy or post-mortem examination as a gold standard. surprisingly, the sensitivity of preoperative histopathology was lower than that of fna cytology (45.5% vs 53.6% for histotype and 72.8% vs 100% for malignancy).4 this could be explained by some inherent limitations of the incisional biopsy as a technique to obtain bone samples, namely limited available tissue for evaluation due to small sample size, presence of artifacts (e.g. crush artifact, artifactual changes due to decalcification), or non-representative specimen (e.g. sampling of necrotic areas or surrounding reactive bone). this finding could be of clinical relevance as cytology is minimally invasive when compared to preoperative biopsy; however, more studies are warranted in order to support this study’s findings. furthermore, in most of the above studies, cytology was associated with a rate of non-diagnostic specimens, ranging from 11.1% to 20.0%,4,8,11 which highlights an inherent limitation of this diagnostic test. even though the sensitivity of cytology for providing a specific diagnosis of osteosarcoma appears to be low, its high sensitivity and specificity for identifying histologically confirmed osteosarcomas as sarcomas is equally important for routine purposes. specifically, the cytological examination can be easily complemented with the use of a special stain for alkaline phosphatase (alp) activity, which was found to be highly sensitive (88–100%) and specific (89–94%) for diagnosing canine osteosarcomas.10,12 importantly, this special staining is a simple and rapid test that can be performed on previously stained cytological slides.12 the main disadvantage of alp staining remains the lack of specificity for malignant osteoblasts, as all osteoblasts normally express this enzyme.10 all the appraised studies are diagnostic validity studies and are therefore, placed high in the evidence hierarchy; nonetheless, several limitations are recognised in them. specifically, given that the calculated accuracy of a diagnostic test is heavily dependent on the prevalence of the target condition, the reported diagnostic accuracy, and especially the specificity, appears to be somewhat biased at least in the studies of britt at al. (2007) and neihaus et al. (2011),8,9 as only rare cases with a diagnosis of non-osteosarcoma were included. moreover, in the aforementioned studies, the authors merely provided a cytological diagnosis of sarcoma without defining the exact histotype of the tumour, which thus, precludes the determination of diagnostic accuracy of cytology for providing a specific diagnosis of osteosarcoma. finally, in the study of sabattini et al. (2017), which was the only one that compared the diagnostic accuracy of cytology to that of preoperative histopathology, a low number of cases were subject to both tests, therefore, a direct comparison of these two tests on the same lesions was limited. in conclusion, there is evidence of moderate strength suggesting that cytology is highly sensitive and specific for providing a diagnosis of sarcoma in cases of histologically confirmed canine osteosarcomas. in terms of identifying the exact histotype (i.e. providing a specific diagnosis of osteosarcoma), the current evidence should be considered overall weak and as such, no definitive conclusions can be drawn at this stage. nonetheless, cytology seems to lack adequate sensitivity for the diagnosis of canine osteosarcomas, but it seems to be highly specific, which is useful for excluding this type of neoplasm. surprisingly, the currently available evidence suggests that the diagnostic accuracy of preoperative histopathology seems not be superior to that of fna cytology for the diagnosis of osteosarcomas, although the former should be considered of weak strength and thus, does not allow definitive conclusions to be drawn. however, an inherent limitation of bone cytology is related to the rate of non-diagnostic specimens, which appears to be relatively low, but it should be taken into consideration and properly communicated to the owner. prospective studies focusing on the diagnostic performance of cytology as compared to that of preoperative histopathology are warranted, in order to provide solid evidence on the use of the two techniques for the diagnosis of canine osteosarcomas prior to surgery. methodology section search strategy databases searched and dates covered: cab abstracts on the ovid interface 1973–2020, week 22 pubmed accessed via the ncbi website 1920–june 2020 search strategy: cab abstracts: (dog or dogs or canine or canines or canis or bitch*).mp. or exp dogs/ or exp bitches/ or exp canis osteosarcoma*.mp. or exp osteosarcoma/ or (bone* and (tumour* or tumor* or neoplasm* or cancer*)).mp. (cytology or cytopathology).mp. or exp cytology/ or (cytologic* and (exam* or evaluat* or diagnos*)).mp. (histopathology or histology).mp. or exp histopathology/ or ((histologic* or histopathologic*) and (exam* or evaluat* or diagnos*)).mp. 1 and 2 and 3 and 4 pubmed: (dog or dogs or canine or canines) and (osteosarcoma) and (cytology or cytopathology) and (histology or histopathology) and (veterinary[sb]) dates searches performed: 11 jun 2020 exclusion / inclusion criteria for the present knowledge summary, only original research articles were considered for inclusion, as the aim was to investigate measures of test performance (i.e. quantitative data) and thus, sources of qualitative evidence (i.e. expert opinion articles, narrative reviews) were excluded even if relevant. conference abstracts were excluded as they were not likely to provide the level of detail needed for the appraisal of the evidence. exclusion: studies investigating species other than dogs/other bone neoplasms case reports non-peer reviewed literature (e.g. conference abstracts, theses, expert opinion articles) narrative reviews studies not written in english studies not available as full texts inclusion: studies investigating dogs with osteosarcoma diagnosis original research articles studies investigating the diagnostic accuracy of cytology either alone or in comparison to histopathology studies written in english search outcome database number of results excluded – not relevant to pico question excluded – case report excluded – review article excluded – conference abstract excluded – not english-written study total relevant papers cab abstracts 143 113 17 4 2 3 4 pubmed 527 449 68 6 0 0 4 total relevant papers when duplicates removed 4 conflict of interest the authors declare no conflicts of interest. references priester, w.a. & mckay, f.w. (1980). the occurrence of tumors in domestic animals. national cancer institute monograph. 1–210. dom, c.r., taylor, d.o.n., schneider, r., hibbard, h.h. & klauber, m.r. (1968). survey of animal neoplasms in alameda and contra costa counties, california. ii. cancer morbidity in dogs and cats from alameda county. journal of the national cancer institute. 40, 307–318. doi: https://doi.org/10.1093/jnci/40.2.307 egenvall, a., nødtvedt, a. & von euler, h. (2007). bone tumors in a population of 400 000 insured swedish dogs up to 10 y of age: incidence and survival. canadian journal of veterinary research. 71(4), 292–299. sabattini, s., renzi, a., buracco, p., defourny, s., garnier-moiroux, m., capitani, o. & bettini, g. (2017). comparative assessment of the accuracy of cytological and histologic biopsies in the diagnosis of canine bone lesions. journal of veterinary internal medicine. 31(3), 864–871. doi: https://doi.org/10.1111/jvim.14696 thompson, k.g. & dittmer, k.e. (2017). tumors of bone. in: meuten dj, ed. tumors in domestic animals, 5th ed. ames, iowa, usa: wiley blackwell; 356–424. mankin, h.j., mankin, c.j. & simon, m.a. (1996). the hazards of the biopsy, revisited. for the members of the musculoskeletal tumor society*. the journal of bone & joint surgery. 78(5), 656–663. doi: https://doi.org/10.2106/00004623-199605000-00004 sharkey, l.c., dial, s.m. & matz, m.e. (2007). maximizing the diagnostic value of cytology in small animal practice. veterinary clinics of north america: small animal practice. 37(2), 351–372. doi: https://doi.org/10.1016/j.cvsm.2006.11.004 britt, t., clifford, c., barger, a., moroff, s., drobatz, k., thacher, c. & davis, g. (2007). diagnosing appendicular osteosarcoma with ultrasound-guided fine-needle aspiration: 36 cases. journal of small animal practice. 48, 145–150. doi: https://doi.org/10.1111/j.1748-5827.2006.00243.x neihaus, s.a., locke, j.e., barger, a.m., borst, l.b. & goring, r.l. (2011). a novel method of core aspirate cytology compared to fine-needle aspiration for diagnosing canine osteosarcoma. journal of the american animal hospital association. 47(5), 317–323. doi: https://doi.org/10.5326/jaaha-ms-5676 loukopoulos, p., rozmanec, m. & sutton, r.h. (2005). cytological versus histopathological diagnosis in canine osteosarcoma. veterinary record. 157(24), 784–784. doi: https://doi.org/10.1136/vr.157.24.784 barger, a., graca, r., bailey, k., messick, j., de lorimier, l-p., fan, t. & hoffman w. (2005). use of alkaline phosphatase staining to differentiate canine osteosarcoma from other vimentin-positive tumors. veterinary pathology. 42(2), 161–165. doi: https://doi.org/10.1354/vp.42-2-161 ryseff, j.k. & bohn, a.a. (2012). detection of alkaline phosphatase in canine cells previously stained with wright–giemsa and its utility in differentiating osteosarcoma from other mesenchymal tumors. veterinary clinical pathology. 41(3), 391–395. doi: https://doi.org/10.1111/j.1939-165x.2012.00445.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. practice what you preach: importance of veterinarian involvement in zoonotic disease prevention – a michigan focus stephanie j.s. baiyasi dvm mph hsac1* rubén juárez mph1 jodi brookins-fisher phd mches fesg1 jeff n. inungu md drph1 thomas m. gehring phd1 zigmond a. kozicki dha msa ma llp2 1central michigan university, 1200 s. franklin st., mount pleasant, michigan, 48859 2university of detroit mercy, 4001 w. mcnichols, detroit, michigan, 48221–3038 *corresponding author (stephaniebaiyasi@yahoo.com) vol 7, issue 2 (2022) published: 27 apr 2022 reviewed by: john chitty (bvetmed certzoomed cbiol mrsb mrcvs) and conor o'halloran (bvsc msc phd mrcvs) doi: 10.18849/ve.v7i2.512 section index:    abstract | introduction | methods | results | discussion | footnotes | conflict of interest | references | supplementary files abstract objective: determine the extent to which practicing veterinarians in michigan, usa engaged in commonly recommended practices for the prevention of zoonotic diseases (zds). background: follow-up to lipton et al. (2008) washington state study. methods: online survey link was emailed february 2020 to 3,410 michigan licensed veterinarians practicing clinical medicine with emails on file with michigan licensing and regulatory affairs. results: 402 veterinarians responded. a high proportion (161/214 [75%]) of respondents agreed it was very important for veterinarians to advise clients about the potential for zd, yet only 34% (74/215) reported they had initiated discussions about zds with clients on a daily basis, although 64% (137/214) indicated they had client educational materials on zds available in their practices. nearly 62% (47/76) of veterinarians who obtained their degree after 2010 were likely to eat / drink in animal handling areas as compared to only 33% (18/54) of those who graduated before 1989. over 30% of respondents (64/210) indicated there were no written infection control guidelines for staff members in the practice, and 28% (60/214) reported having been infected with a zd in practice. conclusion: veterinarians appreciate their important role in zd prevention and welcome increased communication between human and veterinary medicine plus assistance from public health agencies regarding zd prevention. communication / coordination / collaboration among human medicine / animal medicine / environmental health (i.e., one health) is necessary to protect the public’s health from zoonoses.   introduction zoonoses are infectious diseases that are transmitted between species from animals to humans (or from humans to animals) (minnesota department of health, 2019). of the 1,461 infectious diseases recognised to occur in humans, approximately 60% are caused by multihost pathogens, characterised by their movement across various species (bidaisee & macpherson, 2014). of the total number of human diseases, 177 are regarded as emerging or reemerging zoonotic pathogens and are twice as likely to be in this category as are nonzoonotic pathogens (woolhouse & gowtage-sequeria, 2005). the recent pandemic of covid-19 caused by sars-cov-2 (a coronavirus similar to the agent causing ‘severe acute respiratory syndrome [sars]’) is an example of a zoonotic agent’s potential to disrupt human life (khan et al., 2020). exposure to and emergence of zoonotic pathogens can occur in various ways including companion animals (dogs, cats, exotic pets), recreationally (water sports, hunting, and the movement of animals for these and other sporting purposes), globalisation, tourism, livestock movement, and changed land use and urbanisation (cutler et al., 2010). the general population, including most pet owners, are unaware that pets and other animals can carry infectious agents transmissible to people and are not familiar with methods to prevent zoonotic diseases (lipton et al., 2008). stull et al. (2012) found a need for accessible zoonotic disease information for the public and additional efforts to educate clientele were needed from veterinarians, physicians and public health personnel. this study examined the extent that veterinarians in michigan engage in commonly recommended practices for the prevention of zoonotic diseases.   methods study protocol: the study was designed as a cross-sectional survey. a sample of veterinarians licensed in michigan was selected from the michigan licensing and regulatory affairs (lara) office per a freedom of information act (foia) request. the original file included all michigan licensed veterinarians and veterinary technicians (8,052 individuals), including those with and without email addresses as of february 2020. only veterinarians with listed email addresses were included for the survey which produced a list of 3,434 emails. duplicate emails were deleted and 3,410 participants were emailed a request to complete the survey. the study protocol was approved by the university institutional review board. survey instrument: the 40 question survey instrumenta for this research was modified from a previously developed and validated 31 item instrument (lipton et al., 2008) that was used to determine the extent to which practicing veterinarians in king county, washington, engaged in commonly recommended practices for the prevention of zoonotic diseases. this 40 question survey was implemented using commercially available softwareb. the survey link was emailed with an informed consent page to start the survey. most questions were closed-ended and the survey took approximately 15 minutes to complete. the survey began by screening if veterinarians were in clinical practice. if not, they answered the final question of the survey. those in clinical practice answered questions in five main themes. themes: the first theme ascertained demographic characteristics of the respondents, including the type of veterinary medical practice, years in clinical practice, average number of days worked per week, number and type of staff in the practice, gender of respondent, veterinary school attended and year of graduation, plus any advanced degrees or certifications. the second theme determined how often respondents had discussed zoonotic diseases with clients during the past year (including veterinarian-initiated and client-initiated discussions), how many cases of zoonotic disease in animals had been diagnosed in the past 5 years, and how often clients had described themselves or a family member as being at higher risk of infection (e.g. immunocompromised, pregnant, elderly, or having children < 6 years old) and asked about zoonotic diseases during the past year. this theme of questions included the likelihood of discussing zoonotic diseases if a client or client’s family member was known to be at higher risk of infection and the specific zoonotic diseases discussed with clients. respondents were asked whether continuing education courses on zoonotic diseases were available and if they completed any in the last 3 years. the third theme addressed zoonotic disease discussions with client or non-client healthcare professionals (e.g. physicians, physician assistants, nurse practitioners, nurses), public health officials, or wildlife biologists during the past year. this theme also included respondents’ involvement with local and state public health agencies, including questions about how often they had contacted the local or state public health agency or the michigan department of agriculture and rural development (mdard), animal industry division (state veterinarian’s office) to discuss reportable zoonotic diseases in animals during the past year; a self-assessment of respondents’ knowledge of which diseases they were required by state law to report to the michigan department of health and human services (mdhhs); knowledge of who to contact about a suspected case or outbreak of zoonotic disease; and whether and how public health agencies could better assist with issues involving zoonotic diseases. veterinarians that indicated public health agencies could better assist with issues involving zoonotic diseases were asked to choose one or more ways from a list of eight options and describe any other ways public health agencies could assist. the fourth theme addressed the importance of advising clients about zoonotic diseases, as well as the zoonotic diseases covered in and availability of educational materials for clients. additionally, this theme covered whether respondents had ever been infected with a zoonotic disease in practice and what various infection control measures in practice (e.g. washing hands between clients, eating / drinking in animal handling areas, disinfecting exam table frequency, presence of written infection control guidelines) had been used. respondents who indicated that they had been infected with a zoonotic disease were asked to indicate the disease of which they had been infected and whether the diagnosis had been medically confirmed. the final theme addressed the one health initiative. this concept is defined as a collaborative, multisectoral, and transdisciplinary approach that involves working at the local, regional, national, and global levels, with the goal of achieving optimal health outcomes by recognising the interconnection between people, animals, plants, and their shared environment. participants were asked to describe their familiarity with this initiative. statistical analysis: survey data were analysed with standard softwarec. descriptive statistics (frequencies, range of scores, means, standard deviations) were utilised to describe the respondents in terms of their demographic and background characteristics, participation in zoonotic disease prevention activities, and communication about zoonotic disease prevention in the community. to assess the relationship of demographic variables (sex, year of graduation, years in practice, advanced degree) on zoonotic disease prevention practices, a series of chi-square analyses were performed. in cases where respondents had missing data, analyses were conducted only on complete responses. values of p < 0.05 were considered significant. qualitative data were reviewed and coded by hand to identify common responses. our research was approved by the institutional review board at central michigan university (irb # 2020-185).   results general among the 402 respondents, 261 (64.9%) responded after the initial email request, 57 (14.2%) responded after the first reminder email, and 84 (20.9%) responded after the second reminder email. the 269 (66.9%) who self-identified as active veterinarians were directed to the remaining questions of the survey. a total of 215 participants completed at least 65% of the remaining survey and these responses were used in the study analysis. power analysis indicated that our sample size (n = 215) corresponded to a 5% margin of error at a confidence level of 90% and a 6% margin of error at a confidence level of 95%. demographics most respondents (157/215 [73.0%]) practiced small animal medicine as either the sole practice type or in combination with other types (see table 1). 44/215 (20.5%) respondents had two practice types and 21/215 (9.8%) had three or more practice types (see table 2). regarding where the veterinary degree was obtained, 145/215 respondents (67.4%) indicated michigan state university / msu (although ‘msu’ could potentially indicate another out-of-state university), while 69/215 (32.1%) received their veterinary degree from another school, including 17/69 (24.6%) respondents who attended a foreign school. female participants (154/215) comprised 71.6% of the sample, 59/215 were male (27.4%), and 2/215 (0.9%) respondents preferred not to disclose their gender. of the 44 respondents who possessed advanced degrees or certifications, 8/44 (18.2%) were board certified (in dermatology, emergency and critical care, reproductive medicine, internal medicine, laboratory animal medicine, surgery, and / or veterinary behaviour), 5/44 (11.4%) had degrees in public health, and 3/44 (6.8%) had master in business administration (mba) degrees.   type of veterinary practice no. % small animal (dog / cat) 157 73.4% small animal emergency 31 14.5% exotic pets (pocket pets / reptiles / birds / fish, etc.) 29 13.6% livestock (cattle / sheep / pig, etc.) 22 10.3% mixed animal (small and large animal) 14 6.5% shelter medicine 13 6.1% equine 19 8.9% wildlife / zoo 8 3.7% all animal species 1 0.5% aquatic only  1 0.5% government  1 0.5% laboratory animal  1 0.5% lab animal medicine / teaching / small animal  1 0.5% laboratory  1 0.5% poultry   1 0.5% regulatory medicine  1 0.5% relief  1 0.5% specialty, majority small animal with some large and exotics   1 0.5% wellness clinics 1 0.5% total respondents* 215 100% table 1: practice type of veterinarians in michigan, who responded to a survey on zoonotic disease prevention practices. *reflects total number of individuals responding; each respondent may have selected more than one practice type.   table 2. demographic characteristics of veterinarians in michigan that responded to the survey. *responses were missing for one individual. **responses were missing for two individuals.   veterinarian zoonotic disease discussions when asked about their discussions about zoonotic diseases with clients, health care professionals, public health officials, and wildlife biologists, 209/215 (97.2%) respondents reported that they had initiated discussions about zoonotic diseases with clients in the past year, 151/209 (72.2%) did so on a daily or weekly basis, while 147/209 (70.3%) reported that clients initiated discussion about zoonotic diseases monthly or less frequently (see table 3). 114/215 (53.0%) participants indicated they were much more likely to discuss zoonotic diseases if they knew that a client or the client’s family members were at a risk of infection. only 2/215 (0.9%) of surveyed veterinarians indicated that on a daily basis, clients described themselves or their family members as having a higher risk of infection and asked about zoonotic diseases. 113/215 (52.6%) respondents indicated that at-risk clients did this only occasionally, and 58/215 (26.9%) reported at-risk clients never asking the veterinarian about zoonotic diseases. 191/215 (88.8%) respondents indicated discussing zoonotic diseases with health care professionals (e.g. physicians, physician assistants, nurse practitioners, nurses) at least once during the past year. 93/215 (43.3%) respondents indicated they had discussed zoonotic diseases with public health officials at least once during the past year, while 43/215 (20%) respondents indicated they had discussed zoonotic diseases with wildlife biologists at least once during the past year.   frequency veterinarian initiated client initiated daily 74 35.4% 15 7.2% weekly 77 36.8% 47 22.5% monthly 28 13.4% 38 18.2% occasionally 29 13.9% 97 46.4% never 1 0.5% 12 5.7% total 209   209   table 3: zoonotic disease discussion frequency between michigan veterinarians and clients. data are given as number of respondents and percentages.  there were six respondents who indicated that they do not have any client contact in their type of clinical practice.   zoonotic disease topics in the survey, respondents were given a list of 35 zoonotic disease topics and asked to indicate the topics they had discussed with their clients. the 10 most frequently discussed zoonotic disease topics in the order of most to least discussed were internal parasitism, external parasitism, rabies, leptospirosis, dermatophytosis, giardiasis, lyme disease, animal bite prevention, salmonellosis, and feeding raw food diets (see table 4). 73/208 (35.1%) respondents indicated never discussing visceral and ocular larval migrans with their clients, and 114/209 (54.5%) indicated that they never discussed baylisascaris spp. (raccoon roundworm) with their clients. by contrast, 201/212 (94.8%) respondents indicated that they discussed internal parasitism in general with their clients. veterinarians were more likely to initiate discussions about leptospirosis, giardiasis, rabies, internal parasitism, and salmonellosis, whereas clients were more likely to initiate discussion about dermatophytosis / ringworm, feeding raw food diets, animal bite prevention, toxoplasmosis, and lyme disease.     ever discussed never discussed total sum of responses on disease / topic disease or topic veterinarian initiated client initiated either initiated leptospirosis 178 83.6% 7 3.3% 12 5.6% 16 7.5% 213 giardia 159 76.4% 5 2.4% 19 9.1% 25 12% 208 rabies 154 73.3% 8 3.8% 36 17.1% 12 5.7% 210 control of internal parasites 151 71.2% 6 2.8% 44 20.8% 11 5.2% 212 salmonella 137 65.6% 5 2.4% 24 11.5% 43 20.6% 209 scabies 130 62.5% 7 3.4% 17 8.2% 54 26% 208 visceral or ocular larval migrans 127 61.1% 1 0.5% 7 3.4% 73 35.1% 208 raw meat ‘bones and raw food’ (barf) diets 117 56% 26 12.4% 18 8.6% 48 23% 209 control of external parasites 116 55.2% 8 3.8% 74 35.2% 12 5.7% 210 lyme disease 116 55.2% 21 10% 43 20.5% 30 14.3% 210 enteric infections in general 114 54.8% 13 6.3% 30 14.4% 51 24.5% 208 dermatophytosis / ringworm 112 52.8% 29 13.7% 54 25.5% 17 8% 212 animal bite prevention 110 52.1% 22 10.4% 40 19% 39 18.5% 211 toxoplasmosis 110 52.6% 22 10.5% 24 11.5% 53 25.9% 209 e. coli 109 52.9% 6 2.9% 25 12.1% 66 32% 206 methicillin-resistant staphylococcus aureus (mrsa) 98 46.7% 18 8.6% 30 14.3% 64 30.5% 210 cat scratch disease 93 44.5% 21 10.1% 26 12.4% 69 33% 209 rocky mt. spotted fever 86 41.8% 2 1% 6 2.9% 112 54.4% 206 baylisascaris spp. (raccoon roundworm) 85 40.7% 5 2.4% 5 2.4% 114 54.6% 209 cryptosporidium 73 35.3% 4 1.9% 10 4.8% 120 58% 207 campylobacter 64 30.9% 3 1.5% 11 5.3% 129 62.3% 207 brucellosis 63 30% 10 4.8% 6 2.9% 131 62.4% 210 west nile virus 26 12.6% 12 5.8% 23 11.1% 146 70.5% 207 eastern equine encephalitis 25 12% 15 7.2% 21 10.1% 147 70.7% 208 chronic wasting disease 16 7.7% 15 7.2% 17 8.2% 160 76.9% 208 tularemia 16 7.8% 0 0% 6 2.9% 184 89.3% 206 plague 12 5.8% 0 0% 6 2.9% 189 91.3% 207 psittacosis 12 5.8% 2 1% 4 1.9% 189 91.3% 207 scrapie 11 5.3% 4 1.9% 7 3.4% 184 89.3% 206 avian influenza (bird flu) 10 4.9% 18 8.7% 15 7.3% 163 79.1% 206 bse (mad cow) 9 4.3% 9 4.3% 9 4.3% 181 87.0% 208 lymphocytic choriomeningitis 8 3.9% 0 0% 9 4.4% 190 91.8% 207 hantavirus 6 2.9% 0 0% 4 1.9% 196 95.2% 206 monkey pox 5 2.4% 1 0.5% 5 2.4% 196 94.7% 207 rat bite fever 3 1.5% 0 0% 6 2.9% 197 95.6% 206 table 4: specific zoonotic diseases or topics discussed with clients, as reported by veterinarians in michigan.   importance of zoonotic disease advising 161/214 (75.2%) respondents indicated they felt it was very important to advise clients about the potential for zoonotic disease; 35/214 (16.4%) indicated it was moderately important and 15/214 (7.0%) indicated it was somewhat important. 137/214 (64%) respondents indicated that they did have client educational materials on zoonotic diseases available in their practices. the five most common zoonotic diseases included in client educational materials available in practices that had such materials were leptospirosis, rabies, lyme disease, intestinal parasitism, and external parasitism. continuing education the next section on the survey asked participants about their own continuing education on zoonotic diseases. of those who responded, 139/213 (65.3%) indicated they had attended continuing education courses on zoonotic diseases within the past 3 years, and 120/215 (55.8%) indicated they believed that continuing education courses on zoonotic diseases were regularly available. infection control practices when asked about infection control practices, 184/211 (87.2%) respondents indicated they always or most of the time washed their hands between handling individual animals, and only 27/211 (12.8%) indicated that they sometimes, seldom, or never washed their hands between handling individual animals. additionally, 165/206 (80.1%) respondents indicated that examination and treatment tables were always disinfected between patients, and only 9/205 (4.4%) respondents indicated that tables were seldom or never disinfected between patients. 82/210 (39.1%) respondents indicated that veterinarians or staff members ate or drank in animal handling areas daily, 72/210 (34.3%) indicated that veterinarians or staff members ate or drank in animal handling areas occasionally, and 37/210 (17.6%) indicated that veterinarians and staff members never ate or drank in animal handling areas. 106/210 (50.5%) respondents indicated there were written infection control guidelines for staff members in the practice. 64/210 (30.5%) respondents indicated there were no written infection control guidelines for staff members in the practice, and an additional 40/210 (19.1%) were unsure whether the practice had written infection control guidelines. it should be noted that these results were self-reported and therefore subject to potential bias. results (self-reported) suggested that those with less veterinarian experience were more likely to eat and drink in animal handling areas. categorising respondent year of graduation (2010 or later, 2000–2009, 1990–1999, 1989 or earlier), a chi-square test of independence was performed comparing the frequency of categorised year of graduation from veterinarian school and frequency of drinking or eating in animal handling areas. a significant interaction was found (x2(6) = 14.46, p = 0.025), indicating that veterinarians having earned their degree earlier in time were less likely to frequently eat and drink in animal handling areas. to illustrate this trend, the 47/76 veterinarians (61.8%) obtaining their degree in 2010 or later were more likely to eat and drink in handling areas on a daily basis than the 18/54 individuals (33.3%) that graduated in 1989 or earlier. also supporting this pattern, the 15/54 individuals (27.8%) who graduated in 1989 or earlier were also more likely to never eat and drink in handling areas while only 7/76 (9.2%) who obtained their degree in 2010 or later stated the same. an additional chi-square test comparing this same habit against responses about length of practice (categorised as 5 years or less, 6–15 years, and more than 15 years) also provided evidence for a significant relationship (x2(4) = 9.67, p = 0.046), demonstrating a similar trend in which those with less experience were more likely to eat and drink in handling areas. this is illustrated by the fact that 41/108 respondents (38.0%) in practice for more than 15 years were less likely to eat and drink in handling areas than the 27/45 respondents (60.0%) practicing for at most 5 years. additionally, those 7/45 respondents (15.6%) practicing for at most 5 years were less likely to never eat and drink in handling areas than those 24/108 (22.2%) in practice for more than 15 years. since these data were self-reported, there may be potential bias in the responses given. zoonotic disease reporting as far as the reporting of zoonotic disease and infections, 199/215 (92.6%) respondents indicated they had diagnosed zoonotic disease in animals in the past 5 years (see table 5). the 10 most frequently diagnosed zoonotic diseases in animals in order of most frequent to least frequent were: ringworm / dermatophytosis, leptospirosis, roundworms, giardia infection, hookworms, lyme disease, scabies, salmonellosis, toxoplasmosis, and methicillin-resistant staphylococcus aureus (mrsa). 60/214 (28%) respondents indicated they had been infected with a zoonotic disease in practice, with 10 respondents indicating that they had had > 1 zoonotic disease. a total of 66 cases of zoonotic disease, of which 36/65 (55.4%) were not medically confirmed, were listed by these 60 veterinarians (see table 6). the most common zoonotic disease that was reported was dermatophytosis (also referred to as microsporum or ringworm) (n = 34), but only 14/72 (19.4%) cases were reportedly medically confirmed. when conducting a chi-square test between years in practice and whether respondents had been infected with a zoonotic disease at their workplace, no significant relationship was found (x2(3) = 1.61, p = 0.447). additionally, similar insignificant results were found when running chi-square tests between contracting zoonotic diseases and respondent’s year of graduation, sex, knowledge about the one health initiative, having written infection control guidelines, and eating and drinking in animal handling areas. low respondent counts limited the ability to statistically investigate potential relationships between contracting zoonotic diseases in the workplace with cleaning tables and / or frequency of handwashing.   diagnosed cases no. of respondents % more than 10 133 61.9% 2–5 32 14.9% 6–10 26 12.1% none 16 7.4% one 8 3.7% total 215 100% table 5: number of diagnosed cases of zoonotic disease in animals within the past 5 years as reported by veterinarians in michigan.   disease or condition no. of cases medically confirmed no. % ringworm / dermatophytosis / microsporum 34 14 41% cryptosporidiosis 6 1 17% cat scratch disease / bartonellosis 5 3 60% scabies 4 1 25% salmonellosis 3 2 67% campylobacteriosis 2 2 100% giardiasis 2 1 50% leptospirosis 2 0 0% abscess 1 1 100% ehrlichiosis 1 1 100% enteritis 1 0 0% erysipelas 1 0 0% orf 1 1 100% psitticosis 1 1 100% strep 1 1 100% toxoplasmosis 1 1 100% total 66 30 45% table 6: zoonotic diseases reported by veterinarians in michigan.   one health considerations a number of individual factors were examined for potential relationships with knowledge about the one health initiative. a chi-square test assessing the association between respondents’ knowledge about the one health initiative and length of practice demonstrated a significant relationship (x2(2) = 16.28, p < 0.001). although all individuals practicing 5 years or less were familiar with this concept, 31/108 (28.7%) of veterinarians practicing more than 15 years had no knowledge about the initiative. additionally, the year of veterinary degree completion was also statistically significant (x2(3) = 15.89, p = 0.001). a total of 71/76 (93.4%) of those graduating in 2010 or later were familiar with the initiative, and this familiarity decreased to 37/54 (68.5%) among individuals graduating in 1989 or earlier. attending a continuing education (ce) lecture or completing ce credits on zoonotic diseases in the past 3 years was also found to be related to knowledge about one health (x2 (1) = 4.75, p < 0.05), such that, while 115/137 (83.9%) of respondents partaking in this educational opportunity were familiar with one health, 40/57 (70.2%) of those not partaking in such an activity were familiar with the initiative. sex also appeared to have a relationship with familiarity with the one health initiative (x2(1) = 3.92, p = 0.048). while 127/154 (82.5%) of women were aware of one health, familiarity decreased more than 12 percentage points (41/59 [69.5%]) among men. this may have been due to the fact that women comprised a vast majority 61/76 (80.3%) of respondents who completed their degree in 2010 or later as compared to those earning their degree 1989 or earlier 23/54 (42.6%). 185/215 (86%) respondents indicated they knew who to contact if a potential case or outbreak of zoonotic disease was suspected. however, 99/215 (46.1%) respondents indicated there were ways that public health agencies could better assist with issues involving zoonotic diseases and an additional 95/215 (44.2%) were unsure if there were ways that public health agencies could better assist with issues involving zoonotic diseases. the four ways most commonly listed in order of frequency were: maintaining a website with information for veterinarians on zoonotic diseases, providing written information for clients on awareness and prevention of zoonotic diseases, providing written information about local regulations (e.g. rabies laws) and notifiable diseases, and providing written information for veterinarians on recognition and control of zoonotic diseases (see table 7). the other suggestions respondents gave for ways that public health agencies could better assist with issues involving zoonotic diseases included: ‘better authority to enforce needs for protecting from zoonotic disease (no one enforced the legal need for euthanasia of a rabies suspect, neurologic unvaccinated cat). i was left with an order to euthanise from the health department and no backup to make it happen.’ ‘i've noticed over my practice life (25 years) that the public seems to be more uninformed about rabies with time. people really don't know anything about it, don't understand how deadly it is – since our public health system is likely irretrievably broken, not sure how to mount an educational campaign that would effectively teach people about it, but i do find the ignorance pretty frightening.’ ‘more consistency in local regulations and local interpretation of state law. for instance, i am near border of three counties and in cases of bites by owned pets, every county has a different interpretation of state guidelines as to when rabies testing is recommended vs when home quarantine or quarantine at animal control is the allowable option. makes it difficult as a practitioner because clients get conflicting recommendations.’ ‘more money for testing animals for rabies.’ ‘public health addressing the public in general. talking to people about the importance of getting their animals vaccinated, tested and preventatives. if all health care workers discussed with people the importance of these things then veterinarians would have greater compliance and not be looked as the bad guy just looking for money.’ ‘television – mail flyers.’   ways public health could better assist veterinarians in dealing with zoonotic disease no. selected % website with zoonotic disease information for veterinarians  86 86.9% written information for clients on zoonotic disease awareness and prevention 76 76.8% written information about local regulations (e.g. rabies laws) and reportable diseases 75 75.8% written information for veterinarians on zoonotic disease recognition and control 73 73.7% meetings or ce on zoonotic disease held by the public health department 72 72.7% easier access to specific individuals at the public health department for zoonotic disease consultations 47 47.5% on-site educational presentations or training for veterinarians and staff 42 42.4% recorded hotline messages about current zoonotic disease concerns 27 27.3% other* 7 7.1% total 99   table 7: suggestions from michigan veterinarians of ways public health could better assist with zoonoses awareness and prevention. *other suggestions are provided in the text of the article.   discussion the objective of this study was to determine the extent to which practicing veterinarians in michigan engaged in commonly recommended practices for the prevention of zoonotic diseases. the present study found that, of those responding, most 161/214 (75.2%) agreed that it was very important for veterinarians to educate clients on prevention of zoonotic diseases; however, relatively few 77/214 (36%) initiated discussions about zoonotic diseases with clients on a daily basis. additionally, only 137/214 respondents (64%) indicated that they had client education materials on zoonotic diseases available in their practices. these findings are similar to those of lipton et al. (2008) where only 203/356 (57%) of those veterinarians surveyed indicated that they had client education materials on zoonotic diseases available in their practices. stull et al. (2012) found that of pet owners who had taken their pet to a veterinarian in the past year, only 27% reported having ever received information regarding zoonotic diseases. veterinarians, health care professionals (e.g. physicians, physician assistants, nurse practitioners, nurses), public health professionals, and wildlife biologists have necessary roles to play in the prevention of zoonotic diseases and have contact with the public in different settings and for different reasons. the one health initiative stresses communication, coordination, and collaboration among human, animal, environmental health, and other relevant partners (centers for disease control and prevention, 2020b) in order to decrease the incidence of zoonotic diseases. respondents to this survey indicated an interest in increasing communication between human and veterinary medicine and a desire for increased assistance from public health agencies regarding zoonotic disease prevention. in this survey of michigan veterinarians, 99/215 (46.1%) of respondents indicated there were ways that public health agencies could better assist with issues involving zoonotic diseases. in protecting the public’s health from zoonoses, the authors believe a one health approach should be taken. the one health concept is an integrative effort of multiple disciplines (human, animal, and environmental health) working locally, nationally, and globally to achieve optimal health for people, animals, and the environment (ryu et al., 2017). furthermore, the authors believe local public health agencies should take the initiative to begin developing a sustainable collaborative relationship with community veterinarians. this relationship could have four immediate goals: create a one health community infrastructure; form a community one health team; develop a community zoonotic disease website that would be a resource to health care professionals, veterinarians, public health professionals, state and / or federal wildlife management agencies, and the community; and create and distribute to all community veterinarians and health care workers zoonotic disease information handouts that they can share with patients / clients about the prevention, detection, treatment and elimination of zoonotic disease in the community. one campaign that one health team members could use to build and strengthen their interdisciplinary collaborations may be the annual one health day. this day was initiated in 2016 by the one health commission, the one health platform, and the one health initiative team. international one health day is officially celebrated around the world every year on november 3 (one health commission, 2020). this could be a day on which an annual community education seminar (ceu) about zoonotic disease is offered to people involved in health care, animal control, public health, local government and public education. the one health team could also assist in creating / promoting public service announcements (psas) about zoonotic disease to be shared in the community by way of broadcast and social media. over a multiyear timeline, public health agencies working with the one health team could develop infection control guidelines for the community. additionally, there should be a system in place for the local government to enforce infection control guidelines for the community. these guidelines should be congruent with state and national guidelines. in addition, veterinarians should have infection control guidelines for all staff members and the public in their practice (the national association of state public health veterinarians veterinary infection control committee, 2015; the national association of state public health veterinarians animal contact compendium committee, 2017). zoonotic diseases may receive more attention in the future because of coronavirus disease (covid-19). according to the world health organization (2020), ‘this infectious disease caused by a newly discovered coronavirus has become a pandemic. currently, the source of sars-cov-2, the coronavirus (cov) causing covid-19 is unknown. all available evidence suggests that sars-cov-2 has a natural animal origin and is not a constructed virus. sars-cov-2 virus most probably has its ecological reservoir in bats sars-cov-2 belongs to a group of genetically related viruses, which also include sars-cov and a number of other covs isolated from bat populations. mers-cov also belongs to this group, but is less closely related.’ veterinarians and public health professionals should seize the opportunity of the current focus on zoonotic conditions to be included in decisions that are made at the local, state, and national level in regard to these infectious diseases. this study was able to capture the strong support and desire among veterinarians to collaborate with health professionals. the following comments corroborate the aforementioned discussion by demonstrating a need for increased communication between veterinarians and physicians (cornerstones to one health): ‘human health care needs to help veterinary health by supporting the importance of vaccines, preventative and testing.’ ‘human medical personnel tend to be vastly ignorant of zoonotic diseases.’ ‘i feel i talk about parasites with families with puppies and children almost every time. and we discuss lepto daily. but fail at other zoonotic diseases. i state that usually they never hear anything from their doctor or pediatrician and they always confirm it. it seems in my area a lot of ignorance or not taking the time to discuss these things from human health care.’ ‘i feel that human health professionals (mds, dos, etc.) lack zoonotic disease familiarity.’ ‘i think this is a great survey that might bring to light just how little the human medical world knows and educates their clients about diseases they can give to or get from their pets.’ ‘medical professionals do not appear to be receptive to our recommendations and often give differing medical advice than i would recommend. in realising the differences (and understandable confusion by clients) i’ve reached out to discuss it with them and have been met with either no response (won’t return calls) or blatant disrespect for our profession’s knowledge. i’ve reached out to three different mds, two never returned my calls even with repeated attempts, and the one that did not respect our profession’s knowledge of zoonotic transmission.’ ‘i think it would be helpful to educate mds on this topic, vets realise they know more than md on this.’ it appears that, among the respondents, the amount of time practicing as a veterinarian does not expose respondents to zoonotic diseases. of the zoonotic diseases most frequently transmitted to veterinarians in this study, ringworm was the most frequently reported and medically confirmed (see table 6). ringworm was also the most frequently reported zoonotic disease diagnosed in animals in this study. ringworm is a fungal dermatologic (skin disease), treatable with antifungal medications. there is no known preventative for ringworm besides avoiding contact with infected people, animals, and objects. the second most frequently diagnosed zoonotic disease in animals in this study was leptospirosis. leptospirosis was the most commonly 178/213 (83.6%) veterinarian-initiated zoonotic disease discussion topic with clients (see table 4). leptospirosis has been reinstated as a u.s. nationally notifiable condition as of january 2013 and the incidence rate per 100,000 increased from 0.03 to 0.04 during 2016–2018 (centers for disease control and prevention, 2021). since clients only initiated discussions about this topic 3.3% of the time in the present study, this finding underscores the need for public education about zoonotic diseases. dogs can be vaccinated annually to prevent many strains of leptospirosis infection, but clients may not be aware or understand the implications of vaccination. additional survey respondent comments underscore the need for public education about zoonotic diseases: ‘i appreciate this survey because i think more work should be done to educate the public about all of the different zoonotic diseases.’ ‘the present corona virus issue we are dealing with makes us all hyper-vigilant about the possibility of disease transmission and what we are able to do to minimise the risk.’ ‘there is too much responsibility on veterinarians to educate the general public about zoonotic disease. it needs to start with public awareness, adoption facilities, etc.’ ‘there should be state level phone helpline just like poison control help line.’ ‘i would like the state to send out a monthly report of all cases reported and summarising regions where they were diagnosed. i will follow-up personally but very important sort and unfortunately neglected.’ ‘this is an important topic and i am glad you are studying it. i think as the older generation of practitioners who in my experience don't seem to be that concerned about public health in day practice phases out it is a great opportunity to make public health more visible in private practice where we can make a big impact on how our clients interact with their pets and other animals.’ the authors suggest that veterinarians make available attractive, easily read, client educational materials that discuss common zoonotic diseases transmissible from pets and offer practical and effective advice for control. the centers for disease control and prevention maintains several webpages regarding zoonotic diseases and their prevention, including ‘healthy pets, healthy people’, which has links to many client educational resources, such as brochures and posters (centers for disease control and prevention, 2020a). this study had several limitations. the response rate being 402/3410 (11.8%) may have contributed to non-response bias, which may have skewed gender and other differences in results. this bias in response rate may have been due to the time constraint involved. the veterinarians were given less than 30 days to respond to the survey; more time may have resulted in a better response rate. the survey was electronic and not all respondents answered all questions. hohwü et al. (2013) wrote that response rates in most studies have been reported to be lower in web-based questionnaires than in paper-based questionnaires. perhaps a paper survey would have received a better response rate and completion rate. the declining response rates in population-based surveys in general are a challenge to epidemiology (hohwü et al., 2013). the survey was sent via email (obtained from michigan lara), some of which were personal emails, leading to at least three replies the authors perceived as negative feedback. this survey did not have promotion from an organisation like a veterinary medical association or public health institution, which could have increased the response rate. this study took place in march 2020, during which a united states national emergency was announced and the spread of the sars-cov2 virus would eventually be classified as a pandemic. this may have decreased the participation of veterinarians in this survey. the survey question asking for the type of practice allowed respondents to choose more than one option, as well as write in options which made analysis of this question difficult. respondents were allowed to write in their veterinary degree granting institution and some chose to provide acronyms that the author could not confirm. overall, this study found that veterinarians in the state of michigan understood the importance of preventative measures and wished to further work alongside health professionals in human health to prevent (and / or treat) zoonotic diseases. one initiative dedicated to doing this is the one health campaign, with which recent veterinary graduates (since 2010) were more familiar. veterinarians expressed concern that human medical education also needs to stress the importance of one health and the communication between veterinary and human medical fields. additionally, many recent veterinary school graduates reported not practicing zoonotic disease prevention practices, such as not eating / drinking in animal handling areas, which may need to be stressed in veterinary medical education. there also appears to be a need for public health agencies to increase their communication with, and support of, veterinarians in the effort to prevent zoonotic disease transmission including public education on this topic. nevertheless, veterinarians acknowledge the need and express willingness to cooperate in a multidisciplinary approach to addressing zoonotic illnesses. with the third covid-19 wave gaining momentum at the time of this writing, this study points to encouraging signs for the future in establishing concerted efforts in preventing and treating zoonoses, with veterinarians as key players.   footnotes survey instrument available from the corresponding author. qualtrics, version march 2020, provo, ut. spss, version 25.0, spss inc, armonk, ny.   conflict of interest the authors declare no conflicts of interest. acknowledgements: we thank c. chen, central michigan university statistical consulting center, for providing an independent review of our study to determine that our findings and conclusions were appropriate given the sample design and sample size and potential biases. thank you to kaylan fitch, mph, for the technical assistance with qualtrics software.   references bidaisee, s. & macpherson, c.n.l. (2014). zoonoses and one health: a review of the literature. journal of parasitology research. doi: https://doi.org/10.1155/2014/874345 centers for disease control and prevention. (2020a). healthy pets, healthy people. [online] available from: https://www.cdc.gov/healthypets/index.html [accessed 18 nov 2020]. centers for disease control and prevention. (2020b). one health. [online] available from: https://www.cdc.gov/onehealth/index.html [accessed 24 mar 2020]. centers for disease control and prevention. (2021). leptospirosis: healthcare workers. [online] available from: https://www.cdc.gov/leptospirosis/health_care_workers/index.html [accessed 11 apr 2021]. cutler, s.j., fooks, a.r. & van der poel, w.h.m. (2010). public health threat of new, reemerging, and neglected zoonoses in the industrialized world. emerging infectious diseases. 16(1), 1–7. doi: https://dx.doi.org/10.3201%2feid1601.081467 hohwü, l., lyshol, h., gissler, m., jonsson, s. h., petzold, m. & obel, c. (2013). web-based versus traditional paper questionnaires: a mixed-mode survey with a nordic perspective. journal of medical internet research. 15(8). doi: https://doi.org/10.2196/jmir.2595 khan, s., siddique, r., shereen, m.a., ali, a., liu, j., bai, q., bashir, n. & xue, m. (2020). emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2: biology and therapeutic options. journal of clinical microbiology. 58(8). doi: https://doi.org/10.1128/jcm.01297-20 lipton, b.a., hopkins, s.g., koehler, j.e. & digiacomo, r.f. (2008). a survey of veterinarian involvement in zoonotic disease prevention practices. journal of the american veterinary medical association. 233(8), 1242–1249. doi: https://doi.org/10.2460/javma.233.8.1242 minnesota department of health. (2019). zoonotic diseases: disease transmitted from animals to humans. [online] available from: https://www.health.state.mn.us/diseases/animal/zoo/index.html [accessed 11 apr 2021]. one health commission. (2020). one health day. [online] available from: https://www.onehealthcommission.org/en/events_since_2001/one_health_day/ [accessed 18 nov 2020]. ryu, s., kim, b.i., lim, j.-s., tan, c.s. & chun, b. c. (2017). one health perspectives on emerging public health threats. journal of preventive medicine & public health. 50(6), 411–414. doi: https://doi.org/10.3961/jpmph.17.097 stull, j.w., peregrine, a.s., sargeant, j.m. & weese, j.s. (2012). household knowledge, attitudes and practices related to pet contact and associated zoonoses in ontario, canada. bmc public health. 12, 553. doi: https://doi.org/10.1186/1471-2458-12-553 the national association of state public health veterinarians animal contact compendium committee, daly, r. f., house, j., stanek, d., & stobierski, m. g. (2017). compendium of measures to prevent disease associated with animals in public settings. journal of the american veterinary medical association. 251(11), 1268–1292. doi: https://doi.org/10.2460/javma.251.11.1268 the national association of state public health veterinarians veterinary infection control committee. williams, c.j., scheftel, j.m., elchos, b.l. & hopkins, s.g. (2015). compendium of veterinary standard precautions for zoonotic disease prevention in veterinary personnel. journal of the american veterinary association. 247(11), 1252–1277. doi: https://doi.org/10.2460/javma.247.11.1252 woolhouse, m.e.j. & gowtage-sequeria, s. (2005). host range and emerging and reemerging pathogens. emerging infectious diseases. 11(12), 1842–1847. doi: https://dx.doi.org/10.3201%2feid1112.050997 world health organization. (2020). coronavirus disease (covid-19). [online] available from: https://www.who.int/news-room/q-a-detail/q-a-coronaviruses [accessed 18 nov 2020].   supplementary files fig 1. practice type – surveyed michigan veterinarians fig 2. zoonotic disease discussion frequency fig 3. percent of surveyed michigan veterinarians who diagnosed cases of zoonotic disease in animals intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. thank you to our 2022 reviewers | veterinary evidence skip to main content editorial thank you to our 2022 reviewers kit sturgess, ma vetmb phd certvr dsam certvc frcvs 1 vet freedom ltd brockenhurst, hampshire, so42 7qt * corresponding author email: kit@vetfreedom.com vol 8, issue 1 (2023) published: 17 feb 2023 doi: https://doi.org/10.18849/ve.v8i1.662 as 2023, dawns we are faced with a very different world than at the start of 2022, covid-19 is in the rear-view mirror, but we now face the war in ukraine, energy prices and inflation. perhaps this is a glimpse of the ‘new world’ where we will be continually challenged by crisis whether it be conflict, infectious disease or the impacts of global warming. on a more positive note it has been another busy and productive year for veterinary evidence as we strive to continually improve the journal whether you are a reader, author or reviewer. in april we said ‘goodbye’ to daniel edwards who had covered bridget sheppard’s maternity leave as managing editor. i would like to take the opportunity to thank dan for all his hard work for veterinary evidence initiating a number of projects that have come to fruition through the year and to welcome bridget back. as veterinary evidence has grown, we have been fortunate to be able to expand our staff to meet the need and ensure efficient turnaround of submissions so another welcome, william smith has joined the team and is now a permanent full time editorial assistant. it is not just staff changes that happened in 2022, we have also improved the governance of veterinary evidence with the appointment of new board members and creation of a deputy editor-in-chief position ably filled by louise buckley. we also submitted a successful application to cope (the committee on publication ethics) further strengthening the journal’s oversight and reputation. we have had a major website redesign, now live, which has greatly improved the look, feel, and functionality of veterinary evidence for all users. readers can find relevant papers quickly and efficiently. our student awards continue to be a success and i would like to thank the whole team of staff and reviewers for turning round these submissions so quickly. i had the pleasure of talking to the prize-winning authors and it was great to hear their enthusiasm but also how much they have valued the help and support from the journal. we have also been developing our processes for reviewing papers to make sure that papers are ready to go out for review. we are working on ways to make sure that, for papers requiring revision, authors respond to each of the comments made by reviewers, and reviewers can quickly see that there has been an author response to their comments and suggestions. a new submission system, editorial manager, has been implemented that should make life easier for everyone as well as provide accessible data on papers as they go through the system so we can see what we do well and where we can do better. none of this would be possible without the input from our reviewers and i would like to take this opportunity to say a huge thank you to all our reviewers and everyone who has served on the editorial board this year for their tireless efforts on behalf of veterinary evidence – without your support the journal could not exist. this year the board has again had three online meetings, which have been essential in helping develop the strategy for veterinary evidence such as how we ensure our knowledge summaries remain current, what literature should be included in knowledge summaries and how we improve the reviewer and author experience. once again, a massive thank you to everyone who works for and supports veterinary evidence, wishing you all a safe and productive 2023.   kit sturgess editor-in-chief     fergus allerton isabel amores-fuster davina anderson jonathan anderson judy bettridge paul bloom jenny brown louise buckley fernanda camacho john campbell deirdre campion tom candy john carr marios charalambous tim charlesworth john chitty louise clark jacqueline cole francesca compostella michelle dawson nicole detoit jane dobson jacklyn ellis nathan erickson erik fausak john fishwick aaron fletcher barny fraser mary fraser merran govendir mathilde granger kathryn griffiths danielle gunn-moore matthew gurney emily hall alastair hayton guy hinnigan jodie hughes elizabeth jackson simone kirby clare knottenbelt david leicester william mcfadzean anna meredith tristan merlin joanna morris andy morris sue murphy christopher norkus conor o'halloran maureen o'mara catrina pennington roberta perego kiro petrovski robert pettitt simon platt david ramey ian ramsey nicki reed kerry rolph silke salavati richard saunders rebecca schofield ellen singer fiona smith lesca sofyan eva spada fabio stabile jonathan statham essa suleman adam swallow severine tasker theodora tsouloufi hélène vandenberghe nick wojciechowski najat yahia maurice zandvliet   intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use.   veterinary evidence is an rcvs knowledge initiative. issn: 2396-9776 first floor, 10 queen street place, london ec4r 1be resources student awards staff login policies privacy policy accessing information policy cookie declaration terms of use copyright notices stay connected podcasts twitter facebook instagram linkedin back to top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443. comparison of the effect of marine-derived omega-3 fatty acids (n-3 fas) as an adjunct to a non-steroidal inflammatory drug (nsaid) therapy vs nsaid therapy alone, for dogs with osteoarthritis a knowledge summary by lok yee stephanie wong dvm candidate 1* merran govendir phd bvsc med(higher ed) fherdsa 1 1sydney school of veterinary science, the university of sydney, australia *corresponding author (lwon6099@uni.sydney.edu.au) vol 7, issue 1 (2022) published: 12 jan 2022 reviewed by: aaron fletcher (bvetmed mrcvs) and catrina pennington (bvm&s mrcvs) next review date: 15 jul 2023 doi: 10.18849/ve.v7i1.527 pico question does treatment with a non-steroidal anti-inflammatory drug (nsaid) with supplementation of marine-derived  omega-3 fatty acids (n-3fas) compared to the nsaid alone, result in an increased ability to exert force by the osteoarthritic limb(s) of dogs or alleviate other measures of osteoarthritis?   clinical bottom line category of research question treatment the number and type of study designs reviewed two prospective, block-randomised, clinical trials strength of evidence none outcomes reported kwananocha et al. (2016) investigated administration of carprofen supplemented with marine-derived n-3 fas, to carprofen alone, administered over 4 weeks. vijarnsorn et al. (2019) investigated administration of firocoxib supplemented with n-3fa, to firocoxib alone, for 4 weeks.  there were no statistical differences between treatment groups at week 2 and week 4 post-treatment for either study. both studies also reported orthopaedic assessment score (oas) based on scoring the extent of patient lameness and pain in the affected joint. there were no statistical changes in oass between treatment groups at week 2 or week 4 post-treatment for either study conclusion there is no evidence that marine-derived n-3 fas provide additional benefit when used as adjunctive agents with nsaids for the treatment of canine osteoarthritis   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a 4 year old rottweiler (male, neutered) is being treated with nsaids to manage osteoarthritis (oa) of the hip joints. the owners want to try omega-3 fatty acids (n-3 fas) supplementation, and you (the clinician) are unaware about the evidence-basis for this. the evidence two prospective, block-randomised clinical trials were found to match the pico. both studies assessed the effects of administering the same n-3 fas with nsaid therapy compared to nsaid therapy alone. the n-3 fas was a green-lipped mussel extract referred to as pcso-524 marketed as antinol® (pharmalink international ltd [hong kong]). pharmalink provided financial support to both studies, and the same investigators performed both studies. both studies recruited canine hospital outpatients with a diagnosis of oa. patients were randomly assigned to treatment groups. one treatment group was treated with a veterinary registered nsaid, and another was treated with the same veterinary registered nsaid and n-3 fas. both groups were administered their respective medications twice daily for 4 weeks. patients underwent force plate gait analysis, gait observation and an orthopaedic examination that resulted in an oas (moreau et al., 2003) at week 0, and week 2 and week 4 post-treatment (i.e. weeks 6 and 8 of both studies). both studies found no significant benefit in the supplementation of n-3 fas with nsaids, versus nsaids alone with respect to increasing the peak vertical force (pvf) generated by the arthritic limb, nor any improvement in the oas. there are study design limitations in both studies such as inadequate sample size, and other factors such as an insufficient dosage, insufficient duration of dosage and brief study duration. summary of the evidence kwananocha et al. (2016) population: dogs from a client-owned referral population with a history of hindlimb lameness and radiographic changes consistent with hip and/or stifle oa older than 2 years old and within a bodyweight range of 18–50 kg. sample size: 40 dogs (10 dogs in each group). 49 dogs were initially enrolled, and nine were lost to the study or dismissed. intervention details: before the start of the study: washout period of 2 weeks for nsaids and oral nutraceuticals. washout period of 4 weeks for corticosteroids and injectable sodium-pentosan polysulphate. dogs were examined and classified into two categories based on the subjective oas system (moreau et al., 2003) to have: mild/moderate oa; severe oa. allocation of treatment groups at the start of the study (week 0): perna canaliculus lipid complex (pcso-524®) (10 dogs). each pcso-524® capsule contained: pcso-524® (50 mg); olive oil (100 mg); d-alpha-tocopherol (0.225 mg); dosage: two capsules, q12hrs po, for 4 weeks. glucosamine and avocado/soybean unsaponifiables (marketed as dasuquin® by nutramax laboratories veterinary sciences, inc. [usa]) group (10 dogs); dosage: one tablet, q12hrs po for 4 weeks. carprofen group (10 dogs); dosage = 2.2 mg/kg, q12hrs po for 4 weeks. combination group (10 dogs); dosage = carprofen: 2.2mg/kg, q12hrs po; and pcso-524®: two capsules, q12hrs po; both for 4 weeks. only the carprofen and combination treatment groups are relevant to the pico question.   force plate gait analysis to obtain peak vertical force (pvf) values: a single handler led a dog at a trotting pace along a 10 m walkway embedded with dual force plates to obtain a minimum of four valid pvf values. force plate gait analysis was performed at weeks 0, 6 (2 weeks post-treatment) and 8 (4 weeks post-treatment). oas: an orthopaedic examination was performed by a single veterinarian who was blinded to the treatment assignment for each patient. scores for clinical parameters (lameness, articular pain for the hip, and stifle joint) were tallied. oas was performed at weeks 0, 6 (2 weeks post-treatment) and 8 (4 weeks post-treatment). study design: prospective, block-randomised, single-blinded, clinical trial. outcome studied: pvf and oas. main findings (relevant to pico question): pvf results: no significant treatment effects between treatment groups at week 0. significant effects of time were found within treatment groups: when comparing week 6 to week 0, pvf values for the carprofen group and combination group were significantly greater with mean ± sd change 2.58 ± 2.48 % body weight (bw) (p = 0.028) and 4.39 ± 2.56 % bw (p = 0.001), respectively. comparison of week 8 vs week 0, pvf values for carprofen group and combination group were significantly increased with mean ± sd change 4.23 ± 2.33 % bw (p = 0.001) and 5.36 ± 2.98 % bw (p = 0.001), respectively. comparison of week 8 and 6 to week 0, there were no significant changes in pvf values between groups. oas results: no significant treatment effects between treatment groups at week 0. significant time effects were found within treatment groups: when comparing week 8 to week 0, oas for the carprofen and combination groups were significantly greater (p = 0.048 and 0.029, respectively). comparison of week 8 and 6 to week 0, there were no significant changes in oas values between groups. limitations: details regarding the classification of dogs into mild/moderate or severe oa were not provided. it was unclear which limb was to be followed for force plate gait analysis in dogs with bilateral oa. the process of randomisation was not specified. the conditions in which dogs were managed during the study period were unknown. a delay in evaluating outcomes at 2and 4-weeks post-treatment may have also allowed for the exacerbation of any variation, possibly impacting the validity of the results. study period (treatment duration = 4 weeks) may have been too short to detect significant differences (zawadzki et al., 2013). analysis of variables at pretreatment (week 0), body condition score was borderline significant (p = 0.55). this may be a confounder, and it is possible that end-of-treatment results are not solely due to the intervention (pannucci & wilkins, 2010). no sample size calculation was reported. the repeatability of the study may be limited by the lack of detail in the methodology. pvf and oas are surrogate outcomes and may not accurately reflect if the patient's mobility has improved or pain has reduced (administration usfad, n.d.). vijarnsorn et al. (2019) population: dogs from a client-owned referral population with a history of chronic oa of the hip and/or stifle joints (hindlimb lameness and joint pain) and consistent radiographic changes, older than 1 year old, and a bodyweight of at least 20 kg. sample size: 79 dogs. initially, 82 dogs were enrolled, but three were lost to the study or dismissed. intervention details: before the start of the study: a washout period of 2 weeks for nsaids and oral nutraceuticals. a washout period of 4 weeks for corticosteroids and injectable sodium-pentosan polysulphate. a single veterinarian examined and classified all dogs into two categories based on the subjective orthopaedic assessment scoring (oas) system (moreau et al., 2003): mild/moderate oa; severe oa. allocation of treatment groups at the start of the study (week 0): firocoxib group (24 dogs); dosage: firocoxib: 5 mg/kg, q24hrs po; and pcso-524® placebo: 4 capsules/day, q24hrs po for 4 weeks. pcso-524® group (27 dogs). each pcso-524® capsule contains: pcso-524® (50 mg); olive oil (100 mg); d-alpha-tocopherol (0.225 mg); dosage: firocoxib placebo (containing starch only); and pcso-524®: 4 capsules/day, q24hrs po for 4 weeks. combination group (28 dogs); dosage: firocoxib: 5 mg/kg, q12hrs po; and pcso-524®: 4 capsules/day, q24hrs po for 4 weeks. the pcso-524® only treatment group is not relevant to the pico question.   force plate gait analysis to obtain peak vertical force (pvf) values: a single handler led a dog across a 10 m walkway embedded with dual force plates at a trotting pace to obtain a minimum of five valid pvf values. the limb with the smaller pvf value at week 0 was followed throughout the study as the index limb. force plate gait analysis was performed at weeks 0, 6 (2 weeks post-treatment) and 8 (4 weeks post-treatment). oas: the orthopaedic examination was performed by a single veterinarian who was blinded to the treatment assignment. scores for a clinical parameter (lameness, articular pain for the hip and stifle joint) were summed. oas was performed at weeks 0, 6 (2 weeks post-treatment) and 8 (4 weeks post-treatment). owner questionnaire: owners completed a canine brief pain inventory (cbpi) questionnaire (brown et al., 2008), which contains: a severity of oa pain question set to generate a pain severity score (pss). a question set relating to how oa pain interferes with their pet's daily activities to generate a pain interference score (pis). the questionnaire was undertaken weeks 0, 6 (two weeks post-treatment) and 8 (4 weeks post-treatment) by owners. study design: prospective, block-randomised, double-blinded clinical trial. outcome studied: pvf values. oas. pss. pis. main findings (relevant to pico question): pvf results: no significant effects between treatment groups. significant effects of time were found within treatment groups: when comparing week 6 to week 0, pvf values for firocoxib group and combination group were significantly greater with mean ± sd change 03 ± 0.67% body weight (bw) and 2.74 ± 4.41% bw, respectively (p < 0.05 for both). when comparing week 8 to week 0, pvf values for firocoxib group and combination group were significantly increased (p < 0.05) with mean ± sd change 3.25 ± 4.13% bw and 4.11 ± 4.69% bw, respectively (p < 0.05 for both). when comparing week 6 and 8, there were no significant changes in pvf values between groups. oas results: there were no significant treatment effects within and between treatment groups. subjective cbpi questionnaire there were no significant treatment effects for pss and pis significant effects of time were found for pis: when comparing week 8 to week 0, pis was significantly lower in the firocoxib group (p < 0.05). three dogs were lost to follow up due to cranial cruciate ligament rupture (n=1), myasthenia gravis (n=1) and vehicular accident (n=1). limitations: study period (treatment duration = 4 weeks) may have been too short to detect significant differences (zawadzki et al., 2013). the number of patients in firocoxib group was less than the calculated sample size. inadequate sample sizes can result in false-negative results due to insufficient power to detect real differences between treatment groups (sargeant et al., 2014). details regarding the classification of dogs into mild/moderate or severe based on the severity of oa is unclear. losses to follow-up was not accounted for in the sample size calculation. whether allocation concealment was performed to prevent selection bias was not reported (this may be acceptable as this is rarely reported in veterinary trials) (sargeant et al., 2014). there were intrinsic differences in caregiving between treatment groups, such as the conditions in which the dogs were managed during the study period, resulting in bias. pvf, oas, pss and pis are surrogate outcomes and may not accurately reflect if the patient's mobility has improved or pain has reduced (administration usfad, n.d.). appraisal, application and reflection osteoarthritis is a prevalent condition in dogs, with reports of up to 20% of all dogs over 1 year old, in north america affected (anderson et al., 2020). while dogs are typically managed with a multimodal approach involving weight control, exercise moderation and analgesics/anti-inflammatories such as nsaids; (anderson et al., 2020; and belshaw et al., 2016) nutraceuticals such n-3 fas supplements are marketed as an adjunctive therapy to nsaids, for both humans and companion animals (beale, 2004; and johnson et al., 2020). pcso-524® is a source of n-3 fas derived from the new zealand green-lipped mussel, perna canaliculus (kean et al., 2013). it is reported that ingested long-chain n-3 polyunsaturated fatty acids (pufas) are incorporated into inflammatory cell phospholipids resulting in a decrease in the amount of arachidonic acid available for the production of aa-derived eicosanoids, such as inflammatory prostaglandins (calder, 2009). additionally, n-3 pufas may influence inflammatory cytokine production and transcription factors that regulate inflammatory gene expression (calder, 2009). nsaid therapy is considered a mainstay therapy in the management of canine oa (innes et al., 2010), and the efficacy of nsaid supplementation with n-3 fas for the treatment of canine oa does have a theoretical justification.  it is noteworthy that despite a wide search strategy, only two studies were applicable to this pico. both studies used block classification for the severity of oa to ensure even distribution of mild/moderate and severe oa amongst treatment groups adapted from moreau et al. (2003).  as the difference in oa severity is a source of variation between patients, blocking aims to remove some of this variability to emphasise treatment effects (krzywinski & altman, 2014). however, blocking partitions the number of subjects and as the number of treatment groups increases, more subjects are required. blocking may also interfere with maintaining homogeneity between the treatment groups (casler, 2018).  classification of oa severity as either mild/moderate or severe as undertaken in these studies provides some additional areas of concern. firstly, this scoring system is not validated (moreau et al., 2003). secondly, the oas was performed by a single veterinarian in vijarnsorn et al. (2019), and it is unclear whether the oas was performed by a single veterinarian or multiple evaluators in kwananocha et al. (2016).  thirdly, the oas has many subjective parameters, such as assessment of articular pain for the affected joints. the subjective assessment of articular pain can be problematic as it is reported that variability exists between veterinarians in their perception of the level of pain in their canine patients (gruen et al., 2020). randomised allocation of study subjects into treatment groups was performed in both studies. however, the method of randomisation was not reported in kwananocha et al. (2016). as randomisation reduces selection bias during the assignment of treatments (pannucci & wilkins, 2010), the lack of description on the manner of randomisation may cast doubt on the experimental design rigor. to evaluate whether the groups were homogenous before the intervention, the studies undertook statistical analysis of parameters (such as body weight, age, body condition score and breed) between groups. this degree of analysis is discouraged by the consort (consolidated standards of reporting trials) statement as it interferes with proper randomisation within treatment groups (de boer et al., 2015). force plate gait analysis is considered the current gold standard measure of limb function in humans and animals (brown et al., 2013). compared to subjective scoring such as visual observation, it is more sensitive for lameness evaluation (quinn et al., 2007). both studies evaluated peak vertical force (pvf) values generated via force plate gait analysis as an outcome. in bilaterally lame dogs, the index limb (to be followed throughout the study) was elected as the limb with the smaller pvf at week 0 in vijarnsorn et al. (2019), but it was unclear what criteria was used by kwananocha et al. (2016). additionally, peak pvf values and oas are only surrogate indicators and may not accurately reflect improvements in a patient's mobility or whether pain has reduced due to the treatment alone (administration usfad, n.d.). while repeated measurement analysis of pvf values was performed to determine the statistical significance of treatment effects and the effect of time within treatment, only descriptive analyses (i.e. numerical pvf mean values ± sd) were provided for the change in pvf, and no further statistical analyses were reported in both studies (kwananocha et al., 2016; and vijarnsorn et al., 2019). the results provided in both kwananocha et al. (2016) table 3 and vijarnsorn et al. (2019) table 2 must be scrutinised carefully as a greater numerical change from day 28 post-treatment to day 0 pvf value is seen in the combination groups. however, there is no reporting of between group analysis over this time period and consequently no further conclusions can be made, other than within groups. there was no determination of any changes of physiological parameters within the plasma and so there was no evidence that the 3-n fas were absorbed from the gastrointestinal tract. furthermore, the dosage and duration of treatment was possibly insufficient for n-3fas to reach adequate therapeutic levels. the anti-inflammatory effects of n-3 fas are reported dose dependent (calder, 2009) and studies in humans report a daily dosage three times greater than that used in these canine studies (dangardt et al., 2010; and root et al., 2013). another study suggested that a minimum of 70 days of treatment may be required for glucosamine hydrochloride and chondroitin sulphate to take effect in osteoarthritic dogs (mccarthy et al., 2013). additionally, n-3fas were administered daily for 4 weeks to humans and no physiological markers in response to n-3fas administration were detected (root et al., 2013). however, when n-3 fas were administered for 12 weeks to humans, cytokine tumour necrosis factor alpha (tnf-a), interleukin (il)-1β and il-6 had significantly decreased (p = 0.008, 0.023 and 0.035, respectively) compared to the placebo treatment group (dangardt et al., 2010).  sample size calculation was performed and reported in vijarnsorn et al. (2019), but the firocoxib only group did not meet the calculated group size. the insufficient sample size is limiting as it reduces statistical power, which lowers the chance of detecting true treatment effects (button et al., 2013). additionally, the investigators did not account for attrition in their sample size calculation, which is 3.7% in vijarnsorn et al. (2019). this proportion of loss of follow-up is not a concerning source of bias for vijarnsorn et al. (2019); as it has been suggested that losses between 5–20% may confer bias (sargeant et al., 2014). another reason why a larger sample size would be appropriate is to reduce the effect of confounders. this is especially pertinent in kwananocha et al. (2016), wherein body condition score is a possible confounder and may have biased the results. there are evident flaws in the study design in both studies, such as lack of statistical analyses on the mean changes in pvf values rather than the baseline values, short treatment period, and small sample size. additionally, the lack of clarity regarding the randomisation process, absence of sample size calculation and unclear blocking protocols further limits the validity of the results that can be extrapolated from one publication (kwananocha et al., 2016). while the more recent study resolves some of these shortcomings, systematic faults are still present, hindering drawing definitive conclusions about the benefits of n-3 fas supplementation in conjunction with nsaid therapy. the conclusion of this knowledge summary does not align with the conclusions in each study. kwananocha et al. (2016) states: the preliminary results imply the clinical benefits of pcso-524® in combination with carprofen in the treatment of oa (kwananocha et al., 2016). vijarnsorn et al. (2019) states: the results of this study suggested combination of both pcso-524® and firocoxib is more effective in alleviation of inflammation and improvement of weight bearing ability when compared to the uses of either pcso-524® or firocoxib alone (vijarnsorn et al., 2019). both studies were financially supported by the supplier of the pcs0-524®, which may account for the more optimistic conclusions of both studies. a correction has since been published (vijarnsorn et al., 2020) that the competing interests of one of the authors were omitted from vijarnsorn et al. (2019). methodology section search strategy databases searched and dates covered: cab abstracts via web of science (1910—2021) scopus (1970–present) medline via ovidsp (1946—2021) search strategy: (dog or dogs or canine or canines or canis or canid or canids or canidae) and (osteoarthritis or osteo-arthritis or arthritis or "joint disease" or "joint diseases" or djd) and (carprofen or rimadyl or rimifin or canidryl or "carprodyl f" or dolagis or rycarfa or zenecarp or carprogesic or firocoxib or previcox or nsaid or "non-steroidal" or non-steroidal) and ("omega 3" or "omega-3" or "omega 3 oil" or "omega-3 oil" or dha or epa or "eicosapentaenoic acid" or "docosahexaenoic acid" or "hexadecatrienoic acid" or hta or "α-linolenic acid" or "stearidonic acid" or "eicosatrienoic acid" or "eicosatetraenoic acid" or "heneicosapentaenoic acid" or "docosapentaenoic acid" or "clupanodonic acid" or "tetracosapentaenoic acid" or "tetracosahexaenoic acid" or "nisinic acid" or ala or sda or ete or eta or hpa or dpa or "green lipped mussel" or "green-lipped mussel" or mussel or glm or "pcso-524" or "pcso 524") dates searches performed: 15 jul 2021 exclusion / inclusion criteria exclusion: systematic reviews, narrative reviews, in vitro studies, conference papers, book chapters. inclusion: articles relevant to the pico question, randomised controlled trials. search outcome database number of results excluded – irrelevant to pico questions excluded – systematic review excluded – narrative review excluded – in vitro study excluded – conference paper excluded – book chapter total relevant papers cab abstracts 27 10 2 8 0 6 0 1 scopus 28 11 3 10 1 0 1 2 medline 12 6 1 1 3 0 0 1 total relevant papers when duplicates removed 2 n.b a correction to vijarnsorn et al. (2019) has been published (vijarnsorn et al. 2020) conflict of interest the authors declare no conflicts of interest. author contribution: lok yee stephanie wong (lysw) wrote the first draft of the manuscript with feedback from merran govendir (mg). lysw and mg edited the final manuscript and undertook the emendations. references administration usfad. (2018). surrogate endpoint resources for drug and biologic development. [online]. available at: https://www.fda.gov/drugs/development-resources/surrogate-endpoint-resources-drug-and-biologic-development [accessed 25 jul 2021]. anderson, k.l., zulch, h., o'neill, d.g., meeson, r.l. & collins, l.m. (2020). risk factors for canine osteoarthritis and its predisposing arthropathies: a systematic review. frontiers in veterinary science. 7, 220. doi: http://dx.doi.org/10.3389/fvets.2020.00220 beale, b.s. (2004). use of nutraceuticals and chondroprotectants in osteoarthritic dogs and cats. veterinary clinics of north america: small animal practice. 34(1), 271–289. doi: http://dx.doi.org/10.1016/j.cvsm.2003.09.008 belshaw, z., asher, l. & dean, r.s. (2016). systematic review of outcome measures reported in clinical canine osteoarthritis research. veterinary surgery. 45(4), 480–487. doi: http://dx.doi.org/10.1111/vsu.12479 brown, d.c., boston, r.c., coyne, j.c. & farrar, j.t. (2008). ability of the canine brief pain inventory to detect response to treatment in dogs with osteoarthritis. journal of the american veterinary medical association. 233(8), 1278–1283. doi: http://dx.doi.org/10.2460/javma.233.8.1278 brown, d., boston, r. & farrar, j. (2013). comparison of force plate gait analysis and owner assessment of pain using the canine brief pain inventory in dogs with osteoarthritis. journal of veterinary internal medicine 2013;. 27(1), 22–30. doi: http://dx.doi.org/10.1111/jvim.12004 button, k.s., ioannidis, j.p., mokrysz, c., nosek, b.a., flint, j., robinson, e.s. & munafò, m.r. (2013). power failure: why small sample size undermines the reliability of neuroscience. nature reviews neuroscience. 14, 365–376. doi: http://dx.doi.org/10.1038/nrn3475 calder, p.c. (2009). polyunsaturated fatty acids and inflammatory processes: new twists in an old tale. biochimie. 91(6), 791–795. doi: http://dx.doi.org/10.1016/j.biochi.2009.01.008 casler, m.d. (2018). blocking principles for biological experiments. applied statistics in agricultural, biological, and environmental sciences. 53–72. doi: http://dx.doi.org/10.2134/appliedstatistics.2015.0074.c3 dangardt, f., osika, w., chen, y., nilsson, u., gan, l-m., gronowitz, e., strandvik, b. & friberg, p. (2010). omega-3 fatty acid supplementation improves vascular function and reduces inflammation in obese adolescents. atherosclerosis. 212(2), 580–585. doi: http://dx.doi.org/10.1016/j.atherosclerosis.2010.06.046 de boer, m.r., waterlander, w.e., kuijper, l.d., steenhuis, i.h. & twisk, j.w. (2015). testing for baseline differences in randomized controlled trials: an unhealthy research behavior that is hard to eradicate. international journal of behavioral nutrition and physical activity. 12(4). doi: http://dx.doi.org/10.1186/s12966-015-0162-z gruen, m.e., white, p. & hare, b. (2020). do dog breeds differ in pain sensitivity? veterinarians and the public believe they do. plos one. 15:e0230315. doi: http://dx.doi.org/10.1371/journal.pone.0230315 innes, j.f., clayton, j. & lascelles, b.d.x. (2010). review of the safety and efficacy of longâ€�term nsaid use in the treatment of canine osteoarthritis. veterinary record. 166(8), 226–230. doi: http://dx.doi.org/10.1136/vr.c97 johnson, k.a., lee, a.h. & swanson, k.s. (2020). nutrition and nutraceuticals in the changing management of osteoarthritis for dogs and cats. journal of the american veterinary medical association. 256(12), 1335–1341. doi: http://dx.doi.org/10.2460/javma.256.12.1335 kean, j.d., camfield, d., sarris, j., kras, m., silberstein, r., scholey,a. & stough, c. (2013). a randomized controlled trial investigating the effects of pcso-524®, a patented oil extract of the new zealand green lipped mussel (perna canaliculus), on the behaviour, mood, cognition and neurophysiology of children and adolescents (aged 6–14 years) experiencing clinical and sub-clinical levels of hyperactivity and inattention: study protocol actrn12610000978066. nutrition journal. 12(100), 1–10. doi: https://doi.org/10.1186/1475-2891-12-100 krzywinski, m. & altman, n. (2014). points of significance: analysis of variance and blocking. nature methods. 11(7), 699–700. doi: https://doi.org/10.1038/nmeth.3005 kwananocha, i., vijarnsorn, m., kashemsant, n. & lekcharoensuk, c. (2016). effectiveness of disease modifying osteoarthritis agents and carprofen for treatment of canine osteoarthritis. the thai journal of veterinary medicine. 46(6), 363–371. mccarthy, g., o’donovan, j., jones, b., mcallister, h., seed, m. & mooney, c. (2007). randomised double-blind, positive-controlled trial to assess the efficacy of glucosamine/chondroitin sulfate for the treatment of dogs with osteoarthritis. the veterinary journal. 174(1), 54–61. doi: http://dx.doi.org/10.1016/j.tvjl.2006.02.015 moreau, m., dupuis, j., bonneau, n. & desnoyers, m. (2003). clinical evaluation of a nutraceutical, carprofen and meloxicam for the treatment of dogs with osteoarthritis. veterinary record. 152(11), 323–329. doi: http://dx.doi.org/10.1136/vr.152.11.323 pannucci, c.j. & wilkins, e.g. (2010). identifying and avoiding bias in research. plastic and reconstructive surgery. 126(2), 619–625. doi: http://dx.doi.org/10.1097/prs.0b013e3181de24bc quinn, m.m., keuler, n.s., lu, y., faria, m.l.e., muir, p. & markel, m.d. (2007). evaluation of agreement between numerical rating scales, visual analogue scoring scales, and force plate gait analysis in dogs. veterinary surgery. 36(4), 360–367. doi: http://dx.doi.org/10.1111/j.1532-950x.2007.00276.x root, m., collier, s.r., zwetsloot, k.a., west, k.l. & mcginn, m.c. (2013). a randomized trial of fish oil omega-3 fatty acids on arterial health, inflammation, and metabolic syndrome in a young healthy population. nutrition journal. 12(40), 1–6. doi: http://dx.doi.org/10.1186/1475-2891-12-40 sargeant, j.m., kelton, d.f. & o'connor, a.m. (2014). randomized controlled trials and challenge trials: design and criterion for validity. zoonoses and public health. 61(s1), 18–27. doi: http://dx.doi.org/10.1111/zph.12126 vijarnsorn, m., kwananocha, i., kashemsant, n., jarudecha, t., lekcharoensuk, c., beale, b., peirone, b. & lascelles, b.d.x. (2019). the effectiveness of marine based fatty acid compound (pcso-524) and firocoxib in the treatment of canine osteoarthritis. bmc veterinary research. 15, 1–8. doi: http://dx.doi.org/10.1186/s12917-019-2110-7 vijarnsorn, m., kwananocha, i., kashemsant, n., jarudecha, t., lekcharoensuk, c., beale, b., peirone, b. & lascelles, b.d.x. (2020). correction to: the effectiveness of marine based fatty acid compound (pcso-524) and firocoxib in the treatment of canine osteoarthritis. bmc veterinary research. 16, 1. doi: http://dx.doi.org/10.1186/s12917-020-02713-9 zawadzki, m., janosch, c. & szechinski, j. (2013). perna canaliculus lipid complex pcso-524™ demonstrated pain relief for osteoarthritis patients benchmarked against fish oil, a randomized trial, without placebo control. marine drugs. 11(6), 1920–1935. doi: http://dx.doi.org/10.3390/md11061920 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. introduction to statistics mirjam nielen dvm phd dipl. ecvph1* 1utrecht university, domplein 29, 3512 je utrecht, netherlands *corresponding author (m.nielen@vet.uu.nl) vol 2, issue 1 (2017) published: 5 jan 2016 doi: 10.18849/ve.v2i1.85 always wondered why research papers often present rather complicated statistical analyses? or wondered how to properly analyse the results of a pragmatic trial from your own practice? this talk will give an overview of basic statistical principles and focus on the why of statistics, rather than on the how. this is a podcast of mirjam's talk at the veterinary evidence today conference, edinburgh november 2, 2016. find out more about mirjam. view presentation slides comments: in horses with trigeminal-mediated headshaking, is neuromodulation with equipens™ more effective than with electroacupuncture? a knowledge summary by jennifer hindmarsh pgdip vcp (equine) bvsc mrcvs bsc (hons) 1* 1langford vets, university of bristol, langford, bs40 5du *corresponding author (jkhindmarsh@outlook.com) vol 6, issue 1 (2021) published: 21 jan 2021 next review date: 10 may 2022 doi: 10.18849/ve.v6i1.352 pico question in horses diagnosed with trigeminal-mediated headshaking, is equipens™ therapy more efficacious when compared to electroacupuncture in terms of remission of clinical signs?   clinical bottom line category of research question treatment the number and type of study designs reviewed three papers were critically reviewed, all three were descriptive case series strength of evidence weak outcomes reported remission was achieved following both equipens™ and electroacupuncture therapy in a proportion of horses for variable lengths of time. median remission times appear to be longer with repeated treatment of equipens™ compared to electroacupuncture conclusion the evidence for equipens™ treatment is more robust than for electroacupuncture, and remission defined more clearly, and so could be recommended with greater confidence   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are presented with a 7-year-old warmblood gelding used for eventing who has been diagnosed with trigeminal-mediated headshaking. he responds to the use of a nose net but is not allowed to compete in one. the owner has heard that electroacupuncture is a treatment option and would like to know how it compares to equipens™ treatment. the evidence three descriptive case series have been published on the topic of neuromodulation treatment for trigeminal-mediated headshaking in horses, which in terms of strength of evidence, is weak. summary of the evidence roberts et al. (2016) population: horses diagnosed with trigeminal-mediated headshaking, referred to langford veterinary services equine centre between august 2013 and august 2014. horses included were not known to be seasonally affected and thus were all displaying clinical signs at the time of treatment, at least 1 month had elapsed since any prior alternative treatment trials. sample size: seven horses intervention details: the horses were sedated and the skin anaesthetised before the probe was inserted 1 mm superficial to the infraorbital nerve prior to stimulation with frequency alternating between 2 hz and 100 hz every 3 seconds. the voltage was set (0.2 to 2.7 volts) to stimulate facial twitching whilst maintaining patient tolerance for 25 minutes bilaterally. an initial course of three treatments with further treatments on re-emergence of clinical signs was followed. study design: descriptive case series outcome studied: efficacy in terms of remission defined as return to previous level of work or higher. safety in terms of adverse effects. owner reported outcomes (presence and severity of headshaking, and competition record where applicable). follow-up was between august 2013 and august 2014. main findings (relevant to pico question): haematoma formation occurred in three horses; slight increased clinical signs occurred in two. six horses entered remission after their first treatment, five of which continued to respond with further procedures. one horse did not enter remission at all. median remission: 1st treatment: 3.8 days (range: 0–8 days, n = 7) 2nd treatment: 2.5 weeks (range: 0–8 weeks, n = 7) 3rd treatment: 15.5 weeks (range: 0–24 weeks, n = 5) 4th treatment: 20 weeks (range: 12–28 weeks, n = 2) 12 weeks was the minimum time of remission following the 4th treatment in two horses that received the 4th treatment. one horse was in remission at the time of follow-up. limitations: weak level of evidence in terms of study type small sample size owner reported outcomes incomplete follow up and lack of long-term follow-up seasonality unknown in three cases no control group roberts et al. (2020) population: horses diagnosed with trigeminal-mediated headshaking referred for treatment with equipens™ neuromodulation at 13 referral centres that were trained to carry out neuromodulation (uk and europe) between august 2013 and november 2017. on enrolment, horses were not receiving any other treatments. horses must have been in ridden or lunge work before displaying signs of headshaking in order to assess remission. median age: 9 years (2–21) most common breed groups: sports horses 49/160 (31%) and warmbloods 42/160 (26%), other breeds include pony, cold blood/cob, thoroughbred 69/160 (43%) – 8/168 (5%) not recorded sex: geldings 120/165 (73%), mares 42/165 (25%), stallions 3/165 (2%) – 3/168 (2%) not recorded use: general riding 94/168 (56%), other uses include dressage, eventing, showjumping, showing, driving, racing, hunting, trotting, police, lunged 72/168 (43%) – 2/168 (1%) not reported seasonal effect: 21/158 (13%) spring/summer affected, 62/158 (39%) affected all year, 75/158 (48%) unknown as affected for less than 1 year – 10/168 (6%) not reported sample size: 168 horses intervention details: equipens™ was carried out on sedated horses: the skin was anaesthetised before the probe was inserted 1 mm superficial to the infraorbital nerve prior to stimulation with frequency alternating between 2 hz and 100 hz every 3 seconds. the voltage was set (0.2 to 2.7 volts) to stimulate facial twitching whilst maintaining patient tolerance for 25 minutes bilaterally. an initial course of three treatments with further treatments on re-emergence of clinical signs. study design: descriptive case series outcome studied: remission was defined as a return to previous levels of work within 3 weeks of the last treatment. assessment was made by the owners and obtained via telephone. probabilities were calculated for length of remission and response to first/second treatments while management, referral centre and clinical history were assessed as potential hazards to remission. follow-up period was between august 2013 and november 2017. main findings (relevant to pico question): 156/168 horses completed the initial three-procedure course at the time of follow-up, 20 of these were out of work or otherwise lost to follow-up. of 136 horses, 72 (53%) went into remission following the initial course. median remission duration was 9.5 weeks (2 days–156 weeks). complications: 8.8% of all procedures. at the time of follow-up, roughly half the cases (33/72) were in remission, individual response was widely variable with no predictors found. limitations: incomplete patient details no control group owner assessments of treatment efficacy some horses lost to follow-up due to illness or injury preventing the horse from working variable diagnostic work up devereux (2019) population: four horses and two ponies considered to be affected with trigeminal-mediated headshaking by the author and referring vet or referral practice, showing clinical signs of headshaking at the time of presentation. data collected over a 19 month follow-up period. dental and oral examination, nasopharyngeal and guttural pouch endoscopy was performed on all horses. one horse had dental radiographs, and one had computed tomography. all had ‘negative’ results. three horses were sensitive to sunlight, two were known to be seasonally affected. sample size: six horses intervention details: horses were sedated, an acupuncture needle was placed under the infraorbital nerve with a second needle in the brachiocephalic muscle ipsilaterally. with either one of two different electrical stimulators, current was increased in 0.1 ma increments with frequency settings alternating between 2 hz and 80 hz until visible nostril twitch was maintained for 25 minutes. treatment was repeated on re-emergence of clinical signs. study design: descriptive case series outcome studied: headshaking was graded 0–3 at rest and exercise by owners, remission was not defined. main findings (relevant to pico question): reduction in grade of headshaking was seen in all horses. median remission times: 1st treatment: 5.5 days (0–13 days, n = 6) 2nd treatment: 8.5 days (7–21 days, n = 6) 3rd treatment: 18 days (6–71 days, n = 6) 4th treatment: 27.5 days (11 days–23 weeks, n = 6) 5th treatment: 13 weeks 5 days (5–46 weeks, n = 5) 6th treatment: 24 days (13–41 days, n = 3) no complications reported, although post-treatment worsening of clinical signs was seen. limitations: post-treatment, the three horses sensitive to sunlight wore a uv mask and nose net – some of these horses had previously had a good response to nose net or mask, possibly confounding results owner reported response to treatment two different electrical stimulators used small study size no control group remission not defined appraisal, application and reflection trigeminal-mediated headshaking is a neuropathic facial pain condition in horses. clinical signs are of vertical headshaking, often accompanied by sharp vertical ticks and associated with signs of nasal irritation such as snorting, sneezing, rubbing the nose and striking at the face.  when assessing the scale of the welfare implications of this condition it is important to consider prevalence in the population and impact to owners, horses and the industry. a review article by roberts (2019) concludes that about 1% of the uk horse population are significantly enough affected by the pain associated with this condition to require veterinary attention and that more severely affected horses are either unable to perform, dangerous or unmanageable to the point where euthanasia is required due to the pain experienced. in terms of level of suffering, trigeminal-mediated headshaking can be graded, various systems exist for this but essentially the worst affected suffer at rest. these horses experience no relief or respite from their pain, it is not known what proportion of horses are in this category, but this information would further our understanding of the impact. an assumption may be made that the severity of signs is an indication of the severity of pain experienced based on extrapolation of reports from people suffering from neuropathic pain. people describe their nerve pain as anything from tingling sensations to electric shock like pain and that their quality of life is directly affected by increased pain levels (derbrota et al., 2014). aetiopathogenesis for trigeminal-mediated headshaking is poorly understood. the trigeminal nerve appears structurally unaffected (roberts et al., 2017) but is functionally abnormal with a lower threshold for activation (aleman et al., 2013) appearing to result in neuropathic pain. that it is functionally abnormal but structurally normal increases the potential for reversal of the condition which may be supported by the fact that between 1/3 and 2/3 of horses are affected seasonally (aleman et al., 2013; madigan & bell, 2001; and mills et al., 2002) and that 5% can be expected to go into spontaneous remission (mills et al., 2002). there are a number of management options for horse owners to try, none of which are resoundingly successful and provide individual levels of relief (mills et al., 2002). some options are not permitted during certain competitions or levels of competition such as medications or nose nets. electrical neuromodulation has been used as a technique that may offer relief from neuropathic pain (roberts et al., 2016). two such techniques, electroacupuncture and percutaneous electrical nerve stimulation (pens), have been studied and reported above. pens is an approved therapy in people under the national institute for health and care excellence (nice) guidelines for the management of neuropathic pain. no such guidelines were found for the use of electroacupuncture. all three studies reviewed in this knowledge summary suffered from the reduced reliability of owner reported assessments, although all of them attempted to compensate for this by using a grading system and, both equipens™ studies specified remission as return to previous levels of work. similarly, each study had essentially incomplete data sets with some patients lost to follow-up due to illness or injury. length of follow-up and cut off times for publishing data meant that some horses that were still in remission had falsely short remission times reported, this was particularly evident in roberts et al. (2020). the strongest evidence was presented by roberts et al. (2020) with larger sample population, longer-term study and assessment of probabilities of outcome and potential hazards. however, all three studies are descriptive case series and provide no control group, blinding or randomisation. the nature of headshaking precludes ‘strong’ study designs, most pertinently due to the ethics involved in, for example, withholding treatment in a placebo trial or delaying treatment in a cross over design trial. the strength of evidence is also confounded by the fact that headshaking may undergo spontaneous or seasonal remission, is dynamic in its severity, responds so variably to treatments and that its aetiopathogenesis remains elusive. median remission times were comparable in each of the three studies but appear to be longer with ongoing treatments for equipens™ compared to electroacupuncture. current level of evidence for use of neuromodulation in the treatment of trigeminal-mediated headshaking in horses is weak but indicates that it can provide safe and effective remission of varying timescales from days to years for a proportion of horses. the evidence for equipens™ treatment is more robust than for electroacupuncture and so could be recommended with greater confidence. hopefully these two treatment options will continue to be investigated. increasing our understanding of neuromodulation in the treatment of horses with neuropathic pain provides an opportunity for translational research for treatment in people. despite differences in pathogenesis, similarities in symptoms between horses with trigeminal-mediated headshaking and people with trigeminal neuralgia may allow both to benefit from further studies into the use of pens. methodology section search strategy databases searched and dates covered: cab abstracts 1973 to present using the ovid interface pubmed 1910 to present accessed via the ncbi website search strategy: cab abstracts: (horse.mp or horses.mp or equine.mp) (headshaking.mp) (electrical.mp) 1 and 2 and 3   pubmed: (horse.mp or horses.mp or equine.mp) and (headshaking.mp) and (electrical.mp) dates searches performed: 10 may 2020 exclusion / inclusion criteria exclusion: not regarding electrical neuromodulation for the treatment of trigeminal-mediated headshaking in horses not a clinical study inclusion: all clinical studies regarding electrical neuromodulation in the treatment of trigeminal-mediated headshaking in horses search outcome database number of results excluded – not a clinical study excluded – not regarding electrical neuromodulation total relevant papers cab abstracts 7 2 2 3 pubmed 4 1 1 2 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflicts of interest. references aleman, m., williams, d.c., brosnan, r.j., nieto, j.e., pickles, k.j., berger, j., lecouteur, r.a., holliday, t.a. and madigan, j.e. (2013). sensory nerve conduction and somatosensory evoked potentials of the trigeminal nerve in horses with idiopathic headshaking. journal of veterinary internal medicine. 27(6), 1571–1580. doi: https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.12191 devereux, s. (2019). electroacupuncture as an additional treatment for headshaking in six horses. equine veterinary education. 31(3), 137–146. doi: https://doi.org/10.1111/eve.12776 dobrota, v.d., hrabac, p., skegro, d., smiljanic, r., dobrota, s., prkacin, i., brkljacic, n., peros, k., tomic, m., lukinovic-skudar, v. and kes, v.b. (2014). the impact of neuropathic pain and other comorbidities on the quality of life in patients with diabetes. health and quality of life outcomes. 12(1), 171. doi: https://doi.org/10.1186/s12955-014-0171-7 pickles, k., madigan, j. and aleman, m. (2014). idiopathic headshaking: is it still idiopathic? the veterinary journal. 201(1), 21–30. doi: https://doi.org/10.1016/j.tvjl.2014.03.031 madigan, j.e. and bell, s.a. (2001). owner survey of headshaking in horses. journal of the american veterinary medical association. 219(3), 334–337. doi: https://doi.org/10.2460/javma.2001.219.334 mills, d.s., cook, s. and jones, b. (2002). reported response to treatment among 245 cases of equine headshaking. veterinary record. 150(10), 311–313. doi: http://dx.doi.org/10.1136/vr.150.10.311 roberts, v. (2019). trigeminal-mediated headshaking in horses: prevalence, impact, and management strategies. veterinary medicine: research and reports. 10, 1–8. doi: https://doi.org/10.2147/vmrr.s163805 roberts, v.l.h., bailey, m., equipens™ group, patel, n.k., carslake, h.b., malalana, f., mcgowan, c., haggett, e.f., barnett, t., rendle, d.i. and lunden, u. (2020). the safety and efficacy of neuromodulation using percutaneous electrical nerve stimulation for the management of trigeminalâ€�mediated headshaking in 168 horses. equine veterinary journal. 52(2), 238–243. doi: https://doi.org/10.1111/evj.13174 roberts, v.l.h., patel, n.k. and tremaine, w.h. (2016). neuromodulation using percutaneous electrical nerve stimulation for the management of trigeminalâ€�mediated headshaking: a safe procedure resulting in mediumâ€�term remission in five of seven horses. equine veterinary journal. 48(2), 201–204. doi: https://doi.org/10.1111/evj.12394 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. challenges of ebvm as a rvn in a practice setting louise o'dwyer mba bsc(hons) vts(ecc) dipavn(med & surg) rvn 1* 1vets now, penguin house, castle riggs, dunfermline, fife *corresponding author (louise.odwyer@vets-now.com) vol 2, issue 1 (2017) published: 11 jan 2016 doi: 10.18849/ve.v2i1.89 this talk will look at difficulties for rvns working in private practice gaining access to sufficient papers and studies in order to provide the evidence we need, and also looking at the selection of appropriate topics. we will look at sources of information such as the rcvs knowledge library in order to collect evidence, and also how to select appropriate, relevant topics for research which will be useful to other rvns working in practice, and will help in the creation of nursing protocols and nursing care bundles, which will advance nursing and patient care. this is a podcast of louise's talk at the veterinary evidence today conference, edinburgh november 1, 2016. find out more about louise. comments: erratum to: should we prescribe oral metronidazole or probiotics for acute gastroenteritis in dogs? emily moore dvm1* wanda j gordon-evans dvm phd dacvs dacvsmr2 1tufts cummings school of veterinary medicine, 200 westboro rd, north grafton, ma 01536, usa 2university of minnesota college of veterinary medicine, 1365 gortner ave, st paul, mn 55108, usa *corresponding author (moor1662@umn.edu) vol 7, issue 2 (2022) erratum published: 28 jun 2022 original paper published: 18 may 2022 the original article was published in veterinary evidence vol 7, issue 2 (2022): 10.18849/ve.v7i2.393 doi: 10.18849/ve.v7i2.626 erratum unfortunately the original version of the article had the following error. within the references one reference was changed from: d. k., koenigshof, a. m. & mani, r. (2020). metronidazole treatment of acute diarrhea in dogs: a randomized double blinded placebo-controlled clinical trial. journal of veterinary internal medicine. 34(1), 98–104. doi: https://doi.org/10.1111/jvim.15664 to: langlois, d. k., koenigshof, a. m. & mani, r. (2020). metronidazole treatment of acute diarrhea in dogs: a randomized double blinded placebo-controlled clinical trial. journal of veterinary internal medicine. 34(1), 98–104. doi: https://doi.org/10.1111/jvim.15664 this error was in both the html and pdf versions. this has now been updated in both the html and pdf versions.   intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. does the use of supraglottic device in rabbits cause less injury than other airway management devices? a knowledge summary by jasmine gheini 1* sanaa zaki phd bvsc(hons) manzcvs gradcertedstud (higher education) 1 1sydney school of veterinary science, faculty of science, university of sydney, camperdown nsw 2050 *corresponding author (jghe8559@uni.sydney.edu.au) vol 7, issue 4 (2022) submitted: 09 apr 2022 published: 02 dec 2022 next review: 27 may 2024 doi: 10.18849/ve.v7i4.608 pico question in rabbits, undergoing general anaesthesia, does the placement of a v-gel® device result in less airway trauma compared to the use of other airway management devices?   clinical bottom line category of research question treatment the number and type of study designs reviewed three papers were critically appraised, two blinded randomised experimental trial studies and one randomised crossover experimental trial study strength of evidence weak outcomes reported one blinded randomised trial study demonstrated that the trauma to the upper airways of rabbits during anaesthesia is not significantly different between the use of v-gel® and an endotracheal tube. the other blinded randomised trial study demonstrated that the trauma to the upper airway caused by endotracheal intubation is significantly more than that caused by v-gel® placement. the randomised crossover trial study demonstrated that v-gel® placement causes more significant compression to the larynx compared to a laryngeal mask or face mask conclusion the current evidence suggests that use of the v-gel® in rabbits causes less trauma / injury to the airways compared to placement of an endotracheal tube but not compared to the use of a laryngeal or face mask. however, based on the low number and quality of published studies, this evidence is weak, and better-quality studies are required to support the routine use of v-gel® over other airway devices in rabbits. while v-gel® may be a safer alternative for securing airways in rabbits compared to endotracheal intubation, knowing the injuries this device can cause to the upper airways is useful for managing rabbits during post anaesthesia recovery   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario as a veterinarian and owner of a small animal clinic with a high rabbit caseload, you would like to improve the protocols used for rabbit anaesthesia in your practice. you have recently heard of a new supraglottic airway device specific for rabbits named v-gel®, and you are considering introducing v-gel® in your clinic. you are wondering if this device is safer and causes less trauma in rabbits undergoing general anaesthesia compared to your current practice of using face masks for short procedures and endotracheal tubes for longer procedures. the evidence this critical appraisal identified three relevant studies. two blinded randomised experimental trials (comolli et al., 2020; and engbers et al., 2017) and one randomised crossover experimental trial (wenger et al., 2017). comolli et al. (2020) used a blinded randomised experimental trial approach to study on healthy female new zealand white rabbits and determine if the placement of v-gel® would lead to faster, easier secure airways with less histological trauma compared to endoscopic endotracheal intubation with cuffed endotracheal tubes. the second blinded randomised experimental trial, engbers et al. (2017) studied on healthy adult new zealand white rabbits to determine similar goals to comolli et al. (2020) however, the endotracheal intubation was preformed with a blind technique. wegner et al. (2017) preformed a randomised crossover experimental trial study on healthy female new zealand white rabbits to compare v-gel®, endotracheal tube, face mask and laryngeal mask in regard to ease of application, time of application and quality of seal. although randomised trials are considered to represent a moderate level of evidence, due to the small number of studies relevant to this pico, and the study’s limitations such as small sample size, the findings from these three trials provided only a weak level of evidence that v-gel® devices cause less airway trauma when compared to other airway devices used in anaesthetised rabbits. summary of the evidence comolli et al. (2020) population: healthy (based on physical examination and health surveillance report) american society of anesthesiologists (asa) score 1, 12 month old female new zealand white rabbits (oryctolagus cuniculus). the mean body weight ± sd was 2.57 ± 0.15 kg. sample size: 14 rabbits. intervention details: general: rabbits were block randomised into two groups of seven animals each. one group received endoscopic endotracheal intubation intervention (eti group); the second group received v-gel® supraglottic airway device (vgel group). diet: free choice pellets, timothy hay, and water ad libitum. rabbits were not fasted before anaesthesia. induction of anaesthesia by intramuscular injection of ketamine at 35 mg/kg and xylazine at 2 mg/kg and meloxicam at 1 mg/kg injected intramuscularly for analgesia. visual inspection of the airway was performed endoscopically before and after airway device placement. the anaesthesia was maintained via isoflurane and rabbits underwent an ovariohysterectomy then recovered. airway device placement: lubricated endotracheal tube (3.5 mm) was placed for the eti group (n = 7) with the use of an endoscope. lubricated v-gel® was placed for the vgel group (n = 7). all the intubations and v-gel® placements were done by the same experienced anaesthetist. post-mortem: four days after the anaesthetic event the animals were humanely euthanised by intravenous phenobarbital, tissue samples were collected (proximal larynx, distal larynx, 2 cm distal to larynx, and trachea at the tracheobronchial bifurcation) and fixed in formalin. four days after fixation the tissue cross-sections were obtained, processed for histopathologic evaluation. the histological evaluation was performed by a blinded board-certified pathologist. study design: blinded randomised experimental trial study. outcome studied: number of attempts and time of airway device placement. arterial blood gas values (ph, po2, pco2, total co2, hco3, base excess, and haematocrit (hct). histological assessment of proximal larynx, distal larynx, 2 cm distal to the larynx, and trachea at the tracheobronchial bifurcation. main findings (relevant to pico question): all animals recovered without signs of irritation to the airway such as coughing. all animals resumed drinking and eating normally within 12 hours after surgery. no animal died from complications and during the post-mortem examination, no animal had signs of aspiration, pneumonia, or pneumonitis. the histological lesions did not show any significant difference in the severity of inflammation, haemorrhage, and necrosis for either larynx or the trachea between the two techniques. however, mild to moderate signs of laryngeal and tracheal trauma was observed in both groups. no statistically significant difference between the two techniques for histopathological lesions to the larynx and tracheal, however, investigators reported that v-gel® caused more trauma to the larynx and epiglottis whereas endotracheal intubation caused more trauma to the trachea. limitations: no explanation of how visual inspection measurements were recorded or analysed in the paper, despite the authors stating that gross visual inspection of the larynx (before and after the airway device placement) underestimated the laryngeal trauma when compared to histological evaluation. the severity of the trauma present in fixed tissue samples is affected by the harvest time post anaesthesia, in this case 4 days. sampling at multiple time points post anaesthesia would provide a more accurate picture of resulting airway trauma. a small sample size impacts the categorical data analysis and increases the chance of a type ii error. the person who performed the placement of the airway devices could not be blinded to the two treatment groups due to the nature of the procedures. investigators securing airways could be more experienced than a normal general practitioner. experience could be a factor that might affect the severity of trauma while securing airways. engbers et al. (2017) population: healthy (american society of anesthesiologist [asa] score >2) adult new zealand white rabbits (n = 12 males, n = 3 females). sample size: 15 rabbits. intervention details: general: block randomised to two treatment groups: endotracheal tube (ett) placement group, supraglottic airway device (sgad) group / v-gel® number of rabbits allocated to each group is not mentioned. diet: ad libitum pellets, hay, and water with a small amount of fruit and vegetables. rabbits were fasted 2 hours prior to the experiment. animals sedated with dexmedetomidine (0.1 mg/kg) and midazolam (0.5 mg/kg) by intramuscular injection. anaesthesia was induced with alfaxalone (0.3 mg/kg) intravenously, followed by 1 hour of isoflurane anaesthesia after device placement. computed tomography (ct) scan of head and neck performed prior to and after the placement of airway devices by a board-certified radiologist. for nine animals (sgad n = 4, ett n = 5), arterial blood samples were collected via arterial canula. airway device placement: lubricated v-gel® was inserted until further insertion was not possible or the incisors were close to the fixation tabs. if lingual cyanosis was present and was not resolved after three attempts, the rabbit was intubated by endotracheal tube. in the ett group, the blind technique was used for the insertion of ett. each group had a separate investigator for placement of the airway device and investigators conducting device placement received training. post-mortem: post anaesthesia all animals were euthanised with an overdose of intravenous sodium phenobarbital. two hours post euthanasia necropsy was performed and tissue samples (tongue, pharynx, larynx, and trachea) were collected for histological evaluation. study design: blinded randomised experimental trial study. outcome studied: number of attempts and time of placements. blood pressure (bp), heart rate, respiratory rate, and spo2. isoflurane concentration at 15 minutes of anaesthesia. presence of tongue cyanosis or airway obstructions. blood gases and electrolyte analysis (sgad n = 4, ett n = 5). ct imaging measurements to assess airway diameter and laryngeal compression. histological assessment of tongue, pharynx, larynx, and trachea. main findings (relevant to pico question): based on histological valuation, significantly greater tracheal mucosal and submucosal trauma was caused by endotracheal intubation compared to v-gel®. limitations: a small sample size impacts the categorical data analysis and increases the chance of a type ii error. for histological samples, the tissues were collected 2 hours after euthanasia, this could impact the histological results due to possible post-mortem changes on tissue samples. wenger et al. (2017) population: healthy (on basis of physical examination) female new zealand white rabbits aged 7 months with a bodyweight of 5.10 ± 0.05 kg (mean ± sd). sample size: 10 rabbits. intervention details: diet: small amount of produce with ad libitum access to water and hay. no fasting prior to the experiment. the produce provided for rabbits is not explained in the paper. all rabbits were anaesthetised four times with 1–2 week intervals in between and each anaesthesia was for insertion of an airway management device (endotracheal tube (ett), laryngeal mask (lm), supraglottic airway device (v-gel®), and face mask (fm)) in random order. rabbits sedated with fentanyl citrate (0.05 mg/kg) and fluanisone (1.5 mg/kg) injection intramuscularly and anaesthesia induced with propofol intravenously (1 mg/kg). anaesthesia was maintained with propofol boluses (1 mg/kg) to allow multiple attempts for airway device placements until placement was achieved. computed tomography (ct) scans of the head and neck, and abdomen were taken prior to and after controlled manual ventilation (cmv). during recovery meloxicam (1 mg/kg subcutaneously) and ringer’s lactate fluid (10 ml/kg intravenous [iv] over 30 minutes) were administered. airway device placement: ett placed with blind technique and listening to breaths. lubricated lm (deflated) was inserted until the tube could not be inserted further. lubricated v-gel® was placed similar to lm. size r5 was used for rabbits weighing 4.3–5.0 kg and size r6 was used for rabbits weighing more than 5 kg. fm was placed tightly around the nose and mouth and taped around the head. placement of all devices was performed by board-certified anaesthetists or an experienced veterinarian. controlled manual ventilation (cmv): rocuronium (0.3 mg/kg iv) was administered to induce apnoea and cmv (respiratory rate of 30 breaths/min) was performed for 4 minutes, followed by administration of sugammadex (4 mg/kg) before stopping cmv and allowing spontaneous ventilation. study design: randomised crossover experimental trial. outcome studied: dose of propofol, time, and number of attempts for device placement. presence of swallowing during placement or apnoea. amount of leakage from each airway device during spontaneous ventilation (sv) and cmv. cardiorespiratory values every 5 minutes. the peak inspiratory pressure if the leak was >25%. ct scan measurements for: lm and v-gel® positions; presence of compression to larynx with lm, v-gel® placement during sv; presence of gastric tympanism induced by cmv. main findings (relevant to pico question): with the placement of v-gel®, lingual cyanosis was reported in several rabbits, with resolution 30 seconds after removal of the device. the study fails to report the exact number of rabbits that had lingual cyanosis after placement of v-gel®. v-gel® placement caused severe laryngeal compression in one rabbit. based on ct imaging in 5/10 cases v-gel® was positioned correctly. in two of these moderate laryngeal compressions with mucous accumulation was detected and in one case severe laryngeal compression was detected. in 2/10 cases v-gel®, resulted in hypoxaemia due to severe laryngeal compression improper placement. the height and width of the larynx were significantly smaller with the placement of v-gel® compared to lm and fm. limitations: a small sample size impacts the categorical data analysis and increases the chance of a type ii error. multiple investigators were assigned for the placement of the airway. it is not clear if a specific group was allocated to a specific investigator. the experience of investigators could impact the results. this study mainly focuses on rabbits above body weight of 5 kg and discuss v-gel® size for body weight above 5 kg. however, in a clinical setting different breed of rabbits with smaller body weight can be presented and further research is needed to work on v-gel® sizes appropriate for smaller breed of rabbits. appraisal, application and reflection the increasing popularity of pet rabbits and the willingness of owners to pay for veterinary services (mayer et al., 2017) means that more rabbits are presenting to veterinary practices for care. veterinary practices need to accommodate the medical and welfare needs of rabbit patients and provide the necessary services, including general anaesthesia for surgical procedures such as ovariohysterectomy. general anaesthesia in rabbits has higher risks and higher mortality rates compared to cats and dogs (brodbelt et al., 2008). the main factors contributing to this high risk are difficulty establishing a secure airway, underlying respiratory diseases, and cardiorespiratory complications during anaesthesia (brodbelt et al., 2008; and eatwell, 2014). securing the airway in rabbits is made difficult due to their unique airway anatomy. rabbits have small and narrow mouths with large incisors, large molars and large tongues relative to their skull size, which makes it difficult to visualise the larynx for intubation (donnelly & vella, 2020). the most common methods used to secure the airway in rabbits are endotracheal intubation and placement of a well-fitting face mask. however, both endotracheal tubes and face masks have disadvantages that can impact the risk of anaesthesia (eatwell, 2014). face masks allow delivery of oxygen and anaesthetic gases but do not guarantee airway patency, thus can cause clinically significant hypoxaemia and hypercapnia. endotracheal intubation can cause mucosal damage to the upper airways, leading to swelling and potential narrowing (bateman et al., 2005; and hawkins & pascoe, 2021). endotracheal intubation also requires significant training and practice. to address these issues, supraglottic airway devices (sgad), similar to those used in human medicine, have been introduced and trialled as an alternative airway management device for rabbits. the use of a human supraglottic airway device was tested in rabbits and reported to cause lingual cyanosis, possibly due to pressure on the lingual vasculature (crotaz, 2013; and kazakos et al., 2007). in recent years, a new rabbit-specific sgad (v-gel®) has been designed to decrease the risk of complications observed with the use of a human sgad. the three studies included in this critical appraisal reported varied outcomes. significant limitations were identified for all three studies, including small sample size, use of multiple investigators for device placement and the use of rabbit breeds that differ in size from breeds commonly kept as pets. comolli et al. (2020) and engbers et al. (2017) both compare the placement of v-gel® and an endotracheal tube (ett) in rabbits. however, the findings of the two studies are incongruent. comolli et al. (2020) concluded that overall, the trauma caused by v-gel® and ett placement is not significantly different. the authors report that v-gel® caused more injury to the larynx and epiglottis, and ett caused more injury to the trachea, although the differences between the devices were not statistically significant. in contrast, engbers et al. (2017) identified that ett causes more significant injury to tracheal mucosal and submucosal airways compared to v-gel®. the different findings in these two studies could be due to differences in ett placement method, given that comolli et al. (2020) used endoscopic guided endotracheal intubation, while engbers et al. (2017) performed a blind technique for placement of ett. another possible explanation could be the experience of investigators placing the devices. goldmann & ferson (2005) report that training for airway management by anaesthetists can reduce anaesthesia-related morbidity and mortality. the third study (wenger et al., 2017) compared two additional airway devices, laryngeal mask, and face mask, in addition to v-gel® and ett. wenger et al. (2017) mainly studied the amount of laryngeal compression caused by the different devices and found that v-gel® compressed the larynx more significantly than laryngeal mask and face mask. this study did not look at the direct injury to the upper airways, but it was assumed that compression of the larynx would lead to airway damage, and therefore was relevant to the pico question. the methods used to evaluate airway injury were similar between the comolli et al. (2020) and engbers et al. (2017) studies. both papers performed histological evaluation of post-mortem samples following anaesthesia. however, the time of sample collection differed between the studies. in comolli et al. (2020) study samples were collected 4 days after anaesthesia. in engbers et al. (2017) study samples were collected 2 hours after anaesthesia. the different time intervals between device placement and sample collection could impact the observed histological changes to the tissues. collection after 2 hours would show any acute injury changes, such as acute inflammation and damage to tissue integrity, but not long-term damage such as chronic inflammatory infiltrate, fibrosis or stricture formation which could take days or weeks to develop. on the other hand, collection of tissue after 4 days may fail to identify the extent of the acute inflammatory changes immediately following the injury. if the tissue damage is significant but not severe enough to cause chronic change, it may still cause airway complications during the recovery period with resolution prior to sample collection at day 4 (anderson, 2013). the level of experience of the investigators performing the placement of each airway device differed between the three studies. in the two blinded studies (comolli et al., 2020; and engbers et al., 2017) the pathologist evaluating the tissue histology was blinded to treatment, however, the investigators placing the airway devices could not be blinded due to the nature of the procedure. this could impact the technique used by the investigator due to unconscious bias about which device was superior. moreover, in the engbers et al. (2017) study the investigator was more experienced using ett compared to the v-gel®. in wenger et al. (2017) the level of experience with device placement was not clear as multiple investigators were involved. one limitation that stood out in the comolli et al. (2020) study is the use of visual inspection of upper airway. the authors do not describe how the measurements were recorded and analysed for visual inspections of the upper airways. finally, it should be considered that the studies included only one breed of rabbit, that does not reflect the common pet rabbit breeds. considering the findings and limitations of each study, there is currently insufficient evidence to confirm that the use of v-gel® during general anaesthesia in rabbits causes less injury to the upper airways compared to other airway management devices. more research such as randomised blinded clinical trial with larger sample size can be helpful to learn if v-gel® use in rabbits is beneficial to them routinely in the clinical setting, given that less damage to the upper airways, will lead to better recovery from anaesthesia and fewer complications. methodology section search strategy databases searched and dates covered: cab abstracts via web of science (1910–present) scopus (1960–present) web of science core collections (1900–present) medline (pubmed) (1900–present) search strategy: cab abstracts and web of science core collections: (rabbit or rabbits or oryctolagus cuniculus) (anaesthesia or general anaesthesia) (v-gel or supraglottic airway device or sgad) (endotracheal tube or tracheal tube or endotracheal intubation or airway or mask or complications or laryngeal tube) (((1 and) 2 and) 3 and) 4 scopus: (rabbit or rabbits or oryctolagus-cuniculus) (anaesthesia or general-anaesthesia) (v-gel or supraglottic-airway-device or sga) (endotracheal-tube or tracheal-tube or endotracheal-intubation or airway or mask or complications or laryngeal-tube) #1 and #2 and #3 and #4 pubmed: (((rabbit or rabbits or oryctolagus cuniculus) and (anaesthesia or general anaesthesia)) and (v-gel or supraglottic airway device or sga)) and (endotracheal tube or tracheal tube or endotracheal intubation or airway or mask or complications or laryngeal tube) dates searches performed: 27 may 2022 exclusion / inclusion criteria exclusion: papers written in english. case series, case control studies, clinical trials and systemic reviews. study population: rabbits undergoing general anaesthesia. intervention: use of v-gel®. comparator: other airway control devices. outcomes: include measures of airway trauma or damage or inflammation. inclusion: case studies, narrative reviews, opinion pieces, methods papers, non-english publications. search outcome database number of results excluded – it did not include rabbits excluded – non-english papers excluded – did not focus on v-gels® excluded – did not focus on trauma / injury / damage to the airways excluded – case studies, narrative reviews, opinion pieces, methods papers excluded – duplicates total relevant papers cab abstracts 18 1 1 5 4 4 0 3 web of science 10 2 0 1 2 0 5 0 pubmed 16 1 0 4 2 1 8 0 scopus 18 0 0 0 0 0 18 0 total relevant papers when duplicates removed 3 acknowledgements i would like to dedicate this paper in memory of my professor dr frazer allan. i would also like to thank sanaa zaki for holding my hand throughout this project. orcid jasmine gheini: https://orcid.org/0000-0002-7243-6239 sanaa zaki: https://orcid.org/0000-0002-6393-6055 conflict of interest the authors declare no conflicts of interest. references anderson, j. (2013). chapter ii.2.2 – inflammation, wound healing, and the foreign-body response. in: b. ratner, a. hoffman, f. schoen, j. lemons, ed., biomaterial science, 3rd ed. academic press, 503–512. bateman, l., ludders, j., gleed, r. & erb, h. (2005). comparison between facemask and laryngeal mask airway in rabbits during isoflurane anesthesia. veterinary anaesthesia and analgesia. 32(5), 280–288. doi: https://doi.org/10.1111/j.1467-2995.2005.00169.x   brodbelt, d., blissitt, k., hammond, r., neath, p., young, l., pfeiffer, d. & wood, j. (2008). the risk of death: the confidential enquiry into perioperative small animal fatalities. veterinary anaesthesia and analgesia. 35(5), 365–373. doi: https://doi.org/10.1111/j.1467-2995.2008.00397.x comolli, j., schnellbacher, r., beaufrere, h., blas-machado, u., quandt, j., mayer, j. & divers, s. (2020). comparison of endoscopic endotracheal intubation and the v-gel supraglottic airway device for spontaneously ventilating new zealand white rabbits undergoing ovariohysterectomy. veterinary record. 187(10), e84. doi: https://doi.org/10.1136/vr.105746 crotaz, i. (2013). an observational clinical study in cats and rabbits of an anatomically designed supraglottic airway device for use in companion animal veterinary anaesthesia. the veterinary record. 172(23), 606. doi:  https://doi.org/10.1136/vr.100668 donnelly, t. & vella, d. (2020). 11 – basic anatomy, physiology, and husbandry of rabbits. in: quesenberry, c. orcutt, c. mans, & j. carpenter, eds., ferrets, rabbits, and rodents, 4th ed. philadelphia: w.b. saunders, 131–149. eatwell, k. (2014). analgesia, sedation and anaesthesia. in: a. meredith, b. lord, ed., bsava manual of rabbit medicine, 1st ed. england: british small animal veterinary association, 138–159. engbers, s., larkin, a., rousset, n., prebble, m., jonnalagadda, m., knight, c. & pang, d. (2017). comparison of a supraglottic airway device (v-gel) with blind orotracheal intubation in rabbits. frontiers in veterinary science. 4, 49. doi: https://doi.org/10.3389/fvets.2017.00049   goldmann, k. & ferson, d. (2005). education and training in airway management. best practice & research clinical anaesthesiology. 19(4), 717–732. doi: https://doi.org/10.1016/j.bpa.2005.07.007 hawkins, m. & pascoe, p. (2021). 37 – anesthesia, analgesia, and sedation of small mammals. in: quesenberry, c. orcutt, c. mans, & j. carpenter, eds., ferrets, rabbits, and rodents, 4th ed. philadelphia: w.b. saunders, 536–558. kazakos, g., anagnostou, t., savvas, i., raptopoulos, d., psalla, d. & kazakou, i. (2007). use of the laryngeal mask airway in rabbits: placement and efficacy. lab animal. 36(4), 29–34. doi: https://doi.org/10.1038/laban0407-29 mayer, j., brown, s. & mitchell, m. (2017). survey to investigate owners׳ perceptions and experiences of pet rabbit husbandry and health. journal of exotic pet medicine. 26(2), 123–131. doi: https://doi.org/10.1053/j.jepm.2017.01.021 wenger, s., müllhaupt, d., ohlerth, s., prasse, s., klein, k., da silva valente, b. & mosing, m. (2017). experimental evaluation of four airway devices in anaesthetized new zealand white rabbits. veterinary anaesthesia and analgesia. 44(3), 529–537. doi: https://doi.org/10.1016/j.vaa.2016.05.009 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. does the selective serotonin reuptake inhibitor (ssri) fluoxetine modify canine anxiety related behaviour? a knowledge summary by nicole s echeverri dvm candidate 1* merran govendir phd med(higher ed) bvsc 1 1sydney school of veterinary science, the university of sydney, head office jd stewart building university of sydney, nsw, 2006, australia *corresponding author (nech5972@uni.sydney.edu.au) vol 7, issue 4 (2022) submitted: 25 jan 2022 published: 23 nov 2022 next review: 23 feb 2024 doi: 10.18849/ve.v7i4.585 pico question does administration of the selective serotonin reuptake inhibitor (ssri) fluoxetine reduce the severity and / or frequency of some anxiety related behaviours in companion dogs, of at least 8 months of age, when compared with no pharmacological treatment?   clinical bottom line category of research question treatment the number and type of study designs reviewed two studies, both randomised, were critically appraised. each had a placebo control group and the dog's owners were blinded to the treatments strength of evidence moderate outcomes reported both studies provide moderate evidence that fluoxetine, when dispensed at 1–2 mg/kg per day by oral administration and not involving a behavioural modification program for the patient, may reduce some behaviours associated with separation anxiety and / or compulsive disorders. both studies indicate that a reduction in some unwanted behaviours may be observed after 1 week of fluoxetine medication. both studies recommend that behavioural and environmental modifications are important adjuncts to pharmacologic treatment of dogs with either compulsive disorders or separation anxiety. both studies also report that some dogs treated with fluoxetine experienced anorexia / decreased appetite and lethargy, although most of these effects were transient conclusion the clinical recommendation is that fluoxetine at 1–2 mg/kg administered orally, once daily, may be beneficial in reducing the severity of some canine anxiety related behaviours   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario during the covid-19 pandemic many dog owners and their families have worked from home and their dogs have experienced human company full time. as dog owners and family members return to their place of work and other external activities, veterinarians are receiving more enquiries on how to reduce canine anxiety when dogs are left at home, alone. veterinarians are interested in whether there is evidence that a psychotropic medication such as the ssri fluoxetine would be beneficial for those dogs that display separation anxiety or other anxiety related behaviours. the evidence two studies investigated fluoxetine daily administration for 4 weeks in dogs with veterinarian diagnosed   specific separation anxiety behaviours (landsberg et al., 2008) or compulsive disorders (irimajiri et al., 2009). these studies had fluoxetine treatment groups of n = 87 (landsberg et al., 2008) and n =  31 (irimajiri et al., 2009) and the same fluoxetine drug dose / kg body weight was administered to patients. both had comparable study designs as they were  multi-centre, randomised parallel-arm studies, placebo-controlled and blinded to owners (irimajiri et al., 2009);owners and participating veterinarians (landsberg et al., 2008). no behaviour modification program was incorporated into either study. both studies had a 2 week pretreatment stage to assess the behavioural profile of each patient and relied on the reporting of observations of the dogs’ owners every 2 weeks by telephone to the chief investigators. there was moderate evidence that dogs treated with fluoxetine 1–2 mg/kg orally, once daily, for 42 days resulted in a reduction in the severity of patient’s compulsive disorder compared to the control group (irimajiri et al., 2009) after 2 weeks of treatment (p = 0.015), 4 weeks (p = 0.013) and 6 weeks (p < 0.005). however, the mean number and duration of compulsive episodes did not differ significantly between treatment groups. in the other study (landsberg et al., 2008) there was a significant improvement in overall behaviours associated with separation anxiety (sa) at week 1 (p = 0.044) and 4 (p = 0.021) compared to the behaviours of the placebo group, and a significant reduction in destructive / rearranging behaviour at week 4 (p = 0.038), 5 (p = 0.024) and 6 (p = 0.032) of treatment compared to the behaviours of the control dogs. the mean rate of weekly change in the overall separation anxiety (sa) severity score improved for both treatment groups was more rapid for the fluoxetine treated group, however the difference was not statistically significant. the percentage of owner departures that failed to elicit any sa behaviour was significantly greater for fluoxetine treated dogs than for the control group at week 3 (p = 0.040) and 4 (p = 0.048). adverse experiences in some dogs treated with fluoxetine included anorexia / decreased appetite, vomiting, calm/lethargy depression occurred in more than 10% of fluoxetine treated dogs (landsberg et al., 2008). in irimajiri et al., 2009, lethargy (39%), decreased appetite 923%) and similar adverse experiences were reported. summary of the evidence landsberg et al. (2008) population: dogs with a history (> 1 month), displaying one or more separation anxiety (sa) behaviours. the four specific separation anxiety (sa) behaviours included: destructive / rearranging behaviour, excessive salivation, inappropriate defecation, and inappropriate urination. general characteristics: age: at least 6 months of age (average 4.5 years). breed: >60% of the total population were purebred, no breed was over-represented. gender and neuter status: fluoxetine treatment group: 47.5% female (7.1% intact) and 52.5% male (7.1% intact) vs. placebo group 57.6% female (6.1% intact) and 42.4% male (8.1% intact). body weight: 2.7–66.2 kg (average 20.5 kg). exclusion criteria included history of seizures, behaviour disorders other than separation anxiety, used for breeding, concurrent treatment with any other psychoactive medications and / or pheromones, initiation of a behaviour modification plan within the last 30 days, more than four dogs in the household, or more than one dog per household displaying sa behaviours. sample size: 171 dogs. intervention details: two week pretreatment phase – to establish a baseline of the occurrence of four specific behaviours on owners return after an absence: destructive / rearranging behaviour, excessive salivation, inappropriate defecation, and inappropriate urination. physical examination was undertaken, body weight recorded, blood collected for full blood count and biochemistry, urinalysis. every four consecutive dogs at each centre, were assigned to a group, with two dogs in each group assigned randomly to the fluoxetine or placebo groups. treatment (n = 87) fluoxetine 1–2 mg/kg as a beef-flavoured, chewable tablet, by mouth (po), once daily (sid), for 6 weeks. control (n = 84) identical appearance, odour, and packaging to treatment formulation without active ingredient at the same dosage and duration of the treatment group. time course consisted of 6 treatment weeks after conclusion of the 14 day pretreatment period. after 2 and 4 weeks of treatment, supervising veterinarians at each site conducted reports by telephone from each owner and conducted physical examinations at the conclusion of the study. study design: multi-centre, placebo-controlled, double blinded (owners and participating veterinarians), randomised parallel-arm study. outcome studied: at the end of each week of treatment the following outcomes were studied: outcome 1 – comparing global sa scores method: from telephone interviews every 2 weeks between owners and investigators, the incidence of improved global sa severity score was compared each week with the pretreatment score.   outcome 2 – comparing individual sa scores method: as for outcome 1 however individual sa scores i.e., destructive / rearranging behaviour, excessive salivation, inappropriate defecation, and inappropriate urination weekly were compared each week with the respective pretreatment score.   outcome 3 – rate of change in sa behaviours method: rate of change in overall sa behaviour severity scores was calculated for each dog using the regression model formula:   sw = a2 + b2w   sw = subjective owner obtained score on week (w) of the study. a2 = intercept of the regression model and the slope. b2 = estimate for the rate of change in the subjective score.   for the average of the pretreatment week score, w = -0.5 and for the 6 treatment weeks w = 1–6.   outcome 4 – frequency of sa behaviours per owner departure method: each specific sa behaviour was calculated for each dog by dividing the specific sa behaviour by the total number of owner departures.   outcome 5 – adverse experiences reporting method: frequency of adverse events observed by the dog owners and veterinarians during treatment with fluoxetine or placebo. main findings (relevant to pico question): main findings for outcome 1 – comparing global sa scores table 1: percentage of fluoxetine and placebo dogs with improved global separation anxiety scores. significant p value also reported from using a generalised linear mixed model. end of treatment week fluoxetine group % placebo group % p value 1 60.9 44.0 0.044 2 58.6 44.0 0.133 3 58.6 48.2 0.190 4 63.2 43.4 0.021 5 65.1 51.3 0.091 6 65.1 51.3 0.095 bolded p value = statistically significant.   main findings for outcome 2 – comparing individual sa scores compared with placebo treated dogs, fluoxetine treated dogs had a higher incidence of improvement in: destructive / rearranging behaviour at all weeks with significant differences occurring at weeks 4 (p = 0.038), 5 (p = 0.024) and 6 (p = 0.032). inappropriate urination at all weeks and significantly at week 3 (p = 0.045). excessive salivation and inappropriate defecation were generally higher at each week but not significantly different.   main findings for outcome 3 – rate of change in sa behaviours the mean rate of weekly change in the overall sa severity score demonstrated improvement in both groups but was more rapid in fluoxetine treated dogs, with the difference between groups approaching significance (p = 0.052). fluoxetine treated dogs had a significantly faster mean rate of change in destructive / rearranging behaviour (p = 0.028), but not in the rate of change in the other three sa behaviours.    main findings for outcome 4 – frequency of sa behaviours per owner departure the percentage of owner departures that failed to elicit any sa behaviour was greater for fluoxetine treated dogs than for placebo treated dogs at all weekly treatment intervals and significantly greater at weeks 3 (p = 0.040) and 4 (p = 0.048). compared with placebo dogs the fluoxetine treated dogs have a significantly lower frequency per owner separation anxiety related departures (sard) for destructive / rearranging behaviour at weeks 3 (p = 0.023) and 4 (p = 0.044) and inappropriate urination at week 4 (p = 0.029). although relative frequency of sard that resulted in excessive salivation and inappropriate defecation favoured fluoxetine treated dogs versus placebo dogs at all treatment intervals, however differences in these individual sa behaviours were not significant.   main findings for outcome 5 – adverse experiences  seizures occurred in one fluoxetine and one placebo treated dogs. other adverse experiences are provided in table 2. table 2: percentage of fluoxetine and placebo treated dogs recording adverse experiences:   fluoxetine treated % placebo treated % anorexia / decreased appetite 24.2 1.0 vomiting 20.2 18.2 calm / lethargy / depression 18.2 3 diarrhoea 14.1 10.1 shaking / shivering / tremor 5.1 0 aggression 4.0 4 constipation 3.0 0 submissive / fearful 3.0 0 weight loss 3.0 0   limitations: possible selection bias: owner and / or veterinarian misclassification bias of dogs with other concurrent behaviour problems if not adequately reported. restriction of only four sa behaviours, where other common behaviours could have included vocalisation, excessive licking / grooming, and restlessness. however, due to the study design, observations and recordings of the behaviours would be challenging to note since overall severity score (oss)was conducted upon the return of the absent owner. possible information bias such as relying on owner perceptions of changes in pet’s behaviour. definition of overall sa behaviour not provided. construct validity i.e., statistical confirmation that the subjective scores were measuring behavioural severity was not demonstrated for dogs classified as having the same treatment outcome for treatment week 3 for destructive / rearranging behaviour. also, for dogs classified as having ‘worse’ treatment outcomes due to the small number of dogs classified as ‘worse’ limiting the ability to obtain statistical significance. confounding effects from various at home stimuli and interactions not being in a controlled environment to accurately compare the treatment effects. adverse experience reporting from the dog owners and participating veterinarians not detailed in study. irimajiri et al. (2009) population: dogs with a history of compulsive behaviour daily for at least 2 months prior to enrolment. general characteristics: age: 1–9 years (median age = 3.5 years). breed: 10 mixed breeds and the remaining 52 represented 29 various purebreds. gender: 32 females and 30 males. neuter status: four intact females + 28 neutered females vs. 6 intact males + 24 neutered males. body weight: 3.8–54.1 kg (mean = 19.1 kg). exclusion criteria included pregnancy, lactation, history of breeding, psychoactive medications such as tricyclic antidepressants (tcas) or monoamine oxidase inhibitors 30 days prior to study commencement, history of systemic disease such as renal, hepatic, diabetes mellitus, or seizures, and / or uncooperative owners. six clinical diagnosis categories were identified by investigators: bull terriers with spinning, german shepherd dogs with tail-chasing, doberman pinschers with flank-sucking, miniature schnauzers with hind-end checking, dogs of any breed with another oral compulsive disorder (such as acral lick dermatitis, licking of any body part without self-injury, licking objects, and licking in the air), and dogs of any breed with another locomotory compulsive disorder (such as chasing shadows or lights, circling, spinning in dogs other than bull terriers, pacing, tail chasing in dogs other than german shepherd dogs, biting at the air, and fixation).  a centralised randomisation scheme was used so that dogs in these groups were assigned to the treatment and control groups in approximate equal numbers. sample size: 62 were used for statistical analyses. intervention details: two week pretreatment phase – to establish a baseline of dogs’ compulsive behaviour for 14 days: treatment group (n = 31); fluoxetine tablets 1–2 mg/kg, po, sid, for 6 weeks. control group (n = 31); placebo tablet with the same elements as fluoxetine without the active ingredient at the same dosage and duration. study design: randomised, placebo-controlled, blinded (owners), parallel-arm study. outcome studied: outcome 1 – change in owner-reporting severity of the dog’s compulsive disorder at days 14, 28, and 42 compared to baseline severity method: completion of a daily questionnaire, and telephone interviews every 2 weeks between owners and investigators.   outcome 2 – owner-reported change in frequency of the compulsive disorder over the 42 days of treatment method: data for owner maintained daily diaries were summarised for each 14 day period as the mean number of episodes per day.   outcome 3 – owner reported change in duration of episodes of the compulsive disorder over the 42 days of treatment   method: data for owner maintained daily diaries were summarised for each 14 day period as the mean duration of episodes per day.   outcome 4 – adverse experiences reporting method: owner kept daily diary during the 42 days of treatment whether the drug was administered that day, adverse effects observed that day and if so, what effects were seen, hours spent with the dog that day, number of compulsive episodes observed that day, duration of longest observed episode, and whether behaviour ceased on its own or due to intervention. main findings (relevant to pico question): main finding of outcome 1 – change in owner-reporting severity of the dog’s compulsive disorder table 3: summary of the % decrease in compulsive behaviour of dogs in the fluoxetine treatment and placebo group compared to baseline. significant p value reported from c2 statistical analyses. days of treatment treatment group % decrease compared to baseline placebo group % decrease compared to baseline p value (significant) 14 48 19 0.015 28 58 27 0.013 42 70 21 <0.005   after 42 days of treatment, dogs administered fluoxetine were 8.7 times (95% confidence interval (ci) 2.56 to 29.60) as likely to have a decrease in severity of the compulsive disorder, compared with severity during the baseline period, as were dogs administered the placebo.   main finding of outcome 2 owner-reported change in frequency of the compulsive disorder for the entire 42 day treatment period, the mean number of compulsive episodes per day, as determined from analysis of owner diaries, was not significantly different (p = 0.096) between dogs treated with fluoxetine (least squares mean 4.5 episodes/d) and dogs treated with the placebo (6.5 episodes/d).   main finding of outcome 3 – owner reported change in duration of episodes of the compulsive disorder for each of the 2 week periods during the study, the mean duration of compulsive episodes per day was not significantly different between treatment groups, regardless of whether data were analysed for the entire 42 day study period or for each 2 week evaluation period.   main finding for outcome 4 – adverse experiences in the fluoxetine group included lethargy (12/31 [39%]), decreased appetite (7/31 [23%]), aggression (4/31 [12%]), vomiting, excessive vocalisation, excessive licking, anxiety (2/31 [6%]) each.  adverse experiences in the placebo group were vomiting (3/31 [10%]), aggression (2/31 [6%]) and excessive vocalisation (1/31 [3%]). limitations: possible selection bias: owner and / or veterinarian misclassification bias of dogs with other concurrent behaviour problems if not adequately reported. misclassification bias of reliance of owner information could have been inaccurate – inconsistent observations leading to varied treatment success. confounding effects from various at home stimuli and interactions not being in a controlled environment to accurately compare the treatment effects. adverse experience reporting from the dog owners not detailed in study. appraisal, application and reflection the importance of the human-animal bond was accentuated in combating stay-at-home isolation in people due to the covid-19 pandemic, resulting in increasing dog adoption rates and ownership. as people return to their pre-pandemic lives, such as returning to the work-place and external commitments, anxiety related conditions in dogs may become more prevalent: attributed to  overattachment to the owner, traumatic events while alone, and genetic predisposition (flannigan & dodman, 2001). options for minimising problem behaviours in dogs are crucial to minimise pet relinquishment and/or euthanasia (chutter et al., 2019). there is a long history of the use of various human anxiolytic drugs in companion animals, and fluoxetine is a widely prescribed ssri in people and has been used in canine practice (simpson et al., 2007; pineda et al., 2018; chutter et al. 2019; and papich, 2020). it has also been suggested that anxiolytic therapy in conjunction with a behaviour modification program is the best strategy to minimise anxiety disorders in dogs (landsberg, 2001; and overall, 2013). an anxiolytic pharmacological intervention reportedly promotes the animal’s response to a behavioural modification program (pineda et al., 2018). administration of tricyclic antidepressants (tcas), ssris, and benzodiazepines are the more commonly used therapeutic drugs of choice to control anxiety, fear, and/or aggression with varying success in veterinary practice (gruen & sherman 2008). fluoxetine, a ssri registered for dogs is capable of increasing central nervous system (cns) serotonin synapse concentrations with few adverse effects (pineda et al., 2018). fluoxetine delays the reuptake of serotonin resulting in an increase and prolongation of serotonin in those brain synapses where serotonin acts as a neurotransmitter (papich, 2020). this pico question focused on dogs at least 8 months of age, when most dogs have passed the early and late socialisation period (harvey et al., 2016). dogs’ behavioural and social maturity are naturally developed between 12 and 24 months of age, therefore, the period before individuals reaching maturity is important in the development of their future behaviour (harvey et al., 2016). irimajiri et al. (2009)  focused on a reduction in the severity of canine compulsive disorders (irimajiri et al., 2009). compulsive disorders are repetitive behaviours. in dogs this is characterised by the patient engaging in a repetitive, stereotyped behaviour for a significant amount of time (crowell-davis, 2006). behaviours of compulsive disorders are derived from normal behaviours and may arise when the patient is exposed to an under-stimulating, such as prolonged separation anxiety, or from an overstimulating environment (crowell-davis, 2006).     there were numerous similarities between both studies’ designs: they were both run out of multiple veterinary hospitals (multi-centre), placebo controlled, parallel-arm studies, used  board-certified veterinary behaviourists to confirm diagnosis of anxiety behaviours; used  veterinary behaviourists maintaining contact with owners every 2 weeks by telephone, the owners were blinded to the treatment, similar pretreatment conditions, dogs medicated with the same fluoxetine dosage for the same duration, and were reliant on owners reporting their perceptions of their dog’s level of anxiety to the chief investigators. both studies were financially supported by lilly animal health, greenfield, indiana, usa. irimajiri et al. (2009) also analysed the owners’ daily diaries of their pets’ behaviour after 6 weeks of treatment, however, it is not reported if this also occurred in landsberg et al. (2008). there were similarities in the outcomes, both studies reported some significant reduction in some of the target behaviours between the respective placebo treated dogs. landsberg et al. (2008) also reported that fluoxetine treated dogs had a significantly faster mean rate of change in destructive / rearranging behaviour (p = 0.028), but not in the rate of change in the other three sa behaviours. irimajiri et al. (2009) reported that the mean number and duration of compulsive episodes did not differ significantly between groups. possible explanations for the differences in outcomes reported between the two studies could be attributable to both studies being focused on different targeted behaviours. for example; irimajiri et al. (2009) reported 52 of the 62 (84% ) subjects were purebreds with 19% of subjects being german shepherd dogs, while landsberg et al. (2008) reported that > 60% of the dogs in both groups were purebreds, however no breed was over-represented. as irimajiri et al. (2009) did ‘block’ subjects based on clinical diagnosis e.g. ‘german shepherd dogs with tail-chasing’ and distributed such blocks evenly into the treatment and placebo groups, it is difficult to comment whether the proportion of purebreds was a confounding factor in one or both studies. landsberg et al. (2008) showed a significant improvement specifically of destructive / rearranging behaviour within 3 weeks of treatment compared to those dogs treated with a placebo. it was noteworthy that the onset of improvement in overall and individual severity scores was rapid in the fluoxetine treatment group, occurring within a week after treatment was implemented. this is a significant finding as standard literature states that psychotropic drugs can take up to 3 to 5 weeks to take effect (overall, 2013). additionally, a longer treatment period may have been warranted as it has been suggested that at least 8 weeks of treatment  are required to observe a change behaviour when ssris are administer to human patients with obsessive compulsive disease (ocd) (liebowitz et al., 2002). landsberg et al. (2008) also reported that there was a reduction in some of the behaviours such as destructive / rearranging behaviour from baseline in the placebo dogs. landsberg et al. (2008) suggests that the high placebo response study may have been a result of investigators feeling ethically obligated to provide some incompliant guidance to owners on their dog’s behaviour when questioned.   there are numerous limitations inherent within these studies, that include: possible sources of selection bias. it is possible that pets with other concurrent behaviour problems might have been inadvertently enrolled in either study (landsberg et al., 2008).   possible sources of information bias. misclassification bias: reliance of owner information and inaccurate observations may have led to inconsistent and varied treatment success in both studies. for example irimajiri et al. (2009) reported that some owners did not complete all entries on a daily basis and some participants had multiple family members completing diary entries (irimajiri et al., 2009). there is no indication in either study whether the baseline data between the treatment and control groups were comparable prior to commencing either the fluoxetine or placebo dosing. owners were asked to respond to a previously validated (hewson et al., 1998) 5-point likert scale to identify changes in severity of compulsive disorders (irimajiri et al., 2009) whereas landsberg et al. (2008) used a four point scale for the owners to assess the overall level of separation anxiety during the preceding week (0, absent; 1, mild; 2, moderate; 3, severe). this inconsistency in likert score items may have had some effect on determining the outcomes. while both studies use the word ‘frequency’, they determined frequency differently. landsberg et al. (2008) used relative frequency of each specific sa behaviour calculated for each dog by dividing the specific sa behaviour by the total number of owner departures, while irimajiri et al. (2009) used owner observation diary data summarised for each 14 day period as the mean number of episodes per day. it is possible across the 42 treatment days that there was some owner ‘drift’ in their perception of severity of targeted behaviours. no ‘behavioural anchors’ are mentioned as part of the ‘severity’ rating in either study which may have influenced the reliability and validity of each ‘severity rating’.   possible sources of confounding bias. effect of home stimuli such as frequency and duration of interactions with humans (such as owners, family members etc.) or the frequency / and duration of daily exercise on outcomes, questions the accuracy of comparative treatment effects and were not addressed in either study. in both studies (landsberg et al. 2008; and irimajiri et al. 2009) there was no mention the time of day the fluoxetine was administered, nor whether it was administered with or without food. however, the reconcileò chewable tablets label states that the medication can be administered with, or without food.  the most common adverse experiences associated with fluoxetine medication were lethargy (18.2–39%), anorexia (24.2–23%) as well as other adverse experiences that affected only a few subjects (landsberg et al., 2008; and irimajiri et al., 2009). both studies reported in most cases signs resolved within a few weeks or with a dose reduction.  in conclusion, the ssri fluoxetine is a palatable and well-tolerated psychotherapeutic medicine for dogs at recommended doses. based on the outcomes of the two studies provided in this knowledge summary there is moderate evidence that fluoxetine reduces the severity of anxiety related conditions. however, both studies also recommend that behavioural and environmental modifications are important adjuncts to pharmacologic treatment for dogs with separation anxiety (landsberg et al., 2008) and / or compulsive disorders (irimajiri et al., 2009). methodology section search strategy databases searched and dates covered: cab abstracts via web of science (1910–2022) biosis previews via web of science (1926–2022) scopus (1788–2022) search strategy: for each of the databases following terms were used: (“fluoxetine” or “prozac” or “reconcile” or “selective serotonin reuptake inhibitor” or “ssri” or “antidepressant”) and (“dog” or ‘dogs”) and (“anxiety” or “separation anxiety” or “compulsive disorder” or “stress” or “anxious”) dates searches performed: 11 jun 2022 exclusion / inclusion criteria exclusion: study designs that were not controlled trials. irrelevant articles to pico question. duplicates from the three databases used. inclusion: controlled clinical trial (randomised or non-randomised) relevant to pico question, administration of fluoxetine on with no behavioural modification. journal articles only. search outcome database number of results excluded – irrelevant to pico question excluded – not a controlled study excluded – fluoxetine drug combinations or behaviour modification excluded – duplicates total relevant papers cab abstracts 58 50 1 5 0 2 biosis 55 53 0 2 0 0 scopus 12 12 0 0 0 0 total relevant papers 2 acknowledgments the authors would like to thank reviewer dr maureen o’mara for her insightful comments and suggested additions for the appraisal, application and reflection section. orcid nicole s echeverri: https://orcid.org/0000-0003-4308-4374 merran govendir: https://orcid.org/0000-0003-1655-7076 funding this work was completed in partial fulfillment for the requirements of the doctor of veterinary medicine degree, the university of sydney. this research was funded by the sydney school of veterinary science research & enquiry unit of study 2021 fund. conflict of interest the authors declare no conflicts of interest. references chutter, m., perry, p. & houpt, k. (2019). efficacy of fluoxetine for canine behavioral disorders. journal of veterinary behavior. 33, 54–58. doi: https://doi.org/10.1016/j.jveb.2019.05.006 crowell-davis, s. (2006). benzodiazepines veterinary psychopharmacology. crowell-davis sl and murray t. ames, iowa, blackwell publishing. 34–71. flannigan, g. & dodman, n. h. (2001). risk factors and behaviors associated with separation anxiety in dogs. journal of the american veterinary medical association. 219(4), 460–466. doi: https://doi.org/10.2460/javma.2001.219.460 gruen, m. e. & sherman, b. l. (2008). use of trazodone as an adjunctive agent in the treatment of canine anxiety disorders: 56 cases (1995–2007). journal of the american veterinary medical association. 233(12), 1902–1907. doi: https://doi.org/10.2460/javma.233.12.1902 harvey, n. d., craigon, p. j., blythe, s. a., england, g. c. & asher, l. (2016). social rearing environment influences dog behavioral development. journal of veterinary behavior. 16, 13–21. doi: https://doi.org/10.1016/j.jveb.2016.03.004 hewson, c., luescher, u. & ball, r. (1998). measuring change in the behavioural severity of canine compulsive disorder: the construct validity of categories of change derived from two rating scales. applied animal behaviour science. 60(1), 55–68. doi: https://doi.org/10.1016/s0168-1591(98)00145-2 irimajiri, m., luescher, a. u., douglass, g., robertson-plouch, c., zimmermann, a. & hozak, r. (2009). randomized, controlled clinical trial of the efficacy of fluoxetine for treatment of compulsive disorders in dogs. journal of the american veterinary medical association. 235(6), 705–709. doi: https://doi.org/10.2460/javma.235.6.705 landsberg, g. m. (2001). clomipramine--beyond separation anxiety. journal of the american animal hospital association. 37(4), 313–318. doi: https://doi.org/10.5326/15473317-37-4-313 landsberg, g. m., melese, p., sherman, b. l., neilson, j. c., zimmerman, a. & clarke, t. p. (2008). effectiveness of fluoxetine chewable tablets in the treatment of canine separation anxiety. journal of veterinary behavior. 3(1), 12–19. doi: https://doi.org/10.1016/j.jveb.2007.09.001 liebowitz, m. r., turner, s. m., piacentini, j., beidel, d. c., clarvit, s. r., davies, s. o., graae, f., jaffer, m., lin, s.-h., sallee, f. r., schmidt, a. b. & simpson, h. b. (2002). fluoxetine in children and adolescents with ocd: a placebo-controlled trial. journal of the american academy of child & adolescent psychiatry. 41(12), 1431–1438. doi: https://doi.org/10.1097/00004583-200212000-00014 overall, k. (2013). manual of clinical behavioral medicine for dogs and cats-e-book. elsevier health sciences. papich, m. (2020). fluoxetine hydrochloride. papich handbook of veterinary drugs, elsevior: 385–387. pineda, s., anzola, b., ruso, v., ibáñez, m. & olivares, á. (2018). pharmacological therapy with a combination of alprazolam and fluoxetine and use of the trace element lithium gluconate for treating anxiety disorders and aggression in dogs. journal of veterinary behavior. 28: 30–34. doi: https://doi.org/10.1016/j.jveb.2018.07.013 simpson, b. s., landsberg, g. m., reisner, i. r., ciribassi, j. j., horwitz, d., houpt, k. a., kroll, t. l., luescher, a., moffat, k. s. & douglass, g. (2007). effects of reconcile (fluoxetine) chewable tablets plus behavior management for canine separation anxiety. veterinary therapeutics. 8(1), 18. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. irrelevant, irrelevant, irrelevant! time to change our approach to research? rachel dean bvms phd dsam (fel) mrcvs1* 1university of nottingham, nottingham, ng7 2rd *corresponding author (rachel.dean@nottingham.ac.uk) vol 1, issue 4 (2016) published: 8 dec 2016 doi: 10.18849/ve.v1i4.79 to be able to practice evidence-based veterinary medicine, clinicians need high quality relevant evidence to integrate with their clinical decision making. rachel's talk explores how relevance is possibly more important than quality as even the best evidence cannot be used if it can't be applied to veterinary practice... find out more about rachel.  view presentation slides comments: does the extent of the surgical margin affect the likelihood of local recurrence in patnaik grade i or ii cutaneous mast cell tumours? a knowledge summary by christos dorlis dvm afhea mrcvs 1* 1medivet 24 hour enfield, 673 hertford road, enfield, en3 6nh *corresponding author (chrisdorlis@gmail.com) vol 7, issue 1 (2022) published: 10 mar 2022 reviewed by: jane dobson (bvetmed dvetmed dipecvim dipecvim dipecvim-ca frcvs), joanna morris (bvsc bsc phd frcvs) and adam swallow (bvsc mrcvs) next review date: 09 nov 2023 doi: 10.18849/ve.v7i1.508 pico question does the extent of the surgical margin affect the likelihood of local recurrence in patnaik grade i or ii cutaneous mast cell tumours?   clinical bottom line category of research question treatment the number and type of study designs reviewed eight papers were critically reviewed. five were retrospective case series, two prospective clinical trials, and one prospective case series strength of evidence low outcomes reported sequin et al. (2001) reported a local recurrence rate of 5%, but this study is 20 years old. in the studies of simpson et al. (2004), fulcher et al. (2006), pratschke et al. (2013), saunders et al. (2020), and itoh et al. (2021), no local recurrence was observed in grade i and ii mast cell tumours, while in the milovancev et al. (2019) study, only 1/30 low-grade cutaneous mast cell tumors developed local recurrence. therefore, there is some evidence that conservative surgical excision is sufficient to achieve local control with low recurrence rates conclusion there is increasing evidence in the literature for conservative surgical excision of grade i and ii mcts, but because the quality of evidence is low, no clear recommendations can be made. further studies are needed to determine recommendations for surgical excision of cutaneous mcts based on the biological characteristics of the tumour and the completeness of histologic margins   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a 4 year old neutered male pug presents with a 1 cm cutaneous mass in the left flank region. the owner reports that the mass has been there for 3 months and does not change in size. cytologic examination suggests a mast cell tumour (mct). blood work and abdominal ultrasound were unremarkable. what margin would you ideally excise this mass? the evidence the overall quality of evidence is low, consisting predominantly of retrospective observational studies (sequin et al., 2001; simpson et al., 2004; pratschke et al., 2013; chu et al., 2020; saunders et al., 2020; and itoh et al., 2021) and no randomised prospective clinical trials. two prospective observational clinical studies (fulcher et al., 2006; and milovancev et al., 2019) showed a low recurrence rate, but both consisted of a very small sample size (23 and 30 cutaneous mcts, respectively). summary of the evidence seguin et al. (2001) population: medical records of dogs with mast cell tumours (mcts) were diagnosed at colorado state university veterinary teaching hospital (csu-vth) between january 1996 and august 1999. the study included only dogs with grade ii (patnaik) cutaneous mcts treated with surgery alone. 21 of the included tumours were scars from previously incompletely excised mcts. sample size: 55 dogs (60 mcts). intervention details: surgical margins: 2–3 cm lateral margins and one fascial plane as deep margin. adjuvant treatment: none. tumour grading: patnaik grading system. no kiupel grading. histological margins: were categorised as complete, complete but close (tumour cells within 1 mm of surgical margin), or incomplete (tumour cells at the surgical margin). follow-up method: follow-up information was obtained via reassessment at the clinic or telephone calls to referring veterinarians or owners. study design: retrospective case series. outcome studied: local recurrence. completeness of excision. time of local recurrence. survival time (time from surgery until death). main findings (relevant to pico question): tumour diameter: median tumour diameter (range): 2 cm (1–4 cm). tumour grading: 39 grade ii mcts (patnaik). 21 surgical scars from previously incompletely excised mcts. tumour location: the tumours were located on the head and neck = 8 (13%), trunk = 29 (48%), limb =18 (30%), genital region = 3 (5%) and location were not available for 2 (3%) tumours. histological margins results: complete in 54 (90%) tumours, complete but close in 3 (5%) tumours, incomplete in 1 (2%) tumour, information not available in 2 (3%) tumours, two dogs had amputation for definite surgery, all 21 scar excision had complete histological margins. local recurrence: three tumours (5%). the median time to local recurrence was 62 days (range, 51–252 days). median follow-up time 540 days (range, 77–1,804 days). 46/55 (84%) dogs were free of mct during the study period. limitations: small sample size – risk of type ii error. two dogs had amputation for definite treatment and local recurrence was impossible to assess in these two cases. no clear definition of exact margins as a range was given (2–3 cm) and lacked assigned groups. non-objective follow-up in some cases (client follow-up) – potential risk of local recurrence underestimated. definition of local recurrence in relation to the original scar was not specified – the risk of some local recurrences being classified as de novo. retrospective nature – some medical records are incomplete (e.g., tumour size) and therefore cannot provide information for tumours larger than 4 cm. no definite diagnosis of local recurrence with cytology or biopsy. prognostic relationship between histopathological status of surgical margins and recurrence could not be determined because the number of local recurrences was small (5%), and the classification system of histological margins differed from other studies and was therefore difficult to compare. participants’ characteristics not homogeneous – surgery was performed as revision in some cases (21 dogs). simpson et al. (2004) population: client-owned dogs diagnosed with cutaneous mast cell tumours (mcts) based on cytological examination of fine needle aspirates, at animal medical center, new york, usa – time interval not reported. sample size: 21 dogs (23 cutaneous grade i and ii (patnaik) mcts). intervention details: surgical margins: mct removed with 3 cm margins and one fascial plane as deep margin. prior to removal, the skin was marked at 1, 2, and 3 cm from the tumour margin at 0°, 90°, 180°, and 270°. tumours were affixed to cardboard to recreate their original shape. tissues were fixed in formalin and eight 1 cm long full-thickness tissue samples were taken at 3 cm margins. four 1cm long full-thickness tissue sections were obtained at the 1cm and 2cm margins. all tissue margins were examined by one board-certified pathologist. adjuvant treatment: one dog had radiation therapy after incomplete deep margin excision. tumour grading: all tumours were graded by two pathologists using the patnaik system. histological margins: were categorised as complete, complete but close (tumour cells within 1 mm of surgical margin), or incomplete (tumour cells at the surgical margin). follow-up methods: follow-up information was obtained via reassessment at the clinic or telephone calls to referring veterinarians. local recurrence: disease-free interval was defined as the interval from the date of tumour excision to the date of local recurrence. survival time was defined as the interval from the date of tumour excision to the date of death. study design: prospective case series. outcome studied: local recurrence. survival time. main findings (relevant to pico question): tumour diameter: mean tumour diameter was 1.9 cm (median, 1.7 cm; range, 0.35–5.0 cm). tumour location: 15/23 (65%) tumours were located on the trunk, 5/23 (22%) were located on the hind limbs, and 3/23 (13%) were located on the neck. tumour grading: there were three grade i and 20 grade ii tumours. histological margins results: all grade i tumours were completely excised at all margins. 15/20 (75%) of the grade ii tumours were completely excised at the 1 cm margin. 20/20(100%) of grade ii tumours were completely excised at the 2 cm margin. 2/20 grade ii tumours had incomplete deep margins. local recurrence: no local recurrence was noted in any dog. follow-up time: the median follow-up time was 351 days (range, 78–603 days). limitations: this study has a small sample size and is prone to type ii error. this study does not include mcts on the face or inguinal and perineal regions, and no recommendation can be made for these locations. one dog in which mcts were detected within 1 mm of the deep margin received full-course radiation therapy; therefore direct comparison cannot be made for this patient. although there is no statistical correlation between tumour diameter and completeness of excision, most tumours in this study were small. the period during which participants were enrolled in the study was not mentioned. inconsistent method of follow-up. fulcher et al. (2006) population: client-owned dogs with one or more cutaneous mast cell tumours (mcts) diagnosed with a cytological examination of fine needle aspirates, at animal medical center, new york, usa – time interval not reported. sample size: 16 dogs (23 cutaneous mcts). intervention details: surgical margins: mct removed with 3 cm margins and one fascial plane deep margin. prior to removal, the skin was marked at 1, 2, and 3 cm from the tumour margin at 0°, 90°, 180°, and 270°. tumours were affixed to cardboard to recreate their original shape. tissues were fixed in formalin and eight 1 cm long full-thickness tissue samples were taken at 3 cm margins. four 1cm long full-thickness tissue sections were obtained at the 1cm and 2cm margins. all tissue margins were examined by one board-certified pathologist. tumour grading: all tumours were graded by two pathologists using the patnaik system. adjuvant treatment: some dogs had corticosteroids, but no more information was given. histological margins were categorised as complete, complete but close (tumour cells within 1 mm of surgical margin), or incomplete (tumour cells at the surgical margin). follow-up method: follow-up information was obtained via reassessment at the clinic or telephone calls to referring veterinarians. local recurrence was defined as the development of an mct at or within 2 cm of the original surgical site. disease-free interval: time of surgery to local recurrence. study design: prospective clinical trial. outcome studied: local recurrence. disease-free interval. main findings (relevant to pico question): tumour diameter: mean tumour diameter was 1.3 cm (median, 1.1 cm; range, 0.4–3.1 cm). tumour location: 10 (44%) located in the trunk, 7 (30%) on the hindlimbs, 3 (13%) on the forelimbs and 3 (13%) on the head and neck. tumour grading: 4/23 (17%) mcts were grade i tumours, 19/23 (83%) were grade ii tumours. histological margins results: all grade i tumours were completely excised at the 1and 2cm margins. 13/19 grade ii mcts, no mcts were detected at the 1cm margin. 17/19 tumours, no mcts were detected at the 2cm margin. overall, 21/23 (91%) mcts were completely excised. there was no recurrence in two of the grade ii tumours with incomplete margins, although one had revision surgery 2 weeks after the first excision. all had complete deep margins. local recurrence: none of the dogs had local recurrence. follow-up time: the median follow-up interval for all dogs was 379 days (range, 51–538 days). limitations: this study has small sample size and is prone to type ii error. this study does not include mcts on the face or inguinal and perineal regions, and no recommendation can be made for these locations. one dog with incompletely excised mct received additional surgery in 2 weeks therefore direct comparison cannot be made. inconsistent method of follow-up (either clinical examination or telephone update). the period when participants were enrolled in the study was not mentioned. pratschke et al. (2013) population: dogs with cutaneous and subcutaneous mast cell tumours (mcts) were diagnosed either with cytological or histopathological examination at the university of glasgow between 2008 and 2012. sample size: 40 dogs (47 mct [41 cutaneous and six subcutaneous]). intervention details: surgical margins: lateral margins equivalent to the widest measured diameter of the tumour and a minimum depth of one well-defined fascial plane. if tumour size exceeded 4 cm then a fixed 4 cm lateral margin was taken. tumour grading: grading based on patnaik and kiupel system. histological margins: margins were considered clear when the distance between neoplastic cells and non-neoplastic tissue was > 1 mm; otherwise, they were considered incomplete. follow-up methods: retrieved from clinical records and through contact with the referring veterinarians and dog owners. study design: retrospective case series. outcome studied: local recurrence. main findings (relevant to pico question): tumour diameter: tumour diameter ranged from 5 mm to 60 x 40 mm. tumour location: 24/47 (51%) located in the limbs, 9/47 (19%) on the trunk, 9/47 (19%) on the head, and 5 (11%) the inguinal region or prepuce and genital area. tumour grading: 21 tumours grade i, 18 tumours grade ii, two grade iii, and six subcutaneous. adjuvant treatments: five low-grade mcts (four cutaneous and one subcutaneous) had postoperative chemotherapy (all these five had nodal metastasis). one dog with incomplete margins had postoperative radiation therapy. histological margins results: 40/47 (85%) tumours with complete and 7/47 tumors (15%) with incomplete margins. of the excised tumours with incomplete margins, four had one incomplete lateral margin and three had an incomplete deep margin. 5/7 tumours with incomplete margins were located on the limbs. of the dogs with incomplete excisional margins, one had postoperative radiation therapy (disease free interval [dfi]: 300 days) and one had chemotherapy (dfi: 510 days), one died from gastric dilatation-volvulus the day after surgery, one developed local recurrence and was euthanised 1.5 months later, and the other three had no adjunctive treatment and no identified recurrence at follow-up times of 120, 300, and 330 days. local recurrence: only one local recurrence (dog with grade iii mast cell tumour completely excised). follow-up time: follow-up intervals ranged from 0 to 1,140 days after mct excision (median, 420 days). limitations: retrospective nature – incomplete medical records may influence the outcome. lack of control group for comparison (a group with 3 cm margins for example). two dogs with incomplete margins have additional treatments and the other died from another cause and this may influence the low number of recurrences. inconsistent follow-up methods (some cases had owner and referring veterinary surgeon follow-up and other reviewing the clinical records). milovancev et al. (2019) population: client-owned dogs presented to the veterinary teaching hospital at oregon state university for surgical treatment of mast cell tumours (mcts) between august 1, 2014–july 31, 2016. the population include: 38 dogs (52 mcts), 50 low-grade (30 cutaneous and 20 subcutaneous), two mcts high grade. mcts diagnosed via cytological examination. the authors also looked at 19 soft tissue sarcoma cases, but they are not relevant to the pico topic in this study, thus they will not be discussed further. sample size: 38 dogs (30 cutaneous low-grade mcts). intervention details: surgical margins: en bloc removal of a grossly normal surgical margin of at least 1 mm beyond the palpable and visible edge of the tumour (i.e., no grossly visible tumour at the surgical margins). tumour grading: based on kiupel and patnaik system. histological margins: histological margins of 0 mm were considered as incomplete excision whereas histological margins >0 mm (i.e., tumour cells do not reach the inked surgical margin) were considered as complete excision, adjuvant treatment: 4 low-grade tumours had additional chemotherapy (three were clinical stage iii and one was clinical stage iv). follow-up methods: 2 year postoperative active surveillance period with clinical outcome data. local recurrence confirmed by cytological evaluation in a follow-up period of 24 months. study design: prospective clinical trial. outcome studied: local recurrence. main findings (relevant to pico question): tumour diameter: median 15 mm, range 5–52 mm. tumour grading: 30 low-grade mcts (graded as ii on patnaik system and low-grade on kiupel system). narrowest intraoperative margins: two mcts: 5 mm one mct: 8 mm four mcts: 10 mm two mcts: 15 mm 18 mcts: 20 mm one mct: 25 mm two mcts: 30 mm narrowest histological margins: 0 mm: four tumours <1 mm: 11 tumours number of deep fascial planes: 0: two tumours 1: 27 tumours 2: one tumour 1/30 low-grade mct developed local recurrence. this was a completely excised (narrowest histological margin = 10.6 m) cutaneous mct from the ventral abdomen, with local recurrence noted at the 12 month postoperative recheck (confirmed via fine-needle-aspirate cytology). the dog was euthanised 1229 days postoperatively for progressive osteoarthritis. limitations: small number of cases – risk of type ii error. no standardised margin of excision. chu et al. (2020) population: cutaneous mast cell tumours (mcts) excised from dogs between january 1, 2007, and december 31, 2017, at the cornell university hospital for animals were identified from a search of the pathology department’s database. 623 cutaneous mcts were identified (83 tumours grade i and ii met the inclusion criteria). sample size: 68 dogs (83 tumours grade i and ii [patnaik grading system]). intervention details: surgical margins: tumours were assigned to groups. conservative-margin group (n = 46): if they had been excised with lateral margins that were 2 cm for tumours ≥ 2 cm in diameter or equal to the tumour diameter (proportional) for tumours < 2 cm in diameter. wide-margin group (n = 37): if they had been excised with lateral margins of 3 cm, regardless of tumour diameter. a noninferiority margin of > 0.9 cm was used for the risk ratio (probability of complete excision for the conservativevs wide-margin group). neoadjuvant treatment: some dogs had preoperative prednisone administration. tumour grading system: patnaik and kiupel grading system. histological margins: complete excision: classified when results of microscopic examination revealed no mcts with characteristics suggestive of neoplastic behaviour at the lateral or deep edge of the section, whether individually scattered or as part of the neoplasm (pratschke et al., 2013). incomplete excision: all the other instances was classified as incomplete excision. follow-up method: assessment of histological margins for completeness of excision. study design: retrospective observational study. outcome studied: the margin of excision (complete vs incomplete excision as histologically determined) was compared between conservativeand wide-margin groups. main findings (relevant to pico question): median (range) tumour diameter: wide-margin group: 1 cm (0.2–7.0 cm). conservative-margin groups :1.0 cm (0.1–4.0 cm). tumour location: limbs (29), thoracic region (25), abdominal region (11), head (five), and neck region (three). the study did not specify the location of the remaining 10 tumours. tumour grading: all tumours were histologically classified as grade i or ii by the patnaik system. tumours in the wide-margin group were more likely to be classified as grade ii (vs grade i) than were tumours in the conservative-margin group. adjuvant treatments: one dog in the wide margin group and two in the conservative margin group had preoperative prednisone administration. histological tumour-free margins: conservative group: 43/46 (93%). wide margin group: 34/37 (92%). the risk ratio met the criterion for noninferiority. limitations: lack of randomisation: more tumours grade ii in the wide margins group which could induce bias to the study. the outcome was assessed by histological complete / incomplete margins and there is no correlation with clinical recurrence – further studies are needed to assess these groups with clinical recurrence. due to the retrospective nature 473 dogs were excluded due to missing information which may introduce selection bias. histological margin assessment based on radial method only by different board-certified pathologists. saunders et al. (2020) population: dogs presented to the veterinary oncology specialists (underwood, australia) between july and october 2016 and animal referral hospital brisbane (brisbane, australia) between october 2016 and august 2018. sample size: 65 dogs (100 cutaneous mast cell tumours [mcts]). intervention details: surgical margins: the width of proportional margin excision was based on the largest lateral diameter of the mass up to a level of 2 cm. if the tumour diameter was greater than 2 cm, the lateral margins that were used to excise the mass were limited to 2 cm. the tumours were excised in an en bloc manner with the proposed lateral surgical margins and a minimum of at least one fascial plane as deep margin. preoperative neoadjuvant medications: prednisolone (0.5–1 mg/kg po sid ± chlorpheniramine (0.5–1 mg/kg po bid) for 7–10 days prior to surgical intervention. tumour grading: all tumours graded with kiupel system. tumour size: authors created two subgroups based on tumour size: of the low-grade mcts, 42 were < 10 mm in diameter, with the remaining 46 = 10 mm. of the high-grade mcts 5 were < 10 mm and seven were = 10 mm groups. tissues were fixed in formalin and were reviewed by a board-certified pathologist. histological margins: complete excision of the mass was defined as both the lateral and deep margins being clear of infiltration with mcts. incomplete excision was defined as mast cell infiltration in lateral or deep margins. histological margin size was grouped into three categories: ≤2 mm, 2.1–5 mm, and > 5 mm. follow-up method: a follow-up period of at least 365 days by physical examination or owner-contact ± cytological evaluation when appropriate. study design: retrospective cohort study. outcome studied: local recurrence. main findings (relevant to pico question): tumour diameter: low-grade mcts: 42 were < 10 mm in diameter, and 46 being = 10 mm in diameter. high-grade mcts: five were <10mm and seven were =10mm median overall tumour diameter =10.0 mm (range of 1–85 mm). median high-grade tumour diameter = 15.0 mm (range of 3–85 mm). median low-grade tumours diameter = 10.0 mm (range of 1–45 mm). tumour location: (35%) limbs, (23%) flank and abdomen, (15%) thorax, (15%) the prepuce and / or perineal regions, (12%) the head and neck. tumour grading: 88 low-grade mct and 12 high-grade mct. 11 dogs had high grade mcts (one had two tumours). 54 dogs had low-grade mcts (18 multiple). histological margins/completeness of excision: 95/100 (95%) mcts were completely excised. low-grade: 84/88 (96%). high grade:11/12 (92%). small tumours (< 10 mm): all had complete excision 47/47 (100%). large tumours (≥ 10 mm): 48/53 (91%) had complete. histological tumour-free margins (htfm) size: median htfm size of all complete excised tumours: 5 mm (range 0.5–15 mm). median htfm size of high-grade tumours: 5 mm (range 2–14 mm). median htfm size of low-grade tumours: 5 mm (range 0.5–15 mm). no significant association was evident between tumour grade and htfm size. no significant association was evident between the tumour size groups and the htfm size groups. recurrence rate: 3/100 tumours (3%) with a median follow-up period of 593 days (range 180–1460 days) with none on the low-grade group and three on the high-grade group 3/12(25%). of the incompletely excised masses, four were low-grade, and one was high-grade and only the high grade recurred. 45 tumours had neoadjuvant prednisolone and chlorpheniramine administered but there was no significant association between the rates of complete excision between tumours that had neoadjuvant therapy compared to those that did not. limitations: retrospective nature and as such inability to standardise follow-up assessment for recurrence. some dogs had neoadjuvant prednisolone which could affect tumour size, completeness of excision, and margin assessment. 18 dogs were excluded from the margin assessment as no report on histological margins in the clinical records. tumour size may affect the completeness of excision as this relationship was close to statistical significance – potentially with increased sample size groups, the relationship would be more obvious. eight dogs lost to follow-up before the 365 days but all of them were grade i. limitation is also the radial trimming of margins as less sensitive than the tangential method to detect residual tumours at the margins. itoh et al. (2021) population: dogs with cutaneous and subcutaneous mast cell tumours (mcts) presented to aoba animal hospital between november 2013 and september 2018 and were treated with the proportional margin resection technique. 29 dogs had mct surgery in this period. six dogs were excluded because margins were wider or narrower than the proportional diameter. the final population was 23 dogs (25 mcts). from the 25 mcts, the 24 were cutaneous and one subcutaneous. sample size: 23 dogs (24 cutaneous mcts). intervention details: surgical margins: mcts excised with margins equal to the proportional diameter of the tumour as described by pratschke et al. (2013) and at least one fascial plane as deep margin. tumour grading: all tumours graded based on patnaik and kiupel system. adjuvant treatment: no dogs had adjuvant treatment. histological margins: classified as complete, close (tumour cells within 1 mm of the margin), or incomplete (tumour cells in the margin). follow-up method: review of the medical records. study design: retrospective case series. outcome studied: local recurrence. completeness of resection. main findings (relevant to pico question): tumour diameter: the tumour diameter range was 0.3–2.6 cm (median: 0.9 cm). tumour location: trunk (12), extremities (seven), head (two), vagina / perineum (three), and tail (one). tumour grading: all 24 cutaneous mcts grades as low-grade (kiupel). five mcts patnaik grade i and 19 as patnaik grade ii. histological margins results: complete in 20 cases. close (deep margin) in two cases. incomplete (deep margin) in two cases. local recurrence: no local recurrence in a follow-up period of 410–2,219 days (median: 990 days). limitations: local recurrence distance in relation to surgical scar was not specified. small sample size – prone to type ii error. only tumours with small size were included. appraisal, application and reflection historically, it has been recommended that mast cell tumours (mcts) independently of grade, must be excised with 3 cm lateral margins and one fascial plane as deep margin. however, evidence to support this recommendation is lacking, especially for grade i and ii mcts. recent literature suggests that the removal of these low-grade tumours with 2 cm lateral margins and one deep fascial plane, is sufficient to achieve local control and does not increase the incidence of local recurrence (simpson et al., 2004; fulcher et al., 2006; chu et al., 2020; milovancev et al., 2019; and saunders et al., 2020). in the study by seguin et al. (2001), 2–3 cm margins were used to remove mcts, however, the authors did not divide the dogs into groups in terms of margins, so no direct comparison between conservative and wide excision is possible. in this study, only 5% (three tumours) recurred locally; however, the authors based their follow-up not only on clinical examinations but also on referring veterinarians or telephone updates from clients. there is a possibility that this local recurrence rate is underestimated, as some recurrences may be missed by clients. the authors also included dogs with scar tissue of previously incompletely excised mcts, which makes the study population not homogeneous. in addition, two dogs had an amputation as definite treatment, and as such local recurrence could not be evaluated in these dogs. other limitations of this study include its retrospective nature, which may mean that some information was not recorded in the medical records. two later studies, one by simpson et al. (2004) and fulcher et al. (2006), investigated the removal of grade i and ii mcts with 2 cm lateral margins. both studies suffer from small sample sizes, which predispose them to type ii statistical error. when we combine both studies for a total number of 46 mcts (seven grades i and 39 grade ii), 44/46 mcts (95%) were completely excised at 2 cm lateral surgical margin. only two dogs, in the fulcher et al. (2006) study, had incomplete histological margins and none of them suffered local recurrence; however, one dog received revision surgery 2 weeks later. in both studies, no local recurrence was noted at a median follow-up of 351 days and 379 days, respectively. based on these studies, it was suggested that a surgical dose of 2 cm lateral margins and one fascial plane deep should be sufficient to achieve local control without increased rates of local recurrence for grade i and ii mcts. pratschke et al. (2013) first described the approach of surgical excision based on the proportional margin of the tumour. in this study, masses were resected with a lateral margin equal to their widest diameter, with a maximum lateral margin of 4 cm and a well-defined deep fascial plane. complete excision was achieved in 40/47 (85%) of cases, and although 7/47 (15%) of excised tumours had dirty margins, only one recurred locally during a median follow-up of 420 days. this was a completely excised, grade iii mct, highlighting the fact that achieving local control is not only influenced by the completeness of histological margins but also depends on the biological behaviour of the tumour. this study had a small sample size and a relatively short median follow-up time, which may have influenced the local recurrence rate. furthermore, two of the dogs with incomplete margins had adjuvant treatments and another dog with incomplete margins died from gastric dilatation-volvulus 1 day post-surgery. one advantage of this study is that it included tumours in difficult locations such as the face, distal extremities, inguinal and preputial regions. based on the original work by pratchke et al. (2013), two recent studies used a modified proportional margins approach for mct excision. chu et al. (2020) compared the completeness of excision (histologically free of tumour margins) after conservative surgical excision (excision with lateral margins equal to or smaller than 2 cm) and wide surgical excision (3 cm lateral margins) and showed a similar percentage of histologically free margins in both groups (93% and 92%, respectively). the authors concluded that this conservative approach was not inferior to the wide approach in achieving histologically free margins. the main limitation of this study was that the outcome measured was histologically free margins and not local recurrence. milovancev et al. (2019) showed in a prospective clinical study with a follow-up of 2 years that narrow histological margins (1 mm) do not always correlate with local recurrence. in this study, 30 low-grade mcts with a mean intraoperative margin of 20 mm were removed and only one recurred. saunders et al. (2020) used a similar approach to pratchke et al. (2013) and chu et al. (2020), where they excised mcts based on the largest lateral diameter of the mass up to 2 cm and with 2 cm margins for masses greater than 2 cm. this study contains the largest sample size with 100 mcts but both low-grade (88) and high-grade (12) tumours were included. the local recurrence rate was 3% (3/100), similar to pratchke et al’s. (2013) study 1/45 (2%) but occurred only in high-grade tumours. none of the low-grade mast cell tumours included in the study recurred locally. a correlation between conservative versus wide surgical excision and completeness of histological margins could not be established in this review because the classification methods of histologic margins were inconsistent between studies and the sampling methods used by histopathologists were different. in addition, the clinical significance of surgical margins and completeness of excision with the likelihood of metastatic spread could not be evaluated in this review. increased tumour size is a significant risk factor for incomplete excision with a 1.4% increase in the risk of incomplete excision per cm2 (monteiro et al., 2011). the studies in this review failed to show a significant association between tumour diameter and completeness of excision and clear recommendations regarding surgical margins and large diameter tumours (>4 cm) cannot be made because most of the tumours in the included studies were small in diameter. mcts in muzzle, prepuce, inguinal and perineal areas have been associated with aggressive behaviour (hillman et al., 2010; and sfiligoi et al., 2005). in simpson et al. (2004), the location of the mct on the hind limb was significantly associated with incomplete excision and in pratchke et al’s. (2013) study, 5/7 tumours with incomplete margins were located on the limbs. this review cannot evaluate surgical margins and recurrence rates in mcts in difficult locations such as the muzzle, distal extremities, inguinal and perineal areas due to the small number of these tumours in the study populations. this review suggests that most grade i and ii cutaneous mcts can be safely excised without an increase in the recurrence rate using either 2 cm lateral margins (simpson et al., 2004; and fulcher et al., 2006) or the proportional margin approach (pratschke et al., 2013; chu et al., 2020; and saunders et al., 2020) instead of the classic recommendation of wide surgical excision (3 cm lateral margins). nevertheless, the overall evidence is low and further studies, preferably multi-institutional studies with larger study populations, are needed to provide higher quality of evidence. these recommendations do not apply to high-grade mcts, which are biologically more aggressive, locally invasive, and more likely to metastasize. similarly, these recommendations must be used with caution for subcutaneous mcts. there is no grading system for subcutaneous mcts and many times their actual margins are not easily distinguished due to their subcutaneous origin and surrounding oedema. studies by pratchke et al. (2013) and itoh et al. (2021) contained subcutaneous mcts, but due to their low numbers, no correlation between surgical margins and local recurrence could be made. methodology section search strategy databases searched and dates covered: cab abstracts accessed via ovid platform (1980–2021) pubmed database accessed via ncbi (1986–november 2021) search strategy: cab abstracts: (dog or canine or canines or bitch or canid) and (mast cell tumour or mast cell tumor) and (surgical margin or incomplete margin or dirty margin or surgical resection or surgical excision or surgery or margin or resection) and (recurrence or local control or neoplasm recurrence)   pubmed: (dog or canine or canines) and (mast cell tumour or mast cell tumor) and (surgical margin or incomplete margin or dirty margin or surgical resection or surgical excision or surgery) and (recurrence or local control or neoplasm recurrence) dates searches performed: 09 nov 2021 exclusion / inclusion criteria exclusion: single case reports, duplicate articles, review articles, book chapters, or sections. articles which did not directly evaluate the relationship between lateral surgical margins and local recurrence. articles that did not specify the surgical margins at the time of the surgery. articles not available in the english language. inclusion: original peer-reviewed articles including case series, observational, or interventional studies which evaluate the relationship of lateral surgical margins in mct excision and local recurrence. search outcome database number of results excluded – not relevant to pico question excluded – surgical margins at the time of the surgery not reported and studies with only subcutaneous mcts excluded – reviews, case reports and letters excluded – not in english or not available total relevant papers cab abstracts 31 9 5 10 1 6 pubmed 99 58 14 19 0 8 total relevant papers when duplicates removed 8 conflict of interest the author declares no conflicts of interest. references chu, m., hayes, g., henry, j. & oblak, m. (2020). comparison of lateral surgical margins of up to two centimeters with margins of three centimeters for achieving tumor-free histologic margins following excision of grade i or ii cutaneous mast cell tumors in dogs. journal of the american veterinary medical association. 256(5), 567–572. doi: https://doi.org/10.2460/javma.256.5.567 fulcher, r., ludwig, l., bergman, p., newman, s., simpson, a. & patnaik, a. (2006). evaluation of a two-centimeter lateral surgical margin for excision of grade i and grade ii cutaneous mast cell tumors in dogs. journal of the american veterinary medical association. 228(2), 210–215. doi: https://doi.org/10.2460/javma.228.2.210 hillman, l., garrett, l., de lorimier, l., charney, s., borst, l. & fan, t. (2010). biological behavior of oral and perioral mast cell tumors in dogs: 44 cases (1996–2006). journal of the american veterinary medical association. 237(8), 936–942. doi: https://doi.org/10.2460/javma.237.8.936 itoh, t., kojimoto, a., uchida, k., chambers, j. and shii, h. (2021). long-term postsurgical outcomes of mast cell tumors resected with a margin proportional to the tumor diameter in 23 dogs. journal of veterinary medical science. 83(2), 230–233. doi: https://doi.org/10.1292/jvms.20-0281 milovancev, m., townsend, k., tuohy, j., gorman, e., bracha, s., curran, k. and russell, d. (2019). longâ€�term outcomes of dogs undergoing surgical resection of mast cell tumors and soft tissue sarcomas: a prospective 2â€�yearâ€�long study. veterinary surgery. 49(1), 96–105. doi: https://doi.org/10.1111/vsu.13225 monteiro, b., boston, s. & monteith, g. (2011). factors influencing complete tumor excision of mast cell tumors and soft tissue sarcomas: a retrospective study in 100 dogs. canadian veterinary journal. 52(11), 1209–1214. pratschke, k., atherton, m., sillito, j. & lamm, c. (2013). evaluation of a modified proportional margins approach for surgical resection of mast cell tumors in dogs: 40 cases (2008–2012). journal of the american veterinary medical association. 243(10), 1436–1441. doi: https://doi.org/10.2460/javma.243.10.1436 saunders, h., thomson, m., o'connell, k., bridges, j. & chau, l. (2020). evaluation of a modified proportional margin approach for complete surgical excision of canine cutaneous mast cell tumours and its association with clinical outcome. veterinary and comparative oncology. 19(4). doi: https://doi.org/10.1111/vco.12630 seguin, b., leibman, n., bregazzi, v., ogilvie, g., powers, b., dernell, w., fettman, m. & withrow, s. (2001). clinical outcome of dogs with grade-ii mast cell tumors treated with surgery alone: 55 cases (1996–1999). journal of the american veterinary medical association. 218(7), 1120–1123. doi: https://doi.org/10.2460/javma.2001.218.1120 sfiligoi, g., rassnick, k., scarlett, j., northrup, n. & gieger, t. (2005). outcome of dogs with mast cell tumors in the inguinal or perineal region versus other cutaneous locations: 124 cases (1990–2001). journal of the american veterinary medical association. 226(8), 1368–1374. doi: https://doi.org/10.2460/javma.2005.226.1368 simpson, a., ludwig, l., newman, s., bergman, p., hottinger, h. and patnaik, a. (2004). evaluation of surgical margins required for complete excision of cutaneous mast cell tumors in dogs. journal of the american veterinary medical association. 224(2), 236–240. doi: https://doi.org/10.2460/javma.2004.224.236 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. embedding ebvm into practice bradley viner bvetmed msc(vetgp) dprof mrcvs1* 1blythwood vets, 500 uxbridge road, hatch end, middlesex, ha5 4sl *corresponding author (bviner@blythwood.com) vol 2, issue 1 (2017) published: 23 jan 2017 doi: 10.18849/ve.v2i1.95 embracing ebvm as a concept is an important first step, but is of little value unless it is translated into an improvement in patient care. this session will discuss how ebvm can be incorporated into clinical guidelines at a practice level, using a team-based approach to maximise concordance. this is a podcast of bradley's talk at the veterinary evidence today conference, edinburgh november 2, 2016. find out more about bradley.  view presentation slides comments: an assessment of client and clinician satisfaction in veterinary teleconsultation compared to in-person consultations a knowledge summary by maxim bembinov student 1 narakhanti soenardi student 1* 1the royal veterinary college, hawkshead lane, hatfield, hertfordshire, al9 7ta *corresponding author (nsoenardi18@rvc.ac.uk) vol 7, issue 3 (2022) published: 27 jul 2020 reviewed by: maureen o'mara (phd mgis) and adam swallow (bvsc mrcvs) next review date: 22 dec 2023 doi: 10.18849/ve.v7i3.578 pico question compared to in-person veterinary consultations, does teleconsultation lead to similar levels of client and clinician satisfaction?   clinical bottom line category of research question qualitative assessment the number and type of study designs reviewed eight studies were critically appraised. there were six cross-sectional studies, one randomised controlled clinical trial, and one case report strength of evidence weak outcomes reported all eight studies provided weak evidence of similar levels of clinician and / or client satisfaction conclusion teleconsultation can lead to similar levels of client and clinician satisfaction when compared to in-person consultations. however, the evidence is weak due to the subjectivity and varied methods of measuring satisfaction. furthermore, the current applicability of veterinary teleconsultation is still very limited to certain select scenarios in which it is appropriate (e.g., emergency, triage, remote locations, non-complicated routine postoperative checks, nutrition and behavioural consults)   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario since the onset of the covid-19 pandemic and the introduction of the various restrictions, many regulators have been forced to reconsider their stances on telemedicine. the royal college of veterinary surgeons (rcvs) had even temporarily allowed remote prescription in absence of any other option (rcvs, 2020). portugal and many other european countries had similar measures (magalhães-sant’anna et al., 2020) and the us food and drug administration also eased their limits on veterinary telemedicine (fda, 2020). the french government has gone even further and in may 2020 started an 18 month experimental trial of telemedicine (legifrance.gouv.fr, 2020). these developments along with growing technological capabilities and consumer interest make the following scenario more and more likely. you are a practice manager who is considering offering your clients a new service of telemedicine, specifically teleconsultation. several benefits come to your mind such as better covid-19 safety, reduced travel and wait time for the clients, etc. however, before you try offering remote consults you wonder if there is an evidence base to find out if your clients and your clinicians would be satisfied with this service to the same extent they are satisfied with the in-person consults. the evidence eight studies were critically appraised in this knowledge summary, including six cross-sectional studies, one randomised controlled clinical trial, and one case report. most studies looked at opinions of clinicians and clients involving both quantitative and qualitative data, through the means of surveys and interviews. of the six cross-sectional studies, one was exclusively qualitative (butler et al., 2021), and the rest were quantitative or a combination of both. together they provided a comprehensive overview of their participants’ outlook towards teleconsultation. the paper with the strongest design was by bishop et al. (2018) which involved a randomised clinical trial comparing levels of client satisfaction using teleconsultation versus that of a routine in-person postoperative consultation. the case report by donham & wickett (2018) showed how teleconsultation can be useful in a very remote location where veterinary care is not available, although it does not directly answer the pico question. from all the papers, there is a consensus that teleconsultation can provide a similar level of satisfaction when compared to in-person consultations. however, most studies performed looked at very specific situations or demographics and hence the applicability of teleconsultations in other scenarios would be difficult, if not impossible, to assess. overall, the biggest issue with the studies appraised was the fact that most studies (with the exception of griesel, 2017 and bishop et al., 2018) did not directly measure ‘satisfaction’, thus in order to infer satisfaction levels, other phrasings and proxy measures had to be used. furthermore, most of the studies did not have a large enough sample size to confidently draw generalised conclusions. summary of the evidence bishop et al. (2018) population: client-owned dogs who have undergone elective surgical sterilisation and post-surgical recheck examination at the coastal animal hospital in encinitas, california, between september 27, 2017 and february 23, 2018. sample size: 30 owners. intervention details: dogs that were eligible (no complications or other factors that necessitated in-clinic examinations) were randomly assigned to have their recheck examination performed remotely through a videoconferencing application (teleconsultation group – 17 dogs) or in-person at the veterinary clinic (control group – 13 dogs). owners completed a survey following the recheck examination regarding their satisfaction with the exam and their dogs’ behaviour during it. study design: randomised controlled clinical trial. outcome studied: subjective assessments of: owner level of satisfaction with the recheck examination. typical time spent travelling to the clinic. owner perception of quality of service provided during video-conferencing (teleconsultation group only). owner willingness to use teleconsultation in the future (teleconsultation group only). responses to ordinal questions were rated on a likert scale of 1 (strongly agree) to 5 (strongly disagree). mann-whitney u test was used to assess if the two groups had a statistically significant difference. main findings (relevant to pico question): clients were equally satisfied with recheck examination performed remotely and in the clinic. mean ± standard deviation (sd) scores for owners’ responses to perception of veterinarians’ ability to assess postoperative care during the recheck examination were 1.06 ± 0.24 for the teleconsultation group and 1.00 ± 0.00 for the control group but differences were not significant (p = 0.382). based on the likert scale questions, owners in the teleconsultation group responded as having been less inconvenienced by their appointment (mean ± sd = 4.17 ± 0.57) than owners in the control group (mean ± sd = 3.85 ± 1.46) but differences were not significant (p = 0.17). median time for a round-trip travel to the veterinary clinic was 50 minutes (range: 10–60 minutes). owners with dogs in the teleconsultation group (mean ± sd = 4.76 ± 0.55) indicated that ‘their dogs were less afraid or nervous during the examination’ than the owners in the control group (mean ± sd = 3.85 ± 1.51) but the difference did not show to be statistically significant. all 17 owners agreed or strongly agreed that they felt comfortable using the technology, and that they would agree to have another follow-up visit through the teleconsultation application. 15/17 owners agreed or strongly agreed that the visual and sound quality of the videoconference was clear. 14/17 owners agreed or strongly agreed that they thought their dog were more comfortable than it would have been in the veterinary clinic. limitations: small sample size due to duration of study and selection criteria of both dogs and owners. impossible to blind clients and clinicians to interventions, hence may have biased results of the survey. study was carried out in one hospital and hence the technology and other features of the hospital might not be applicable to other establishments. travel time reported might be longer than the average client of the hospital as the hospital receives many referrals from other clinics for laparoscopic ovariectomy (inclusion criteria for female dogs in this study). study might have suffered from positive (positive satisfaction bias) since respondents are more likely to give positive answers when directly asked if they are satisfied (choi & pak, 2005). bishop et al. (2021) population: veterinarian members of the veterinary information network (vin) working in small animal general practice in north america. sample size: 550 veterinarians. intervention details: anonymous online survey consisting of 20 to 28 questions assessing use and insight into synchronous video-based teleconsultation. survey was sent to 69,488 recipients, 680 responded, and 550 of them reported to work in small animal general practice and had north american internet protocol addresses. response collected between september 28 and october 21, 2020. study design: cross-sectional study. outcome studied: respondents who reported use of synchronous video-based teleconsultation were asked about frequency of use, percentage of participating clients, time required, financial compensation, impact on client relationships, ease of adaptation, and intentions for its use once covid-19 restrictions are lifted. main findings (relevant to pico question): teleconsultations lead to similar levels of satisfaction compared to in-person consultations with it being more suited for some types of consultations than others. most clinicians would use teleconsultation less, except for the same or increased level of use with postsurgical care (23/51) and nutrition consultations (12/24). from the 135 respondents who started using synchronous video-based teleconsultation and who answered the questions: 98/135 (72.6%) indicated that teleconsultation took either the same or less amount of time as in-person consultations. 86/130 (66.2%) clinicians reported little to no difficulty in adapting to videoconferencing. all 135 found it was somewhat more difficult to foster a good client relationship and to convey information. 103/135 (76.3%) reported somewhat less or much less financial compensation. limitations: teleconsultation was defined only as synchronous videoconferencing with clients, and not other forms e.g., phone, email, texts. study has a low response rate 680/69,488 (1.0%) which could lead to bias towards clinicians who had a positive experience with, or a keen interest in teleconsultation. butler et al. (2021) population: uk racehorse trainers and racehorse veterinarians. sample size: 10 trainers (four female and six male) and 10 veterinarians (all male). intervention details: veterinarians and trainers were found through snowball sampling and qualitative semi-structured interviews were carried out between september 2020 and january 2021. study design: cross-sectional (qualitative) study. outcome studied: during the interviews the following topics were discussed: ‘trainer–vet relationship (pre covid-19 pandemic)’ ‘changes in trainer–vet relationship during the first ‘lockdown’’ ‘beneficial changes for racehorse veterinary care’ ‘problematic changes for racehorse veterinary care’ ‘management changes enforced during the first ‘lockdown’’ ‘innovative features of veterinary advice, diagnosis and treatment (veterinarians) and information sources of new veterinary practises (racehorse trainers)'. thematic analysis of the transcripts of three video conferences and 17 telephone calls obtained during the semi-structured interviews, was carried out. frameworks of critical realism and social constructionism were combined to carry out the thematic analysis. main findings (relevant to pico question): as the use of teleconsultation increased during covid-19, both the veterinarians and the trainers have found it to be useful to exchange images and videos to triage or deal with simple cases; however, not as universal replacement for in-person consultations. therefore, the conclusion is that it can provide satisfaction levels similar to those of in-person consults, yet only for select cases when it is appropriate. some of the criticism was poor connectivity, poor quality of the images and videos. some trainers were also unhappy to be billed for remote consultations. limitations: while semi-structured interviews have a plethora of benefits, (e.g., facilitating quicker triage of the emergency cases, providing quick advice on simple problems) the absence of quantitative data means that the conclusions rely entirely on the study authors’ subjective analysis of the transcripts. snowball sampling also meant that there was an inherent bias in the selection of the respondents; however, this is a common issue when a specific small group needs to be sampled. nonetheless, this means that care needs to be taken when extrapolating the conclusions from this study. the interviewer was not blinded to the hypothesis and the purpose of the research, and thus the study might have suffered from the bias associated with the interviewer consciously or subconsciously selecting data that fits with the existing hypothesis. donham & wickett (2018) population: critically ill military working dog (mwd) presented to the canadian north atlantic treaty organization (nato) role ii facility in iraq without in-person veterinary support. sample size: 1 dog. intervention details: an mwd in a remote outstation was sent to a canadian role ii facility to be evaluated, as it seemed critically ill and sepsis was a concern. role ii medical providers consulted with the mwd unit’s veterinarian through facetime (synchronous video-conferencing application). study design: case report. outcome studied: whether the facetime call could provide evaluation, treatment, and prioritisation of medical evacuation in this scenario where veterinary care is not immediately available. main findings (relevant to pico question): while this case report does not have a commercial client, the client is the nato military, and since the military was satisfied this can be considered as client satisfaction. facetime allowed the unit veterinarian to help coordinate care including initial diagnostics and treatment. however, they were unable to definitively diagnose the disease. limitations: involves military physicians and personnel who had access to medical resources (e.g., laboratories and imaging facilities) which might not be applicable to the general population. very specific case presentation and so might not be applicable to other disease processes. case report is a low level of evidence. dubin et al. (2021) population: small animal veterinarians working in the usa. sample size: 93 veterinarians (47 in primary care and 46 in specialty practice). intervention details: an online survey (21 questions) was sent between 15 june and 15 july 2020. all veterinarians offering clinical rotations in small animal medicine for 3rd and 4th year students according to the western university of health and sciences college of veterinary medicine database were all sent an invitation to participate in the survey. questions asked about changes in the use of telehealth, demographics, perception of client’s concerns regarding the transmission of covid-19 via pets, and changes in caseloads before and after the beginning of the covid-19 pandemic. study design: cross-sectional study. outcome studied: data was reported as proportions and percentages of the total. several statistical analysis methods were used for the demographics section of the study; however, these findings are outside of the scope of the current knowledge summary. main findings (relevant to pico question): dermatology (9/33) and ‘triage or emergency’ (9/33) were by far most often put as consults most frequently done remotely. the ‘most commonly ranked first benefits’ of client-facing teleconsultation were safety 10/21 (48%) followed by positive feedback from clients 8/21 (38%) and efficiency (5/21) (24%). when asked about problems encountered while implementing teleconsultation the overall most common challenges were technology (6/20) and client interest (5/20). limitations: most of the veterinarians who responded to the survey were from california, which means that the results should not be blindly extrapolated as the study found statistically significant relationships between practises offering telemedical services and various demographic factors. in this study, not all of the respondents have answered all of the questions. so even though the total sample size is 93, respondents could pick and choose which questions to answer leading to some questions having 30 total responses or even lower. this could lead to a selection bias, as those feeling more strongly about teleconsultation are more likely to have responded. given the high number of questions (21 question in total) and high number of questions left unanswered by some respondents (number of answers to pico relevant questions ranged between 20 to 33 out of 93 total responses), it is possible that some answers given were affected by response fatigue. as it is more likely that once tired of answering questions a respondent will give all ‘yes’ or all ‘no’ answers towards the end (choi & pak, 2005). grisel (2017) population: horse owners and trainers (mainly in the south-eastern usa). sample size: 83 owners / trainers. intervention details: survey was sent to 3,200 trainers and horse owners identified using the practice database of the atlanta equine clinic. study design: cross-sectional study. outcome studied: the main themes in the survey were about the basic demographic profile, the current extent of video acquisition of lame horses, current utilisation of the internet to post video footage of lame horses, number of requests of professional review of video footage and petition for future veterinary telemedical services. the responses were processed to obtain percentages and when appropriate means and standard deviations. main findings (relevant to pico question): this study found that 59/83 (71.1%) of respondents already used telemedical evaluation of their horse’s lameness. 51/59 (86.4%) were satisfied with the review their horse’s lameness received. 65/81 (78.3%) of total respondents reported that they would prefer veterinarians to offer telemedical reviews as a service. 81/83 (97.6%) of respondents said that they would pay for this service if it was offered. limitations: this is a 2017 study, which means that the sentiments and the data collected in this survey might not be accurate in the current climate, as teleconsultation and its technological capabilities are rapidly changing. survey had a very low response rate (83/3200) 0.02%. the author has a declared conflict of interest as he is an owner of a company that is involved in remote assessment of lameness. while the authors did not limit their sample to a certain geographical location, most of their respondents were from south-eastern usa due to the location of their clinic. this poses a risk as data might not hold true across other populations. magalhães-sant’ana et al. (2020) population: portuguese veterinarians. sample size: 41 veterinarians. intervention details: as a part of a larger policy delphi study* the veterinarians, identified through snowball sampling, were sent an online questionnaire over the period between september and december 2018. the questionnaire had four main themes: ‘role of the ordem dos médicos veterinários (omv), the local veterinary regulatory body in portugal, in telemedicine’, ‘remote consultations’ and ‘teleconsulting and teleadvice’. the veterinarians were then asked to provide a grade using the 5-point likert scale (1 – strongly disagree; 5 – strongly agree), n/a was also always an option. then veterinarians were asked to write a text explanation for their answer. *policy delphi study is a study method that aims to explore both pro and con arguments of a policy, rather than achieve a consensus. (linstone & turoff, 2002). study design: cross-sectional study (with text explanation being a qualitative addition). outcome studied: means and standard deviations were calculated for the likert scale values, which was then interpreted to quantitatively assess the extent to which the respondents agreed with the statements. subjective interpretation of the comments provided by the veterinarians to explain their responses was also carried out. main findings (relevant to pico question): overall, the veterinarians had a positive outlook on remote consultations. 21/41(51%) agreed that ‘video-conference remote consultations can, in certain cases, replace face-to-face consultations.’ 25/41 (61%) agreed that ‘remote veterinary consultations are an opportunity to improve animal healthcare.’ however, 28/41 (68%) broadly agreed that remote consultations should be preceded by a physical exam. though, in cases of emergencies (e.g., poisonings or heatstroke) in which the speed of receiving guidance can mean the ‘difference between life and death’; or in behavioural medicine where it could be the only way of achieving an accurate diagnosis (as the animal would be in its normal environment), remote consultations are vital even without a physical exam. one large animal practitioner pointed out that remote consultations had already been a part of farm practice for a very long time as a lot of consultations would be done via the telephone. limitations: since in the snowball sampling the authors have decided to prefer reaching out to respondents with further qualifications or experience in policy-making which excluded many of the younger veterinarians, therefore 61% of the veterinarians surveyed were male and only 39% female, which does not accurately reflect the current veterinary population in portugal (70% of veterinarians are female) (federation of veterinarians of europe, 2019). the sample selection did not require first-hand experience with teleconsultation. this might have led to preconceived impressions being expressed rather than true satisfaction. the dates during which the data was collected are not provided in the study, since teleconsultation is a rapidly developing field it might be outdated. the study might have suffered from ‘end aversion’ bias, which is common when respondents are given a scale on which to express their attitude towards a question and they gravitate towards the middle. this is especially common when the scale consists of an odd number of points, thus promoting a neutral answer. (choi & pak, 2005). roca & mccarthy (2019) population: pet owners on a popular telemedicine website. sample size: 398 owners. intervention details: pet owners were divided into two groups – those who had a traditional / in-person veterinarian (group 1 – 298 owners) and those who did not (group 2 – 93 owners). group 1 were asked if they would use teleconsultation if their traditional care veterinarian would provide it whilst group 2 were asked if they would like a referral to a traditional veterinarian. owners were then asked if a traditional veterinary consult was recommended and if they followed-up after using telemedicine 159 owners who proceeded to follow up were then asked a set of questions.  study design: cross-sectional study. outcome studied: in the follow-up, the following questions were asked: if owners felt better informed or misinformed about their pet's illness. if their traditional veterinarian (agreed / disagreed) with the recommendation from the ‘telemedicine expert’. if owners were ‘able to communicate their concerns and understand their veterinarians’ recommendations more effectively’ after using telemedicine. main findings (relevant to pico question): pet owners were generally satisfied after using teleconsultation services on the website. 231/384 (60%) owners that used the telemedicine website warranted a follow up with a traditional care veterinarian, of which 159/231 (68.8%) followed through 142/159 (89.3%) felt better informed about their pets’ illness after using teleconsultation however, 14/159 (8.8%) felt misinformed about their pets’ illness after. 131/159 (82.4%) of pet owners reported that their veterinarian agreed with the recommendation from the ‘telemedicine expert’. 138/159 (86.8%) of owners were ‘able to communicate their concerns and understand their veterinarians’ recommendations more effectively’ after using teleconsultation. limitations: survey was limited to one website, hence a bias towards people who are already using teleconsultation and so are more likely to have a positive attitude towards it. selection bias due to voluntary surveys as owners with a more positive outlook towards teleconsultation could be more likely to complete survey. ‘telemedicine expert’ included veterinarians but also ‘other highly qualified pet experts’. the study could have suffered from the ‘positive skew’ (a.k.a. positive satisfaction bias) since respondents are more likely to give positive answers when directly asked if they are satisfied (choi & pak, 2005). appraisal, application and reflection telemedicine is a blanket term which can be generally broken down into three main fields: remote consults (veterinarian to client); referrals (veterinarian-to-veterinarian); mobile health (teller & moberly, 2020). in this study the authors have investigated remote consultations (veterinarian to client) for it to be offered as a permanent service and not a reaction to covid-19 pandemic, during which it became more widespread (dubin et al., 2021). this can only be encouraged if satisfaction levels of clients and clinicians need to be at least similar or equal to those of in-person consultations. if the evidence base yields positive, the benefits of teleconsultations are immense, for example for those in remote locations where veterinary expertise is very hard to reach or in cases of emergency where the speed of veterinary advice is vital. eight papers with varying levels of evidence were critically appraised. however, only one was a randomised controlled clinical trial, making the overall level of evidence weak. this was the study by bishop et al. (2018) which assessed client and clinician satisfaction when comparing in-person to teleconsultation (videoconference) postoperative recheck examinations. clients were more satisfied with the teleconsultation in terms of perceiving the veterinarians’ ability to assess their dog, convenience, and their dogs’ being less afraid or nervous. however, the difference was not statistically significant. nevertheless, all or the majority of clients were comfortable in using the teleconsultation technology provided, were satisfied with the visual and sound quality, and agreed that their dog was more comfortable getting examined remotely. the six cross-sectional studies provided weak evidence regarding client and clinician levels with regards to veterinary teleconsultation. three papers (bishop et al., 2021; dubin et al., 2021; and magalhães-sant’ana et al., 2020) assessed levels of clinician satisfaction, two papers (grisel, 2017; and roca & mccarthy, 2019) assessed client satisfaction, and butler et al. (2021) looked at both clinician and client satisfaction. all six papers have a general consensus that when teleconsultation is feasible, levels of satisfaction can be similar (or even higher) to that of traditional or in-person consultations, however there are caveats and exceptions to this. in the equine industry, butler et al. (2021) found that both veterinarian and trainer found it useful to triage racehorses by exchanging images and videos. problems were found with some trainers being reluctant to be billed and it was agreed that teleconsultation is not a replacement to traditional veterinary care. grisel (2017) found that 59/83 (71%) of horse owners and trainers already used telemedical evaluation for lameness at least once, with 51/59 (86%) being satisfied with the review. 65/83 (78%) of clients prefer if veterinarians offered telemedical review as a service and almost all 81/83 (97.6%) would pay for this service if it was provided. although not an issue of the method, this paper focused only on lameness consults. while lameness is a very important part of equine medicine, these results should be extrapolated with care as they are based only on one specific presentation that lends itself nicely to remote consultations. only one of the six papers briefly touched on farm animal practice, which highlighted that teleconsultation was already done for a very long time as often consultations would be done via a telephone call (magalhães-sant’ana et al., 2020). in small animal practice, teleconsultation may result in both satisfaction for clinicians and clients alike. most veterinarians (98/135 [72.6%]) spend the same or less amount of time, and have little to no difficulty in adapting to videoconferencing (86/130 [66.2%]) (bishop et al., 2021).  a study on portuguese veterinarians found that half of them (21/41 [51%]) agreed that remote consultations can replace consults in certain areas, and the majority (25/41 [61%]) agreed that it would improve animal healthcare (magalhães-sant’ana et al., 2020). dubin et al. (2021) listed positive client feedback, improved covid-19 safety, and increased efficiency, as benefits of teleconsultation. in a survey of nearly 400 users of a teleconsultation website, 142/159 (89.3%) of users (pet owners) felt better informed after using their teleconsultation service, and 131/159 (82.4%) of veterinarians agreed with the recommendation from the telemedicine expert (veterinarian or non-veterinarian), implying a good level of both client and clinician satisfaction. majority of owners were also able to communicate their concerns and understand their veterinarians’ recommendations more effectively (roca & mccarthy, 2019). in general, clinicians are found to have more concerns compared to clients when it comes to teleconsultation. in one study, 103/135 (76%) veterinarians reported less financial compensation and all 135 found it more difficult to foster a good client relationship and to convey information (bishop et al., 2021). 28/41 (68%) veterinarians agree that whilst teleconsultation is useful, it should be preceded by a physical exam (magalhães-sant’ana et al., 2020). nevertheless, despite the weak nature of the evidence, the current review suggests that there are areas in which teleconsultation would be appropriate such as post-surgical care (bishop et al., 2019; 2021), nutrition (bishop et al., 2021), emergency medicine and triage (magalhães-sant’ana et al., 2020; donham & wickett, 2018; and dubin et al., 2021), behavioural medicine (magalhães-sant’ana et al., 2020), and dermatology (dubin et al., 2021). however, more studies specifically looking at satisfaction are required to substantiate these claims further. there is one more paper (donham & wickett, 2018) that supported the positive outlook of veterinary teleconsultation, despite not directly assessing satisfaction levels. donham & wickett (2018) produced a case report that demonstrated the benefits of teleconsultation in remote locations where veterinary care is not available, showing that it can be vital in emergency cases. evidence compiled in the systematic literature review found that teleconsulting between the veterinarian and client was generally favoured by both parties (teller & moberly, 2020). it described various benefits of teleconsultation including ‘improving access, convenience, enhanced veterinary-to-client bond, reduced workload on front office staff, and is a better option than consulting the internet’. arguments for its use is especially strong for that of remote locations, or in consults such as behavioural medicine when specialists are limited. the main issue with the body of evidence reviewed is the subjectivity of measuring satisfaction. the lack of clear definitions of subjectivity and approaches of measuring it, led to each study using different methods which varied greatly (e.g., the outcomes of a semi-structured interview (such as butler et al., 2021) are very different to a semi-quantified questionnaire (such as magalhães-sant’ana et al., 2020). even within one format such as a questionnaire, different authors asked differently phrased questions, and used subjective non-standardised terms like ‘excellent’, ‘good’, ‘poor’ to calculate semi-quantitative scores. for example, both roca & mccarthy (2015) and bishop et al. (2021) looked at owner satisfaction, but their questions were geared towards their sample populations concerns and were phrased slightly differently. all this makes interpretation and comparison of the results difficult, hence overarching conclusions are unreliable. furthermore, while some studies measured satisfaction of clients or clinicians directly (grisel, 2017; and roca & mccarthy, 2019), some others did not. some of them set out to primarily investigate the benefits and complications associated with remote consultations instead. for example, in dubin et al., 2021 most survey questions explored the positive and negative aspects of teleconsultations and most appropriate clinical scenarios to apply teleconsultations, and while providing a very meaningful insight did not measure satisfaction directly. another issue found across the studies evaluated was the relatively small sample size e.g., magalhães-sant’ana et al’s. (2020) study used a sample size of 41 to represent the whole population of veterinarians in portugal. in addition, since participation in all of the studies was voluntary, those with strong feelings towards the subject were more likely to respond to the surveys and questionnaires. it is also likely to be the cause for all client satisfaction data being strongly positive, since only a very small proportion of the total population of clients was sampled. as opposed to the veterinarians, which are a much smaller population and a relatively more representative sampling might have occurred. therefore, the field requires further research with both larger sample sizes and study designs aimed at measuring satisfaction directly. randomised controlled study is the ideal design to measure satisfaction directly, since blinding is impossible in this context. the randomised controlled study carried out by bishop et al. in 2018 can be used as a model of what could be done, yet while that study focused only on post-surgical checks, similar studies could be done for other types of consultations to see if the satisfaction levels found by bishop et al. (2018) are validated. this is important, as it was found after reviewing the studies, that not all types of consultations suit remote consults equally, with some being even better than in-person (e.g., behavioural) (magalhães-sant’ana et al., 2020; and teller & moberly, 2020). other important areas of further study are the growing fields of veterinarian-to-veterinarian consulting and mobile health, which were both outside of the scope of this investigation, yet they constitute a large part of telemedicine and are playing an increasing role in the modern veterinary practice. furthermore, despite farm veterinary medicine having employed teleconsultation (via telephone consultations) for a much longer time than other fields, to the authors’ knowledge, no literature is available in that field. while the evidence is, overall, weak, the studies appraised demonstrated that teleconsultation may lead to similar levels of client and clinician satisfaction when compared to in-person consultations but only in very limited circumstances as discussed previously. however, due to varying approaches of measuring satisfaction, each study assessed slightly different aspects of satisfaction. therefore, there is no conclusive consensus on the totality of the components of satisfaction. this finding is in line with what was found in a review of human telehealth where it was concluded that ‘in most cases, telehealth was equivalent to in-person care, and in some areas, like telerehabilitation and telenutrition, it was better’ (teller & moberly, 2020). however, with veterinary teleconsultation being an emergent subject, not enough evidence is available to substantiate this conclusion and further studies, ideally randomised controlled trials, are needed. the current applicability of veterinary teleconsultation was still found to be very limited to certain select scenarios in which it is most appropriate. relating back to the question raised in the clinical scenario, the existing evidence suggests that teleconsultation can provide similar levels of satisfaction compared to in-person consults in certain circumstances, however the clinician must take into account the number of caveats mentioned previously. when scheduling consults, it is important to select which cases lend themselves best to this format. methodology section search strategy databases searched and dates covered: cab abstracts accessed via cab direct platform (1973–december 2021) pubmed ncbi (1988–december 2021) web of science (1900–december 2021) search strategy: cab abstracts: (owner* or client* or trainer* or farm* or veterinar* or clinician*) (telemedicine* or teleconsult* or telehealth* or telecommunication* or telediagno* or telemetr* or televet* or teletriage* or “e-health" or “virtual consult*” or “remote consult*” or “online consult*” or “video conferenc*”) (“in-person*” or “face-to-face*” or “real life*” or “in person*” or “real-life*” or normal* or “in-clinic*” or clinic* or traditional* or office* or consult*) (satisfaction* or impact* or perception* or opinion* or effective* or efficien* or attitude* or perspective* or perceive* or view*) ab:(“veterinar*”) 1 and 2 and 3 and 4 and 5 pubmed: (((owner* or client* or trainer* or farm* or veterinar* or clinician*)) and (telemedicine* or teleconsult* or telehealth* or telecommunication* or telepathology* or telediagno* or telemetr* or televet* or teletriage* or “e-health” or “virtual consult*” or “remote consult*” or “online consult*” or “video conferenc*”)) and ("in-person*" or "face-to-face*" or "real life*" or "in person*" or "real-life*" or normal* or "in-clinic*" or clinic* or traditional* or office* or consult*)) and (satisfaction* or impact* or perception* or opinion* or effective* or efficien* or attitude* or perspective* or perceive* or view*) and ("veterinar*"[title/abstract]) web of science: ((((ts=(owner* or client* or trainer* or farm* or veterinar* or clinician*)) and ts=(telemedicine* or teleconsult* or telehealth* or telecommunication* or teleradiolog* or telepatholog* or telediagno* or telemetr* or televet* or teletriage* or “e-health” or “virtual consult*” or “remote consult*” or “online consult*” or “video conferenc*”)) and ts=(“in-person*” or “face-to-face*” or “real life*” or “in person*” or “real-life*” or normal* or “in-clinic*” or clinic* or traditional* or office* or consult*)) and ts=(satisfaction* or impact* or perception* or opinion* or effective* or efficien* or attitude* or perspective* or perceive* or view*)) and ab=(veterinar*) dates searches performed: 22 dec 2021 exclusion / inclusion criteria exclusion: not in english language, not related to pico question, not related to first opinion veterinary consultations, not related to satisfaction levels, not a primary source. inclusion: related to pico question, related to first opinion veterinary consultations, related to satisfaction levels. search outcome database number of results excluded – not related to first opinion veterinary consultations excluded – not related to satisfaction levels excluded – not a primary source total relevant papers cab abstracts 21 11 3 1 6 pubmed 32 24 0 1 7 web of science 25 18 1 0 6 total relevant papers when duplicates removed 8 conflict of interest the authors declare no conflicts of interest. references bishop, g.t., evans, b.a., kyle, k.l. & kogan, l.r. 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[online] available at: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-helps-facilitate-veterinary-telemedicine-during-pandemic [accessed 14 january 2022]. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. joined up clinical governance: learning from our mistakes pam mosedale bvetmed mrcvs1* 1royal college of veterinary surgeons, belgravia house, 62-64 horseferry road, london, sw1p 2af *corresponding author (p.mosedale@rcvs.org.uk) vol 2, issue 1 (2017) published: 01 feb 2017 doi: 10.18849/ve.v2i1.98 this podcast discusses how a significant event can lead to the practice examining what happened, looking at the evidence base, revising protocols and auditing implementation of the new protocols. a significant event is an event thought by anyone in the team to be significant in the care of patients or the conduct of the practice. this is a podcast of pam's talk at the veterinary evidence today conference, edinburgh november 1, 2016. find out more about pam. comments: gastric dilatation volvulus in dogs: utility of lactate as a predictor of survival a knowledge summary by david mackenzie bsc(hons) ma vetmb phd certvc certavp(sam) certavp(ecc) pgcert(vps) mrcvs 1* 1moorview referrals, northumberland business park, cramlington, ne23 7rh *corresponding author (dps21@cantab.net) vol 7, issue 4 (2022) submitted: 09 sep 2021 published: 02 nov 2022 next review: 23 feb 2024 doi: 10.18849/ve.v7i4.537 pico question in dogs presenting with gastric dilatation volvulus, is an admission or pre-operative lactate level a reliable predictor of survival to discharge?   clinical bottom line category of research question prognosis the number and type of study designs reviewed 15 studies (12 retrospective and 3 prospective) were critically appraised strength of evidence moderate outcomes reported at a population level, lower blood lactate concentration, or lactate concentration that decreases following fluid resuscitation, are associated with a better prognosis. at a population level, higher blood lactate concentration, or lactate concentration that fails to decrease following fluid resuscitation, is associated with a worse prognosis. however, the lower sensitivity across studies means that a high lactate, or one that does not decrease following fluid therapy, should be interpreted more cautiously than a low lactate; i.e., low lactate predicts survival better than high lactate predicts non-survival. in all studies, there was a significant overlap in individual blood lactate concentration between survivors and non-survivors conclusion blood lactate level should only be used to help guide broad, cautiously worded conversations with owners. it should not be used to give a prognosis for individual patients. the overlap between survivors and non-survivors, and the high overall survival rate, suggest that exploratory laparotomy should be advised irrespective of the blood lactate level   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are presented with a dog in which the clinical and radiographic findings are consistent with a diagnosis of gastric dilatation volvulus (gdv / gastric torsion). you advise initial stabilisation followed by surgical de-rotation and gastropexy as the treatment for this condition. before embarking on surgery with high associated costs, the owners wish to know the likelihood of survival to discharge. you suggest that measurement of blood lactate concentration may help answer this question. the evidence 15 studies (12 retrospective and 3 prospective) were identified and appraised based on the predefined inclusion criteria. four further studies examining lactate concentration in dogs with a range of conditions (not restricted to gdv), and two review papers, were also appraised. summary of the evidence de papp et al. (1999) population: dogs with gastric dilatation volvulus (gdv) confirmed radiographically or at necropsy. mixed population represented. lactate measured using stat profile plus 9, nova biomedical. sample size: 102 dogs, of which 23 dogs received fluid therapy prior to measurement of lactate concentration. intervention details: one dog died prior to surgery. it is implied that the remaining 101 dogs underwent surgery for gdv. study design: retrospective observational case-control study./td> outcome studied: correlation between initial admission plasma lactate concentration and survival to discharge. correlation between initial admission plasma lactate concentration and gastric necrosis. main findings (relevant to pico question): overall survival of dogs undergoing surgery was 87/101 (86%). survival of dogs with lactate <6.0 mmol/l (69/70, [99%]) was significantly higher than dogs with lactate >6.0 mmol/l [18/31, 58%]) (sensitivity = 68%, specificity 88%; p <0.001). logistic regression analysis showed an increasing probability of survival with decreasing pretreatment lactate level. limitations: retrospective study. 23 dogs received fluid therapy prior to lactate measurement but these were included in the overall analysis together with dogs that did not receive such treatment. zacher et al. (2010) population: dogs with gastric dilatation volvulus (gdv) confirmed radiographically and at surgery, no pretreatment prior to referral, > 1 measurement of plasma lactate level prior to surgery (pre and post-fluid therapy and stabilisation prior to surgery). mixed population represented. lactate measured using stat profile 9, nova biomedical. sample size: 64 dogs. intervention details: all dogs underwent resuscitation with fluid and decompression followed by corrective surgery. study design: retrospective observational case-control study. outcome studied: correlation between admission blood lactate level and survival to discharge, and lactate clearance following resuscitation and survival to discharge. main findings (relevant to pico question): overall survival 49/64 (77%). initial plasma lactate for survivors (6.2 ± 3.2 mmol/l) was significantly lower than non-survivors (10.3 ± 3.2 mmol/l) p <0.05. final lactate concentration (post fluids and decompression) for survivors (3.3 ± 2.3 mmol/l) was significantly lower than non-survivors (8.0 ± 3.3 mmol/l) p <0.05. percentage change in lactate between initial level and the level post fluids and decompression was significantly different between survivors (49.1 ± 28.8%) and non-survivors (24.6 ± 19.4%) p <0.05, although absolute change was not significant. for all dogs, a cut-off for initial lactate of 9.0 mmol/l predicted survival with sensitivity 74% and specificity 73%. a cut-off for final lactate of 5.6 mmol/l predicted survival with sensitivity 84% and specificity 80%. a percentage change in lactate cut-off of 42.2% predicted survival with 61% and specificity 100%. subset of dogs with 'high lactate' (hil) were analysed separately. in this group, initial lactate did not differ between survivors and non-survivors. final lactate (post fluids and decompression) was significantly different between survivors (5.1 ± 2.2 mmol/l) and non-survivors (9.9 ± 2.7 mmol/l) p <0.05. absolute change in lactate was significantly different between survivors (6.3 ± 2.0 mmol/l) and non-survivors (2.6 ± 2.3 mmol/l) p <0.05. percentage change in lactate was significantly different between survivors (53.2 ± 17.1%) and non-survivors (18.9 ± 20.5%) p <0.05. for this subset of dogs, a cut-off of 6.4 mmol/l in final lactate (post fluid and decompression) predicted survival with sensitivity 77% and specificity 91%. for this subset of dogs, a lactate cut-off of 4.0 mmol/l in absolute change in lactate predicted survival with sensitivity 92% and specificity 82%. for this subset of dogs, a cut-off of 42.5% in percentage change in lactate predicted survival with sensitivity 85% and specificity 100%. limitations: retrospective study. small sample size (power analysis not reported). three dogs with initial plasma lactate concentration within the reference range were excluded from the study. variation in pre-surgery fluid therapy. no definitive endpoint for resuscitation was reported. non-survivors included dogs euthanised at surgery based on subjective impression of gastric necrosis, which may have introduced bias. green et al. (2011) population: dogs with a radiographic diagnosis of gastric dilatation volvulus (gdv), admission blood lactate level measured and subsequent surgery. mixed population represented. lactate measured using stat profile 9, nova biomedical. sample size: 84 dogs. intervention details: all dogs underwent stabilisation with intravenous fluid therapy and decompression, followed by corrective surgery for gdv. study design: retrospective observational case-control study. outcome studied: correlation between admission blood lactate level and survival to discharge. correlation between change in plasma lactate levels (lactate clearance) and survival to discharge. correlation between admission blood lactate level and presence of gastric wall necrosis. correlation between gastric wall necrosis and survival to discharge. main findings (relevant to pico question): overall survival 74/84 (88%). significant difference in admission lactate concentration between non-survivors (median 6.80 mmol/l [range 1.4–16.9 mmol/l]) and survivors (median 3.4 mmol/l [range 0.7–16.1 mmol/l]), p <0.0074. of 74/84 (88%) that survived, 55/74 (74.4%) of dogs had initial blood lactate <6.0 mmol/l, while 19/74 (25.6%) of dogs had initial blood lactate ≥0 mmol/l. initial blood lactate <4.1 mmol/l had a sensitivity of 60.3% and specificity 90.9% for predicting survival (p = 0.0133). serial lactate measurements were available for 52/84 (62%) of dogs. of these 52 dogs, 40/52 (77%) had a raised (>2.5 mmol/l) initial lactate concentration, and 37/40 (92.5%) of these dogs survived. 26/37 (70%) of these survivors had a reduction in serial lactate of >= 50% from baseline. of the3/40 (7.5%) of dogs that did not survive, the serial lactate failed to fall ≥ 50% from baseline. limitations: retrospective study. some dogs had treatment prior to referral and were not excluded, which may have introduced bias. according to the protocol described in the paper, the treatment that each dog received may have been variable (e.g., some dogs may have received transfusion). serial lactate results were difficult to interpret, with variability in timing of serial lactate measurements. also, not clear if some serial lactate results were pre-surgery or post-surgery. statistical analysis was also not performed on this, including no multivariate analysis, and this may be because the group size was too small. the statistics presented do not readily support the assertion that reduction in lactate from baseline may be a better prognostic indicator than single baseline lactate measurement. green et al. (2012) population: dogs with a radiographic diagnosis of gastric dilatation volvulus (gdv) with measurement of blood lactate level at presentation. mixed population represented. lactate measurement method not specified. sample size: 101 dogs. intervention details: dogs underwent corrective surgery for gdv. other resuscitative interventions not specified. study design: retrospective observational case-control study. outcome studied: survival to discharge correlated with plasma lactate level. correlation between survival and risk factors for survival (signalment, time of presentation, presenting clinical signs), decompression, and thoracic radiographic findings. main findings (relevant to pico question): overall survival rate 85/101 (84%). evidence for cardiomegaly on preoperative thoracic radiographs was associated with decreased survival. after controlling for cardiomegaly, lactate <6 mmol/l at presentation had an odds ratio of 7.3 of survival compared with dogs with lactate ≥ 6. limitations: retrospective study. lactate cut-off results were reported after controlling for the presence of cardiomegaly. case selection made on basis of presence of thoracic radiographs which was incomplete, which may have introduced bias. not clear from the data why a lactate cut-off of 6 mmol/l was taken for calculating odds ratio. possibilities of type i and type ii errors due to incomplete records. israeli et al. (2012) population: dogs with a radiographic diagnosis of gastric dilatation volvulus (gdv), confirmed at surgery, and admission blood lactate level measured. mixed population represented. lactate measured using either advia 120 (siemens medical) or abacus or arcus (diatron). sample size: 66 dogs. intervention details: all dogs underwent corrective surgery for gdv. study design: blood samples collected prospectively, and records retrospectively reviewed. outcome studied: correlation between plasma lactate concentration at admission and survival to discharge. correlation between plasma lactate concentration at admission and degree of gastric wall necrosis. correlation between plasma markers serum canine pepsinogen-a, crp, and cpli and survival to discharge and degree of gastric wall necrosis. main findings (relevant to pico question): overall survival 51/66 (77.3%). no significant difference in lactate concentration between non-survivors (7.9 mmol/l [range 1.1–25.3 mmol/l] and survivors (4.8 mmol/l [range 0.1–19.1 mmol/l]). limitations: retrospective study. non-survivors included dogs euthanised for a variety of reasons including subjective impression of gastric necrosis, owner request, or deterioration during hospitalisation. variation in resuscitative intervention between dogs not specified. lactate concentration was analysed using two different analysers. power analysis not reported. santoro beer et al. (2013) population: dogs with a radiographic diagnosis of gastric dilatation volvulus (gdv) with no concurrent disease with no prior intervention, and venous blood sample at time of admission, and subsequently underwent corrective surgery for gdv. mixed population represented. lactate measured using stat profile critical care xpress, nova biomedical. sample size: 78 dogs. intervention details: 68 dogs underwent corrective surgery for gdv (10 dogs were euthanised prior to surgery). study design: retrospective observational case-control study. outcome studied: correlation between admission blood lactate level and survival to discharge. correlation between presence or absence of gastric necrosis and survival to discharge. correlation between admission base excess and presence of gastric necrosis and survival to discharge. main findings (relevant to pico question): overall survival rate 65/78 (83%). initial plasma lactate was significantly associated with survival (non-survivors 9 mmol/l [range 5.6–15 mmol/l), survivors 4.5 mmol/l [range 0.8–14.54 mmol/l] p <0.001). a cut-off admission lactate value of 7.4 mmol/l had sensitivity 75% and specificity 89% for predicting survival to discharge. limitations: retrospective study. potential variation in treatment based on initial plasma lactate may have introduced bias. study included patients euthanised for financial or other unknown reasons. o'neill et al. (2017) population: dogs presenting alive or dead with a confirmed or presumptive diagnosis of gastric dilatation volvulus (gdv), with lactate measured for cases presenting alive. mixed population represented. lactate measurement method not specified. sample size: 492 dogs total, 483 dogs presented alive of which 285/483 (57.9%) underwent surgery. 181/492 cases (36.8%) had blood lactate levels measured. intervention details: 285/483 (57.9%) of dogs presenting alive underwent corrective surgery. study design: retrospective observational cross-sectional study. outcome studied: survival to discharge vs non-survival correlated with admission (pretreatment) blood lactate level. population regression modelling to identify risk factors associated with presumptive diagnosis of gdv. main findings (relevant to pico question): overall survival (of dogs undergoing surgery) was 226/285 (79.3%). for dogs arriving alive, blood lactate concentration at presentation was not associated with likelihood of surgery. dogs with blood lactate concentrations <4 mmol/l had an increased probability of survival to discharge both overall (p <0·001) and among the surgical cases (p <0·001). limitations: retrospective study. multi-centre study with variability in case decision-making and surgery. diagnosis of gdv was presumptive in some cases. lactate concentration was not complete (36.8% of presenting population) therefore bias relating to missing data may have been present. missing data in case records may not have been a random effect which may have introduced bias. 198/492 (40.2%) of cases did not undergo surgery (of which 184/198 [92.9%]) were euthanised. also, of the 285/492 (57.9%) of dogs that did undergo surgery, 59/285 (20.7%) did not survive, of which 37.59 (62.7%) were euthanised. as the decision to euthanise involves a number of factors, this may have introduced bias into the overall survival rate. verschoof et al. (2017) population: dogs with gastric dilatation volvulus (gdv) confirmed radiographically and for which blood samples were available. mixed population represented. lactate concentration measured using blood gas analyser cobab b 221 (roche diagnostics, switzerland). sample size: 20 dogs. intervention details: all dogs received preoperative stabilisation with intravenous fluid therapy and gastric needle decompression. all dogs subsequently underwent corrective surgery for gdv. study design: prospective case control study. outcome studied: correlation between survival to discharge and initial blood lactate level. correlation between initial blood levels of coagulation variables (platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, protein c, protein s, and d-dimers) and inflammatory biomarkers (crp, wbc count, lymphocyte and neutrophil numbers) and survival to discharge. main findings (relevant to pico question): overall survival 15/20 (65%). initial plasma lactate was significantly higher in non-survivors (11.8mmol/l [range 7.5–16.2 mmol/l] than overall survivors (6.2mmol/l [range 1.9–9.7 mmol/l]) p <0.01. plasma lactate on day 1 post surgery was significantly different between non-survivors and survivors (p = 0.0078). (values not given, but significant overlap between populations displayed graphically). for surviving dogs, plasma lactate decreased significantly between initial lactate, day 1 and day 2 post-surgery (this data was not compared with non-survivors). limitations: small sample size (power analysis not reported). two dogs were euthanised during surgery due to subjective impression of severe gastric necrosis. five dogs were euthanised post-surgery due to sepsis and disseminated intravascular coagulation (dic). oron et al. (2018) population: dogs with gastric dilatation volvulus (gdv) that underwent corrective surgery and which had blood samples taken from both cephalic and saphenous veins. mixed population represented. lactate measured using a 'dry' analyser or 'wet' chemistry autoanalyser (reflotron®, boehringer mannheim or reflovet plus, roche). sample size: 41 dogs in final analysis. intervention details: fluid resuscitation and gastric decompression (details varied between subjects and between centres). all dogs underwent corrective surgery. study design: prospective study. outcome studied: survival to discharge vs non-survival correlated with admission (pretreatment) blood lactate concentration. comparison of lactate concentration between cephalic and saphenous sampling sites. main findings (relevant to pico question): overall survival 37/45 (82.9%). no significant difference detected in lactate between the saphenous and cephalic sampling sites. initial median saphenous and cephalic lactate concentration for all dogs was significantly higher in non-survivors (3.9 mmol/l [range 0.7–17.8 mmol/l] and 3.8 mmol/l [range 0.78–21.9 mmol/l] from saphenous and cephalic sites respectively), compared to survivors (11.2 mmol/l [range 6.6–11.8 mmol/l] and 11.4 mmol/l [range 3.8–19.4 mmol/l] respectively), p = 0.01. when dogs that had undergone gastric decompression prior to blood sampling (n = 10) were removed from the above analysis results remained significant at: non-survivors 10.7mmol/l [range 6.8–11.2 mmol/l] and 11.1mmol/l [range 3.8–11.4 mmol/l] and survivors 3.5 mmol/l [range 0.7–17.8 mmol/l] and 3.1mmol/l [range 0.7–19 mmol/l] (from saphenous and cephalic respectively) p <0.001. limitations: dogs that died or were euthanised before surgery were excluded from analysis which potentially biases the results by restricting analysis to a more stable population. the total study population was drawn from different populations, a) from a teaching hospital (n = 39) and b) from three specialty referral clinics (n = 6), these populations were combined in the subsequent analysis despite potential variation in resuscitation protocols and treatment. lactate was analysed using different analysers. reporting of results for all dogs included those that had already undergone an intervention (gastric decompression). spinella et al. (2018) population: dogs diagnosed with gastric dilatation volvulus (gdv) and dogs diagnosed with intestinal obstruction (io) (control group). mixed population represented. lactate measured with portable lactate analyser (lactate scout +, ekf diagnostics, cardiff, uk). sample size: 22 dogs with gdv, 16 dogs with io. intervention details: all dogs in both groups underwent corrective surgery. study design: prospective observational case-control study. outcome studied: survival to discharge vs non-survival correlated with admission (pretreatment) blood lactate level. correlation between initial admission serum lipase activity, canine pancreatic lipase immunoreactivity (cpli) and c-reactive protein concentration and survival. main findings (relevant to pico question): overall survival 16/22 (73%). no significant difference between lactate level of non-survivors (7.1 mmol/l [range 3.1–12.1 mmol/l]) and survivors (5.25 mmol/l [range 1.8–10.3 mmol/l]). limitations: basis for diagnosis of gdv not specified. control group used was dogs with io which is not a 'disease free' control group. presurgical interventions mentioned but not specified and not clear if applied to all dogs. some dogs (number not stated) were euthanised based on subjective impression of gastric wall necrosis, with potential for bias. small number of dogs in study and authors state that number of dogs studied was lower than required to make assessment of mortality risk. troia et al. (2018) population: dogs with a clinical and radiographic diagnosis of gastric dilatation volvulus (gdv). mixed population represented. lactate measurement technique not specified. sample size: 29 dogs. intervention details: preoperative stabilisation (details not specified). corrective surgery for gdv. study design: prospective observational case control study. outcome studied: survival to discharge vs non-survival correlated with admission (pretreatment) blood lactate level. correlation between admission (pretreatment) levels of the biomarkers cell-free dna, high mobility group box-1, procalcitonin, lactate, and applefast score, with survival, evidence of gastric necrosis, and occurrence of postoperative complications. main findings (relevant to pico question): lactate concentration was not different between survivors and non-survivors. limitations: three dogs received treatment prior to presentation. small sample and no power analysis performed. four dogs were euthanised based on subjective assessment of gastric necrosis which may have biased the outcome results. although blood samples were taken prospectively, records were analysed retrospectively with missing data or variation between subjects (e.g., timing between onset of clinical signs and admission / surgery). two different centres contributed to the study with potential for differences in case management which may have affected outcomes. grassato et al. (2020) population: dogs with a radiographic or surgical diagnosis of gastric dilatation volvulus (gdv) with no prior treatment, that subsequently underwent corrective surgery, and for which blood lactate measurement was available. mixed population represented. lactate measured on presentation (t0) and 24 hours (t24) and 48 hours (t48) after surgery. method of lactate measurement not specified. sample size: 45 dogs. intervention details: all dogs received intravenous fluid resuscitation, antibiotic therapy and gastric decompression via orogastric tube and / or percutaneous needle. all dogs subsequently underwent corrective surgery for gdv. study design: retrospective observational case-control study. outcome studied: survival to discharge vs non-survival correlated with t0, t24 and t48 blood lactate concentration and change in lactate concentration between time points. presence or absence of gastric necrosis correlated with t0, t24 and t48 blood lactate concentration, and change in lactate concentration between time points. main findings (relevant to pico question): overall survival 31/45 (69%). no significant difference detected in lactate concentration between at any of the three time points (all values in mmol/l). t0: non-s 3.25 mmol/l (2.1–12.7 mmol/l), s 3.2 mmol/l (0.9–16.4 mmol/l); t24: non-s 1.1 mmol/l (0.7–9.1 mmol/l), s 1.2 mmol/l (0.6–4.2 mmol/l); t48: non-s na (0.6–6.2 mmol/l), s 0.9 mmol/l (0.6–2.5 mmol/l). no significant difference in lactate concentration between either group (survivors versus non-survivors) at any time point. despite the above, a lactate level of < 4.45 mmol/l was reported as distinguishing survivors from non-survivors with sensitivity 33% and specificity 77%. lactate concentration for survivors (when reported as mean ± sd in table format) at t24 and t48 was significantly lower than at t0 whereas this was not the case for non-survivors (significance not given). limitations: retrospective study. method of lactate measurement not reported, nor how accurate timing of postoperative blood lactate levels was achieved. small number of cases (power analysis not reported). data regarding pre-hospitalisation factors was not available. the tabulated data showed survivors had a significant reduction in lactate between time-points compared to non-survivors when data was presented as mean ±sd, but not when reported as median with range. however, reductions were also reported in lactate levels in dogs both with and without gastric necrosis when presented as mean ±sd but not when reported as median with range. this led to a confusing discussion where the authors mixed discussion of gastric necrosis and outcome and concluded that reduction in lactate levels could not be used as a prognostic indicator. apparent contradiction between results section and table as described above. significance levels not reported – as described above. rauserova-lexmaulova et al. (2020) population: dogs with a radiographic diagnosis of gastric dilatation volvulus (gdv) with no prior treatment, that subsequently underwent corrective surgery, with blood lactate samples taken at admission prior to any treatment. mixed population represented. initial (pretreatment) lactate measured only. lactate measured using konelab 20i analyser (thermo fisher scientific, finland) processed within 15 minutes or stored frozen and analysed the following day with same analyser. sample size: 75 dogs. intervention details: all subjects underwent corrective surgery for gdv. other interventions not specified. study design: retrospective observational case-control study. outcome studied: survival to discharge vs non-survival correlated with admission (pretreatment) blood lactate level. presence or absence of gastric necrosis correlated with admission (pretreatment) blood lactate level. correlation between initial values of ph, pco2, bicarbonate, base excess (be) and electrolytes (sodium, potassium, chloride, total calcium and inorganic phosphorous), anion gap (ag), strong ion difference (sid) and surgical finding of gastric necrosis and survival to discharge. main findings (relevant to pico question): overall survival 61/75 (81.3%.) initial plasma lactate concentration was significantly associated with mortality (non-survivors median 9.68 mmol/l, [range 5.84–13.49 mmol/l] vs. survivors, median 3.36 mmol/l, [range 2.42–5.64 mmol/l] p ë‚ 0.0001). however, in multivariate logistic regression analysis, lactate concentration was not independently associated with mortality. optimal cut-off points to predict patient survival were lactate ≤ 5.62 mmol/l (75.4% sensitivity, 85.7% specificity). limitations: retrospective study. samples from both arterial and venous sources were used for the comparison of lactate. pre-surgical intervention / stabilisation was not specified. risk of possible concurrent diseases (e.g., cardiac, liver, and renal) could not be excluded. relatively small number of patients (power analysis not undertaken). sharp et al. (2020) population: dogs with a radiographic diagnosis of gastric dilatation volvulus (gdv) with no prior treatment. mixed population represented. method of lactate measurement not specified. sample size: 498 dogs, of which 429 dogs had lactate measured at presentation. intervention details: 116 dogs were euthanised preoperatively, with 382 dogs undergoing corrective surgery. study design: retrospective observational case-control study. outcome studied: survival to discharge vs non-survival correlated with presentation lactate measurement. non-survivors were further categorised as: euthanised preoperatively, euthanised intraoperatively, euthanised postoperatively, and died. main findings (relevant to pico question): overall survival 275/429 (64.1%). initial plasma lactate (3.7 mmol/l [range 0.5–20 mmol/l]) was significantly different between survivors and those that were euthanised preoperatively (6.1 mmol/l [range 1.5–19.4 mmol/l]), intra-operatively (8.15 mmol/l [range 2.7–15.7 mmol/l]), and died postoperatively (10.1 mmol/l [1.6–19 mmol/l]) (p <0.001 for all), but not for those that were euthanised postoperatively (5.65 mmol/l [range 2.1–16.5 mmol/l]). many dogs in the survivor group had very high lactate concentration (range 0.5–20 mmol/l). limitations: retrospective study. number of dogs in some outcome groups were quite small (power analysis not reported). some cases were excluded based on presumptive diagnosis of gdv. high percentage of dogs were euthanised preoperatively (without intent to treat and without radiographic confirmation of diagnosis) which accounted for the majority of mortality in this study, with potential for bias of results. method of lactate measurement not specified. white et al. (2021) population: dogs with a physical and radiographic diagnosis of gastric dilatation volvulus (gdv) and in which orogastric decompression and gastric lavage had been performed. mixed population represented. lactate measurement technique not specified. sample size: 41 dogs. intervention details: intravenous fluid resuscitation, gastric decompression, gastric lavage. surgical correction of gdv (immediate or as a staged procedure as described below). study design: retrospective observational case-control study. outcome studied: survival vs non-survival correlated with initial plasma lactate concentration. survival vs non-survival correlated with percentage change in plasma lactate concentration following gastric decompression and stabilisation. survival vs non-survival correlated with performing surgical correction for gdv under the same anaesthesia as for decompression, or as a staged procedure with corrective surgery being performed some hours later following gastric decompression and medical stabilisation prior to exploratory laparotomy. main findings (relevant to pico question): non-survivors had a mean initial plasma lactate concentration of 7.3 mmol/l (range 2.7–11.1 mmol/l) while survivors had a mean initial plasma lactate concentration of 3.2 mmol/l (range 1.2–7.8 mmol/l) (p <0.001). larger percentage decreases in plasma lactate concentration following decompression and stabilisation were associated with higher likelihood of survival to discharge (p <0.03) – full data not provided but 14/15 dogs that survived decreased their plasma lactate by ≥ 50%. limitations: retrospective study. dogs were excluded if orogastric intubation was not included as part of gastric decompression. dogs were excluded if, following decompression and stabilisation, they were discharged or transferred to another hospital for corrective surgery. timing of lactate measurement post stabilisation was not standardised. appraisal, application and reflection of the 15 studies appraised, many did not have the pico question given above (association between plasma lactate concentration and outcome) as their primary objective. rather, plasma lactate was measured as part of a broader study assessing other variables and / or outcomes. whilst this did not affect results, it meant that, in some cases, statistical analysis was not as detailed or as focused on the pico question of this knowledge summary as might otherwise have been the case (for example, some studies reported receiver operating characteristic (roc) analysis and optimal sensitivity and specificity, while others did not). this explains why these studies did not have 'lactate' as a title keyword. however, the six studies of rauserova-lexmaulovaa et al. (2020), grassato et al. (2020), santoro beer et al. (2013), green et al. (2011), zacher et al. (2010) and de papp et al. (1999) did have the pico question of the knowledge summary (association between survival and plasma lactate level) as the primary study focus. twelve of the 15 studies were retrospective, with the limitations inherent to retrospective studies, as described above, in particular there was variation both within and / or between studies in the presenting signs, characteristics of the study population, and analysis and presentation of data. median overall survival across all studies = 78.4% (range 64.1–88%).   single pre-intervention plasma lactate measurements thirteen studies reported an initial (pre-intervention) lactate level in survivors vs non-survivors. in 11 papers this was reported as median with range for the two groups, in one paper (white et al., 2021) this was reported as mean with range for the two groups; while in three studies (o'neill et al., 2017 green et al., 2012; and de papp et al., 1999) this was reported as number of cases above and below a pre-selected lactate cut-off value (> 4 mmol/l in the first and > 6 mmol/l in the latter two studies respectively). of the total 15 studies appraised 11 papers reported a significant difference in initial lactate concentration between survivors and non-survivors,4 papers reported no significant difference in initial lactate concentration between survivors and non-survivors. in all studies, the range of lactate values reported for both survivors (range 0.1–20 mmol/l) and non-survivors (range 1.1 25.3 mmol/l) was very wide, with, in all cases, significant overlap in values between the two groups (summarised in the table below). in many of the studies, the sample size was small (as indicated above and below), and in no study was power analysis undertaken to detect a significant difference between lactate levels in survivors versus non-survivors. this raises the possibility that those studies reporting non-significance were under-powered to detect significance in plasma lactate levels between survivors and non-survivors. even in those studies where a significant difference was found between populations, the broad range of values (and overlap between survivors and non-survivors) has important implications for decision-making in individual animals. in practical terms, although clinicians may (correctly) infer that a 'high lactate’ (hil) value is more commonly associated with non-survival compared to a 'lower lactate’ level, the range of lactate values within these two groups, and the substantial overlap between them, makes prediction at the level of individual cases difficult. this data is summarised in the table below:   table 1: summary of studies appraised in the knowledge summary, showing median lactate concentration and range for survivors vs. non-survivors study number included in study overall survival % initial median lactate and range (survivors) mmol/l initial median lactate and range (non-survivors) mmol/l significance (survivors vs non-survivors) white et al. (2021) 41 88 mean 3.2 (1.2–7.8) mean 7.3 (2.7–11.1) p <0.001 rausterova-lexmaulovaa et al. (2020) 75 81.3 3.36 (2.42–5.64) 9.68 (5.84–13.49) p <0.0001 grassato et al. (2020) 45 69 3.2 (0.6–16.4) 3.25 (2.1–12.7) ns sharp et al. (2020) 429 64.1 3.7 (0.2–20) 6.1 (1.5–19.4) [cases euthanised pre-operative]; 8.15 (2.7–15.7) [euthanised intra-operative]; 10.1 (1.6–19) [died postoperative] p <0.001 oron et al. (2018) 45 82.9 3.9 (0.7–17.8) 3.8 (0.78–21.9)* 11.2 (6.6–11.8)* 11.4 (3.8–19.4)** p = 0.01 spinella et al. (2018) 22 73 5.25 (1.8–10.30) 7.1 (3.1–12.1) ns troia et al. (2018) 29 76 2.8 (1.1–10.6) 5.2 (2.6–11.9) ns o’neill et al. (2017) 181 79.3 stratified ≤4 associated with increased survival –  p <0.001 verschoof et al. (2017) 20 75 6.2 (1.9–9.7) 11.8 (7.5–16.2) p <0.01 santoro beer et al. (2013) 78 83 4.5 (0.8–14.4) 7.9 (5.6–15) p <0.001 green et al. (2011) 84 88 3.4 (0.7–16.1) 6.80 (1.4–16.9) p <0.0074 green et al. (2012) 101 84 – – – israeli et al. (2012) 66 77.3 4.8 (0.1–19.9) 7.9 (1.1–25.3) ns zacher et al. (2010) 64 77 6.2 (0–12.6) 10.3 (3.9–16.7) p <0.05 de papp et al. (1999) 102 lactate <6 mmol/l 99%; >6 mmol/l 58% 3.5 (0.1–14.1) 8.5 (2–13.8) p <0.001 */**concentration reported measured from saphenous* and cephalic** vein respectively   receiver operating characteristic (roc) analysis six studies performed receiver operating characteristic (roc) analyses to determine a cut-off for lactate which optimised sensitivity and specificity for survival vs non-survival. the paper of de papp et al. (1999) stated that a cut-off lactate value of 6 mmol/l was chosen so as to slightly increase specificity at the expense of sensitivity, while in the other studies it was implied that a cut-off which maximised both sensitivity and specificity was chosen. however, this data is problematic for clinicians faced with making decisions for individual patients, because the selected optimal cut-offs across studies ranged from a lactate of 4.1 to 9.0 mmol/l. in other words, it is not clear from the literature what lactate value should be used as a cut-off to optimise sensitivity and specificity. in all studies, the sensitivity was moderately low (highest 75.4%, range 60.3–75.4%) while the specificity was somewhat higher (highest 90.9%, range 73–90.9%). the paper of green et al. (2012) expressed the cut-off as an odds ratio of survival, rather than sensitivity and specificity. this data is summarised in the table below:   table 2: summary of studies in which receiver operating curve (roc) analysis was reported, showing optimum cut-off in lactate concentration for survival vs. non-survival and associated sensitivity and specificity study plasma lactate cut-off for survival to discharge (mmol/l) sensitivity % specificity % green et al. (2011) < 4.1 60.3 90.9 rauserova-lexmaulovaa et al. (2020) ≤ 5.62 75.4 85.7 green et al. (2012) < 6 odds ratio 7.3 – de papp et al. (1999) < 6 61 88 santoro beer et al. (2013) < 7.4 75.0 89.0 zacher et al. (2010) < 9.0 74 73   the problem of a low sensitivity is the relatively high false negative rate therefore, a significant proportion of dogs would be classified falsely as having a 'low lactate' (i.e., below the cut-off and therefore considered more likely to survive). the implication of this is that such dogs (approximately 25% with a sensitivity of 75%) may be given a falsely optimistic prognosis. in practical terms this may affect the decision to proceed to surgery (with cost implications for the owner) but with a poor outcome. this is, arguably, less problematic than having a low specificity, with the corresponding false positive rate. for example, taking a specificity of 88%, would mean 12% of dogs being given a falsely poor prognosis. such dogs may, in fact, have a good outcome but the owners may be advised otherwise (i.e., advised not to proceed with surgery and instead consider euthanasia) in this proportion of cases. however, having these statistics allows the clinician to advise owners accordingly, for example a dog with a 'high lactate' (i.e., above the chosen cut-off) has an approximate 75% chance that this is a true value and that the prognosis for survival to discharge should be correspondingly guarded. conversely, a dog with a 'low lactate' (i.e., below the chosen cut-off) has an approximately 86% chance that this is a true value and a more optimistic outlook for survival to discharge should be given. the summary of these findings is that a 'low' plasma lactate concentration is, in general, a better predictor of survival than a 'high' plasma lactate concentration is a predictor of non-survival, and owners should be advised accordingly. the principal difficulty is in choosing the most appropriate cut-off, given the variation in this value in the literature. the logistic regression analysis provided in the paper of de papp et al. (1999) provides, perhaps, the most useful representation of data, and goes some way to addressing this question, as it gives a graphical representation of probability of survival vs plasma lactate concentration. in this paper, a preoperative plasma lactate of 6 mmol/l gave an approximate survival to discharge of 90%. this probability then fell steeply and almost linearly for lactate values > 6 mmol/l, with a lactate level of 8 mmol/l associated with an approximate 70% survival, and 10 mmol/l with an approximate 50% survival (de papp et al., 1999).   change in lactate concentration following intervention (lactate clearance) in addition to assessing lactate concentration at a static point in time, five papers examined changes in lactate concentration (lactate clearance) over a determined period of time. these findings are summarised in the table below:   table 3: summary of studies in which change in lactate concentration over time (lactate clearance) was reported, and its relationship to survival study difference in initial lactate survivors vs non-survivors time points results white et al. (2021) yes p <0.001 admission, then at variable time points following fluid stabilisation and decompression the paper reports that larger percentage decreases in lactate concentration (following stabilisation and decompression) were associated with high likelihood of survival to discharge (p = 0.03), further statistics were not provided but 14/15 dogs that survived decreased their plasma lactate by ≥ 50%. grassato et al. (2020) no admission (t0), then 24hrs (t24) and 48hrs (t48) post-surgery no significant difference between survivors and non-survivors at any time point. the results section suggested that surviving dogs reduced their lactate concentration by a greater amount than non-survivors, however this appeared to be contradicted in the discussion section (see comments below). significance levels were not reported. zacher et al. (2010) yes, p <0.05 initial (admission) and then following fluids and gastric decompression. final lactate concentration (post fluids and decompression) for survivors (3.3 ± 2.3) was significantly lower than non-survivors (8.0 ± 3.3) p <0.05. percentage change in lactate between initial level and the level post fluids and decompression was significantly different between survivors (49.1 ± 28.8%) and non-survivors (24.6 ± 19.4%) p <0.05, although absolute change was not significant. a percentage change in lactate cut-off of 42.2% predicted survival with sensitivity 61% and specificity 100%. verschoof et al. (2017) yes, p <0.0078 admission, then day 1 post-surgery. lactate concentration day 1 after surgery was significantly different between survivors and non-survivors. green et al. (2011) yes, p <0.0074 admission, then variable time-points, median 6hrs later. 70% of surviving dogs showed a reduction in lactate of >50% from baseline.   the study of grassato et al. (2020) has limitations as significance levels were not given, and some statements in the text of the results and discussion section appeared to be contradictory to those of the tabulated data. for example, significant differences were described in the results table between mean initial lactate concentration (t0) and concentration at both t24 and t48 for dogs without gastric necrosis and dogs surviving; and at t24 only for dogs with gastric necrosis. no differences in any group and at any time point were recorded in the results table for median values. however, the terms mean and median were interchanged in the text of the discussion section. the discussion also stated that a decrease in median lactate of ≥ 50% was detected for 'all the considered categories' however no significant differences were recorded in the results table, so it was not clear which description was correct. the absence of stated significance levels, and the discussion of gastric necrosis and survival together (without multivariate analysis) made the results and discussion difficult to understand. the four other papers all reported that lactate concentration reduced to a greater extent in survivors compared to non-survivors (as well as showing a difference in static initial lactate concentration). it is difficult to directly compare these studies, as the time points for subsequent lactate measurements were different, following fluid plus decompression in zacher at al. (2010), at variable time-points in green et al. (2011) and white et al. (2021) and preand post-surgery in verschoof et al. (2017). the most challenging initial decision facing owners of a dog presenting for gdv is whether to proceed to surgery or not, and risk incurring charges of (usually) several thousand pounds. guidance on likely outcome pre-surgery would be the most useful. the paper of zacher et al. (2010) may be the most helpful in guiding practitioners since it looked at lactate preand post-resuscitation but prior to surgery and showed a more significant reduction in lactate in survivors compared to non-survivors. using a cut-off of change in lactate of 42.2% predicted survival with sensitivity 61% and specificity 100%. in other words, these values suggest a false negative rate of 39% (i.e., 39% of dogs did not reduce their lactate by 42.2% but were survivors); and a false positive rate of 0% (i.e., 0% of dogs reduced their lactate by 42.2% but were not survivors). this suggests that a dog displaying a reduction in lactate of 42.2% should be given a good prognosis, whilst failing to show this reduction in lactate should be interpreted more cautiously. however, when considering this study, the limitations described above should be noted. the general summary of these papers is that, at a population level, dogs that reduce their lactate concentration compared to admission level are likely to have a better prognosis than those dogs who do not. the difficulty, as for static levels, is in using this information to make decisions for individual animals.   additional information from non-gdv studies looking at lactate as a prognostic marker a number of studies have examined lactate as a prognostic marker in cases other than dogs with gdv. the paper of stevenson et al. (2007), looking at lactate in a variety of systemically ill dogs (n = 80), concluded that there was no significant difference in initial lactate between survivors and non-survivors; however, a reduction in lactate by ≥ 50% at 6 hours following resuscitation was associated with increased survival. in the large (n = 566) retrospective study of kohen et al. (2018), also looking at dogs presenting with a variety of different conditions, admission lactate was found to be a significant independent predictor of survival. further, univariate analysis showed that odds of mortality increased with an increasing magnitude of hyperlactataemia. however, consistent with the gdv-specific studies, there was a significant overlap in lactate values between survivors and non-survivors. in the more recent paper of blutinger et al. (2021), a prospective study looking at lactate in dogs (n = 71) with shock due to a variety of conditions, it was found that there was no difference in mean admission lactate between survivors and non-survivors; however, the percentage change in lactate post-resuscitation was a significant predictor of survival. similarly, the recent paper of ortolani & bellis (2021), looking at critically ill dogs with a range of different conditions (n = 267), also showed that there was a significant difference in admission lactate concentration between survivors and non-survivors. again, however, there was a significant overlap in lactate values between survivors and non-survivors. power analysis was not reported in any of the above papers. however, the extent of overlap in lactate values between survivors and non-survivors, which is a consistent finding in all of the above studies, suggests that, in those cases with smaller populations, the study was more likely to be under-powered to detect a significant difference in lactate concentration between survivors and non-survivors.   summary and application the overall weight of evidence suggests that, at a population level, admission plasma lactate concentration is significantly different between survivors and non-survivors. however, in all studies, the range of lactate values between survivors (range 0.1–20 mmol/l across all studies) and non-survivors (range 1.1–19.4 mmol/l across all studies) was very broad, with significant overlap in values between the two populations. this likely reflects, firstly, that many factors contribute to elevations in lactate, and secondly, that the magnitude of increase in plasma lactate does not indicate its reversibility. the measured plasma lactate concentration at any given time is the balance between tissue production vs metabolism and excretion. in dogs with gdv, the main causes of lactate production are proposed to be from gastric necrosis, and systemic distributive shock, and gastric necrosis is believed to be the main factor affecting survival (de papp et al., 1999; zacher et al., 2010; green et al., 2011; santoro beer et al., 2013; and mooney et al., 2014). as treatment protocols differed between the studies described, direct comparison between studies, and in particular determination of a specific lactate level that should be used to guide decision-making, is difficult. the differences in sensitivity and specificity discussed above, also suggest that a high lactate should be interpreted with somewhat greater caution when advising owners compared with a low lactate. in general, a dog with a lower lactate, or one which shows a reduction in lactate following fluid resuscitation, should be given a better prognosis, and corrective surgery would be recommended. a dog with a higher lactate, or one which does not decrease following adequate fluid resuscitation, should cautiously be given a more guarded prognosis, but owners should be advised that many dogs with higher lactate, and those that do not have a decrease in lactate following fluid resuscitation, may still have a reasonable expectation of survival, and exploratory laparotomy should still be strongly considered. methodology section search strategy databases searched and dates covered: cab abstracts (accessed via vetmed resource) 1972–2022 pubmed (accessed via pubmed.ncbi.nlm.nih.gov/) 1920–2022 search strategy: cab abstracts: gastric and dilatation and volvulus and (dog or canine) and lactate gastric and (dilatation or dilation) and (dog or canine) and lact* gdv and lact* gastric and (dilatation or dilation or torsion) and lact*   pubmed: gastric and dilatation and volvulus and (dog or canine) and lactate gastric and (dilatation or dilation) and (dog or canine) and lact* gdv and lact* gastric and (dilatation or dilation or torsion) and lact* dates searches performed: 23 feb 2022 exclusion / inclusion criteria exclusion: dogs presenting for gdv where blood lactate measurement was not reported. inclusion: all papers related to dogs presenting with gdv for which lactate measurements were taken, even if this was not the primary focus of the study. search outcome database number of results excluded – not relevant excluded – review paper excluded – not related to pico question excluded – duplicate paper total relevant papers cab abstracts 31 4 4 7 1 15 pubmed 15 0 0 0 15 0 total relevant papers 15 orcid david mackenzie: https://orcid.org/0000-0002-8751-4295 conflict of interest the author declares no conflicts of interest. references blutinger, a., zollo, a-m., weltman, j. & prittie, j. 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(2010). association between outcome and changes in plasma lactate concentration during presurgical treatment in dogs with gastric dilatation-volvulus: 64 cases (2002–2008). journal of the american veterinary medical association. 236(8), 892–897. doi: https://doi.org/10.2460/javma.236.8.892 contribute to the evidence there are two main ways you can contribute to the evidence base while also enhancing your cpd: tell us your information need write a knowledge summary either way, you will be helping to add to the evidence base, and strengthen the decisions that veterinary professionals around the world make to give animals the best possible care. learn more here: https://veterinaryevidence.org/index.php/ve/guidelines-for-authors a comparison of supraglottic airway devices versus endotracheal intubation for use in rabbit anaesthesia a knowledge summary by sarah daphne foo ba bvbiol 1* 1sydney school of veterinary science, the university of sydney, head office jd stewart building university of sydney, nsw, 2006, australia *corresponding author (sfoo8590@uni.sydney.edu.au) vol 7, issue 3 (2022) published: 06 jul 2022 reviewed by: louise anne buckley (phd fhea rvn) and john chitty (bvetmed certzoomed cbiol msb mrcvs) next review date: 30 dec 2023 doi: 10.18849/ve.v7i3.563 pico question in domestic rabbits undergoing anaesthesia, how does the use of supraglottic airway devices compare to endotracheal intubation for ease of use in achieving a patent airway and maintaining a stable anaesthesia?   clinical bottom line category of research question treatment the number and type of study designs reviewed five papers were reviewed to answer this clinical question including four randomised controlled trials, one of which was a randomised crossover trial and one peer-reviewed conference proceeding strength of evidence moderate outcomes reported there is evidence to support that supraglottic devices were easier and faster to insert than endotracheal tubes and were used effectively to achieve and maintain a patent airway and anaesthesia. they were however, more easily displaced and took up more space in the oral cavity. evidence also supports endotracheal intubation can be used to effectively achieve a patent airway and maintain a stable anaesthesia however, can result in more damage to tracheal mucosa when attempted blindly and required higher doses of induction drugs to use conclusion based on current available evidence, endotracheal intubation is an excellent option for maintaining a patent airway and anaesthesia in rabbit patients as it is a tried and tested method, however, can cause tracheal damage if conducted blindly. supraglottic airways devices can be used as an alternative where endotracheal intubation is unsuccessful. they can also be used where speed of obtaining a patent airway is imperative such as in an emergency as they may be easier and faster to apply, especially in inexperienced practitioners without the necessary equipment for safe endotracheal intubation. supraglottic devices are unsuitable for procedures that require access to the oral cavity and / or patient movement, due to the size and easier loss of seal during movement potentiating risk of aspiration. both supraglottic devices and endotracheal intubation are superior to face masks which evidence shows have more leakage, dead space and increased risk of hypercapnia   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario rabbits are becoming more popular as pets and as their numbers increase, so does the requirement for veterinary care including procedures that require a general anaesthetic. there is a relatively high anaesthetic death risk for rabbits of up to eight times greater of that of cats and dogs (brodbelt et al., 2008). complications one may experience with endotracheal intubation in rabbits include airway obstruction, damage to the tracheal mucosa, oesophageal perforation and in some cases death as a result of tracheitis or airway obstruction (phaneuf et al., 2006; grint et al., 2006; and ranchère et al., 1992). endotracheal intubation can be complex in rabbits due to the restricted size of the oropharynx, the position of the tongue and laryngeal spasms which can be exacerbated when using a blind technique instead of visualising the trachea using a modified otoscope, laryngoscope, or endoscope (manning et al., 1994; benito et al., 2021; tran et al., 2001; thompson et al., 2017; and corleta et al., 1992). supraglottic devices such as laryngeal mask airway devices are commonly used in human medicine, and prevalence of use is increasing in animal medicine (cook, 2003; and crotaz, 2010). the rabbit specific supraglottic airway device (sgad), the v-gel®, was developed as an alternative to laryngeal mask airway devices to try to reduce complications such as lingual cyanosis (kazakos et al., 2007). the v-gel® has been demonstrated to be suitable to maintain a patent airway in rabbit anaesthesia and may be faster to insert than endotracheal tubes (ett) (bateman et al., 2005; and crotaz, 2013). this is especially useful in a clinical setting where achieving a patent airway quickly is imperative such as in respiratory arrest, or where multiple endotracheal intubation attempts have been unsuccessful. this knowledge summary investigates the differences between endotracheal intubation and placement of a supraglottic airway device when maintaining anaesthesia and a patent airway in rabbit patients. the evidence the studies reviewed included four randomised controlled trials, one of which was a randomised crossover trial and one peer-reviewed conference proceeding. randomised controlled trials are strong study designs however all studies had small sample sizes which would have affected the power of the results. the studies looked at only two breeds, norfolk rabbits and new zealand white rabbits, making it difficult to generalise the results to the general rabbit population (cruz et al., 2000; engbers et al., 2017; comolli et al., 2020; toman et al., 2015; and wenger et al., 2017). all studies also only looked at healthy, adult rabbits with low anaesthetic risk based on the american society of anesthesiologists (asa) (2020) physical status grading scale. only one study assessed the difference between endotracheal intubation and use of supraglottic airway devices whilst the subjects were undergoing a surgical procedure common in general practice. thus, the results of the other studies may be less representative of in clinic rabbit patients undergoing anaesthesia for surgery. the main outcomes considered between the devices were mucosal damage, loss of airway seal, ability to achieve positive pressure ventilation and ease of application. a consistent finding across all studies is that the application of a supraglottic airway device was faster than intubation with an endotracheal tube, however this may be due to lack of training. all studies demonstrated that anaesthetic parameters such as heart rate, respiratory rate, temperature and depth did not differ depending on which device was used. the studies also showed that supraglottic devices were more easily displaced during patient movement and that endotracheal intubation could cause more mucosal damage if using the blind technique. both airway devices have evidence supporting their effective use in rabbit anaesthesia and taking into account the limitations and benefits of each device will allow the general practitioner to choose the best option for their patients. summary of the evidence engbers et al. (2017) population: adult new zealand white laboratory rabbits with no indication of systemic illness (asa classification status of 2 or less). sample size: initial sample size: 15 rabbits. final sample size: 13 rabbits (reasons for exclusion addressed in ‘intervention details’). intervention details: subjects were acclimated to environment for 1 week prior to the experiment. the subjects were allocated to groups via randomised block selection: v-gel® device (supraglottic airway device [sgad]) – seven rabbits. orotracheal intubation (endotracheal tube [ett]) – six rabbits. subjects were fasted for 2 hours and underwent a physical exam prior to the experiment. all subjects were premedicated with a mixture of midazolam and dexmedetomidine intramuscularly with alfaxalone used for induction. two ct scans were taken, one baseline before insertion, and one 10 minutes after the devices were inserted. the scans were from the margin of the nose to the thoracic inlet. the sgad devices were selected based on the subject mass. lubricating spray was applied to the larynx prior to insertion with the tongue positioned outside the mouth. the device was inserted until resistance was felt or when the device fixation tabs were positioned within 1–2cm of the incisors. a capnograph was used to confirm successful placement. the ett group was intubated with endotracheal tubes using the blind technique with sizes being selected based on the experience of the operator. the subjects were placed in sternal recumbency with hyperextension of the head and neck. lidocaine was sprayed into the oropharynx 30 seconds prior to intubation. placement was confirmed with a positive capnograph reading. both sgad and ett devices were secured behind the ears with a bandage tie. blood pressure, heart rate, respiratory rate and oxygen saturation were recorded every 30 seconds for 5 minutes and at 15 minutes after the devices were inserted. at 15 minutes isoflurane concentration was measured 5 cm away from the mouth. the airway seal was tested by closing the airway valve and squeezing the reservoir bag to assess for leakage. in four sgad and five ett subjects, arterial blood samples were collected to measure blood gasses and electrolytes. the subjects were maintained under general anaesthesia for a total of 60 minutes using a bain non-rebreathing system. all subjects were euthanised at the conclusion of the anaesthetic with intravenous sodium pentobarbital. one operator was used for each group. exclusions: two rabbits were excluded from the results, one due to failure of intubation and the other due to prolonged intubation time due to presence of faecal matter in the oropharynx. study design: randomised controlled trial. outcome studied: time to successful device insertion: measured from when the sgad or ett passed the incisors to confirmation of six waveforms using a capnograph. number of attempted device placements: in the absence of a positive capnograph signal, adjustments were made, and the number of attempts was recorded. narrowest region of upper airway: in the sgad group, computed tomography (ct) scans were used to assess the narrowest region of the upper airway in relation to the tip of the sgad. in the ett group, ct scans were used to measure the cross-sectional area of the lumen. airway sealing pressure: assessed by closing the circuit and squeezing the reservoir bag with peak inspiratory pressures being increased by 5 cmh2o increments until reaching 20 cmh2 histological score of tracheal tissue: necropsies were performed on all subjects up to 2 hours following euthanasia by a pathologist (blinded). the tongue, trachea, pharynx and larynx were fixed in formalin and stained with haematoxylin and eosin (h&e). the following areas were examined: larynx at the level of vocal folds. trachea immediately caudal to larynx. trachea 1 cm caudal to larynx. a histological score of tracheal tissue was given with scores for the sections from the same regions (above) averaged to give a total score out of six: 0 = normal. 1 = mild focal erosion of mucosa with little or no leukocytic infiltration and minimal to mild locally extensive congestion of submucosa. 2 = multifocal erosion or ulceration with oedema of lamina propria, moderate mixed leukocytic infiltration, and haemorrhage of mucosa and moderate diffuse congestion and mild perivascular oedema of submucosa. 3 = extensive erosion or ulceration with marked mixed leukocytic infiltration, cellular debris, haemorrhage, and possibly surface exudate of the mucosa and moderate diffuse congestion and oedema with or without haemorrhage, and leukocyte infiltration associated with overlying ulcer or erosion. arterial blood gases and electrolytes: the following were assessed: potential hydrogen (ph), partial pressure of oxygen (pao2), partial pressure of carbon dioxide (paco2), base excess (be), bicarbonate (hco3), arterial oxygen saturation (sao2), sodium (na+), potassium (k+), ionised calcium, haematocrit, haemoglobin. statistically significant differences were determined as those with a p value of less than 0.05. main findings (relevant to pico question): time to successful device insertion: the device insertion time was significantly shorter and more consistent in the sgad group compared to the ett group (p = 0.02), where sgad device insertion had a mean of 33 seconds with a range from 14–38 seconds and ett device placement had a mean of 59 seconds with a wider range from 29–171 seconds. number of attempted device placements: no significant difference (p = 0.99). narrowest region of upper airway: there was no significant distance between the caudal edge of the basihyoid bone and the rostral edge of the thyroid cartilage (p = 0.16). the cross-sectional area of the narrowest point decreased significantly between the baseline ct scan of both groups, but there was no significant difference between the ett and sgad groups (p = 0.93). airway sealing pressure: the median airway seal was higher in the ett group but there was no statistical difference (p = 0.06). histological score of tracheal tissue: the ett group had significantly higher mean histological score than the sgad group where the ett group had a mean score of 3.3 with a range of 1.0–5.0, and the sgad group had a mean score of 0.67 with a range of 0.33–3.67 (p = 0.03). arterial blood gases and electrolytes: there was no significant difference in any of the measured variables with hypercapnia being present in both groups (p >0.05). limitations: the method of endotracheal intubation was blind. other methods may result in reduced tracheal injury due to visualisation of the airway. the subjects were all laboratory animals of the same breed and size with a low asa status and no surgical procedure was performed limiting the result’s extrapolation to the rabbits seen in clinical practice undergoing surgical procedures. immediate assessment of damage to tracheal mucosa does not indicate if there are long-term effects and all subjects were euthanised following the study. this also meant assessment of recovery was not assessed which is an important factor when considering client owned rabbits. intermittent positive pressure ventilation (ippv) was not used in this study and thus airway sealing pressures were not assessed. operators were trained to use the sgad via an online training course and on two euthanised rabbits. more extensive training could have altered the results as speed of placement would likely have decreased. operators were also the same for each group which means their technique may have improved over the course of the study, and that a direct comparison of one operator’s experience with the two different devices is not possible. majority of outcomes showed no significant statistical difference, and this could be due to small sample size reducing power. the original sample size of 15 meant uneven randomised allocation, with the final subjects (13) also being uneven which would again affect the statistical results. comolli et al. (2020) population: adult female new zealand white rabbits undergoing ovariohysterectomy with american society of anesthesiologists (asa) status less than 1 (excluded if any signs of illness resulting in higher asa status). healthy on physical examination. sample size: 14 rabbits. intervention details: the subjects were block randomised into two groups with seven animals each: endotracheal intubation (eei). rabbit specific supraglottic device, v-gel® (sgad). the subjects were induced with ketamine, meloxicam and xylazine and maintained with isoflurane in 100% oxygen. an endoscope was used to visualise the larynx and glottis. endotracheal tubes were lubricated and after intubation connected to capnograph with the cuff inflated until a seal was created. the v-gel® was introduced with capnograph attached until mild resistance was detected. the ovariohysterectomy was performed using standard techniques. following anaesthetic an endoscope was used again to assess the appearance of the larynx and glottis. 4 days following study, all animals were euthanised and post-mortem examinations were performed with samples taken from the proximal and distal larynx and the tracheobronchial bifurcation. the samples were preserved in formalin, embedded in paraffin and stained with haematoxylin and eosin (h&e). heart rate, electrocardiogram (ecg), oxygen saturation (spo2), blood pressure, respiratory rate, end tidal carbon dioxide (etco2) and rectal temperature were recorded every 5 minutes. the circuit used was a modified jackson-rees non-rebreathing circuit, oxygen flow rate of 1–2.5 l/m. study design: randomised controlled trial. outcome studied: placement time of devices: v-gel® placement considered successful when normal waveform was present on capnograph and breathing bag showed normal movement. endotracheal intubation considered successful when seal was formed, and positive capnograph signal seen. number of attempts taken to achieve placement of each device. required level of isoflurane concentrations to maintain surgical plane of anaesthesia. arterial blood gas values: potential hydrogen (ph), partial pressure of oxygen (po2), total carbon dioxide (tco2), bicarbonate (hco3), base excess (be), haematocrit (hct). gross laryngeal and laryngotracheal histopathology evaluation: evidence of inflammation, haemorrhage and necrosis using scoring system of 1–4: 1 = minimal 2 = mild 3 = moderate 4 = severe. distribution focal, multifocal, diffuse using scoring system of 1–3: 1 = focal 2 = multifocal 3 = diffuse. statistically significant differences were determined as those with a p value of less than 0.05. main findings (relevant to pico question): placement time of devices: it took significantly longer to endoscopically intubate rabbits (median placement time 48 seconds, range 20–126 seconds) versus v-gel® placement (median placement time 6 seconds, range 2–20 seconds) (p = 0.003). number of attempts required for placement of devices: all v-gel® placements required only one attempt; two endotracheal tube intubations required three attempts. there was no statistically significant difference (p = 0.17). required level of isoflurane concentrations to maintain surgical plane of anaesthesia: there was no statistical difference (p = 0.59). arterial blood gas values v-gel® had statistically significant (p = 0.045) increased levels of pco2 with an increased mean of 7.5 mmhg (95% confidence intervals -0.9–14.1 mmhg) compared with endotracheal intubation (ett) but the effect of time was not significant. all other values / differences were not statistically significant (p >0.05). gross laryngeal and laryngotracheal histopathology evaluation: airway trauma was present in histopathological examination of both groups but there was no statistically significant difference between groups (p >0.05). it should also be noted that when changing position of the subject, the v-gel® device was more easily displaced which although was not compared statistically is an important consideration. limitations: all intubations and v-gel® placements were performed by the same experienced anaesthetist making is difficult to extrapolate to general practitioners who may have less experience. using different operators would mean skill level would have varied, which may have affected the time to place devices. the anaesthetist was also not blinded and may have improved in skills over time with repeated procedures. the same breed and procedure may impact application to the general rabbit population and different surgical procedures. intermittent positive pressure ventilation (ippv) was not used in this study and thus airway sealing pressures were not assessed. the small sample size may reduce the power of the results. a type ii error is possible as the sample size was limited for categorical data analysis.   toman et al. (2015) population: adult new zealand white rabbits 2.5–3 kg, laboratory animals with no clinical abnormalities detected. sample size: 24 rabbits. intervention details: subjects were allocated to four groups with six animals in each group, and anaesthetised four times with the order of airway device being randomised: endotracheal intubation (ett). laryngeal mask airway (lma). perilaryngeal airway (pla). v-gel® rabbit (v-gel®). blood pressure, heart rate and electrocardiogram (ecg) were measured at 1 minute, 5 minutes, and 30 minutes after placement of devices and establishment of anaesthesia. xylazine and ketamine were used for premedication. rocuronium bromide was used to suppress respiration –after complete paralysis the devices were placed. animals were manually ventilated with 1.15% isoflurane with 50% air and oxygen mixture under 15 cm h2o pressure. animals that regained spontaneous respiration after 30 minutes were given neostigmine and atropine prior to extubation. study design: randomised controlled trial. outcome studied: q-t intervals corrected for heart rate (qtc) intervals: qt duration determined measuring time from onset of q wave to end of t wave with qt interval measured with bazett formula. mean arterial pressure (map): invasive reading through left auricular artery. blood gas values. heart rate. all above parameters were measured at baseline, 1, 5, 15 and 30 minutes. statistically significant differences were determined as those with a p value of less than 0.05. main findings (relevant to pico question): qtc intervals at baseline, 1, 5, 15 and 30 minutes: there was no statistically significant difference between groups for baseline intervals. the qtc intervals at 1 and 5 minutes was significantly increased in the ett group (approximately 285 milliseconds and 292 milliseconds respectively) compared to other groups which were all less than approximately 262 milliseconds (p <0.05). there was a significant increase (p <0.05) in qtc interval at 15 and 30 minutes between the pla (approximately 255 milliseconds) and v-gel® groups (approximately 251 milliseconds). there was a significantly higher(p<0.05) qtc interval in the lma group (approximately 260 milliseconds) at the 5th minute compared to the v-gel® group (approximately 248 milliseconds). mean arterial pressure (map): there was no statistically significant difference in all groups at baseline, 1, 5, 15 and 30 minutes. there was a significant difference in map value at 5 minutes when comparing the ett (approximate map = 86) and v-gel® group (approximate map = 69). blood gas values: there was no statistically significant difference between groups at baseline, 10 and 30 minutes. heart rate: there was no statistically significant difference between the baseline for all groups. the heart rate values of the ett group (approximately 180–205 bpm) were significantly higher than the pla (approximately 160–170 bpm) and v-gel® (approximately 140–170 bpm) group (p <0.05). the heart rate in the lma group (approximately 170–190 bpm) was significantly higher than the pla (approximately 160–170 bpm) and v-gel® group (approximately 140–170 bpm) at 1, 5, 15 and 30t minutes after intubation (p <0.05). limitations: all intubations, v-gel® placements and manual ventilation was performed by the same anaesthetist making it difficult to extrapolate to general practitioners who may have less experience. differences in operator skills may have changed which results were statistically significant in this study. the anaesthetist was also not blinded and may have improved in skills over time with repeated procedures. exclusion of rabbits with ‘no clinical abnormalities’ lacks detail and specifics such as asa status, age, health status which may have affected study outcomes. small sample size may limit power of results. same breed / weight and lack of surgical procedure may impact application to the general rabbit population and common surgical procedures under general anaesthesia. the results were provided in graphs with no numerical data or standard deviations given so it was difficult to extrapolate specific differences between factors such as heart rate, qtc interval and map. wenger et al. (2017) population: adult female new zealand white rabbits (7 months old), healthy based on physical examination. rabbits showing signs of upper respiratory obstruction or oxygen saturation (spo2) of less than 90% for more than 60 seconds were excluded. sample size: initial sample size: 10 rabbits. final sample size: nine rabbits (reasons for exclusion addressed in section intervention details). intervention details: subjects were acclimated to the environment for 1 week prior to experiment. subjects were not fasted prior to experiments. each subject was anaesthetised four times for each of the four-airway device. subjects randomly allocated to four groups: endotracheal tube (ett) laryngeal mask (lm). v-gel® supraglottic airway device (v-gel®). face masks (fm). subjects were sedated with fentanyl citrate and fluanisone. after 25 minutes the subjects were induced with propofol with an initial dose of 1 mg/kg. jaw tone, palpebral reflex, reaction to lidocaine spraying of larynx and protraction of tongue were assessed to determine if the subject was suitably induced for placement of the airway devices. propofol doses were repeated until successful placement of airway devices. the devices were placed blindly (without use of endoscope). the leakage of each device during spontaneous ventilation was assessed by calculation of difference between expiratory and inspiratory tidal volume over ten breaths. a computed tomography (ct) scan of the head, neck and abdomen was performed. rocuronium bromide was administered and once apnoea was present, controlled mechanical ventilation (cmv) was started at 30 breaths per minute. leakage was measured for increments of 2 cmh2o from 6 cmh2o to 15 cmh2 exclusions: one rabbit had to be excluded from the cmv experiment due to signs of upper airway obstruction. study design: randomised crossover experimental trial. outcome studied: required dose of propofol. time taken to secure airway device. number of attempts to secure airway device. airway leakage at different peak inspiratory pressures (pip). ct of head, neck, abdomen to evaluate: position of the sgad and measurements of the larynx for the fm, v-gel® and lm groups. severity of the laryngeal compression caused by the sgad (measured in sgad application only). measure the total volume of stomach and gas present dorsally, a sign of gastric tympany due to controlled mechanical ventilation (cmv). statistically significant differences were determined as those with a p value of less than 0.05. main findings (relevant to pico question): required dose of propofol: significantly less propofol (p <0.05) was needed in the fm (2.0 mg/kg ± 0.5 mg/kg) group compared with ett (5.5 mg/kg ± 1.4 mg/kg), lm (4.8 mg/kg ± 1.2 mg/kg) and v-gel® (5.1 mg/kg ± 2.1 mg/kg) groups. there was no significant difference between the other groups (p >0.05). time taken to secure airway device: significantly less time was needed in the fm group (82 seconds ± 34 seconds) compared with ett (315 seconds ± 147 seconds), lm (275 seconds ± 89 seconds) and v-gel® (302 seconds ± 124 seconds) groups (p <0.001). there was no significant difference between the other groups (p >0.05). number of attempts to secure airway device: significantly less attempts were needed in the fm group (one attempt, range 1–1) compared with ett (one attempt, range 1–10), lm (one attempt, range 1–2) and v-gel® (one attempt, range 1–4) groups (p <0.029). there was no significant difference between the other groups (p >0.05). airway leakage at different peak inspiratory pressures (pip): there was significantly more leakage at lower pip in the fm group (pip 6–8 centimetres of water [cmh2o] compared with the ett (pip > 16) , v-gel® (pip 6 to >16 cmh2o) and lm (6 to >16 cmh2o) groups (p = 0.0001). the v-gel® (pip 6 to >16 cmh2o) group showed a leak at significantly (p <0.05) lower pressure than ett (pip > 16). ct of head, neck, abdomen: the ct scans showed significantly smaller laryngeal widths (p = 0.004) and heights (p = 0.001) of the larynx in the v-gel® (width 1.9 mm ± 1.0 mm, height 2.8 mm ± 2.2 mm) group compared with the fm (width 2.3 mm ± 0.6 mm, height 5.8 mm ± 1.0 mm) and lm (width 3.1 mm ± 0.5 mm, height 6.2 mm ± 1.3 mm). the measurements were not done for the subjects in the ett group. severe laryngeal compression was seen in one v-gel® subject, with moderate laryngeal compression being seen in two v-gel® subjects although significant differences between groups was not assessed. there was a significant increase in gas in the stomach in the fm (0.2 cm3, -1.6–1.5) and lm (0.1 cm3, -1.0–-1 cm3) groups (p = 0.007) compared to ett (-0.3 cm3, -1.1–6 cm3 and v-gel® (-0.5 cm3, -3.9–0.0 cm3). there was no significant difference in total gastric volume between groups before and after cmv (p >0.05). limitations: airway devices were placed by board certified anaesthetists so results may not be extrapolatable to general practitioners. small sample size may limit power of results. same breed / weight and lack of surgical procedure may impact application to the general rabbit population. the four treatments were applied to the same animal and this could have lead to laryngeal trauma that made application of a later device more difficult. the degree of tympanism could have been more profound as the gas was not assessed within the ingesta of the stomach, only in the dorsal gaseous phase. for ct scans the ett group did not have width and height measurements so it is not possible to compare possible differences with other groups. the authors commented on laryngeal compression noted in ct scans for three v-gel® subjects but did not give us a comparison to other groups so it is not possible to determine the significance of this. cruz et al. (2000) population: female norfolk rabbits (2.4–3.1 kg). sample size: eight rabbits. intervention details: subjects were anaesthetised twice 1 week apart. all eight subjects were intubated with endotracheal tube during first anaesthesia. all eight subjects had laryngeal masks applied during second anaesthesia. subjects were premedicated with methotrimeprazine, thiopentone was used for induction intravenously. 5 ml of barium sulphate as a radiographic contrast was administered into the stomach via an intragastric tube. intubation was attempted by the same inexperienced operator for two attempts. following this, an experienced operator performed intubation. a bain circuit was used to maintain anaesthesia for 60 minutes with isoflurane. values were recorded for heart rate, blood pressure (direct via auricular artery), electrocardiogram (ecg), arterial blood gases, oxygen saturation, tidal volume, temperature and respiratory rate every 15 minutes. immediately after removal of the endotracheal tube or laryngeal mask, thoracic and cervical radiographs were taken to assess for regurgitation and aspiration of the contrast. study design: repeated measure trial (conference proceeding). outcome studied: regurgitation of stomach contents following anaesthesia assessed via radiographs. the dose of thiopentone required. the difference between anaesthetic parameters: heart rate, blood pressure, ecg, arterial blood gas, oxygen saturation, tidal volume, temperature and respiratory rate. the number of attempts taken to apply the airway device. statistically significant differences were determined as those with a p value of less than 0.05. main findings (relevant to pico question): regurgitation of stomach contents following anaesthesia assessed via radiographs: there was no significant regurgitation in either group (p >0.05). the dose of thiopentone required: a significantly (p <0.05) higher dose of thiopentone was required for endotracheal intubation (36 mg/kg) compared to laryngeal mask application (24 mg/kg). the difference between anaesthetic parameters: there was no significant difference between the groups for any variable (p >0.05). the number of attempts taken to apply the airway device: endotracheal intubation was successful in 3/8 animals at the first attempt. laryngeal masks were placed in all eight animals at the first attempt but there was no statistically significant difference between groups (p >0.05). limitations: small sample size may limit power of results. lack of surgical procedure may impact application to the general rabbit population. rabbits were larger breeds weighing between 2.3 and 3.1 kg which limits application to smaller dwarf breeds commonly seen in clinical practice. there were no details on exclusions / inclusions for subjects and as such we do not know if age / health status impacted results. ‘norfolk’ is not a recognised rabbit breed so it is unclear which breed of rabbit was used. the same inexperienced practitioner performed all airway device applications but only had two attempts before an experienced practitioner stepped in. in clinical practice more than two attempts may be required which makes it difficult to extrapolate the results to general practitioners. the inexperienced practitioner may also have improved in technique as the study progressed. confidence intervals and ranges were not reported so it is more difficult to interpret statistically significant results. appraisal, application and reflection facemasks are commonly used in first opinion practice for rabbit patients due to the difficulty of endotracheal intubation by veterinarians with limited experience with rabbit patients. current evidence suggests that face masks are inadequate for airway maintenance as it is difficult to achieve an effective seal to provide adequate oxygen leading to hypoxaemia, hypercapnia and an inability to achieve positive pressure ventilation in the event of apnoea (wenger et al., 2017). endotracheal tubes have been used successfully in animal practice for many years and when using a technique allowing visualisation of the trachea, are an excellent choice for maintaining a patent airway in rabbit patients. the use of the blind technique can result in mucosal damage and multiple intubation attempts. for those practitioners who are untrained in endotracheal intubation in rabbits, supraglottic devices may be an alternative. there are a range of supraglottic devices available including the rabbit specific v-gel®. both endotracheal tubes and supraglottic airway devices have evidence demonstrating their effective use in maintaining anaesthesia with no significant differences in anaesthetic parameters. all studies used subjects that were healthy and young and with low american society of anesthesiologists (asa) scores and only one study assessed the use of both devices whilst the subjects were undergoing a procedure (comolli et al., 2020). only one study assessed the recovery of patients (crotaz, 2013), and the subjects of two studies were euthanised whilst still under anaesthesia (engbers et al., 2017; and comolli et al., 2020). considering this, it is difficult to extrapolate the findings to rabbits seen in general practice who would be put under anaesthesia for surgical procedures where recovery is an important part of an anaesthetic protocol. rabbit patients may also present with higher asa scores due to age or disease and selection of premedication and induction agents may be limited by clinic protocol, availability of different agents and patient requirements. additionally, no studies looked at dwarf breeds and whether application of a supraglottic device or endotracheal tube was easier or possible given the smaller oral cavity size. majority of studies used new zealand white rabbits as subjects (enbers et al., 2017, comolli et al., 2020, tman et al., 2015; and wenger et al., 2017). this breed is commonly used for research purposes and as such the results of these studies may be more readily applicable in a research setting. crotaz et al. (2010) concluded that the v-gel® supraglottic airway device was simpler to use which is further supported by other studies which demonstrated that the time to place v-gel® was faster, more consistent and required fewer attempts when compared to endotracheal intubation (crotaz, 2010; cruz et al., 2000; engbers et al., 2017; and comolli et al., 2020). as induced patients are at risk of apnoea, the length of time it takes to achieve a patent airway is critical to prevent hypoxaemia (navarrete-calvo et al., 2014). this is even more clinically significant when considering patients in respiratory arrest where fast airway access is imperative. cruz et al. (2000) demonstrated that a significantly higher dose of induction agent, in this case thiopentone, was required to achieve endotracheal intubation than supraglottic device insertion15. however, the studies premedicated and induced their patients with a variety of different agents, including induction chamber or facemask with isoflurane, intravenous administration of thiopentone, propofol, ketamine and xylazine or alfaxalone. the use of different agents could impact the ease or difficulty of the application of different airway devices as would impact sedation quality at induction and the stress levels of each subject. in patients where using less anaesthetic agents would be ideal such as geriatric patients or patients with organ dysfunction, supraglottic devices may be a the better choice if available premedication and inductions drugs at higher dosages increases risk for these patients. power calculations were only undertaken in one study (wenger et al., 2017). as all studies had small sample sizes, it is possible that differences between the groups were only insignificant because there were not enough subjects in each group, resulting in a type 2 error. when comparing mucosal damage to the trachea, engber et al. (2017) found histological evidence of damage to the tracheal mucosa was significantly higher when using an endotracheal tube, whereas comolli et al. (2020) found no significant difference between either device (engbers et al., 2017; and comolli et al., 2020). whilst this could be a type 2 error due to small sample size, it could also be explained by the fact that the engber et al. (2017) study used the blind technique, resulting in multiple intubation attempts and leading to more mucosal damage. there could also be bias in histological scoring. comolli et al. (2020) in contrast visualised the trachea during endotracheal intubation, thus reducing the attempts required to achieve intubation. the wenger et al. (2017) study showed that more attempts were required to place the endotracheal tube than there were with the supraglottic device, which could explain why there was further damage to the oral cavity and tracheal mucosa. use of the blind technique could also increase the risk of oesophageal perforation (ranchère et al., 1992) and this must also be considered as it may have long term effects on patients. long-term recovery was not assessed in these studies; thus, it is not possible to assess whether mucosal damage to the trachea has significance to a patient’s recovery and future health or is clinically significant. other studies have shown that tracheal damage can lead to tracheal strictures which can increase patient morbidity and mortality (grint et al., 2006). bateman et al. (2005) provided good evidence that supraglottic devices could be used successfully in rabbit patients but resulted in gastric tympanism in some cases when positive pressure ventilation was provided. further investigation is warranted to see if gastric tympany has any long-term effects of clinical significance, especially when considering that gut stasis is a common complication of recovery. cruz et al. (2000) by use of barium sulphate as a radiographic contrast directly into the stomach of the subjects concluded that there was no regurgitation present on radiographs following use of endotracheal tubes or supraglottic devices. however, one should note that gastric oesophageal reflux is highly unlikely in rabbits due to their strong cardia preventing backflow of gastric contents. crotaz et al. (2010) and bateman et al. (2005) noted that there was no evidence that the supraglottic v-gel® device would protect against aspiration of fluids and was displaced easily during patient movement, increasing the likelihood of aspiration (bateman et al., 2005; crotaz, 2013; and comolli et al., 2020). dental procedures are common in rabbit patients, and it may be risky to use supraglottic devices without knowing if the seal is adequate to prevent aspiration considering the fluid produced and introduced into the patient’s oral cavity via dental instruments. engbers et al. (2017) used computed tomography (ct) scans to measure the height and width of the larynx, showing that it was significantly narrower in subjects using the v-gel® supraglottic device when compared to the laryngeal mask airway device or facemask. the wenger et al. (2017) study used ct scans to assess the correct placement of the v-gel® supraglottic device where half of the subjects required readjustment with three subjects showing laryngeal compression with increased mucous accumulation. this is an important consideration when using supraglottic devices as narrowing of the larynx due to the device size or mucous accumulation can lead to laryngeal compression which may result in an increased breathing effort as a result of increased airway resistance. considering this, monitoring of respiratory effort when using supraglottic devices is warranted, although the clinical significance of increased breathing effort was not discussed. whilst a device may be effective for spontaneous ventilation, positive pressure ventilation or controlled mechanical ventilation may be required in the event of apnoea. bateman et al. (2005) showed that in four of the six subjects using supraglottic devices, gastric tympany was noted and there was leakage of anaesthetic gas. this suggests whilst controlled mechanical ventilation can be achieved with supraglottic devices, there is leakage into the environment and the alimentary tract, which can make it more difficult to provide adequate ventilation in apnoeic patients. this would also potentiate environmental contamination with the gaseous anaesthetic agent which is an important consideration for the safety of staff and other patients. bateman et al. (2005) suggested that keeping the pressure below 14 cmh2o could mitigate some leakage however, this would likely also decrease alveolar ventilation and lead to hypercapnia. comolli et al. (2020) demonstrated that endotracheal intubation is the most effective device to decrease dead space as supraglottic devices showed higher levels of paco2. however, in the event of unsuccessful endotracheal intubation, supraglottic devices are still superior to facemasks as controlled mechanical ventilation has been shown to lead to much more significant leakage, increased dead space and paco2 in facemasks compared to supraglottic devices (bateman et al., 2005; and wenger et al., 2017). more research is warranted in clinic specific settings to determine the suitability of supraglottic airway devices in rabbit patients. the easier loss of airway seal during movement when using a supraglottic device is not ideal in procedures that require repositioning. they also take up more space in the oral cavity, making them difficult to use in dental procedures, and potentially more difficult to use in smaller breeds. v-gels® do have the benefit of being easily sterilised via autoclave which can reduce bacterial growth and contamination which can be important in patients where respiratory defences are compromised. they may also be easier to apply in rabbit patients, providing an alternative for the practitioner lacking the experience or equipment to perform endotracheal intubation safely. endotracheal intubation is more effective than supraglottic devices in achieving positive pressure ventilation in the case of apnoea and may be a better option for dental procedures as less space is taken up in the oropharynx and the better seal reduces the risk of aspiration. it should be noted however, that the blind technique has a higher risk for mucosal damage and increased likelihood of repeated intubation attempts. the current evidence demonstrates that both devices can be used effectively to maintain anaesthesia in rabbit patients and that the final choice of airway maintenance device should be based on availability of equipment, the training of the practitioner and the procedure to be undertaken. methodology section search strategy databases searched and dates covered: cab abstracts via web of science platform (1973–present) medline via ovid sp (1946–present) search strategy: cab abstracts:  ti=(rabbit or rabbits) and ti=(intubation or supraglottic or endotracheal v-gel or airway) and ts=(anaesthetic or anaesthesia or anesthetic or anesthesia) and la=(english) refined by: research areas: (veterinary sciences) timespan: all years. indexes: cab abstracts.   medline: ((rabbit or rabbits) and (intubation or supraglottic or endotracheal v-gel or airway) and (anaesthetic or anaesthesia or anesthetic or anesthesia)).m_titl. limit 1 to english language dates searches performed: 30 dec 2021 exclusion / inclusion criteria exclusion: articles not relevant to the pico question (not direct comparison of endotracheal intubation and supraglottic devices), article summaries, literature reviews, case reports (provided no comparison as were reports on individual patients), case series (comparison over time not relevant), non-peer reviewed conference proceedings, articles not in english language. inclusion: articles relevant to the pico question (comparisons of endotracheal intubation and supraglottic devices), randomised controlled trials, cohort studies, case control studies, cross-sectional studies, peer-reviewed conference proceedings. search outcome database number of results excluded – case study / report excluded – summary article excluded – not relevant to pico question total relevant papers cab abstracts 36 1 8 22 5 medline 11 1 0 6 4 total relevant papers when duplicates removed 5 conflict of interest the author declares no conflicts of interest. references american society of anesthesiologists. (2020). asa physical status classification system. available at: https://www.asahq.org/standards-and-guidelines/asa-physical-status-classification-system accessed 1 jan 2022. bateman, l., ludders, j.w., gleed, r.d. & erb, h.n. (2005). comparison between facemask and laryngeal mask airway in rabbits during isoflurane anesthesia. veterinary anaesthesia and analgesia. 32(5), 280–288. doi: https://doi.org/10.1111/j.1467-2995.2005.00169.x benito, s., hadley, s., camprubí-camprubí, m. & sanchez-de-toledo, j. (2021). blind endotracheal intubation in neonatal rabbits. journal of visualized experiments. 168. doi: https://doi.org/10.3791/61874 brodbelt, d.c., blissitt, k.j., hammond, r.a., neath, p.j., young, l.e., pfeiffer, d.u. & wood, j.l.n. (2008). the risk of death: the confidential enquiry into perioperative small animal fatalities. veterinary anaesthesia and analgesia. 35(5), 365–373. doi: https://doi.org/10.1111/j.1467-2995.2008.00397.x cook, t.m. (2008). novel airway devices: spoilt for choice? anaesthesia. 58(2), 107–110. doi: https://doi.org/10.1046/j.1365-2044.2003.03047.x comolli, j., schnellbacher, r., beaufrere, h., blas-machado, u., quandt, j., mayer, j. & divers, s.j. (2020). comparison of endoscopic endotracheal intubation and the v-gel® supraglottic airway device for spontaneously ventilating new zealand white rabbits undergoing ovariohysterectomy. veterinary record. 187(10), 84–84. doi: https://doi.org/10.1136/vr.105746 corleta, o., habazettl, h., kreimeier, u. & vollmar, b. (1992). modified retrograde orotracheal intubation technique for airway access in rabbits. european surgical research. 24, 129–132. doi: https://doi.org/10.1159/000129198 crotaz, i.r. (2010). initial feasibility investigation of the v-gel® airway: an anatomically designed supraglottic airway device for use in companion animal veterinary anaesthesia. veterinary anaesthesia and analgesia. 37(6), 579–580. doi: https://doi.org/10.1111/j.1467-2995.2010.00566.x crotaz, i.r. (2013). an observational clinical study in cats and rabbits of an anatomically designed supraglottic airway device for use in companion animal veterinary anaesthesia. veterinary record. 172(23), 606–606. doi: https://doi.org/10.1136/vr.100668 cruz, m.l., sacchi, t., luna, s.p.l., braz, j.r.c. & cassu, r.n. (2000). use of a laryngeal mask for airway maintenance during inhalation anaesthesia in rabbits. veterinary anaesthesia and analgesia. 27(2), 115–116. doi: https://doi.org/10.1046/j.1467-2995.2000.00018-5.x engbers, s., larkin, a., rousset, n., prebble, m., jonnalagadda, m., knight, c.g. & pang, d.s.j. (2017). comparison of a supraglottic airway device (v-gel®) with blind orotracheal intubation in rabbits. frontiers in veterinary science. 4, 49–49. doi: https://doi.org/10.3389/fvets.2017.00049 grint, n.j., sayers, i.r., cecchi, r., harley, r. & day, m.j. (2006). postanaesthetic tracheal strictures in three rabbits. laboratory animals limited. 40(3), 301–308. doi: https://doi.org/10.1258/002367706777611415 kazakos, g.m., anagnostou, t., savvas, i., raptopoulos, d., psalla, d. & kazakou, i.m. (2007). , use of the laryngeal mask airway in rabbits: placement and efficacy. lab animal. 36, 29–34. doi: https://doi.org/10.1038/laban0407-29 manning, p.j., ringler, d.h. & newcomer, c.e. (1994). the biology of the laboratory rabbit. elsevier science & technology, saint louis. navarrete-calvo, r., gómez-villamandos, r.j., morgaz, j., manuel domínguez, j., fernández-sarmiento, a., muñoz-rascón, p., lópez villalba, i. & del mar granados, m. (2014). cardiorespiratory, anaesthetic and recovery effects of morphine combined with medetomidine and alfaxalone in rabbits. veterinary record. 174(4), 95–95. doi: https://doi.org/10.1136/vr.101293 phaneuf, l.r., barker, s., groleau, m.a. & turner, p.v. (2006). tracheal injury after endotracheal intubation and anesthesia in rabbits. journal of the american association for laboratory animal science. 45(6), 67–72. doi: https://pubmed.ncbi.nlm.nih.gov/17089996/ ranchère, j.y., gordiani, b., lupo, c., serror, p.m. & bobin, j.y. (1992). oesophageal perforation during an endotracheal intubation attempt. annales françaises ’d’anesthésie et de réanimation. 11(1), 100–102. doi: https://doi.org/10.1016/s0750-7658(05)80326-0 thompson, k.l., meier, t.r. & scholz, j.a. (2017). endotracheal intubation of rabbits using a polypropylene guide catheter. journal of visualized experiments. 129. doi: https://doi.org/10.3791/56369 toman, h., erbas, m., sahin, h., kiraz, h.a., uzun, m. & ovali, m.a. (2015). comparison of the effects of various airway devices on hemodynamic response and qtc interval in rabbits under general anesthesia. journal of clinical monitoring and computing. 29, 727–732. doi: https://doi.org/10.1007/s10877-015-9659-x tran, h.s., puc, m.m., tran, j.l.v., del rossi, a.j. & hewitt, c.w. (2001). a method of endoscopic endotracheal intubation in rabbits. laboratory animals limited. 35(3), 249–252. doi: https://doi.org/10.1258/0023677011911705 wenger, s., müllhaupt, d., ohlerth, s., prasse, s., klein, k., da silva valenta, b. & mosing, m. (2017). experimental evaluation of four airway devices in anaesthetized new zealand white rabbits. veterinary anaesthesia and analgesia. 44(3), 529–537. doi: https://doi.org/10.1016/j.vaa.2016.05.009 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in small animal surgery are alcoholic hand rubs superior to scrubbing brushes and antimicrobial soap at reducing bacterial counts? a knowledge summary by alison mann bsc (hons), dip he cvn, dip avn (small animal), rvn1 1university of bristol, senate house, tyndall ave, bristol bs8 1th *corresponding author (alison.mann@bristol.ac.uk) vol 1, issue 4 (2016) published: 26 oct 2016 reviewed by: victoria arbona (dvm, ms) and louise buckley (bsc hons, ba hons, pg cert (tlhep), pgdip, phd, rvn) next review date: 26 oct 2018 doi: 10.18849/ve.v1i4.51 clinical bottom line the current literature suggests that the use of alcohol hand rubs provide similar, if not better, reductions in bacteria colony forming units, both immediately after hand antisepsis and in the immediate postoperative period. question in small animal surgery are alcoholic hand rubs superior to scrubbing brushes and antimicrobial soap at reducing bacterial counts? the evidence the majority of the literature found was author narrative or looking at the current attitudes and habits that veterinary surgeons have regarding surgical hand preparation. two relevant papers were found comparing alcohol hand rubs (ahrs) to traditional methods of hand preparation. they differed slightly in that the first paper did not use an abrasive brush in any of the regimes; it only looked at alcohol in different formulations against antimicrobial soap. the second paper did look at the traditional hand scrub with a brush and antimicrobial soap as one of the comparisons. many human studies were found, with a number of them having relevance in all areas of the pico question apart from the population, so these were excluded. summary of the evidence chou (2016) population: 3rd year veterinary students sample size: 45 intervention details: the participants were randomly assigned to carry out 4 of the 12 possible combinations: non-abrasive hand scrub with 4% chlorhexidine gluconate (chg) antimicrobial soap ahr with 30% 1-propanol and 45% 2 –propanol ahr with 70% 2 –propanol ahr with 61% ethanol solution with 1% chg all the above products could have had any one of the below contact times thus making 12 possible combinations 1.5, 3 or 5 minutes. using shuffled cards the participants were assigned 4 of the possible 12 combinations study design: prospective randomised controlled outcome studied: to compare the antibacterial efficacy of different surgical hand antisepsis protocols used by veterinary students both at the recommended and at extended contact times antibacterial efficacy was assessed before surgical hand preparation, after surgical hand preparation and at the end of surgery. reductions in bacterial colony forming units and positive aerobic culture rates were compared using multivariable analysis or variance and multivariable logistic regression. main findings (relevant to pico question): after hand preparation the ahr with 61% ethanol/1% chg and the chg non abrasive antimicrobial soap scrubs were more effective at reducing log colony forming units (cfus) when used at the manufacturer recommended contact time. increasing contact time for any of the products did not have an effect on bacterial reduction immediately after hand preparation at the end of surgery, the product used, the contact time and the product/ contact time interaction all had effects on cfu reductions at the end of surgery, the ahr with 61% ethanol/ 1% chg and the ahr with 30% 1-propanol and 45% 2propanol had significantly increased bacterial reductions with increasing contact time at the end of surgery, at the manufacturer recommended contact time the ahr with 61% ethanol/ 1% chg had significantly higher cfu reduction compared to the ahr with 70% 2-propanol limitations: authors and participants not blinded to the products used or the contact time. veterinary students may not be as experienced in the methods of pre-surgical hand preparation. there were guidelines, however there was likely to be some variability between participants. there was some variability between surgical times (57-255 mins) which may have affected the final samples taken. however, in the discussion it is stated that the average surgery time was relatively short there was no comparison with an abrasive scrubbing brush; the scrubbing method used a sponge as opposed to a brush. verwilghen (2011) population: small animal and equine surgeons sample size: 3 equine and 2 small animal surgeons. a total of 64 samples were obtained for ahrs (sterilium) (50 equine, 14 small animal) and 30 obtained for antimicrobial soap (chg) (20 equine, 10 small animal). intervention details: a preliminary study was carried out comparing povidone iodine (pvp), chg and sterilium. following this preliminary study it was found that the actions of the pvp were not comparable to the others and so the clinical in use study was carried out only using chg and sterilium. sample sizes are discussed above.  the chg was used in a 5 minute scrubbing technique and the sterilium was used according to manufacturer’s instructions at 1.5 minutes after a 1 minute’s hand wash with neutral soap. fingertips were pressed for 10 seconds onto a blood agar plate (separate for each hand) and bacterial growth was quantified by counting the cfus grown after 24 hours of incubation. this was performed prior to hand antisepsis, immediately after hand antisepsis and after surgery during which the surgeon was double gloved (the first pair discarded after draping the patient). mean surgery time was 1.5 hours. study design: clinical trial outcome studied: to compare ahrs to chg in a surgical setting main findings (relevant to pico question): a preliminary study was carried out comparing pvp, chg and sterilium and found that pvp was not comparable to the other 2 products and so this was not taken forward into the further study. 4 sterilium samples were excluded due to contamination during surgery, 1 was excluded due to an infected wound by the nail of one of the surgeons creating an extreme growth of staphylococcus aureus. prior to hand antisepsis samples were significantly different to after hand antisepsis and after surgery samples for both products. no difference was found in cfus between after hand antisepsis and after surgery samples for sterilium. the clinical in use trial found that there was a significantly greater reduction factor for the sterilium compared to chg. the results of this study agreed with previous studies carried out in this area (parienti et al 2002; kampf and osteomeyer, 2005; loffler and kampf, 2008 and tanner et al 2008). limitations: residual activity of chg is difficult to assess without the use of a neutralising agent as bacteriostatic concentrations of the chg will remain. the decision was made to not use a neutralising agent as it wasn’t used in similar studies. more than double the amount of samples were gained for the sterilium group, although some of these did have to be discarded. appraisal, application and reflection two relevant studies were found for this particular pico question, which both conclude that alcohol is as effective, if not more, than antimicrobial soap for pre surgical hand preparation when used according to the manufacturer guidelines. the ahrs used in the 2 studies, however, was of different formulations. in the first study (chou et al, 2016) there were 2 formulations of alcohol used: propanol (of different strengths) and alcohol with chg, of which the alcohol with chg was found to be the most effective. in the second study (verwilghen et al 2011) the only alcohol formulation used was propanol (sterilium). the pico question only specifies ahrs rather than particular formulations so both studies are relevant.  another difference between the studies was that chou et al (2016) did not use an abrasive method of hand scrubbing as one of the comparisons; their non-abrasive scrub method was with the use of a sponge rather than bristles. as the pico question in this instance was asking for a comparison between scrubbing brushes and ahrs there are some discrepancies between this and the pico question, but the decision was made to include it. verwilghen et al (2011) did use the more traditional surgical scrub with a brush as one of their variables, making it very suited to the pico question. on reflection, whether in human or veterinary surgery, the end point of pre-surgical hand antisepsis is the same; to have reduced bacterial colony forming units on the hands. the author therefore feels that a future knowledge summary with a slight change to the pico to include human surgery would still be relevant to veterinary professionals to draw evidence from. methodology section search strategy databases searched and dates covered: pubmed and cab abstracts 1973-2016 week 29 search terms: small animal or veterinary surgery or companion animal or (cats or cats or feline or felis or dogs or dog or canis or canine) or small animal surgery and (chlorhexidine gluconate or povidone iodine or antimicrobial soap) or scrubbing brush or (hand and scrub*) or scrub and (alcohol rub or alcoholic rub or ethanol or propanol) or (hand and rub) or rub* dates searches performed: 6/8/2016 cab abstracts 5/10/16 pubmed exclusion / inclusion criteria exclusion: large/farm animal studies, human studies, narrative reviews, any studies on skin preparation of patients as opposed to the surgeon, any studies that are not relevant to the pico question inclusion: small animal/companion animal studies comparing the 2 hand preparation techniques search outcome database number of results excluded – narrative excluded – not relevant to the pico excluded – human study excluded – duplicate excluded – large animal study total relevant papers cab direct 19 1 18 0 0 0 1 ncbi pubmed 554 0 542 11 1 1 1 total relevant papers when duplicates removed 2 conflict of interest the author declares no conflicts of interest. references chou, p. et al (2016) antibacterial efficacy of several surgical hand preparation products used by veterinary students. veterinary surgery, 45 (4) pp. 515-522 http://dx.doi.org/10.1111/vsu.12473 kampf, g. and osteomeyer, c. (2005) efficacy of two distinct ethanol based hand rubs for surgical hand disinfectiona controlled trial according to pren 12791. bmc infectious diseases, vol 5 (19). http://dx.doi.org/10.1186/1471-2334-5-17 loffler, h. and kampf, g. (2008) hand disinfection: how irritant are alcohols? journal of hospital infection, 70 (s1) pp. 44-48 http://dx.doi.org/10.1016/s0195-6701(08)60010-9 parienti, j. j. et al (2002) hand rubbing with an aqueous solution vs traditional surgical hand scrubbing and 30 day surgical site infection rates: a randomised equivalence study. journal of the american medical association, 288 (6) pp. 722-727 http://dx.doi.org/10.1001/jama.288.6.722 tanner, j., swarbrook, s. and stuart, j. (2008) surgical hand antisepsis to reduce surgical site infection. [cochrane database systematic review] [online]. available from:  http://onlinelibrary.wiley.com/doi/10.1002/14651858.cd004288.pub2/full doi http://dx.doi.org/10.1002/14651858.cd004288.pub2 [accessed 1 october 2016] verwilghen, d. r. et al (2011) surgical hand antisepsis in veterinary practice: evaluation of soap scrubs and alcohol based rub techniques. the veterinary journal, 190 (3) pp. 372-377 http://dx.doi.org/10.1016/j.tvjl.2010.12.020 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. a comparison of gonadotropin-releasing hormone and human chorionic gonadotropin in dairy cows with ovarian follicular cysts a knowledge summary by katy kesler dvm ms 1* grace longcore dvm 1 alex russell dvm 1 1michigan state university college of veterinary medicine, 736 wilson rd., east lansing, mi 48824, usa *corresponding author (keslerka@msu.edu) vol 7, issue 2 (2022) published: 21 apr 2022 reviewed by: john campbell (dvm dvsc) and jonathan statham (ma vetmb dchp frcvs) next review date: 20 dec 2023 doi: 10.18849/ve.v7i2.509 pico question in adult dairy cows with ovarian follicular cysts, does treatment with gonadotropin-releasing hormone (gnrh) compared to human chorionic gonadotropin (hcg) result in a more rapid return to cyclicity?   clinical bottom line category of research question treatment the number and type of study designs reviewed the publications consisted of six non-blinded randomised comparative or controlled trials strength of evidence weak outcomes reported recovery time, clinical cure, and interval to conception were consistently evaluated. many studies also evaluated other fertility parameters such as first estrus or first treatment conception, overall pregnancy and conception risks, and breedings per conception conclusion at this time, there is insufficient evidence to suggest whether gnrh or hcg is more efficacious for treating ovarian follicular cysts in dairy cattle. ultimately, further research is essential to elucidate which treatment results in a more rapid return to cyclicity for dairy cattle afflicted with cystic ovarian follicles   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario cystic ovarian disease (cod) has been reported to occur at an incidence of between 6% and 30% of dairy cattle and is generally accepted as a common cause of reproductive failure in the dairy cow (silvia et al., 2002; ono et al., 2018; de rensis et al., 2008; and kesler & garverick, 1982). cystic ovarian disease is the presence of an anovulatory follicle ≥25 mm in diameter that persists for a minimum of 10 days in the absence of a functional corpus luteum (cl) (ono et al., 2018; de rensis et al., 2008; garverick, 1997; and kesler & garverick, 1982). there are predominantly two classifications of ovarian cysts, follicular and luteal, distinguishable by the presence or absence of luteal tissue and circulating progesterone concentrations (jeengar et al., 2014).  cystic ovarian follicles have been reported to extend the calving interval by 20–64 days and, therefore, are of great economic importance to dairy producers (silvia et al., 2002; and de rensis et al., 2008). moreover, the economic impact that results from the labour required for treatment and exogenous hormonal therapy for return to cyclicity cannot be overlooked. many reports utilise exogenous hormones such as gonadotropin-releasing hormone (gnrh) and human chorionic gonadotropin (hcg) for cyst luteinisation (gundling et al., 2015 rizzo et al., 2011; kawate et al., 2011; and nakao et al., 1980). this knowledge summary will address the question about which luteinising hormone results in a faster return to cyclicity. you are a veterinarian performing routine herd health utilising ultrasound on a commercial dairy in the usa. the producer mentions that they are experiencing a high number of cystic cows on herd check. this producer asks you for recommendations regarding treating these cows; specifically, they want to get these cows cycling as quickly as possible. the evidence the literature search elicited six publications that met our criteria for inclusion. the six publications consisted of five randomised non-blinded comparative or controlled trials of level 3 (lower quality controlled trials [howick et al., 2011]), (taktaz et al., 2015; mollo et al., 2012; garverick et al., 1976; elmore et al., 1975; and nakao et al., 1992) and one randomised controlled trial of level 2 (well-designed controlled trial [howick et al., 2011]), (verma & dabas, 1994). additionally, many articles did not compare gnrh and hcg treatments directly or did not utilise time as a metric for evaluation and thus were excluded from this knowledge summary. dairy cattle were used in all of the evaluated articles, with 1/6 studies involving holsteins, 2/6 studies involving crossbred cattle, 1/6 studies involving friesians, and 2/6 studies involving guernsey and holstein cattle. all articles involved classification of ovarian follicular cyst size and persistence of at least one week; three articles evaluated cattle for the presence of luteal tissue either utilising ultrasound (taktaz et al., 2015) or progesterone assays (garverick et al., 1976; and nakao et al., 1992). cystic ovarian follicles were treated in all of the articles with gnrh and hcg therapy. the number of cows in each study ranged from relatively small studies with 20 cows to moderately sized comparisons, with 150 cows. the number of cows allocated for each treatment was highly variable per study ranging from 3–70 animals. three studies had large treatment groups (30–70 animals per treatment) (mollo et al., 2012; taktaz et al., 2015; and elmore et al., 1975), 1/6 studies had moderately sized treatment groups (17–18 animals per treatment) (nakao et al., 1992), and 2/6 had very small treatment groups (10 animals per treatment) (verma & dabas,1994; and garverick et al., 1976). clinical cure (return to oestrus or cyst luteinisation), first oestrus conception, and interval to conception were consistently evaluated in the vast majority of studies. additionally, many studies evaluated parameters such as recovery time, overall conception risk, pregnancy risk, breedings per conception, and interval to insemination. in studies utilising a negative control group with no treatment, there was no significant difference in clinical response or subsequent fertility between gnrh and hcg, while both therapies outperformed the control group (verma & dabas, 1994). a higher percentage of animals treated with gnrh responded after one treatment than hcg; however, there were no significant differences in the number of animals that responded to either treatment or how quickly they responded to each treatment (verma & dabas, 1994). in studies that evaluated clinical cure as a return to oestrus, there were mixed results, with two studies showing hcg was more effective (mollo et al., 2012; and garverick et al., 1976) and two studies showing gnrh had more favourable results (verma & dabas, 1994; and elmore et al., 1975). one study evaluated clinical cure as luteinisation of the cystic ovarian follicle (cof), and they found that hcg luteinised (14/17, 82.3%) 21.2% more cows than gnrh (11/18, 61.1%) (nakao et al., 1992). articles that studied interval to conception resulted in contradictory evidence, with two studies finding hcg treatment protocols required fewer days to conception (taktaz et al., 2015; and nakao et al., 1992) and two studies finding that gnrh had a shorter interval to conception (garverick et al., 1976; and elmore et al., 1975). five out of six studies evaluated recovery time as days to first oestrus, and while there were no biologically or statistically significant differences, the majority of articles found that hcg required fewer days to first oestrus than gnrh treatment (taktaz et al., 2015; mollo et al., 2012; and elmore et al., 1975), although one article had conflicting results (garverick et al., 1976). verma & dabas (1994) listed their responses as a range of days to first oestrus for each treatment, and there was significant overlap between the gnrh treatment (15–30 days) and hcg treatment (17–31 days). henceforth, there is still much research that needs to be conducted as to which treatment induces a more rapid return to cyclicity in dairy cattle with cod. many studies evaluated additional fertility parameters such as conception after first treatment or artificial insemination (ai), overall pregnancy or conception risks, and breedings per conception. studies that evaluated conception after the first treatment or first ai had mixed results, with two articles indicating that hcg resulted in higher conception (taktaz et al., 2015; and mollo et al., 2012) and three articles suggesting gnrh had higher conception risks (verma & dabas, 1994; elmore et al., 1975; and nakao et al., 1992). when overall pregnancy risk was evaluated, taktaz et al. (2015) at 70 days post treatment and mollo et al. (2012) at 7 weeks post ai, found that hcg resulted in higher pregnancy risks; however, at 100 days, the taktaz et al. (2015) group found that gnrh had a higher pregnancy risk. moreover, when overall conception risk was evaluated, two groups found hcg to be more favourable (elmore et al., 1975; and nakao et al., 1992), while one group found gnrh to result in a higher conception risk (garverik et al., 1976). lastly, two studies evaluated the number of breedings per conception, while insignificant, both found that hcg treatment required more breedings per conception than gnrh treatments (garverick et al., 1976; and elmore et al., 1975). summary of the evidence mollo et al. (2012) population: cystic friesian cows diagnosed with follicular structures > 25 mm, persistent for > 7 days, in the absence of a corpus luteum. sample size: n = 150. intervention details: group 1: 20 ug gonadotropin-releasing hormone (gnrh) (n = 70). group 2: 3,000 international units (iu) human chorionic gonadotropin (hcg) (n = 50). group 3: progesterone releasing intravaginal device for 10 days (n = 30). all animals were checked twice daily for oestrus. cows were artificially inseminated 12 hours after oestrus detection. study design: prospective non-blinded, randomised controlled trial. outcome studied: cure rate: the ratio between cows in oestrus within 30 days post-treatment and treated cows. recovery time: the time between treatment and standing oestrus. first oestrus conception rate (pregnant cows / inseminated cows). overall pregnancy rate (pregnant cows / treated cows). main findings (relevant to pico question): no statistical differences were found between cure rates, conception rates, and overall pregnancy rates.  cure rates* (%): 64.3, 66.0, and 63.3; conception rates* (%): 45.2, 47.8, and 46.2; pregnancy rates* (%): 20.0, 22.0, and 20.0; recovery time* (days ± confidence interval [ci]) 17.9 ± 3.1, 17.7 ± 3.2, 19.7 ± 4.7. *for groups 1,2, and 3 respectively. limitations: long study window (4 years): weather variation; protocol drift. animals were only observed twice daily for oestrus detection. taktaz et al. (2015) population: lactating holstein dairy cattle (35–120 days in milk), diagnosed with ovarian cysts > 25 mm and ultrasonically classified as follicular or luteal. sample size: n = 144. intervention details: group 1 (n = 47): day 0: 0.02 mg gonadotropin-releasing hormone (gnrh) (buserelin); day 10: 500 ug prostaglandin f2α (pgf2α) (cloprostenol). group 2 (n = 47): day 0: 0.02 mg gnrh (buserelin) and 500 ug pgf2α (cloprostenol): day 10: 500 ug pgf2α (cloprostenol). group 3 (n=50): day 0: 1500 iu human chorionic gonadotropin (hcg) (chorulon);and 500 ug pgf2α (cloprostenol); day 10: 500 ug pgf2α (cloprostenol). all cattle were artificially inseminated 12 hours after the onset of oestrus. study design: prospective non-blinded, randomised controlled trial. outcome studied: recovery time. interval to conception. conception rate at first artificial insemination (ai). pregnancy rate by day 70 and day 100. main findings (relevant to pico question): no statistical differences were found between groups for recovery time, interval to conception, conception rate at first ai, and pregnancy rate by days 70 and 100: recovery time* (days ± confidence interval [ci]): 18.1 ± 1.5, 16.7 ± 1.5, 15.4 ± 1.4; interval to conception* (days ± ci): 55.9 ± 8.2, 76.1 ± 13.3, 57 ± 7.3; conception rate* (%): 45.4, 34.5, 44.4; pregnancy rate by day 70* (%): 78.8, 69, 69.4; pregnancy rate by day 100* (%): 81.8, 75.9, 75.0. *for groups 1, 2 and 3 respectively with follicular cysts. limitations: the majority of cysts diagnosed in this study were follicular cysts (98/144, 68%), with substantially less luteal cysts (46/144, 32%); pgf2α has been reported to be less efficacious for follicular cysts. this may have impacted the response to treatment for groups who received pgf2α on day 0 (groups 2 and 3). verma & dabas (1994) population: crossbred cattle with confirmed cystic ovarian disease (semiweekly rectal palpation for 1 month) with a history of irregular oestrus and persistently enlarged cysts on ovaries. sample size: n = 21. intervention details: gonadotropin-releasing hormone (gnrh) group (n = 8): 200 mcg gnrh (receptal). human chorionic gonadotropin (hcg) group (n = 10): 3000 iu hcg (chorulon). control group (n = 3): sterile saline. all cattle were evaluated behaviourally and via transrectal palpation starting 3 days post-treatment for response to therapy. all animals with a positive response to therapy were subsequently artificially inseminated. study design: prospective non-blinded, randomised controlled trial. outcome studied: a positive response to therapy was recorded if normal oestrus cycle followed or subsequent conception. a negative response to therapy was recorded if no change in cyst structure was observed. main findings (relevant to pico question): 5/10 (50%) of animals treated with hcg showed normal oestrus within 17–31 days: all five animals were artificially inseminated and successfully conceived. 5/8 (62.5%) of animals treated with gnrh showed normal oestrus within 15–30 days: all five animals were artificially inseminated and successfully conceived. no change was observed in the control group. limitations: small sample size. cysts were classified as follicular cysts based on rectal palpation and irregular oestrus, which is less accurate than progesterone assays or ultrasound classification. confidence intervals were unavailable. elmore et al. (1975) population: 69 holstein, 15 guernsey cattle diagnosed with at least one ovarian cyst 2.5 cm or larger via rectal palpation. sample size: n = 84. intervention details: gonadotropin-releasing hormone (gnrh) group (n = 43): 100 mcg gnrh. human chorionic gonadotropin (hcg) group (n = 41): 10,000 iu hcg. all cattle had their ovaries examined via rectal palpation 14 days post-treatment for response to therapy; if a change was noted or suspected animals were reexamined within two weeks. study design: prospective non-blinded, randomised controlled trial. outcome studied: a positive outcome was recorded if subsequent oestrus behaviour and fertility were observed. a negative outcome was recorded if no changes in the site, size, or character of the cyst(s) were observed. main findings (relevant to pico question): no statically significant differences were found between groups. more cows treated with gnrh had a positive outcome (34/43, 79%) than those treated with hcg (28/41, 68%). cows treated with hcg had a faster onset of oestrus at 19.7 ± 3.4 (days ± ci) versus cows treated with gnrh 21.2 ± 3.3 (days ± ci).  cows treated with gnrh required fewer breedings (1.4 ± 0.7 per conception) and fewer days to conception (37.4 ± 4.9) as compared to those treated with hcg (1.8 ± 0.9 and 47.8 ± 5.6, respectively). limitations: no attempt was made to differentiate between follicular and luteal cysts. garverick et al. (1976) population: holstein and guernsey cattle were diagnosed with at least one smooth, fluctuant, round structure 2.5 cm in diameter minimally on one or both ovaries. sample size: n = 20. intervention details: gonadotropin-releasing hormone (gnrh) group (n = 10): 100 mcg gnrh. human chorionic gonadotropin (hcg) group (n=10): 10,000 iu hcg. all cattle were observed for oestrus behaviour, blood samples were collected, and rectal palpation was performed every 4 days post-treatment until oestrus for up to 30 days. blood samples were collected, and rectal palpations were performed on days 0, 1, 5, 9, and 13 post-oestrus. study design: prospective non-blinded, randomised controlled trial. outcome studied: a positive outcome was recorded if the animal established a normal oestrus cycle or conceived. a negative outcome was recorded if no change was observed in the character, size, or location of the cyst within a 2–4 week period. main findings (relevant to pico question): differences in clinical response and subsequent fertility between gnrh and hcg treated cattle were not significantly different. more cattle positively responded to hcg treatment (9/10, 90%) than gnrh treatment (8/10, 80%). more days from treatment to first oestrus were seen with hcg treatment (20.5 ± 0.6 days) than gnrh treatment (17.8 ± 2.4 days). cattle treated with hcg required more services per conception (3.5 ± 0.6) and had more days from treatment to conception (91 ± 23 days) than gnrh treated cattle (2.7 ± 0.2 and 59.7 ± 9 days, respectively). limitations: small sample size. changes in ovarian structures were detected via rectal palpation; ultrasound is more accurate for detecting changes in ovarian structures. nakao et al. (1992) population: crossbred dairy cattle were diagnosed with persistent ovarian cysts at least 2.5 cm in diameter (two successive rectal palpations 7 days apart) and no functional luteal tissue as confirmed by retrospective milk progesterone analysis. sample size: n = 57, post progesterone exclusion n = 35. intervention details: gonadotropin-releasing hormone (gnrh) group (n = 18): 20 mcg gnrh (buserelin). human chorionic gonadotropin (hcg) group (n=17): day 0: 10,000 iu hcg (gestron). all cattle were transrectally palpated 10–14 days post-treatment; animals with luteinised cysts were artificially inseminated when they came into oestrus. study design: prospective non-blinded, randomised controlled trial. outcome studied: milk progesterone concentration indicative of luteinisation. oestrus behaviour. conception following artificial insemination. main findings (relevant to pico question): more cattle treated with hcg (14/17, 82.3%) successfully responded to treatment than cattle treated with gnrh (11/18, 61.1%). there were more days from treatment to luteinisation with hcg treatment (5 ± 2, days ± standard deviation (sd)) than gnrh treatment (4 ± 2, days ± sd). there were more days from treatment to conception with gnrh treatment (36 ± 14 days) than hcg treatment (31 ± 7 days). more cattle conceived after the first treatment with the gnrh treatment (7/18, 38.9%) than hcg treatment (5/17, 29.4% cows). days from treatment to conception were equivocal, 42 ± 18 days regardless of treatment. limitations: animals with luteal cysts were retrospectively excluded utilising a progesterone assay; if this would have been performed before enrollment or ultrasound was utilised in conjunction, the authors may have been able to increase enrollment. appraisal, application and reflection ovarian follicular cysts are a common reproductive problem in the dairy industry, affecting approximately 6–30% of dairy cows (silvia et al., 2002; ono et al., 2018; de rensis et al., 2008). however, the incidence of follicular cysts is likely underestimated, as 60% of the cysts that form before the first ovulation after freshening resolve without intervention (ijaz et al., 1987; jeengar et al., 2014; kesler & garverick, 1982). an ovarian follicular cyst has been described as a follicle that is 25 mm or larger in diameter and is persistent for at least 10 days in the absence of a cl (garverick, 1997; ono et al., 2018; de rensis et al., 2008; kesler and garverick, 1982). follicular cysts have been shown to add approximately 20 to 64 days to a dairy cow's open period (silvia et al., 2002; de rensis et al., 2008). resulting in a significant negative economic impact for dairy producers, as a delay in conception leads to decreased milk yield, and resolution of the cyst often requires the expense of veterinary treatment. the cause of ovarian follicular cysts is currently unknown (vanholder et al., 2006, amweg et al., 2013). there are several different treatment options for ovarian cysts, including manual rupture, aspiration, and hormonal injection.  exogenous hormones are the most commonly used and successful form of treatment (gundling et al., 2015 rizzo et al., 2011, kawate et al., 2011). recently, manual rupture has become controversial due to results indicating that it may cause ovarian trauma that leads to the development of harmful haemorrhage and adhesions that can reduce fertility (jeengar et al., 2014). many reports argue the beneficial effects of gonadotropin-releasing hormone (gnrh) and human chorionic gonadotropin (hcg) for treating ovarian luteal and follicular cysts (taktaz et al., 2015). in addition, prostaglandin-f2α (pgf2α) has been shown to be effective against luteal cysts but not for follicular cysts. it is difficult to accurately determine whether a cyst is follicular or luteal by rectal palpation, and while accuracy is improved via ultrasound, progesterone assays remain the most definitive way of differentiating luteal and follicular cysts (taktaz et al., 2015; farin et al., 1992; jeengar et al., 2014). given the difficulty of distinguishing luteal and follicular cysts, taktaz et al. (2015) suggested utilising a combination of pgf2α and either gnrh or hcg to treat cod. however, taktaz et al. (2015) did not find this combination therapy beneficial in shortening recovery time, interval to conception, conception risk, or pregnancy risk. determining the most effective treatment method for ovarian follicular cysts is of utmost importance to dairy producers and veterinarians. the purpose of this knowledge summary is to evaluate the evidence comparing the length of time to return to ovarian cyclicity with the treatment of either gnrh or hcg. the literature review resulted in six studies that met the inclusion criteria. cystic ovarian follicles were identified utilising transrectal ultrasound or transrectal palpation. mollo et al. (2012) evaluated recovery time, defined as the number of days between treatment and standing oestrus. cattle were treated with gnrh (20 µg), hcg (3000 iu), or progesterone (1.55 g progesterone releasing intravaginal device for 10 days). however, the hcg group outperformed alternative treatments in every category (cure risk, pregnancy risk, and recovery time); no statistical or biologically significant differences were detected (mollo et al., 2012). these results are further supported by taktaz et al. (2015), who reported an insignificant 1.6 day reduction in recovery time with hcg (1500 iu) compared to conventional treatment (gnrh analogue) in cows with follicular cysts. however, previous literature has suggested conflicting results, with garverick et al. (1976) indicating cattle treated with gnrh had a substantially shorter interval to conception (59.7 ± 9 vs 91 ± 23 days) and required 2.7 fewer days from treatment to first oestrus or ovulation when compared to hcg treatment. additionally, a recent study has suggested that cattle treated with hcg ovulate significantly later than cattle treated with gnrh, 4.9 hours on average regardless of dioestrus periods (liu et al., 2019). moreover, elmore et al. (1975) found that cattle treated with hcg required 1.9 fewer days from treatment to first oestrus; however, the interval from treatment to conception was 10.4 days longer than their gnrh-treated counterparts. this may be partially due to the fact that hcg-treated cattle, on average, required more breedings per conception than the gnrh-treated group. henceforth, there is still much debate amongst the scientific community on which treatment induces a more rapid return to cyclicity in dairy cattle afflicted with cod. it has been suggested that low-circulating progesterone concentrations may have a role in the pathogenesis of cofs due to the role of progesterone in regulating the effects of oestradiol (wiltbank et al., 2002). understandably, many publications have investigated luteal profiles (progesterone concentrations and cl diameter), the number of cl present on the ovary, circulating progesterone concentrations, as well as the effects of hcg and gnrh on follicular luteinisation. there was no clear consensus on the effects of hcg and gnrh on the aforementioned parameters. while two articles suggested that there was no significant difference in circulating progesterone concentrations (yotov et al., 2014 nakao et al., 1980), another article indicated that cattle treated with hcg (3000 iu) had significantly higher plasma progesterone levels suggesting that hcg may be more effective at luteal phase induction (singh et al., 2012). moreover, singh et al. (2012) found that post-ai luteal profiles were significantly more favourable in hcg treated cattle; it was proposed that this could be the result of elevated pre-conception plasma progesterone concentrations. the efficacy of gnrh and hcg in treating bovine ovarian follicular cysts should be further evaluated with more controlled studies. most of the articles found during the literature review for this knowledge summary were small studies that did not include a control group receiving no therapeutics in the study design. further analysis to ensure that spontaneous resolution of ovarian cysts that occur naturally are accounted for in the study design or with statistical modeling would be beneficial; since the rate of spontaneous cure has been reported to be as high as 60% in fresh cows that have not yet ovulated (ijaz et al., 1987; jeengar et al., 2014; kesler and garverick, 1982). some articles achieved this by comparing the proportion of animals in each treatment group relative to their days in milk (dim), suggesting that if proportions of cows less than 40 dim were equivocal, then the spontaneous cure rates should not be impacting results (taktaz et al., 2015). moreover, a network analysis comparing the efficacy of treatment methods may be beneficial. however, due to the heterogeneity of the studies identified, at this time, the treatments are unequivocal, and network analysis cannot be performed (lean et al., 2009). for example, many studies were excluded as they did not directly compare gnrh and hcg treatments; nakao et al. (1979) performed a small crossover trial where animals were enrolled in subsequent treatment groups when they failed to respond to previous therapy, making it challenging to differentiate subsequent treatment failures from individual differences in fertility. to provide more guidance for the clinical recommendation and treatment of ovarian follicular cysts, the route of administration of the chosen therapeutics should also be further investigated. rizzo et al. (2011) compared the intramuscular and epidural use of lecirelin, a gnrh analogue, to treat bovine ovarian follicular cysts. they found that epidural administration of lecirelin in cows with follicular cysts resulted in a higher percentage of cows returning to oestrus than those cows which received an intramuscular injection of lecirelin (rizzo et al., 2011). this effect was attributed to the action of lecirelin on gnrh receptors in the spinal cord and ovary, and possibly on the pituitary gland directly through the epidural canal (rizzo et al., 2011). these findings support the possibility of further improvements in the treatment of bovine ovarian follicular cysts by altering existing treatment methods. moreover, studies to determine the safest and most efficacious dose of hcg may also be beneficial. among the studies in this knowledge summary, the dose of hcg administered to cows with ovarian follicular cysts ranged from 1,500 iu (taktaz et al., 2015) to 3,000 iu (mollo et al., 2012; verma & dabas, 1994; garverick et al., 1976; nakao et al., 1992) to as high as 10,000 iu hcg (elmore et al., 1975). other reports have published dosages ranging from 500 iu (yotov et al., 2014 to 20,000 iu (nakao et al., 1979). human chorionic gonadotropin has a high molecular weight and carbohydrate content and thus can lead to the production of hcg antibodies and anaphylaxis in cattle (de rensis et al., 2010; giordano et al., 2012). to decrease the likelihood of administering an excessive amount of hcg and causing an immune response, the minimum effective dose should be established to guide future treatment plans. alternatively, treatment with hcg may be divided into multiple smaller doses of hcg, as this has been shown to be equally effective as a single large dose in modulating ovarian follicular development in dairy cows with cystic ovarian follicles (ono et al., 2018). as a final note, it was indicated in the literature that hcg, which historically was the treatment of choice for cod and for unknown reasons, became challenging to acquire and cost-prohibitive for producers (seguin et al., 1976). seguin et al. (1976) suggested cost increases were due to challenges in obtaining hcg as it is isolated from pregnant women's urine and speculated that the synthetic molecule gnrh would provide a more cost-effective and stable supply chain (seguin, 1976). moreover, ngategize et al. (1987) found that it was more economical to treat cattle with gnrh than with hcg; however, both treatment options were found to be more economically advantageous than no treatment or spontaneous resolution (ngategize et al., 1987). this conclusion was based on assumptions that gnrh resulted in the more successful resolution of cof, cost less than hcg, but required a longer recovery (ngategize et al., 1987). regardless, ngategize et al. (1987) suggest that days to first oestrus (recovery time) would need to decrease by 50% for hcg to compete out gnrh therapy (ngategize et al., 1987). in conclusion, at this time, there is insufficient evidence to suggest whether gnrh or hcg is a more efficacious treatment for ovarian follicular cysts, and further research is required to elucidate which treatment results in a more rapid return to cyclicity for cattle afflicted with cystic ovarian follicles. without additional evidence when considering practical implementation in field conditions, gnrh is a more appropriate first-line therapeutic for cystic ovarian disease due to challenges surrounding the immunogenicity, availability, and cost of hcg therapy. methodology section search strategy databases searched and dates covered: cab abstracts database accessed on wos platform (1973–2021) pubmed central accessed on ncbi website (1910–2021) search strategy: cab abstracts: (dairy or lactating or cow or cattle or heifer or bovine) and ((cystic or cysts) and ovarian and (disease or follicle or follicular)) (reproductive performance or ovulation or estrus or conception or pregnancy or preg rate or oestrus) (human chorionic gonadotropin or hcg) and (gonadotropin releasing hormone or gnrh) 1 and 2 and 3   pubmed: (dairy or lactating or cow or cattle or heifer or bovine) and ((cystic or cysts) and ovarian and (disease or follicle or follicular)) and (reproductive performance or ovulation or estrus or conception or pregnancy or preg rate or oestrus) and (human chorionic gonadotropin or hcg) and (gonadotropin releasing hormone or gnrh) dates searches performed: 20 dec 2021 exclusion / inclusion criteria exclusion: non-english language, non-primary literature, non-bovine, studies not relevant to the pico question. inclusion: use of gnrh and hcg for the treatment of ovarian follicular cysts, time as a metric for evaluation. search outcome database number of results excluded – non-english language publication excluded – non-primary literature excluded – non-bovine excluded – not relevant to pico question total relevant papers cab abstracts 67 21 17 5 19 5 pubmed 20 4 7 3 5 1 total relevant papers when duplicates removed 6 conflict of interest the authors declare no conflicts of interest. the authors are veterinary students at michigan state university (east lansing, mi, usa) that completed this knowledge summary as part of the lcs 679 food animal production medicine 1 course. references amweg, a. n., salvetti, n. r., stangaferro, m. l., paredes, a. h., lara, h. h., rodríguez, f. m. & ortega, h. h. (2013). ovarian localization of 11β-hydroxysteroid dehydrogenase (11βhsd): effects of acth stimulation and its relationship with bovine cystic ovarian disease. domestic animal endocrinology. 45(3), 126–140. doi: https://doi.org/10.1016/j.domaniend.2013.07.001 de rensis, f., bottarelli, e., battioni, f., capelli, t., techakumphu, m., garcía-ispierto, i. & lópez-gatius, f. (2008). reproductive performance of dairy cows with ovarian cysts after synchronizing ovulation using gnrh or hcg during the warm or cool period of the year. theriogenology. 69(4), 481–484. doi: https://doi.org/10.1016/j.theriogenology.2007.10.018 de rensis, f., lópez-gatius, f., garcia-ispierto, i. & techakumpu m. (2010). clinical use of human chorionic gonadotropin in dairy cows: an update. theriogenology. 73(8), 1001–1008. doi: https://doi.org/10.1016/j.theriogenology.2009.11.027  elmore, r. g., bierschwal, c. j., youngquist, r. s., cantley, t. c., kesler, d. j. & garverick, h. a. (1975). clinical responses of dairy cows with ovarian cysts after treatment with 10,000 iu hcg or 100 mcg gnrh. veterinary medicine, small animal clinician. 70(11), 1346–1349. farin, p. w., youngquist, r. s., parfet, j. r. & garverick, h. a. (1992). diagnosis of luteal and follicular ovarian cysts by palpation per rectum and linear-array ultrasonography in dairy cows. journal of the american veterinary medical association. 200(8), 1085–1089. garverick, h. a., kesler, d. j., cantley, t. c., elmore, r. g., youngquist, r. s. & bierschwal, c. j. (1976). hormone response of dairy cows with ovarian cysts after treatment with hcg or gnrh. theriogenology. 6(4), 413–425. doi: https://doi.org/10.1016/0093-691x(76)90108-4 garverick, h. a. (1997). ovarian follicular cysts in dairy cows. journal of dairy science. 80(5), 995–1004. doi: https://doi.org/10.3168/jds.s0022-0302(97)76025-9 giordano, j. o., wiltbank, m. c. & fricke, p. m. (2012). humoral immune response in lactating dairy cows after repeated exposure to human chorionic gonadotropin. theriogenology. 78(1), 218–224. doi: https://doi.org/10.1016/j.theriogenology.2012.02.003 gundling, n., drews, s. & hoedemaker, m. (2015). comparison of two different programmes of ovulation synchronization in the treatment of ovarian cysts in dairy cows. reproduction in domestic animals. 50(6), 893–900. doi: https://doi.org/10.1111/j.1439-0531.2009.01342.x howick, j., chalmers, i., glasziou, p., greenhalgh, t., heneghan, c., liberati, a., moschetti, i., phillips, b. & thornton, h. (2011). the 2011 oxford cebm evidence levels of evidence (introductory document). oxford center for evidence based medicine. [online] available from: https://www.cebm.ox.ac.uk/resources/levels-of-evidence/ocebm-levels-of-evidence [accessed 05 aug 2021]. ijaz, a., fahning, m. l. & zemjanis, r. (1987). treatment and control of cystic ovarian disease in dairy cattle: a review. british veterinary journal. 143(3), 226– doi: https://doi.org/10.1016/0007-1935(87)90085-6 jeengar, k., chaudhary, v., kumar, a., raiya, s., gaur, m. & purohit, g. n. (2014). ovarian cysts in dairy cows: old and new concepts for definition, diagnosis and therapy. animal reproduction. 11(2), 63–73. kawate, n., watanabe, k., uenaka, k., takahashi, m., inaba, t. & tamada, h. (2011). comparison of plasma concentrations of estradiol-17β and progesterone, and conception in dairy cows with cystic ovarian diseases between ovsynch and ovsynch plus cidr timed ai protocols. journal of reproduction and development. 57(2), 267–272. doi: https://doi.org/10.1262/jrd.10-066t kesler, d. j. & garverick, h. a. (1982). ovarian cysts in dairy cattle: a review. journal of animal science. 55(5), 1147–1159. doi: https://doi.org/10.2527/jas1982.5551147x lean, i. j., rabiee, a. r., duffield, t. f. & dohoo, i. r. (2009). invited review: use of meta-analysis in animal health and reproduction: methods and applications. journal of dairy science. 92(8), 3545–3565. doi: https://doi.org/10.3168/jds.2009-2140 liu, t. c., ho, c. t., li, k. p., chang, c. c. & chan, j. p. w. (2019). human chorionic gonadotropin (hcg)-induced ovulation occurs later but with equal occurrence in lactating dairy cows: comparing hcg and gonadotropin-releasing hormone protocols. journal of reproductive development. 65(6): 507–514. doi: https://doi.org/10.1262/jrd.2019-037 mollo, a., stradaioli, g., gloria, a. & cairoli, f. (2012). efficacy of different ovarian cysts treatments (gnrh, hcg and prid) in dairy cows. journal of animal and veterinary advances. 11(21), 4058–4063. doi: https://doi.org/10.3923/javaa.2012.4058.4063 nakao, t., tsurubayashi, m., horiuchi, s., nomura, t., ishibashi, y., kubo, m. & kawata, k. (1979). effects of a systematic application of human chorionic gonadotropin, gonadotropin-releasing hormone analog and bovine anterior pituitary gonadotropin in cows with cystic ovarian disease. theriogenology. 11(5), 385–397. doi: https://doi.org/10.1016/0093-691x(79)90062-1 nakao, t., kawata, k. & numata y. (1980). therapeutic effects of an analog of luteinizing hormone-releasing hormone (des-gly10-lh-rh-ethylamide) on cows with cystic ovary. the japanese journal of veterinary science. 42(4), 459–462. doi: https://doi.org/10.1292/jvms1939.42.459 nakao, t., tomita, m., kanbayashi, h., takagi, h., abe, t., takeuchi, y., ociai, h., moriyoshi, m. & kawata, k. (1992). comparisons of several dosages of a gnrh analog with the standard dose of hcg in the treatment of follicular cysts in dairy cows. theriogenology. 38(1), 137–145. doi: https://doi.org/10.1016/0093-691x(92)90225-g ngategize, p. k., kaneene, j. b., harsh, s. b., bartlett, p. c. & mather, e. l. (1987). a financial analysis of alternative management strategies of cystic follicles. preventive veterinary medicine. 4(5–6), 463–470. doi: https://doi.org/10.1016/0167-5877(87)90031-6 ono, t., takagi, m., kawashima, c., wijayagunawardane, m. p. b., vos, p. l. a. m., taniguchi, m. & otoi, t. (2018). comparative effects of different dosages of hcg on follicular development in postpartum dairy cows with cystic ovarian follicles. frontiers in veterinary science. 5, 130. doi: https://doi.org/10.3389/fvets.2018.00130 rizzo, a., campanile, d., mutinati, m., minoia, g., spedicato, m. & sciorsci, r. l. (2011). epidural vs intramuscular administration of lecirelin, a gnrh analogue, for the resolution of follicular cysts in dairy cows. animal reproduction science. 126(1–2), 19–22. doi: https://doi.org/10.1016/j.anireprosci.2011.04.013 seguin, b. e., convey, e. m. & oxender, w. d. (1976). effect of gonadotropin-releasing hormone and human chorionic gonadotropin on cows with ovarian follicular cysts. american journal of veterinary research. 37(2), 153–157. silvia, w. j., hatler, t. b., nugent, a. m. & da fonseca, l. l. (2002). ovarian follicular cysts in dairy cows: an abnormality in folliculogenesis.domestic animal endocrinology. 23(1–2), 167–177. doi: https://doi.org/10.1016/s0739-7240(02)00154-6 singh, j., ghuman, s. p. s. & honparkhe, m. (2012). reproductive performance following gnrh or hcg and pgf2α administration in crossbred cattle with ovarian cysts. veterinary practitioner. (1), 57–59. taktaz, t., kafi, m., mokhtari, a. & heidari, m. (2015). reproductive responses of dairy cows with ovarian cysts to simultaneous human chorionic gonadotropin or gonadotropin-releasing hormone and cloprostenol compared to gonadotropin-releasing hormone alone treatment. veterinary world. 8(5), 640–644. doi: https://doi.org/10.14202/vetworld.2015.640-644 vanholder, t., opsomer, g. & de kruif, a. (2006). aetiology and pathogenesis of cystic ovarian follicles in dairy cattle: a review. reproduction nutrition development. 46(2), 105–119. doi: https://doi.org/10.1051/rnd:2006003 verma, m.c. & dabas, y.p.s. (1994). treatment of ovarian cysts in cows. indian journal of animal reproduction: journal of the indian society for the study of animal reproduction. 15(2), 125–126. wiltbank, m. c., gümen, a. & sartori, r. (2002). physiological classification of anovulatory conditions in cattle. theriogenology. 57(1), 21–52. doi: https://doi.org/10.1016/s0093-691x(01)00656-2 yotov, s. a., atanasov, a. s., georgiev, g. b., dineva, j. d. & palova, n. a. (2014). investigation on some biochemical parameters and effect of hormonal treatment in anoestrous dairy cows with cystic ovarian follicle. asian pacific journal of reproduction. 3(1), 41–45. doi: https://doi.org/10.1016/s2305-0500(13)60183-9 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. erratum to: does the use of supraglottic device in rabbits cause less injury than other airway management devices? | veterinary evidence skip to main content knowledge summary keywords: anaesthesia; rabbit; intubation; endotracheal tube; trauma; injury; airway management; v-gel®; supraglottic airway device; face mask; laryngeal mask erratum to: does the use of supraglottic device in rabbits cause less injury than other airway management devices? jasmine gheini1* sanaa zaki, phd bvsc(hons) manzcvs gradcertedstud (higher education)1 1 sydney school of veterinary science, faculty of science, university of sydney, camperdown nsw 205 * corresponding author email: jghe8559@uni.sydney.edu.au vol 8, issue 2 (2023) erratum published: 05 may 2023 original paper published: 02 dec 2022 the original article was published in veterinary evidence vol 7, issue 4 (2022): https://doi.org/10.18849/ve.v7i4.608 doi: https://doi.org/10.18849/ve.v8i2.663 erratum unfortunately the original version of the article was missing the following statement. this knowledge summary has reviewed the available evidence on the use of a sgad (v-gel®) in rabbit anaesthesia. since writing a new design of a single use supraglottic airway device (sgad) has been introduced; currently there is no published evidence on whether this new device has an impact on the risk of injury. this error was in both the html and pdf versions. this has now been updated in both the html and pdf versions, and can be found in the clinical bottom line and the evidence section. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use.   veterinary evidence is an rcvs knowledge initiative. issn: 2396-9776 first floor, 10 queen street place, london ec4r 1be resources student awards staff login policies privacy policy accessing information policy cookie declaration terms of use copyright notices stay connected podcasts twitter facebook instagram linkedin back to top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443. in horses undergoing volatile anaesthesia, is recovery quality superior with sevoflurane compared to isoflurane? | veterinary evidence skip to main content knowledge summary in horses undergoing volatile anaesthesia, is recovery quality superior with sevoflurane compared to isoflurane? alexandra robinson, dvm manzcvs 1* tsim christopher sun, bvsc gcert mphil manzcvs mrcvs 1, 2 eduardo uquillas, bvm dvm dacvaa 2 1 university veterinary teaching hospital sydney, 65 paramatta road, camperdown 2050 nsw, australia 2 university veterinary teaching hospital camden, 410 werombi road, brownlow hill 2570 nsw, australia * corresponding author email: arr945@outlook.com vol 8, issue 1 (2023) submitted 20 jan 2022; published: 18 jan 2023; next review: 26 may 2024 doi: https://doi.org/10.18849/ve.v8i1.582 pico question in horses undergoing volatile anaesthesia, is recovery quality superior with the use of sevoflurane compared to isoflurane during the maintenance phase? clinical bottom line category of research treatment. number and type of study designs reviewed seven papers were available for critical appraisal. of the seven papers, six were prospective, randomised trials and four of these were of crossover design. of the same seven papers, three were experimental and four were clinical. strength of evidence moderate. outcomes reported five out of seven critically appraised articles found that there was no clinically significant improvement in recovery quality following volatile anaesthesia with sevoflurane compared to isoflurane. two of the seven articles did find improvement in recovery quality following the use of sevoflurane over isoflurane, but both studies were of crossover design, one of these studies used non-blinded evaluators and the second study used both unblinded and blinded evaluators and a recovery quality scoring scale that did not show interobserver reliability. conclusion in healthy horses presented for elective surgical and diagnostic imaging procedures in a clinical setting, there is no significant difference in recovery quality following the use of sevoflurane or isoflurane for the maintenance phase. how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a 3-year-old thoroughbred filly is presented to your clinic for a left carpal arthroscopy. the filly is race fit and is noted by her trainer to be highly strung. she comes with a history of having a ‘poor recovery’ following a previous anaesthetic required to facilitate the removal of an osteochondritis dissecans (ocd) lesion in a fetlock prior to beginning her race training. you are concerned about her demeanour and behaviour during the recovery phase and are interested in formulating an anaesthetic protocol for her that will minimise her fight-or-flight tendency during recovery. you have both isoflurane and sevoflurane available for use at your clinic, and you need to know if one volatile agent over the other will assist you in achieving a better recovery quality in this patient. the evidence recovery quality following general anaesthesia in horses is a multifactorial process. there were seven articles discovered that were relevant to the pico question. there was high quality evidence in the form of three prospective, randomised, controlled clinical trials. the last four articles were of crossover design, which introduces population bias in the evaluation of recovery quality, as recovery quality has been shown to improve following successive anaesthetic episodes (platt et al., 2018). there is no compelling evidence available in the current literature to suggest that either sevoflurane or isoflurane has any significant benefit over the other in terms of improvement of recovery quality when used in healthy patients presenting for elective procedures. summary of the evidence brosnan et al. (2012) population: healthy adult horses (research herd): five quarter horses, three thoroughbreds. four mares, four geldings. 6 ± 2 years. 526 ± 49 kg (mean ± sd). sample size: eight horses (40 recoveries). intervention details: each horse was anaesthetised five times; at least 7 days washout period between anaesthetics. randomly assigned a treatment order: treatment groups differed in volatile agent used and insufflation method during recovery phase. the five treatment groups were as follows: isoflurane / 100% o2, isoflurane / 5% co2, isoflurane / 10% co2, sevoflurane / 100% o2, sevoflurane / 5% co2. anaesthesia: guaifenesin 75 ± 16 mg/kg intravenous (iv) was administered prior to induction of anaesthesia with propofol 2.1 ± 4 mg/kg iv. maintained at 1.2 minimum alveolar concentration (mac) isoflurane (end-tidal isoflurane [etiso] 1.57%) or sevoflurane (end-tidal sevoflurane [etsevo] 3.41%), as confirmed by agent monitoring, for 120 minutes in left lateral recumbency. dobutamine was infused at a rate of 0–5.5 mcg/kg/min iv to maintain arterial blood pressure > 70 mmhg (measured invasively). mechanical ventilation used until 20 minutes prior to recovery phase. recovery: recovered unassisted from left lateral recumbency. insufflation of gases in the recovery phase consisted of 100% o2 or 5–10% co2 in o2 (certified mixture), depending on treatment group, at a rate of 15 l/min. arterial and venous blood gas and end tidal respiratory gas analysis samples drawn at 5 and 10 minutes post-disconnection. recoveries were directly observed and evaluated for objective variables by the same investigator. recordings of recoveries were evaluated by two independent, blinded investigators who scored the recoveries with a visual analogue scale (vas). study design: prospective, randomised, crossover, experimental study. outcome studied: objective: time to first spontaneous movement (head or limbs); time to sternal recumbency; number of attempts to attain sternal recumbency; time to standing; number of attempts to attain standing position. subjective: 100 mm vas (combined scores from two blinded investigators); 100 mm = perfect recovery; 0 mm = catastrophic recovery. main findings (relevant to pico question): hypoventilation during recovery, although present in every treatment group, was significantly greater in sevoflurane anaesthetised horses. hypercapnic hyperpnea caused a significant reduction in recovery time. time to first purposeful movement and time to sternal recumbency were not different among treatments. sevoflurane produced significantly longer recovery times. strong correlation between the subjective vas scores from the two blinded investigators (p < 0.001). no significant difference in recovery quality due to volatile agent or co2 treatment existed. vas scores (mean) differed widely between individual horses. limitations: not indicative of clinical practice – lack of typical premedication agents (α2 adrenergic agonists, phenothiazines, opioids), atypical induction regimen, no surgical stimulus, insufflation with co2 not routinely practiced. crossover design is inherently biased for evaluation of recovery quality as horses have been shown to have improved recovery qualities with successive anaesthetics. no sample size calculation. population of horses in this study is not reflective of the breadth seen in clinical practice.   grosenbaugh & muir (1998) population: healthy adult horses (research herd): five grade (unregistered) quarter horses, two quarter horses, one thoroughbred. 5–12 years. 482 ± 55 kg. sample size: eight horses (32 recoveries). intervention details: each horse was anaesthetised four times; at least 10 days washout period between anaesthetics. treatment order randomly assigned to each horse: concerned with the cardiopulmonary and recovery-related effects of the three volatile agents as well as two commonly used anaesthetic adjuncts (ketamine, thiopental). four treatment groups: 1.3% halothane (group 1; 1.5 minimum alveolar concentration [mac]), 2.0% isoflurane (group 2; 1.5 mac), 3.4% sevoflurane (group 3; 1.5 mac), 4.6% sevoflurane (group 4; 2 mac). in group 1, 2 and 3, at the 30 and 60 minute mark, horses reduced to 0.5 mac and re-anaesthetised with either ketamine (0.5 mg/kg iv) or thiopental (0.5 mg/kg iv). in group 4, the vaporiser was set to 7% and intermittent positive-pressure ventilation (ippv) used to achieve end-tidal sevoflurane concentration (etsevo) of 4.6% instead of using an ancillary anaesthetic agent (1.5 mac sevoflurane administered for all but the final 30 minutes of the anaesthetic). horses were anaesthetised for 90 minutes. anaesthesia: premedication: xylazine 1 mg/kg iv, guaifenesin (approximately 50 mg/kg iv) administered 10 minutes after xylazine until ataxia developed. induction: ketamine 2.0 mg/kg iv. horses were positioned in right lateral recumbency and breathed spontaneously (unless in group 4, in which ippv was used to ensure horses achieved mac sevoflurane). all volatile agents were delivered in o2. 16/32 (50%) of the study participants were administered xylazine 0.2 mg/kg intravenous (iv) prior to the recovery phase. recovery: unassisted recovery in padded stall. video recording of recovery in its entirety. study design: prospective, randomised, crossover, experimental study. outcome studied: objective: time to extubation; number of attempts to sternal recumbency; time to sternal recumbency; number of attempts to standing; time to standing. subjective: simple descriptive scale (own manufacture). main findings (relevant to pico question): recovery quality from sevoflurane anaesthesia was superior to isoflurane, but similar to halothane. time to standing in sevoflurane horses was not significantly different than that for isoflurane, but were more rapid than halothane. times to standing appeared equalised by the administration of xylazine 0.2 mg/kg iv prior to disconnection from the circuit. limitations: horses involved in this study had a general anaesthetic prior to the study’s commencement for transposition of the left carotid artery. crossover design is inherently biased for evaluation of recovery quality as horses have been shown to have improved recovery qualities with successive anaesthetics. no sample size calculation. population of horses in this study is not reflective of the breadth seen in clinical practice. used a simple descriptive scale for recovery quality scoring – this scale is insensitive, and the inclusion of objective data (time points, risk to attending personnel) is questionable. no clarification of who performed the recovery scoring in this study; assumption therefore is that the observer was not blinded, which increases risk of bias (suggest that sevoflurane anaesthesia produced a more coordinated recovery, which is entirely subjective). recovery quality assessment was secondary to the elucidation of cardiopulmonary effects of volatile and intravenous anaesthetic agents in this study.   leece et al. (2008) population: healthy, client-owned adult horses: american society of anaesthesiologists (asa) physical status classification of i–ii. undergoing anaesthesia for magnetic resonance imaging (mri) of the distal limb. seven thoroughbreds, 36 thoroughbred crosses, two arabians, 29 warmbloods, two ponies and one draft breed. the treatment groups were not different in age or body weight. sample size: 100 horses (77 recoveries; 23 were excluded due to incomplete recovery recordings). intervention details: randomisation of each horse to receive either isoflurane or sevoflurane in oxygen during maintenance phase: 38 horses received isoflurane; 39 horses received sevoflurane. anaesthesia: phenylbutazone 2.2 mg/kg intravenous (iv) and acepromazine 0.02 mg/kg iv administered 45 minutes prior to induction. romifidine 0.08 mg/kg iv for premedication. ketamine 2.2 mg/kg and diazepam 0.06 mg/kg iv for induction of anaesthesia 5 minutes after romifidine administration. all horses were maintained with intermittent positive-pressure ventilation (ippv); initial o2 flow rates were 10 l/min for 10–20 minutes, then down to 5 l/min. dobutamine was administered by constant rate infusion (cri) to maintain mean arterial blood pressure (map) > 60 mmhg. recovery: horses were positioned to recover in the same laterality as required for imaging. oxygen demand valve utilised until spontaneous ventilation resumed; o2 insufflation at 15 l/min. xylazine 0.25 mg/kg iv used in any patient exhibiting lightness of anaesthetic plane during hoisting or positioning in the recovery box (two in each group). recoveries were recorded from prior to placement in the recovery box until the horse was walking steadily. study design: prospective, randomised, clinical study. outcome studied: peri-anaesthetic subjective scoring (adapted from donaldson et al. 2000): individual temperament; sedation score (5 minutes post-romifidine); induction score; maintenance score; depth of anaesthesia on arrival to the recovery box. recovery objective events: time to first movement; time to first head lift; time to first attempt at sternal recumbency; time to attain sternal recumbency; time to first attempt at standing position; time to attain standing position; time to full coordination (no muscle tremors or ataxia, ability to move without incoordination). recovery subjective scoring: recovery score – subjective scoring system (adapted from young & taylor, 1993); recovery score – numerical scoring system (adapted from donaldson et al. 2000). main findings (relevant to pico question): no differences between treatment groups in duration of anaesthesia or times to specific recovery events. no difference in recovery scoring, number of attempts to sternal recumbency or number of attempts to standing. no difference between groups for xylazine requirements. strong, significant correlation between the two scoring systems. significant negative correlation between an individual horse’s pre-anaesthetic temperament was found with subjective recovery scores. significant positive correlation between time spent in sternal recumbency and subjective recovery score. no correlation between time to standing and recovery score. limitations: acepromazine administration is associated with slow, smooth recoveries and could pose a confounding factor. romifidine has a long half-life and the duration of anaesthesia was short, which could act as a confounding factor. short duration of anaesthesia provides no real opportunity for volatile agent accumulation. only one blinded observer was utilised to qualitatively score the recovery phase – this introduces bias, and may be in part why the scoring systems showed correlation. post hoc power calculation, based on number of horses needed to detect differences in recovery time. human error led to the loss of 23 recovery recordings.   matthews et al. (1998) population: healthy adult horses (research herd): nine arabians. three mares, three geldings, three stallions. 4–20 years. 318–409 kg. sample size: nine horses (27 recoveries). intervention details: each horse anaesthetised three times; at least 6 days washout period between anaesthetics. randomised treatment order allocation: treatment groups were isoflurane, sevoflurane and sevoflurane with xylazine prior to recovery. anaesthesia: premedication: xylazine 1.1 mg/kg intravenous (iv). induction: diazepam 0.03 mg/kg iv and ketamine 2.2 mg/kg iv. anaesthesia was maintained for 90 minutes with the volatile agent in oxygen. agent monitor ensured 1.2 minimum alveolar concentration (mac). horses positioned in right lateral recumbency. dobutamine continuous rate infusion (cri) to maintain mean arterial pressure (map) > 65 mmhg. recovery: xylazine 0.1 mg/kg iv given prior to recovery in sevoflurane/xylazine treatment group. breathed room air during recovery phase. recovery period videotaped. study design: prospective, randomised, crossover, experimental study. outcome studied: objective: time to first movement. time to extubation (when horse swallowed). time to sternal recumbency. number of attempts to stand. time to standing. time to coordination. subjective: recovery assessment scale (simple descriptive scale that range from 1–6 with 1 being the best score) used by 3 blinded veterinarians (experienced in equine recovery). coordination assessment scale (simple descriptive scale that ranged from 1–3 with 1 being the most coordination) used by 3 blinded veterinarians (experienced in equine recovery) to score horses at 10 minutes post-standing. main findings (relevant to pico question): no difference between treatments for time to extubation or sternal recumbency. mean time to first movement significantly longer in sevoflurane / xylazine treatment group. mean time to standing significantly lower in sevoflurane only group. no difference in the mean number of attempts to stand between isoflurane and sevoflurane treatments, but the mean number of attempts to stand between isoflurane and sevoflurane / xylazine was significantly different. recovery score means were significantly better in sevoflurane versus isoflurane treatment (p = 0.0004) and in sevoflurane / xylazine versus isoflurane treatment (p = 0.0092). ataxia scores were significantly lower in sevoflurane versus sevoflurane / xylazine (p = 0.0001) and in sevoflurane versus isoflurane treatment (p = 0.0158). time to safe coordination was significantly faster in sevoflurane versus isoflurane treatment (p = 0.0003) and in sevoflurane versus sevoflurane/xylazine (p = 0.0099). time to safe coordination significantly lower in sevoflurane treated animals than in sevoflurane / xylazine or isoflurane treated animals. individual variation in recovery score from horse to horse independent of treatment group. limitations: no sample size calculation. crossover design is inherently biased for evaluation of recovery quality as horses have been shown to have improved recovery qualities with successive anaesthetics. scored all three anaesthetic recoveries from the same horse sequentially – removes some of the blinding and may increase the risk of bias. unblinded reviewer’s scores were also used for statistical analysis – this introduces the unmistakable potential for risk of bias. made own recovery scoring systems – subjective in nature and perhaps insensitive as categories show vast differences. their recovery scoring system showed less interindividual variability in sevoflurane recoveries than in isoflurane recoveries – this finding suggests reduced reliability with their scale. population of horses in this study is not reflective of the breadth seen in clinical practice. absence of surgical stimulus is not indicative of clinical practice.   read et al. (2002) population: six appaloosa / appaloosa-quarter horse foals: healthy based on physical examination. sevoflurane treatment: 92.3 ± 34.8 kg. isoflurane treatment: 127.8 ± 22.0 kg. sample size: six foals (12 recoveries). intervention details: first anaesthetic at 1 month of age; second anaesthetic at 3 months of age. randomised treatment order allocation: foals required surgical intervention for angular limb deformity and were scheduled for surgical procedures to occur at 1 and 3 months of age. 5/6 foals were assigned sevoflurane for their first intervention; 1/6 were assigned isoflurane for their first intervention. anaesthesia: no premedication drugs utilised. induction via volatile agent (5% isoflurane, 7% sevoflurane) delivered via nasotracheal tube in o2. butorphanol 0.1 mg/kg intravenous (iv) administered post-induction to provide intraoperative analgesia. mechanical ventilation used. dorsal recumbency for surgery. recovery: left lateral recumbency for recovery. room air during recovery. recovery was assisted by two handlers blinded to treatment group. gentle restraint in lateral recumbency until the foal deemed to be conscious and strong enough to attempt standing. study design: prospective, randomised, crossover clinical study. outcome studied: objective: time to first movement. time to swallowing. time to standing. subjective: simple descriptive scale (1–3) (own manufacture). evaluated by a single observer unaware of treatment group, but involved in the hand-assisted recovery. main findings (relevant to pico question): no difference in anaesthetic duration between groups. no difference, in any of the variables under study, were noted in the recovery phase between isoflurane and sevoflurane treated foals. limitations: crossover design is inherently biased for evaluation of recovery quality as horses have been shown to have improved recovery qualities with successive anaesthetics. manipulation and intervention during recovery phase introduces bias, as foals not permitted to attempt sternal or standing until deemed ready for such tasks. recovery scoring scale was simple descriptive, and perhaps over-simplified the recovery process. only one evaluator precluded the deduction of the recovery quality scoring scale’s validity. random assignment of treatment order saw skewed groups – differences in body weight and age as most (5/6 foals) received sevoflurane first. a foal’s tolerance to restraint would largely be a function of their familiarity with handling; bias here may be that foals presented for their second surgical procedure had already gone through hospitalisation, anaesthesia, recovery and serial bandage changes prior to presenting for their second procedure.   valverde et al. (2005) population: healthy adult horses (client owned): physical examination and haematology used to categorise as american society of anaesthesiologists (asa) physical status of i–ii. all weighed > 300 kg. surgeries lasted > 60 minutes (arthroscopies excluded). sample size: 54 horses (six treatment groups, nine horses per group). intervention details: 27 horses received isoflurane; 27 horses received sevoflurane. random allocation to one of six groups: treatment groups were characterised by the volatile agent used, the presence or absence of a lidocaine continuous rate infusion (cri) and the time at which the lidocaine cri was discontinued. groups were: isoflurane / saline, isoflurane / lidocaine, isoflurane / lidocaine (discontinued 30 minutes prior to recovery), sevoflurane / saline, sevoflurane / lidocaine, sevoflurane / lidocaine (discontinued 30 minutes prior to recovery). anaesthesia: premedication: xylazine 1.0 mg/kg intravenous (iv). induction: midazolam 0.02 mg/kg and 2.0 mg/kg ketamine iv. intermittent positive pressure ventilation, o2 flow rate of 5 l/min. maintained near 1.0 minimum alveolar concentration (mac) for all treatment groups. discontinued administration of volatile agent 10–20 minutes prior to recovery, continued intermittent positive-pressure ventilation (ippv), maintained appropriate anaesthetic depth with xylazine / ketamine intermittent bolus injections. recovery: recovered in lateral recumbency on padded mat. oxygen insufflation at a rate of 12 l/min during recovery. recovery was videotaped for later individual scoring (one blinded, one not blinded to treatment group). recovery quality scoring system used to grade horses on common behaviours exhibited during the recovery phase; this information compiled to complete a descriptive recovery score. study design: prospective, randomised, controlled clinical trial. outcome studied: objective: move to sternal recumbency. time spent in sternal recumbency. move to stand. number of attempts to stand. knuckling. subjective (adapted from donaldson et al., 2000): overall attitude. strength. balance and coordination. accident occurrence. main findings (relevant to pico question): no effect of inhalant type of volatile (p = 0.29) or the duration of anaesthesia (p = 0.20) on the degree of ataxia. descriptive recovery score not significantly influenced by type of inhalant (p = 0.22). no significant effect of type of inhalant on times to sternal, extubation and standing. no significant difference in the descriptive recovery scores between sevoflurane and isoflurane anaesthetised horses (when all groups considered). horses entered the box with significantly decreased volatile concentrations (0.42 ± 0.11% isoflurane; 0.79 ± 0.20% sevoflurane). limitations: only one recovery scorer was blinded to treatment group; no difference between recovery quality score or descriptive recovery score between the two. large number of additional anaesthetic drugs (xylazine, midazolam, ketamine, lidocaine) used during the peri-anaesthetic period. no sample size calculation.   white et al. (2021) population: healthy horses (client owned): american society of anaesthesiologists (asa) physical status class of i (based on thorough physical examination). undergoing elective surgery. older than 6 months. had not been sedated in the 24 hours prior to anaesthesia. groups not significantly different in age, body weight, sex, duration of surgery, duration of anaesthesia, type of surgery, position during surgery or antibiotic administration. sample size: 103 horses (101 recoveries). intervention details: random allocation to one of two groups: isoflurane in oxygen for maintenance phase or sevoflurane in oxygen for maintenance phase. 49 horses received isoflurane; 52 horses received sevoflurane. power calculation performed. anaesthesia: premedication: acepromazine 0.03 mg/kg and flunixin 1.1 mg/kg intravenous (iv) at least 30 minutes prior to induction; romifidine 80 mcg/kg and morphine 0.2 mg/kg iv 10 minutes prior to induction. induction: diazepam 0.06 mg/kg and ketamine 3 mg/kg iv. intermittent positive-pressure ventilation (ippv) throughout. volatile agent titrated to maintain adequate surgical depth of anaesthesia in each case (rather than chasing a certain minimum alveolar concentration (mac) multiple). dobutamine constant rate infusion (cri) administered to maintain mean arterial pressure (map) > 60 mmhg. ketamine or thiopental iv as rescue agents in the event of light planes of anaesthesia. recovery: no additional use of sedatives for the recovery phase. demand valve used until spontaneous ventilation resumed. recoveries recorded for evaluation by two european college of veterinary anaesthesia and analgesia (ecvaa) diplomats who were blinded. two horses excluded due to incomplete recovery recordings. study design: prospective, randomised, blinded clinical study. outcome studied: objective: time to extubation. time to sternal recumbency. time to standing. subjective: quality of recovery scored using a previously reported system (young & taylor, 1993), where 0 = catastrophic recovery and 5 = perfect recovery. main findings (relevant to pico question): no significant difference in: mac hours, hypotensive indexes, mac multiple at disconnection. median time to extubation was the same, but the range was significantly different. time to sternal recumbency was significantly longer in sevoflurane than isoflurane horses (p = 0.03). no difference in time taken to stand or the number of attempts to stand between groups. no difference in recovery score between isoflurane and sevoflurane horses between the blinded evaluators or the attending anaesthetist although the attending anaesthetist did assign higher values to the sevoflurane recoveries. limitations: acepromazine administration is associated with slow, smooth recoveries and could be a confounding factor. romifidine has a long half-life and the duration of anaesthesia was short, which could act as a confounding factor. using anaesthetic-related data from four different anaesthetists can introduce variability, but the anaesthetic regimen was protocolised which may act as a control for this variation.   appraisal, application and reflection equine anaesthesia is associated with an overall mortality rate of 1.0% (gozalo-marcilla et al., 2021) which is a modest improvement from mortality rates of 1.9% reported nearly 20 years ago (johnston et al., 2002). certain patient demographics are at higher risk of mortality than others, such as those with high american society of anaesthesiologists (asa) physical status, extremes of age, body weight, fracture reparation, emergency laparotomy, increased anaesthetic time, procedures occurring out of hours, patients induced without premedication and maintenance with volatile agents (johnston et al., 2002; and johnston et al., 1995). causes of anaesthetic-related mortality are variable and can include intraoperative cardiac arrest, fractures, luxations, neuropathy, myopathy, spinal cord malacia and respiratory obstruction (dugdale & taylor, 2016). recovery from general anaesthesia has long been incriminated as the most dangerous part of the perianaesthetic period for equine patients, with 92% of overall morbidity and mortality occurring within this period (laurenza et al., 2020). as such, the elucidation of specific anaesthesia-related factors for the improvement of recovery quality has been of considerable interest. a review of the literature was carried out to answer the pico question, followed by an article exclusion process resulting in seven peer-reviewed publications appropriate for critical appraisal. all seven articles have clear relevance to the pico question. of the seven articles, all are prospective, randomised trials. four of these were crossover in design. there was, at least partial, blinding of recovery evaluators to treatment group in six of the articles. four of the articles used client-owned horses, whereas the other three used research herds. the clinical trials, of which there were three, were most reflective of current standards in equine clinical anaesthesia. the articles retrieved were relatively recent, spanning only the last two decades. in several large-scale multiand single-centered epidemiological morbidity and mortality studies, volatile anaesthetic agents have been incriminated as a risk factor for mortality (bidwell et al., 2007; dugdale et al., 2016; and johnston et al., 2002). the volatile anaesthetic agents are well known for their dose-dependent cardiorespiratory depression (grosenbaugh & muir, 1998). such depression can lead to deleterious clinical sequelae such as hypotension, hypoventilation, hypercapnia and hypoxemia. although direct causal relationships have not been identified, the presence of hypotension and hypoxemia have deleterious effects on muscle perfusion and tissue oxygenation, which could negatively impact recovery quality. despite this, volatile agents are unlikely to be abandoned in equine anaesthesia due to their use during long and invasive procedures, minimal metabolism, ventilation-dependent elimination, titratability, and the ease with which their concentrations are monitored. this critical appraisal was limited to sevoflurane and isoflurane, as they are the predominant volatile agents currently in use (gozalo-marcilla et al., 2021). sevoflurane has been proposed to produce superior recovery quality in equine patients compared to isoflurane (grosenbaugh & muir, 1998). the pharmacokinetic and pharmacodynamic profile of sevoflurane suggests that it should have clinical advantages over isoflurane (steffey, 2002). sevoflurane has a lower blood / gas partition coefficient, indicating lower solubility of the agent in the blood. this results in a more rapid equilibration of partial pressure between the alveolar space and the blood and brain, leading to more rapid induction and recovery phases. this may increase the speed in which anaesthetic depth can be changed through titration of volatile agent delivery. sevoflurane accumulated in the adipose tissue during long periods of general anaesthesia is also more rapidly eliminated than isoflurane, which may be an important factor during the recovery phase where horses can experience emergence delirium and dysphoria due to the continued presence of a volatile agent in their system. it may be that the advantage in using sevoflurane over isoflurane may only become evident after long (>3 hour) duration anaesthetics, although there are no comparative studies available that have investigated this. recoveries of good quality are characterised by the absence of emergence delirium, dysphoria or ataxia and the presence of adequate musculoskeletal strength. these characteristics lead to balanced and coordinated recoveries, reduced knuckling and falling events with fewer attempts to sternal recumbency and standing. recoveries with these characteristics are likely to be qualitatively calm and smooth, reducing the opportunity for self-inflicted injury. horses are prone to displaying fight-or-flight responses during emergence from general anaesthesia, and it has been postulated that the individual horse’s temperament may influence recovery (brosnan et al., 2012; leece et al., 2008; and matthews et al., 1998). in addition, time spent in lateral recumbency, number of attempts to sternal recumbency, time spent in sternal recumbency, number of attempts to standing and time to standing are common objective variables used to characterise the recovery phase. the assessment of recovery quality following use of a specific volatile agent is challenging. the use of ancillary anaesthetic agents is necessitated as part of a balanced anaesthetic technique and may include the use of injectable drugs for premedication, induction, rescue anaesthesia and the use of additional sedative and analgesic drugs in the recovery phase. the effects of ancillary agents in the recovery phase can be difficult to quantify, especially where long-lasting agents, such as acepromazine are involved in the anaesthetic protocol (knych et al., 2018). recovery quality will most likely be attributable to the volatile agent if the use of other ancillary agents within the protocol is standardised. furthermore, it has become standard practice to administer additional sedative drugs during the recovery phase to improve recovery quality by decreasing opportunity for disorientation and volatile agent-related dysphoria (santos et al., 2003; and white et al., 2021). leece et al. (2008) and white et al. (2021) published results from prospective clinical trials using stringent anaesthesia protocolisation devoid of recovery sedatives. the results from each study concluded that there was no significant difference in recovery quality following sevoflurane versus isoflurane anaesthesia. there were no articles available for appraisal that evaluated volatile agents without the use of ancillary drugs. the scoring of recovery quality following general anaesthesia is often subjectively assessed and qualitative in nature. vettorato et al. (2010) investigated the reliability of four distinct recovery quality scoring systems (rqss) through use of two groups of evaluators, 117 final-year veterinary students and 12 experienced equine anaesthetists. the four rqss evaluated were a visual analogue scale originally reported by hubbell in 1999, a composite scoring system (donaldson et al., 2000), a simple descriptive scale (young & taylor, 1993) and the edinburgh scoring system (vettorato et al., 2010). results revealed that the four rqss exhibited moderate-high reliability, suggesting that there was significant interobserver agreement amongst scores given by blinded evaluators and that the scales were reliable even when used by inexperienced operators. ideally, high interobserver agreement of recovery scales should be identified to reduce bias and enable meaningful comparisons between studies. although a perfect rqss has not yet been developed, recovery scales should be objective, sensitive in detecting recovery quality differences and be adapted to accommodate the conditions of the study facility (valverde et al., 2005). in addition to this, researchers should seek to limit bias by blinding recovery evaluators to treatment groups. of the seven studies evaluated, four utilised rqss that were recognised as being reliable by vettorato et al. (2010). valverde et al. (2005) utilised a modified composite scoring system, leece et al. (2008) utilised a modified combination of a composite scoring system and simple descriptive scale, brosnan et al. (2012) utilised a visual analogue scale and white et al. (2021) utilised a simple descriptive scale. each of these scales had roots in the published grandfather articles referenced in vettorato et al. (2010). all four articles used recovery evaluators that were blinded to treatment group, thus minimising the possibility of bias. valverde et al. (2005) even proved the reliability of their modified composite scoring system by having one blinded and one unblinded evaluator to score recoveries. none of the rqss used in these studies detected significant differences in recovery quality between sevoflurane and isoflurane recoveries. the remaining three articles used simple descriptive scales of their own manufacture that resulted in discrepant results (matthews et al., 1998), had non-existent blinding processes (grosenbaugh & muir, 1998), and utilised hand-assisted recovery techniques (read et al., 2002), thus increasing the potential for bias and possibly misleading results. a recent publication by platt et al. (2018) showed that habituation and learning during the recovery phase following sequential general anaesthetic episodes in equine patients occurs and culminates in improvement of recovery quality. this phenomenon may reduce the reliability of crossover designed research studies when determining recovery quality in horses. four of the appraised articles were crossover designs. interestingly, there were contrasting results. two studies reported no difference in recovery quality when using sevoflurane versus isoflurane (brosnan et al., 2012; and read et al., 2002), while the other two suggested that sevoflurane recovery quality was superior (grosenbaugh & muir, 1998; and matthews et al., 1998). study participants were anaesthetised on as little as two (read et al., 2002) to as many as five (brosnan et al., 2012) separate occasions for study purposes. the crossover design and ample opportunity for learned behaviour development make the results of these articles difficult to interpret. three of the four crossover designed studies had additional significant limitations that clouded their clinical relevance, such as unblinded recovery evaluators (grosenbaugh & muir, 1998), an insensitive and unreliable rqss that may have precluded detection of specific aspects of recovery behaviour (matthews et al., 1998) and hand-assisted recovery techniques (read et al., 2002). the use of anaesthesia-naïve animals may be the most logical population in which to study recovery quality. of the articles appraised, three were clinical trials in which anaesthesia-naïve animals were enrolled (leece et al., 2008; valverde et al., 2005; and white et al., 2021). these three studies also had the strongest study designs, used reliable rqss, had large sample sizes, reflected the general horse population and used anaesthetic protocols common in clinical practice. in addition to this, both valverde et al. (2005) and white et al. (2021) cases were surgical procedures and those in leece et al. (2008) involved diagnostic imaging, both scenarios of which are relevant to clinical practice. furthermore, the studies produced by leece et al. (2008) and white et al. (2021) were only concerned with recovery quality differences, thus making their results highly relevant to our analysis. for these reasons, these three articles likely offer the most accurate and unbiased information available to answer the pico question. none of these studies detected any significant difference in recovery quality following sevoflurane versus isoflurane anaesthesia. the finding from this critical appraisal was supported by the findings of a recent systematic review. loomes & louro (2021) deduced that there is no conclusive evidence that any given volatile agent is superior to another in terms of recovery quality. loomes & louro (2021) recognised that there is a relative dearth of literature on the topic, but the articles available typically have strong study designs with blinded recovery quality evaluators and the use of a validated rqss. limitations in the articles were the inconsistent use of sedatives prior to the recovery phase, general lack of power calculations, although leece et al. (2008) did perform a post hoc power, and the presence of multiple study objectives. these limitations were also present in the currently appraised articles, and they seem to be common limitations in articles involving equine anaesthesia in general. despite these limitations, loomes & louro (2021) suggest that there is moderate evidence to support their conclusion. a recently published expert opinion (bettschart-wolfensberger, 2021) combining extensive clinical experience and an independent dissection of the literature has culminated in the same conclusion. after complete appraisal of the evidence, the authors conclude that there is moderate evidence in the literature to support that there is no clinical difference in recovery quality following sevoflurane versus isoflurane anaesthesia in healthy horses under clinical and experimental conditions. sevoflurane and isoflurane both provide rapid, smooth recoveries of good quality. in the absence of clear and causal relationships between specific volatile anaesthetic agents and anaesthetic outcome, an individual clinician’s choice of volatile agent should be based on user familiarity, relative anaesthetic risk of the patient, anticipated duration of anaesthesia and the potential environmental impacts. continued research into the benefits of administering additional sedative drugs in attempts to improve recovery quality are required. further evaluation of volatile agent influence on recovery quality may require the use of sick horses and long (> 3 hour) durations of anaesthesia. methodology search strategy databases searched and dates covered: cab abstracts on web of science platform: 1910–2022 pubmed accessed via ncbi: 1950–2022 search strategy: cab abstracts: ts=(horse* or equus or equin* or equid* or mare or mares or gelding* or stallion* or pony or ponies or broodmare* or foal* or colt* or filly or fillies) ts=((volatile* or inhalation*)near/2(anaesthe* or anesthe* or agent*)) ts=(isoflurane) ts=(sevoflurane) #1 and (#2 or (#3 and #4))   pubmed: “horses” [mesh:noexp] horse* or equus or equin* or equid* or mare or mares or gelding* or stallion* or pony or ponies or broodmare* or foal* or colt* or filly or fillies “anaesthesics, inhalation” [mesh:noexp] “volatile anaesthetic” or “volatile anaesthetics” or “volatile anaesthesia” or “volatile anesthetic” or “volatile anesthetics” or “volatile anesthesia” or “inhalation anaesthetic” or “inhalation anaesthetics” or “inhalation anaesthesia” or “inhalation anesthetic” or “inhalation anesthetics” or “inhalation anesthesia” or “volatile agent” or “volatile agents” or “inhalation agent” or “inhalation agents” isoflurane sevoflurane (#1 or #2) and (#3 or #4 or (#5 and #6)) dates searches performed: 26 may 2022   exclusion / inclusion criteria exclusion: articles irrelevant to pico question. expert opinion. not available in english. systematic review. duplicates. inclusion: relevant to pico question, peer-reviewed and available in english.   search outcome database number of results excluded – irrelevant excluded – expert opinion excluded – not in english excluded – systematic review total relevant papers cab abstracts 877 867 1 1 1 7 pubmed 536 529 0 0 1 6 total relevant papers when duplicates removed 7   acknowledgements the authors wish to acknowledge the assistance of ms monica cooper in the process of formulating a literature search strategy for this review. orcid alexandra robinson: https://orcid.org/0000-0003-4937-9552 tsim christopher sun: https://orcid.org/0000-0003-1033-8251 eduardo uquillas: https://orcid.org/0000-0002-4227-2173 conflict of interest the authors declare no conflicts of interest. references bettschart-wolfensberger, r. 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(1993). factors influencing the outcome of equine anaesthesia: a review of 1,314 cases. equine veterinary journal. 25(2), 147–151. doi: https://doi.org/10.1111/j.2042-3306.1993.tb02926.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use.   veterinary evidence is an rcvs knowledge initiative. issn: 2396-9776 first floor, 10 queen street place, london ec4r 1be resources student awards staff login policies privacy policy accessing information policy cookie declaration terms of use copyright notices stay connected podcasts twitter facebook instagram linkedin back to top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443. is radiography or ultrasonography superior at detecting intestinal obstructions in dogs with acute abdominal signs? | veterinary evidence skip to main content knowledge summary keywords: ultrasound; radiography; small intestine; obstruction; diagnosis; dogs; diagnostic imaging is radiography or ultrasonography superior at detecting intestinal obstructions in dogs with acute abdominal signs? josephine corrick, bsc bvmsci mrcvs1* 1 vsm building, university of surrey, daphne jackson rd, guildford gu2 7al * corresponding author email: jlcorrick@gmail.com vol 8, issue 2 (2023) submitted 10 oct 2021; published: 15 june 2023; next review: 06 feb 2025 doi: https://doi.org/10.18849/ve.v8i2.483 pico question in dogs with acute abdominal signs is radiography or ultrasonography superior at detecting surgical patients with intestinal obstructions? clinical bottom line category of research diagnosis. number and type of study designs reviewed six relevant studies were identified and reviewed, all diagnostic validity studies. four had cross sectional designs in place and two have a prospective cohort study design. strength of evidence moderate. outcomes reported all studies showed that ultrasound and radiography were useful in the diagnosis of small intestinal obstruction in dogs. one study with moderate evidence showed that ultrasound is superior to three-view abdominal radiography for diagnosing small intestinal mechanical obstructions in dogs with acute vomiting (p = 0.013). most of the studies suggested that ultrasound might be more accurate than radiography at detecting surgical patients with intestinal obstructions, but no sufficient evidence was reported. in some studies, the results are too similar for a statistically significant difference to be claimed without further investigation. all studies suggest that the experience of the person who performs or estimates the diagnostic imaging studies can affect the accuracy of each technique, but no statistical comparisons were made to support this hypothesis. conclusion the results of these studies suggest that both techniques are helpful in the diagnosis of small intestinal obstructions in dogs. there are limitations on each technique and factors that can affect accuracy, like the level of training and expertise but more studies are needed to estimate that. future studies should focus on the comparison of results when ultrasonography is performed in a general practice setting and knowledge base rather than specialists. the majority of studies included in this summary suggest that ultrasound is generally superior if only one modality can be used, but this is mostly based on weak evidence and further investigations to confirm statistical significance are needed. considering that all studies were performed by diagnostic imaging experts, the only conclusion that can be safely made is that abdominal ultrasound is superior to three-view abdominal radiographs for diagnosing small intestinal mechanical obstructions in dogs with acute vomiting. additionally it suggests this modality combined with a good level of training on ultrasonography interpretation or, if possible, cooperation with an expert to get the most out of this tool while treating future patients with relevant issues. how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a dog presents with acute abdominal signs, due to financial constraints only one diagnostic imaging method can be used; either abdominal radiograph or ultrasonography. which one is superior at detecting the need for surgical intervention by accurately diagnosing small intestinal mechanical obstruction? the evidence all six identified studies were testing diagnostic validity. of the six studies appraised the ones with moderately strong evidence are the most recent three (drost et al., 2016; elser et al., 2020; and winter et al., 2017) as they are prospective cohort studies. the other three; shanaman et al. (2013), sharma et al. (2010) and tyrrell & beck (2006) all had weaker evidence as they all had a cross sectional design with a varied level of blinding involved to try to reduce bias. summary of the evidence elser et al. (2020) population: client owned dogs and cats presenting with clinical suspicion of mechanical obstruction at matthew j. ryan veterinary hospital of the university of pennsylvania, usa, between 2008–2015. this paper will focus only on the results of the dog patients. sample size: dogs: n = 40 intervention details: animals were presenting with abdominal radiographs (ventrodorsal or dorsoventral and left lateral or right lateral views) that were inconclusive for presence or absence of gastrointestinal obstruction. viewed by radiologist or radiology-resident on duty at the time. four reviewers were used, two board-certified radiologists with 16 and 10 year’s experience, one board-certified emergency and critical care specialist with 2 year’s experience and one first year radiology resident. radiographs were subjectively assessed with no objective parameter for obstructions. reviewers recorded their diagnosis on a likert scale of 5 categories: not obstructed; probably not obstructed; unsure; probably obstructed; obstructed. reviewers were aware of the study goals but were blinded to all clinical information other than initial concern for obstruction. a second set of abdominal radiographs were taken 7–36 hours after the initial radiographs. the radiographs were reviewed twice: the first phase included reviewing radiographs from both the initial set and the second set of images, one of either set for each patient, to reduce potential for recall bias. the corresponding image for each patient was then reviewed at least a week later. in phase 2, which was at least a month after, the initial and second set radiographs were reviewed again in concert for each patient. medical management was provided at the discretion of the attending clinician between sets of radiographs. an abdominal ultrasound was done within 3 hours of the second set of radiographs, this was performed by board-certified radiologist or a radiology resident under direct supervision of a board-certified radiologist. study design: prospective cohort study. outcome studied: assessment of the initial radiographs was compared to the combined assessment of initial and follow up radiographs in phase 2. the abdominal ultrasound performed in all animals within 3 hours of the second set of radiographs was considered contextualised care. sensitivity, specificity and percent accuracy of the radiography were calculated for each reviewer at each step; initial radiographic examinations and combined assessment of the two sets of radiographic examinations. statistical analysis of the area under the curve was done, and agreement between diagnosis measured using cohen’s kappa. main findings (relevant to pico question): on ultrasound: 11/40 (27.5%) dogs were diagnosed to have a small intestinal mechanical obstruction with ultrasound. one of these dogs was diagnosed with a partial obstruction – this was statistically counted as obstructed. all obstructions were foreign bodies. all of the foreign bodies were non-radiopaque and so were not readily seen on radiographs. the foreign bodies in the dogs included: five linear foreign bodies, one squeaky toy, one rubber material, three non-specified foreign body, one not mentioned. concurrent foreign material in the stomach, either separate or extending from small intestine was present in 4/11 (36.4%) dogs. on radiographs: the following analysis was made for the entire population of the study which included cats and dogs. sensitivity for the reviewers on the initial assessment in phase 1 ranged from 36.8–89.5%. sensitivity for the reviewers for the combined assessment of initial and second set of radiographs ranged from 26.3–84.2%. specificity for the reviewers diagnoses on the initial assessment ranged from 71.1–94.7%. specificity for the reviewers diagnoses for the combined assessment ranged from 73.7–97.4%. accuracy for the initial radiographic examination ranged from 66.7–80.7% across the reviewers. and accuracy for the combined assessment ranged from 70.2–89.5%. three of the four reviewers increased their percentage accuracy in the second phase of combined assessment as compared to the initial assessment, however this was not statistically significant for any observer. there was poor agreement with one of the reviewers and the other three, and three of the reviewers having moderate agreement between their diagnoses. presence or absence of an obstruction was not seen to be associated with time interval between the initial and follow-up radiographs. limitations: population is pre-selected from the radiographic findings where only patients that had a clinical suspicion of obstruction were included that had inconclusive initial radiographs. this would lead to a negative bias towards the use of radiographs in diagnosing small intestinal obstruction, as all cases that were diagnosed on initial radiographs were excluded for this study. since all patients were treated according to their own individual clinical situation during the interim of sets of radiographs, there was no standardisation of treatment between subjects. different medical treatment may have had an effect on the second set of radiographs and ultrasound images taken, especially in relation to hydration status. this study looked at the usefulness of taking sequential radiographs in increasing accuracy of diagnoses, one limitation of this study was the length of time between sets of radiographs. there is a wide variety in duration of clinical signs, ranging from less than 24 hours to 3 weeks. this would have an effect on the images taken, worsening of inflammation / thickening of the intestines could have been easier to spot and diagnose with the patients who had a longer duration of clinical signs. while all cases had orthogonal radiographs available for the initial study, there was no standardisation as some were of ventrodorsal and left lateral, some were ventrodorsal and right lateral and one case was dorsoventral and had left lateral. this variety, while more realistic in a general practice setting, does not provide a replicable approach. all of the obstructions were caused by non-radiopaque foreign material, so this study does not include the more obvious cases in which radiograph reviews may be more accurate in diagnosing, reducing its apparent accuracy against ultrasound. the number of patients in this study is low, the number of patients in this study is low, therefore results are not representative of the greater / general population. there was a selection bias of cases that were willing to wait for a second set of radiographs to then be included in the study. this excludes those who may have needed more immediate treatment and included those who may have been more stable. if they had included those more severe cases it may have reflected a more realistic accuracy of diagnosis with radiographs, as they may have contained more obvious causes of obstruction. no universal definition or objective parameter for the diagnosis of obstruction was applied, there were diagnostic limitations for radiographs related to different body conditions, serosal detail and pathology (e.g. free fluid), dogs with inconclusive initial radiographs, patients with foreign bodies and no obstruction could develop obstruction at a later time and show signs only in the follow-up radiographs. the radiologists could not know if a dog just vomited which would change the appearance of imaging, and there is no immediate comparison of ultrasound and radiography at the time of initial presentation. there is also a variety of breeds, ages and numbers of each sex which would not be possible to replicate.   winter et al. (2017) population: client owned dogs suspected of having a complete or partial gastrointestinal obstruction without clinically important comorbidities. presenting at the small animal hospital of the university of florida, usa between 15 september 2013 and 15 december 2014. sample size: dogs n = 16. intervention details: prior to enrolment a history, physical examination, complete blood count (cbc), serum biochemical analysis and abdominal radiography were performed. dogs were sedated (14 dogs) or anaesthetised (two dogs) prior to ultrasonography and computerized tomography (ct): the dogs had abdominal ultrasound examinations, in dorsal recumbency, performed by a board-certified radiologist or radiology resident under the supervision of a board-certified radiologist. abdominal ct examinations were done on all dogs, positioned in dorsal recumbency and routine abdominal-volume acquisition protocols were used. all dogs underwent laparoscopy, exploratory laparotomy and surgical treatment of their primary gastrointestinal disease. the ultrasound images were reviewed in real time and findings were discussed with the attending veterinary surgeon. image analysis and evaluation was performed by a board-certified radiologist. images were assessed for the presence and location of obstruction and for diagnosis. the ultrasound diagnosis of obstruction was based on subjective assessment of the intestinal dilation, recognition of two distinct groupings of bowel differing in diameter, an identification of intestinal plication or the presence of a foreign body which indicated complete mechanical obstruction only when intestinal dilation of two distinct bowel groupings were also present. ct images were assessed similarly by identifying the presence of intestinal dilation and two distinct groupings of bowel differing in diameter, with or without the identification of a foreign body. each measurement of bowel diameters and ratios were taken three times and a mean was used. study design: controlled trial study. outcome studied: sensitivity, specificity, positive predictive value (ppv), and negative predictive value (npv) of abdominal ct and ultrasonography for the diagnosis of gastrointestinal obstruction were calculated, with exploratory surgery being considered as reference standard. main findings (relevant to pico question): based on ct and exploratory laparotomy findings 10 dogs had a complete obstruction, three had partial obstruction and three had no obstruction. sensitivity and specificity of abdominal ultrasound for the diagnosis was 100% and 67% respectively, using exploratory laparotomy as a reference standard. the ppv for ultrasonography was 93% and npv was 100%. for ct sensitivity and specificity for diagnosis of obstruction was 100% for both, and ppv and npv were also 100%. there was only one disagreement between modalities, where a false positive diagnosis of an obstruction was made on ultrasonography. limitations: abdominal radiography was performed prior to enrolment into study, and so standardisation of views and machines used could not be done. choice of sedation and doses were at the discretion of the attending anaesthesiologist and veterinary surgeon. as the images of the ultrasound exam were reviewed in real time, there may have been some bias due to reviewer not being blinded to signalment and presenting signs of each patient. having such a small sample size limits the study’s ability to represent a wider population, especially since there were only three dogs without gastrointestinal obstructions included in the study. the patients included in this study are not wholly representative to a wider population as they all presented to a referral hospital instead of a general practice, and so this may not represent the sort of cases and results replicable in a general practice setting. as noted in the study, results of the abdominal ultrasonography can be operator dependent, and an experienced ultrasonographer may not also be available, and so results can differ between reviewers. no statistical analysis on comparisons of accuracy of ultrasonography and ct was performed and so statistical significance cannot be made. there is no comparison between radiology and ultrasound, the nature of the included dogs presented a limitation as all enrolled dogs were suspected of having mechanical gastrointestinal obstruction based on clinical signs, physical examination and abdominal radiography. the study does not mention if previous imaging results were concealed or not, dogs were excluded if they had radiographic evidence of intestinal plication. there is also a variety of breeds, ages and numbers of each sex which would not be possible to replicate.   drost et al. (2016) population: 20 dogs with a diagnosis of mechanical intestinal obstruction. from november 2011 to may 2013: four entire males, five castrated males, one entire female, 10 neutered females. five dogs were enrolled based on radiographic signs of mechanical intestinal obstruction. three dogs were enrolled without clinical signs of mechanical obstruction but for which abdominal surgery was planned. the remaining 12 dogs had clinical signs of mechanical intestinal obstruction. sample size: dogs n = 20. power and sample size calculator used to get sample size. intervention details: digital abdominal radiographs and computerized tomography (ct) examinations of the right lateral, left lateral and ventrodorsal views were taken. surgical exploration of the abdomen was performed within 24 hours of the imaging and the results were used as a reference standard. three experienced board-certified radiologists reviewed the abdominal radiographs and ct examinations. the reviewers were blinded to clinical history and the images were reviewed at least 12 months after the date images were taken. the images were reviewed in a random order and separately. study design: case-control study. outcome studied: abdominal radiographs were evaluated subjectively for signs of gastrointestinal obstructions. with the following criteria: definitely not obstructed. likely not obstructed. equivocal obstruction. likely obstruction. definitely obstructed. should the dog go to surgery: yes or no? radiographs were then reevaluated using selected objective measurements: diameter of most distended intestinal segment on lateral projection. diameter of most distended intestinal segment on ventrodorsal view. midbody height of l5, width of l5 and width of twelfth rib. after objective measurements, each reviewer was asked again if the dog had a mechanical obstruction with the same criteria above. the same data was also then collected for the ct examinations. presence of gastrointestinal obstruction was recorded within surgical exploration: not all dogs had surgical treatment, those that did not were followed for 2 weeks to rule out an incorrect diagnosis i.e. a missed obstruction. resolution of clinical signs with medical therapy for more than 2 weeks was used as confirmation of a non-obstruction. surgical results were used as reference standard. diagnostic sensitivity and specificity for diagnosing mechanical intestinal obstruction using radiographs and ct were calculated for each radiologist and the combined group of radiologists. the subjective criteria above were sectioned into objective criteria: definitely and probably obstructed = obstructed, equivocal, probably not and definitely not = not obstructed. main findings (relevant to pico question): 17/20 (85%) dogs had abdominal surgery. 8/17 (47%) had small intestinal mechanical obstruction and nine did not. included in the nine that did not have obstructions were the three dogs scheduled for unrelated abdominal surgery. the 3/20 (15%) dogs that did not have surgery were considered to not have any obstruction after a 2 week follow-up and clinical signs had resolved. so out of the total 20 dogs: eight had small intestinal mechanical obstructions, 12 did not have an obstruction. sensitivity and specificity for the diagnosis of small intestinal obstruction using ct was 95.8% and 80.6% respectively. sensitivity and specificity for the diagnosis of small intestinal obstruction using radiographs was 79.2% and 69.4% respectively. sensitivity and specificity for correctly recommending abdominal surgery after subjective evaluation: radiography sensitivity: 91.7%, specificity: 83.3%. ct sensitivity: 83.3%, specificity: 72.2%. sensitivity and specificity for correctly recommending abdominal surgery after incorporating objective measurements: radiography sensitivity: 91.7%, specificity: 83.3%. ct sensitivity: 83.3%, specificity: 80.6%. ct was found to be more sensitive and specific at diagnosing intestinal obstruction, but the difference was not significantly important. for recommending abdominal surgery for obstruction radiography was shown to be more sensitive and specific then using ct but the results were not significantly important. sensitivity and specificity between radiographic results between reviewers and ct results between reviewers were not significantly important. limitations: dogs with radiographic signs of a linear foreign body were excluded from this study, which means the findings cannot be representative to all types of mechanical obstructions that present in general practice. diagnosis was made on a subjective scale, with 3/5 (60%) options stating non-obstructed. this has a bias towards choosing non-obstructed and may have had an effect on the results. the experience of the reviewers is not representative of many clinicians in general practice and so the results have differed with less experienced reviewers. while a power calculation supported the number of animals in the study a larger sample size may have been more representative to a wider population. this study focusses on diagnostic accuracy of radiography and ct and does not include ultrasonography, and so only the accuracy of radiography in the diagnosis of intestinal foreign bodies can be seen without comparison. there is also a variety of breeds, ages and numbers of each sex which would not be possible to replicate.   shanaman et al. (2013) population: 19 client owned dogs. admitted to illinois veterinary teaching hospital for acute abdominal signs between december 2010 and january 2012. aged between 4– 5.2 years old. eight neutered female dogs. 11 male dogs: four intact, seven neutered. to be involved in the study each animal required the cytologic, survey radiographic and / or sonographic detection of a condition requiring immediate surgical intervention or alternatively sonographic changes consistent with acute pancreatitis or gastrointestinal (gi) neoplasia. sample size: dogs n = 19. intervention details: all patients underwent abdominal radiography, b-mode and contrast enhanced ultrasonography (ceus) and multi-detector helical computerised tomography (mdct). all radiographs as well as computerized tomography (ct) examinations were reviewed in a randomised order by the first author and two board-certified radiologists, all of them being blinded in regards to signalment, presenting clinical signs and final diagnosis. eight additional digitally acquired three-view abdominal radiographic examinations of normal or non-acute abdominal issues as well as eight ct examinations requiring a minimum of a dual phase protocol, were randomly incorporated for interpretation to prevent reviewer bias but were not included in the statistical analysis. routine abdominal b-mode ultrasound was performed with a dedicated machine using a microconvex curvilinear array transducer and / or a linear array transducer. the selection of the probe and frequency, depth of field, overall gain, time-gain compensation and focal gain were all adjusted at the choice of the sonographer interpreting at the time to optimise image quality. the ultrasonography was performed and interpreted by either a primary resident or board-certified imaging faculty member at the illinois teaching hospital. thirdly, the routine b-mode ultrasonography was immediately followed by ceus. all patients finally underwent mdct, comprising of a dual-phase contrast enhanced abdominal ct, using a 16-slice helical ct scanner. ‘every attempt’ was made to scan animals awake – details of which are not described, and intravenous (iv) sedation was used where this was not possible. study design: cross-sectional study. outcome studied: variables assessed in radiographic interpretations: presence / absence of pneumoperitoneum, small intestinal plication, visible small intestinal foreign material, presence of small bowel distension, whether it was a surgical or non-surgical case based off image interpretations, peritoneal serosal detail was considered as an ordinal variable: i.e. if normal, focal loss of detail, multifocal loss of detail and generalised loss of detail. variables assessed by ultrasonography: presence or absence of pneumoperitoneum lesions, hyperechoic mesentery, small intestinal plication, visible zone of transition if bowel plication or distension (only small intestine included), whether it was a surgical or non-surgical case based on interpretations alone, volume of peritoneal free fluid was considered as an ordinal variable (i.e. none, focal, multifocal or generalised). variables assessed through non-imaging modes: exploratory laparotomy or necroscopy with histopathology was used as the reference standard for diagnosing surgical underlying conditions such as; small intestine mechanical obstruction, visceral abscess, traumatic diaphragmatic hernia or gastrointestinal perforation. lesions that were surgically excised and gross pathological lesions were assessed histologically by a single pathologist. cases that were humanely euthanised had necroscopies to confirm non-surgical conditions. cases that survived to discharge had overall survival time in days recorded – anything surviving more than 30 days were recorded under the assumption that prolonged survival meant that the underlying condition in the patient did not require immediate surgical intervention. in cases of acute pancreatitis shown by sonographic imaging results of canine pancreatic lipase immunoreactivity (cpli) and ultrasound (us) guided fine needle aspirate was also required for inclusion into the study. statistical analysis: statistical tests and analysis were selected and performed by one of the primary authors. commercial software was used for statistical analysis and a p-value of < 0.05 was used to be considered statistically significant. continuous variables were assessed using a shapiro-wilk test for normality, and those that that met the assumption for normality a leven’s test was performed for homogeneity of variance. categorical and ordinal variable agreement between the modalities was assessed with a cohen’s kappa coefficient and weighted kappa. interpretation of the kappa coefficient was split into seven categories: 0 = chance agreement < 0.2 = poor agreement 21–0.40 = fair agreement 41–0.60 = moderate agreement 61–0.80 = good agreement > 0.8 = very good agreement 0 = perfect agreement the agreement between b-mode an ceus were assessed using a bland-altman plot relating to the size of pancreatic lesions. specificity, sensitivity, positive predictive value (ppv), negative predictive value (npv) and accuracy for differentiation was also assessed for each modality for if it was a surgical or non-surgical case. main findings (relevant to pico question): 8/19 (42%) patients of cases were considered to have a non-surgical underlying condition. 11/19 (58%) patients were considered to have a surgical intervention causing underlying condition. 10/11 (90.9%) cases had surgical and / or histologic confirmation of disease. 6/10 (60%) cases were foreign bodies: four linear foreign bodies; cloth, bandage material with sponge, multiple solid objects with fibrous connection, unknown material, one corn cob obstruction in the proximal jejunum, one combined gastric and jejunal cloth obstruction. radiography results: survey radiographs correctly identified 8/9 (88.9%) cases as surgical for which a conclusion could be made with imaging findings alone. a single-false negative radiographic diagnosis was made which was a linear foreign body with extension from the pylorus to the distal duodenum. ultrasound results: ultrasonography correctly identified 8/9 (88.9%) cases as surgical for which a conclusion could be made with imaging findings alone. the false-negative diagnosis was made in the case of gastric perforation due to an inability to identify pneumoperitoneum. ct results: if a surgical condition could be identified with imaging findings alone, the correct assessment was made by ct in 9/9 (100%) cases. both radiography and ultrasound were able to identify 8/9 (88.9%) patients correctly that needed surgical intervention. there was moderate to good agreement between modalities with reference against ct as contextualised care, however, both modalities missed one patient for different reasons. sensitivity, specificity, ppv, npv and accuracy of each modality for a diagnosis of a surgical condition, excluding two cases for which cytology was required: ce-mdct = 100% for all. ultrasonography and radiography together: sensitivity 89%. specificity 100%. ppv 100%. npv 89%. accuracy 94%. limitations: it is not made clear how 9 cases were found to be surgical, only that imaging was not enough to make a conclusion. some animals were scanned awake and some sedated, nine animals were imaged awake while 10 received sedation. evaluation of this new variable may have shown differences in ability to interpret images, and also drug choice may have changed some parameters of the variables interpreted. for example, the use of opioids and possible reduction of gastrointestinal motility. it is not detailed which animals had sedation, or which drugs were used. there is no mention of a power calculation when taking sample size into consideration, even without the calculation it can be seen the sample size is small. the timings between diagnostic imaging are not consistent for all cases and so may have had an impact on what could be seen within the images due to continued gut motility or progression of illness or gross change of the lesions. in 17/19 (89.5%) cases a three-view abdominal series of radiographs were taken (right lateral, left lateral and ventrodorsal views), whereas a two-view series (only right or left lateral and a dorsoventral view) were obtained in the remaining two cases. having one fewer image to assess may have limited the evaluation for the cases. 18/19 (94.7%) cases had digital radiographs whereas one case had analogue films obtained by the referring veterinarian that were later scanned into the system. this creates an additional variable of image quality and may have had an impact on the results for this case. radiographs were taken by various people, and so apart from routine procedure guidelines there is not a methodology to replicate, it is also clear by the fact that one case had analogue film sent in that the radiographs were not all taken in the same place and so routine procedure for taking the radiographs could be varied by practice. in 10/19 (53%) cases the evaluation with ultrasound (us) of the abdomen was considered only partial due to inability to visualise specific organs, while not specifically the small intestines this may still have had an impact on visualising surrounding features. results of ultrasonography and radiographic as individual modalities were not shown in relation to sensitivity, specificity, ppv, npv or accuracy. due to the fact that majority of cases required the sonographic detection of a specific lesion to be included in the study there may be bias towards the diagnostic accuracy of ultrasound above the other modalities. assessment of the 7 grades of how the modalities agree with each other with the kappa coefficient are subjective. all exams and interpretations were not completed by the same examiner. ultrasonography interpretation is dependent on the experience and skill of the reviewer and so results in general practice may vary. duration of clinical signs prior to hospitalisation was variable; and so, timings of imaging from onset of clinical signs are not consistent or replicable. radiography and ultrasound cannot be performed at the same time and so time between them and movement of patient and possible obstruction could have had an influence on results. in standard practice two orthogonal views are commonly used rather than the three-view abdominal radiography procedure that was performed in the majority in this study. no cases of milder acute abdominal pain were included in the study, there was high heterogeneity of diseases in the study. there is also a variety of breeds, ages and numbers of each sex which would not be possible to replicate.   sharma et al. (2010) population: dogs older than 4 months. admitted to hospital for acute vomiting between february 1, 2008 and may 31, 2009. sample size: dogs n = 82. intervention details: all 82 dogs had both abdominal radiography and abdominal ultrasound along with one reference procedure: exploratory laparotomy, necroscopy or follow-up phone call to owner at least 1 month after discharge from hospital. order of imaging was varied due to hospital scheduling. radiographic and ultrasonographic imaging were performed and interpreted by different blinded board-certified radiologists. abdominal radiography was performed in left lateral, right lateral and dorsal recumbent positions using one of two radiographic machines and commuted radiography. positioning order was not standardised. radiographic examinations were evaluated by board-certified radiologists with a minimum of 10 years experience. ultrasonography was performed by imaging residents with at least 6 months of training or by a board-certified radiology faculty with at least 6 years of experience. if a resident performed the study, they were supervised by the board-certified specialist. one of two ultrasound machines were used with a variety of transducers. dogs were placed in dorsal recumbency, fur clipped or parted and coupling gel applied to skin. practice standardised abdominal ultrasound examination was performed. laparotomies and necroscopy examinations were performed by attending resident(s) or a board-certified surgeon and pathologist. study design: cross-sectional study. outcome studied: variables assessed in radiographic interpretations: determination of small intestinal mechanical obstruction (subjective measurement). height of the fifth lumbar vertebral body (l5). maximal small intestinal diameter. pattern of small intestinal dilatation. measurements of the height of the l5 vertebral body (l5) and the small intestinal diameter (si); and calculation of the ratio of these (si/l5). variables assessed by ultrasonography in addition to practice standardised examination: determination of small intestinal mechanical obstruction (subjective measurement), potential obstructing lesion (subjective measurement), number of gastric contractions, number of small intestinal contractions, small intestine diameter, small intestine wall thickness, small intestine lumen diameter, small intestine wall layering (subjective measurement), peritoneal fluid (subjective measurement), mesenteric echogenicity (subjective measurement). all measurements were objectives except for those noted as subjective. other outcomes studied: partial or complete small intestinal mechanical obstruction was confirmed during laparotomy or necroscopy. dogs were classified as not obstructed if not identified during laparotomy or necroscopy, or if alive and well more than 30 days after discharge from hospital. statistical analysis was performed using commercially available software. accuracy of diagnosing small intestinal mechanical obstructions by ultrasound or radiography was determined by calculating area under roc curve for each modality. statistical significance was set at p < 0.05 (two sided). agreement between diagnostic methods was determined used the weighted kappa statistic. main findings (relevant to pico question): 27/82 (33%) of dogs had small intestinal mechanical obstructions confirmed by surgery (n = 26) or necroscopy (n = 1). foreign bodies were caused by cloth; plastic bag; toy ball; shoe-string; phytobezoar and dental floss. three cases were diagnosed incorrectly as small animal intestinal foreign body. there was one false positive based on decisions from ultrasonography alone (found negative in exploratory laparotomy). there was moderate agreement of tests. radiography produced a definitive result of whether there was an obstruction or not in 58/82 dogs (70.7%). ultrasonography produced a definitive result of whether there was an obstruction or not in 80/82 dogs (97.6%). with receiver operating characteristic (roc) curve analysis: overall accuracy of three view abdominal radiography – area under curve (auc) 0.82, se 0.054, 95% confidence interval (ci) 0.72–0.89. overall accuracy of abdominal ultrasound – auc 0.95, se 0.029, ci 0.88–0.99. p = 0.013. same results between radiography and ultrasound were produced 52/82 (63%). different results were produced 12/82 (15%). subjective findings: confident results (definitely not obstructed, definitely obstructed) were increased after ultrasound exams (n = 80) compared to radiography (n = 58). intermediate or questionable results (questionably not obstructed, indeterminate, questionably obstructed) were produced more after radiographic interpretations (n = 24) than after ultrasound (n = 2). limitations: assessment on deciding if there was an obstruction was slightly subjective as the grading was based on confidence of reviewer. all exams and interpretations were not completed by the same examiner. ultrasonography interpretation is dependent on the experience and skill of the reviewer. while attempts at no conferring between interpreters were made in separating ultrasonography and radiology areas and limiting the available information about patients (interpreters only knew that the patients were vomiting dogs), this study was not completely blinded and bias may have taken place. duration of clinical signs prior to hospitalisation was variable; and therefore timings of imaging from onset of clinical signs are not consistent or replicable. sedation and medication inconsistencies were not evaluated or described which may have influenced imaging. this was particularly seen in a dog that was eventually diagnosed with myasthenia gravis. radiography and ultrasound cannot be performed at the same time and so time between and movement of patient and possible obstruction could have had an influence on results. positioning was consistent for imaging but not the order of positions, or order of modalities used, this may have also impacted the results. the study included only small-intestinal, not gastrointestinal mechanical obstructions. the foreign bodies might have changed position before or during surgery due to manipulations. there is also a variety of breeds, ages and numbers of each sex which would not be possible to replicate.   tyrrell & beck (2006) population: dogs with clinical signs of a gastrointestinal foreign body, presenting at the university of melbourne veterinary clinic and hospital (umvch) australia, between june 2003 and september 2004. sample size: dogs n = 11. intervention details: dogs presenting to umvch that had abdominal radiography and ultrasound with a suspected foreign body were screened for the study. after the foreign body was confirmed, either through removal via endoscope or surgically or it passed naturally in the faeces, the animals were included in the study. abdominal radiographs were taken for each patient in recumbent lateral and ventrodorsal positions. a complete abdominal ultrasound exam was then performed straight after the radiographs. they were performed by either of the authors using an acuson aspen with multifrequency 5–7 mhz microconvex transducer or a linear array 7–13 mhz transducer. study design: cross-sectional study. outcome studied: radiographs were analysed by one of the authors (d.t.) for the following changes consistent with a foreign body: serosal detail, intestinal plication, gastric distension and overdistension of the small intestines. gastric distension was also recorded if the fundus was greater than three intercostal spaces. small intestines were recorded as being distended in dogs if the ratio compared to the body of the fifth lumbar vertebrae was greater than 1.6. accumulation of fine, opaque particulate material was also noted. ultrasonographic images were assessed for presence and location of any foreign bodies by either author. they were found by identifying their shape, strong distal acoustic shadowing and variable degrees of surface reflection. gastric and intestinal wall thickness was measured, wall layering was estimated and the presence of gastric and intestinal distension was assessed subjectively. other assessments were the gastrointestinal contents, lymphadenopathy, intestinal plication, increased echogenicity of the mesentery and if there was effusion present. main findings (relevant to pico question): radiograph findings: 9/16 (56%) cases of a foreign body were detected by radiography, this result includes five cats used in the study. the percentage of dogs found to have foreign bodies through radiography was not defined. ultrasonographic findings: 11/11 (100%) of the canine cases with foreign bodies were detected with ultrasound. surgical results: foreign bodies were removed from the small intestines in nine dogs. one gastric case had the foreign body removed endoscopically, and one colonic foreign body case passed in the faeces. the types of foreign bodies were: fruit pits, corn cobs, pieces of rubber toy, trichobezoars, an ear plug and elastic meat wrapping. all animals recovered from surgery and clinical signs resolved. limitations: the study did not define the percentage of dogs found to have a foreign body through radiography. there may have been bias when analysing the radiographs as the interpreter was not blinded to the signalment and clinical sign of the patient. while the radiographs were interpreted by one person, the ultrasound examination and interpretation were done by either of the two authors, this may have caused a variation in method and interpretation. this also means some animals could have had both modalities performed by the same person which could introduce more bias into the results. clinical sign duration varied greatly between the animals, and so timings between onset of signs and imaging are not possible to replicate. there is also a variety of breeds, ages and numbers of each sex which would not be possible to replicate. while the study shows the percentages of correct diagnoses from each modality there are no statistics to show if they are significantly different, and no detail given to which animal or material of foreign body was missed on radiography. within the ultrasound examination the intestines were considered distended only through a subjective measurement, this could have varied slightly and may have even been biased from other findings in the image, it would be necessary to create a quantitative measurement in order to analyse the degree of fluid accumulation and distension. there were varying types of foreign bodies, while this makes it apply more to general practice it does not focus on how well ultrasound or radiography can detect each one as there is no detail given to which foreign body was missed on radiography, it also makes the study hard to replicate to see if the results are repeated. there is a small sample size and so unlikely to represent a greater population. it was noted that ultrasonic observation of the peristaltic activity may be an important indicator of obstruction, however it was inconsistently recorded in this study and so was not entered as a variable, this may have had an impact on the results if it had been included. only animals with gastrointestinal foreign bodies were included in the study. this was known to the interpreters. minimal to no measures were taken to reduce bias from the interpreters. there is also a variety of breeds, ages and numbers of each sex which would not be possible to replicate.   appraisal, application and reflection it is essential to quickly and accurately diagnose a surgical condition such as small intestinal obstructions in dogs presenting with acute abdominal signs, as prompt treatment is necessary in providing the best care and prognosis. it is therefore important to understand which modality would be most accurate in detecting the need for surgical intervention, enabling prompt action in investigating cases further. the most common imaging diagnostic tools readily available in first opinion practice are radiography and ultrasonography. this appraisal summarises the findings from six relevant studies to compare the two modalities for when making those decisions for surgical intervention. elser et al. (2020) study population included 40 dogs with clinical suspicion of mechanical obstruction and inconclusive initial radiology, presenting with acute abdominal signs. this study has been included for completeness however, the extent to which it answers the question posed in this summary is limited, this is due to multiple issues including the selection criteria of the patients; patients were included in the study only if there was an inconclusive radiographic finding. this places a bias against the usefulness of radiography to diagnose small intestinal obstruction due to all patients with a conclusive radiograph findings being excluded. ultrasound was used as the contextualised care and radiograph results were referenced against those findings and accuracy was looked at between interpreters rather than overall. there was shown to be a wide range of agreement among the reviewers, based on their experience level. however, the accuracy of correct diagnosis of intestinal obstruction, measured in a mixed animal population (40 dogs and 17 cats) ranged high from 70.2– 89.7% overall through reviewing radiographs. winter et al. (2017) compared ultrasound against computerised tomography ct diagnostic imaging, with the contextualised care of exploratory laparotomy for a definitive diagnosis, this allows the accuracy of using ultrasound to be investigated. ultrasonography showed to have a sensitivity of 100% and specificity of 67% for a correct diagnosis, whereas ct was 100% for both. this shows ultrasound is an extremely useful tool when investigating dogs with acute abdominal signs when ct is not available. drost et al. (2016) compared abdominal radiography and ct, for detection of canine mechanical intestinal obstruction, again using exploratory laparotomy as a reference. the sensitivity and specificity of ct on the diagnosis of obstruction were shown to be slightly lower in this investigation at 95.8% and 80.6% respectively, whereas the radiography sensitivity and specificity were 79.2% and 69.4% but the differences were not statistically significant. if directly compared to winter et al. (2017) ultrasound results against the same referencing standard ultrasound had a higher sensitivity and a higher specificity for diagnosis. however, both studies investigated ct too and found different results in ct specificity and sensitivity. this shows that there were differences, limitations and possible study design problems between the two. drost et al. (2016) also had the added evaluation of sensitivity and specificity of recommending abdominal surgery after reviewing the radiograph images, this increased the radiographic interpretation with sensitivity rising to 91.7% and specificity to 72.2%. therefore, even if a definitive diagnosis cannot be given, the important decision of correct intervention is likely to be chosen. it would have been interesting to compare a similar measurement in winter et al. (2017) methodology using ultrasound in a similar manner if it had been evaluated. shanaman et al., (2013) used a cross-sectional design, this study compared both ultrasonography with radiography against exploratory laparotomy and ct in dogs presenting with intense pain and acute abdominal signs. this study did not only focus on small intestinal obstructions but also a wide range of other underlying causes of acute abdominal signs, but it does address the question of which modality was more accurate by comparing them to the contextualised care of ct. the study showed the level of agreement between the modalities in diagnostic accuracy. both radiography and ultrasonography correctly identified 8 out of 9 surgical cases, with one false negative for each for different reasons, relative to their limitations. also, there was shown to be good agreement between the two modalities and ct, which was used as the contextualised care, along with abdominal surgery or necropsy. finally, the study suggests an impression of superiority from abdominal radiographs compared to ultrasound in cases with pneumoperitoneum, but further studies are needed. this is important as intestinal obstructions that caused intestinal ruptures, which are true surgical emergencies, might be better and more quickly diagnosed with radiographs. tyrrell & beck (2006) used a similar approach by also using a cross-section design to their diagnostic validity study, and this study differs from shanaman et al. (2013) by focusing purely on gastrointestinal foreign bodies not a wider range of underlying conditions. this study looked at the use of radiography versus ultrasonography to diagnose foreign bodies in small animals, and so included cats and dogs in their population. while the pico of this knowledge summary focuses on dogs it was not defined in their radiographic results what the exact number of positive foreign body findings were in the dog population versus cats. tyrrell & beck’s (2006) study give clear results on percentages of the accurate diagnoses of the modalities but it does not have any statistical evaluation of comparing them to each other to see if they are significantly different. out of the 16 cases, of both cats and dogs, radiography identified 56% of the foreign bodies and ultrasound (us) detected 100% of the cases. all of the cases were confirmed through the removal of the material in surgery, endoscopically, or in one case letting it pass naturally in the faeces. while this study supports the findings found in the other studies that us may be more sensitive in detecting foreign bodies in the small intestine in small animals, it does not evaluate its results through statistical analysis, the differences between the modalities are not proven significantly important, the sample is very small, and the risk of bias is high. results found in the study by sharma et al. (2010) were that 58/82 (70.7%) dogs had a definitive result with radiology showing patients being obstructive or unobstructed in the small intestine. and ultrasonography produced definitive results in 80/82 (97.6%) of dogs. and they concluded ‘abdominal ultrasound was more accurate, with fewer equivocal results and provided greater diagnostic confidence compared with radiography, in small intestinal foreign body mechanical obstruction’. one limitation that most of the studies have are the small sample sizes, with only one mention of a power calculation in which we can apply the results to a wider population (drost et al., 2016) and one study with a bigger sample population compared to the rest (sharma et al., 2010). both elser et al. (2020) and tyrrell & beck (2006) studies had the inclusion of cats into their sample population as well as dogs, this reduces the sample size relevant to this summaries question even further, and so it may be difficult to apply these findings into a much wider population without future studies supporting these results. there are a variety of levels of attempts of blinding within each study to consider. winter et al. (2017) had the ultrasound images reviewed in real time and findings were discussed with the attending surgeon, this may have introduced bias based on signalment and clinical signs as well as introducing additional views and potential influence from other clinicians. however, this bias is reduced with the addition of objective measurements used in the assessment, not just subjective views. in the study by drost et al. (2016), the reviewers were blinded to clinical history and the images were reviewed at least 12 months after the date of the study and viewed in random order. this strengthens the level of blinding and reduces bias. shanaman et al. (2013) had various people take the radiographs and then interpreters assessed the images, this creates a level of blinding, where the case details were hidden including the signalment and presenting signs of the animal. the primary author was involved through the three assessed modalities, this could have introduced bias as having looked at the previous modality there could be links made between the previous images unconsciously. so instead there may be confirmation of diagnosis rather an independent diagnosis. however, this hypothesis cannot be proven and gets weaker if we consider that the patient history was unknown and the studies were seen retrospectively. sharma et al. (2010) had a higher level of blinding in that radiographs and ultrasound exams were not done by the interpreters to reduce bias. with tyrrell & beck (2006) it was the authors that performed the exams and interpreted them knowing both the patient history and that all animals included in the study had a gastrointestinal foreign body, so there was no blinding possible to the results of the other modality and of the signalment and presenting signs of the case. the radiographs in the study were all viewed by one interpreter and the ultrasound images were analysed by two different people, this may have had an impact on the results due to method and interpretations. an important limitation of all the studies is the use of highly trained individuals in reviewing the diagnostic images, in comparison to the wider population in general practice. as seen in elser et al. (2020) study with the use of four reviewers, with a range of experience from first year radiology resident to board-certified radiologist with 16 years experience, there was found to be a wide range of levels of agreement between the reviewers. and this disagreement was with a group of highly trained individuals, since the first year radiology resident had 6 years of veterinary experience including a 1 year diagnostic imaging specialty internship prior to residency. this shows the degree to which experience has an effect on correct interpretation and decision-making, which is an important limitation when extrapolating the results in this summary into the wider population of general practice. however, there were several more problems and limitations in this study that were previously mentioned, that might have affected its results. in conclusion, it can be seen with the studies evaluated here that both radiology and ultrasound are highly valuable diagnostic tools that can both increase the accuracy of diagnosis and correct decision-making for surgical intervention. it can also be seen that ultrasound has the potential to be superior than radiography at detecting surgical patients with intestinal obstructions in dogs with acute abdominal signs. this potential is highly correlated to the experience of the observer, and so it is recommended that those in general practice should focus on encouraging development and experience in further imaging training, including ultrasound and radiography assessment for patients with acute abdominal signs in order to increase accuracy and confidence in making future surgical intervention decisions. there are major limitations within the studies observed here; focusing mainly on small sample sizes in most of them, which reduces the ability to apply the findings to larger populations, lack of significant differences between radiographic and ultrasound investigations, or even lack of statistical analysis. while there are differences observed the lack of continuous significant differences highlights the fact that there needs to be further research in this area, ideally with larger sample sizes and without the limitations discussed in this summary. methodology search strategy databases searched and dates covered: cab abstracts on cab direct (from 1990 – 6 february 2023) pubmed database (from 1990 – 6 february 2023) search strategy: cab abstracts: (dog or canine) (ultraso* and radiograph*) (obstruct* or foreign body or surg* or acute abdomen) (diagnos* or detect*) (intestin* or bowel) 1 and 2 and 3 and 4 and 5 pubmed: (dog or canine) and (ultraso* and radiograph*) and (obstruct* or foreign body or surg* or acute abdomen) and (diagnos* or detect*) and (intestin* or bowel) dates searches performed: 06 feb 2023   exclusion / inclusion criteria exclusion: not in english. pre-1990. not a direct comparison between ultrasound and radiography to each other or another modality. not small intestine obstruction. not including dogs. not relevant to pico. ultrasound as treatment not diagnostic. inclusion: in english. direct comparison between ultrasound and radiography to each other or another modality. on small intestinal obstructions. dogs. relevant to pico. diagnostic studies.   search outcome database number of results excluded – not in english excluded – not relevant to pico excluded – not on small intestinal obstructions excluded – not diagnostic comparison study excluded – on treatment not diagnosis total relevant papers cab abstracts 11 3 1 1 5 0 1 pubmed 65 4 7 21 22 5 6 total relevant papers when duplicates removed 6   orcid josephine corrick: https://orcid.org/0000-0002-4442-5516 conflict of interest the author declares no conflicts of interest. references drost, w.t., green, e.m., zekas, l.j., aarnes, t.k., su, l. & habing, g.g. (2016). comparison of computed tomography and abdominal radiography for detection of canine mechanical intestinal obstruction. veterinary radiology & ultrasound. 57(4), 366–375. doi: https://doi.org/10.1111/vru.12353 elser, e.b., bagshaw, h., mai, w., suran, j.n., reetz, j.a. & thawley, v. (2020). serial abdominal radiographs do not significantly increase accuracy of diagnosis of gastrointestinal mechanical obstruction due to occult foreign bodies in dogs and cats 10. veterinary radiology & ultrasound. 61(4), 399–408. doi: https://doi.org/10.1111/vru.12870 shanaman, m.m., schwarz, t., gal, a. & o’brien, r.t. (2013). comparison between survey radiography, b-mode ultrasonography, contrast-enhanced ultrasonography and contrast-enhanced multi-detector computed tomography findings in dogs with acute abdominal signs. veterinary radiology & ultrasound. 54(6), 591–604. doi: https://doi.org/10.1111/vru.12079 sharma, a., thompson, m.s., scrivani, p.v., dykes, n.l., yeager, a.e., freer, s.r. & erb, h.n. (2010). comparison of radiography and ultrasonography for diagnosing small-intestinal mechanical obstruction in vomiting dogs. veterinary radiology & ultrasound. 52(3), 248–255. doi: https://doi.org/10.1111/j.1740-8261.2010.01791.x tyrrell, d. & beck, c. (2006). survey of the use of radiography vs. ultrasonography in the investigation of gastrointestinal foreign bodies in small animals. veterinary radiology & ultrasound. 47(4), 404–408. doi: https://doi.org/10.1111/j.1740-8261.2006.00160.x winter, m.d., barry, k.s., johnson, m.d., berry, c.r. & case, j.b. (2017). ultrasonographic and computed tomographic characterization and localization of suspected mechanical gastrointestinal obstruction in dogs. journal of the american veterinary medical association. 251(3), 315–321. doi: https://doi.org/10.2460/javma.251.3.315 contribute to the evidence there are two main ways you can contribute to the evidence base while also enhancing your cpd: tell us your information need write a knowledge summary either way, you will be helping to add to the evidence base, and strengthen the decisions that veterinary professionals around the world make to give animals the best possible care. learn more here: https://veterinaryevidence.org/index.php/ve/guidelines-for-authors licence copyright (c) 2023 josephine corrick intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use.   veterinary evidence is an rcvs knowledge initiative. issn: 2396-9776 first floor, 10 queen street place, london ec4r 1be resources student awards staff login policies privacy policy accessing information policy cookie declaration terms of use copyright notices stay connected podcasts twitter facebook instagram linkedin back to top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443. in dogs diagnosed with osteoarthritis, how safe and effective is long-term treatment with bedinvetmab in providing analgesia? | veterinary evidence skip to main content knowledge summary keywords: canine; osteoarthritis; bedinvetmab; monoclonal antibody; canine nerve growth factor; analgesia; chronic osteoarthritis associated pain; safety; effectiveness in dogs diagnosed with osteoarthritis, how safe and effective is long-term treatment with bedinvetmab in providing analgesia? katrin kronenberger, phd1* 1 university of edinburgh, royal (dick) school of veterinary studies, easter bush campus, midlothian eh25 9rg * corresponding author email: k.kronenberger@sms.ed.ac.uk vol 8, issue 1 (2023) submitted 15 feb 2022; published: 01 feb 2023; next review: 25 aug 2024 doi: https://doi.org/10.18849/ve.v8i1.598 pico question in dogs diagnosed with osteoarthritis (oa), how safe is treatment with bedinvetmab, when compared to a placebo and how effective in long-term reduction of the severity of the clinical signs associated with oa-related pain? clinical bottom line category of research treatment. number and type of study designs reviewed two papers were critically reviewed. one was a randomised, blinded, multi-arm laboratory safety study; the other a multi-center field trial consisting of a block-randomised, double blind, placebo-controlled phase, followed by a non-comparative, open-label case series study. strength of evidence weak. outcomes reported one study rated the reduction of the severity of clinical signs associated with oa pain using owner canine brief pain inventory (cbpi) ratings and non-validated veterinary clinical assessments (vcas). safety was addressed by evaluating adverse health effects (ahes), concentration of antidrug antibodies (adas), and clinical pathology. significant improvements in pain scores and vcas were reported in this treatment study. the second safety-only study used clinical observation to evaluate ahes. both studies reported ahes. conclusion a single study suggests that treatment with bedinvetmab is effective. two studies support the drug having few ahes. both studies have significant design limitations preventing the evaluation of bedinvetmab effectiveness. there is weak / inconclusive evidence for long-term efficacy and short-term safety of oa treatment with bedinvetmab. the decision to use bedinvetmab remains dependent on the judgement and experience of the clinician. how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a 12-year-old laika-cross has been diagnosed with canine osteoarthritis (oa), affecting his coxofemoral and stifle joints.  meloxicam helped manage the dog’s pain for over 12 months successfully. however, the owner is concerned about the risk of adverse effects and asks for alternative treatment options not involving non-steroidal anti-inflammatory drugs (nsaids). you are considering bedinvetmab (librela, zoetis), which has only recently become available. you want an understanding of efficacy, effectiveness, and safety evidence before deciding whether this is an alternative treatment option to suggest to the owner. the evidence the krautmann et al. (2021) pre-clinical laboratory study addressed the safety effects of bedinvetmab in healthy, mature laboratory beagles. the authors neither describe the process of random assignment to the three study groups, nor further assignment to the smaller subgroups within these separate studies. in this study, dogs were stratified by sex. the small cell sizes (n = 8) within each study condition raise concerns of overall potential sample bias or cell-specific sample bias. generalising from mature laboratory beagles to an older target oa population may be a concern, although this is how most other analgesics are tested. the corral et al. (2021) ‘change from baseline’ study assessed both efficacy and safety of bedinvetmab in client-owned dogs with oa. pretreatment canine brief inventory (cbpi) pain scores were used as baseline comparison and included in the efficacy analysis of bedinvetmab. standardisation instructions on using the cbpi explicitly indicate that the first cbpi score should be discarded due to potential regression to the mean (rtm) (brown et al., 2008). corral et al. (2021) did not follow this guidance to use the second pain score as baseline, which may have resulted in treatment and control groups being significantly different. interpretation of this difference was confounded by 7 days of bedinvetmab treatment preceding this second score. this multi-site, multi-national trial spanned several countries with different numbers of sites in each country and different numbers of dogs at each site. the cbpi was not translated into the target languages, potentially impacting its reliability / validity. loss to follow-up affected placebo and treatment groups differentially, which may increase the risk of bias. 22/146 (15.1%) of the dogs randomised to the placebo group, and 9/141 (6.4%) of the dogs randomised to the bedinvetmab group were excluded from the efficacy analysis. loss to follow-up and blinding was incomplete. limitations of study design and execution of both studies suggest there currently is only weak evidence for long-term efficacy and short-term safety of bedinvetmab for the alleviation of oa-related pain in dogs. summary of the evidence corral et al. (2021) population: client–owned dogs of any breed, sex, and body weight. eligibility criteria for inclusion: dogs aged ≥ 12 months at enrollment. osteoarthritis (oa) in at least one joint of the pelvic or thoracic limbs (confirmed by orthopaedic examination and supported by radiographic evidence). canine brief pain inventory (cbpi): dogs with an initial pain severity score (pss ≥ 2) and a pain interference score (pis ≥ 2) (owner-assessed) were confirmed eligible. orthopaedic examination: dogs with at least one of three components of the veterinary clinical assessment (vca) assessed as ‘moderately affected’ on day 0 (1. lameness / weight-bearing; 2. pain on palpation / manipulation of joint(s); 3. general musculoskeletal condition), were confirmed eligible. no other uncontrolled concurrent disease or concomitant treatment, and satisfactory blood and urine clinicopathological results. criteria for exclusion: enrollment in a clinical trial of any type ≤ 30 days prior to day 0. previous treatment with an anti-nerve growth factor monoclonal antibody (anti-ngf mab). pregnancy, lactating or intended use as a breeding animal. anticipated surgical intervention, enrollment in physical therapy or in a weight loss program < 8 weeks before day 0. lameness known to be related to neoplasia, primary neurologic or immunologic disorder, infection, recent joint trauma, or non-healed fracture. history of intervertebral disc disease or evidence of injury resulting in neurologic deficits. administration of any of the prohibited medications. sample size: 287 dogs. initial 3 month randomised, controlled, blinded comparative phase: client-owned dogs diagnosed with osteoarthritis (n = 287) enrolled from 26 veterinary practices across europe (hungary [n = 8], ireland [n = 6], germany [n = 3], portugal [n = 9]). n = 22 dogs were removed requiring rescue treatment before day 84: n = 19 in the placebo group and n = 3 in the treatment group. 6 month single-armed, open-label continuation phase: a non-randomised subset of bedinvetmab-treated dogs with a ‘positive response’ to treatment (n = 89) enrolled from 14 veterinary practices across europe (portugal [n = 5], hungary [n = 4] and ireland [n = 5]). n = 11 dogs were removed before study completion; n = 10 developed unrelated medical conditions and one case required rescue treatment. reported numbers of dogs in both phases of the study do not match reported number of dogs at start and after rescue removal. n = 23 dogs (8.01%) were removed from the study, mainly due to worsening of clinical signs of oa. sample size estimates (≥ 120 dogs / group) were derived from power calculations based on variance and effect sizes from unpublished data. aim was to achieve at least 80% power at a significance level of ɑ = 0.05 (two-sided). cbpi pain scores pss and pis were analysed using a generalised linear mixed model for repeated measures. pre-treatment scores (baseline) were used as covariates; treatment and interaction between treatment and day of study were used as fixed effects in the model. random effects included site, block within site, interaction between site, treatment and day of study, and error. primary outcome response variables are binary (treatment success yes / no) and were analysed using a generalised linear mixed model with binomial distribution and logit link with level of significance set at ɑ = 0.05 (two-sided). fixed effect was treatment and random effects site, block within site, and interaction between site and treatment. back-transformed least square mean (lsm) proportion, 95% confidence interval (ci) and standard error (se) were used to report the estimated proportion of dogs having achieved treatment success. intervention details: intervention bedinvetmab (librela, zoetis) dosage between 0.5–1.0 mg/kg was administered subcutaneously (sc) monthly for a maximum of 9 months. control 9% saline was administered sc at a dose volume equivalent to bedinvetmab administered monthly for 3 months. initial 3 month randomised, controlled, blinded, comparative phase: blocked randomisation: two eligible dogs per block were assigned at random to the placebo (n = 146) or the bedinvetmab group (n = 141) ensuring an allocation ratio of 1:1 at each test site in order of entry, based on a randomisation protocol developed by a statistician. a dispenser used an electronic data capture system to randomise the dogs. blinding: owners and all study personnel were blinded to group assignment, apart from the treatment dispenser at each test site, who was responsible for preparation and administration of study treatment. pretreatment data were collected at enrollment and used as baseline for analysis. first treatment administration on day 0. dogs were examined and samples collected for haematology, serum chemistry and urinalysis during seven visits on days 0, 7, 14, 28, 42, 56 and 84. dosing occurred on days 0, 28 and 56. 6 month single–armed, open–label, uncontrolled continuation phase: bedinvetmab–treated dogs who had ‘responded positively’ to treatment (n = 89) enrolled; 78 (n = 78) completed seven additional monthly visits over 6 months. during each visit: owners completed the cbpi. a veterinarian performed a physical examination and completed a vca. blood samples were collected (haematological variables, serum chemistry, bedinvetmab, total ngf serum concentration and anti-drug antibodies (adas) analysed. every 3 months urine was collected for urinalysis and evaluation of protein creatinine ratio. dogs could be withdrawn at any time by owner or veterinarian. after exiting the study, dogs could resume conventional oa treatment. in case of worsening clinical signs of oa or perceived lack of efficacy (loe), a rescue treatment i.e., a prohibited treatment, was considered and the dog defined as ‘not having improved’. study design: a randomised, double-blind, placebo-controlled, parallel-arm, multi-site experimental field study, followed by a 6 month single-arm, open-label case series study. outcome studied: primary efficacy outcome measure (subjective) cbpi-based treatment success was defined as a reduction of ≥ 1 in the pain severity score (pss) and of ≥ 2 in the pain interference score (pis) on day 28 compared with owner-assessed pretreatment (baseline) pss and pis scores. secondary efficacy outcome measures (subjective) cbpi treatment success for all other assessed time points. owner-assessed pss and pis scores (cbpi) for all other time points. owner-assessed overall impression of quality of life (qol). percentage of dogs having a ‘very good’ or ‘excellent’ life at each time point. assessment of the overall improvement of the vca across the three components compared to baseline a) improved in at least one component and the others not worse and b) improved scores in at least two components and the other score worse or unchanged. a dog was defined as ‘not having improved’ if neither a or b could be applied, or if a dog had been withdrawn because of perceived loe or had received rescue treatment.  safety outcome measures (objective) all animals enrolled in both phases were included in the safety data analysis. phase 1: placebo group n = 146 and bedinvetmab group n = 141; phase 2: n = 89 bedinvetmab-treated dogs. frequencies of dogs with at least one adverse health event (ahe) were summarised by clinical sign and clustered in organ classes. clinical haematology and urinalysis: reference ranges were compared to baseline and between treatment groups. immunogenicity data (development of adas) were evaluated by integrating the ada data with bedinvetmab and total ngf concentrations. main findings (relevant to pico question): efficacy of bedinvetmab a significantly greater proportion of dogs in the bedinvetmab group 58/133* (43.5%) achieved cbpi-based treatment success versus placebo group 22/137* (16.9%) on day 28 (p = 0.0017). the difference between the groups is statistically significant (the null hypothesis that treatment with bedinvetmab is no different to treatment with placebo can be rejected), yet the mean difference in response rates between groups is small. maximum bedinvetmab treatment effect was observed on day 42: 70/134* (52.6%) of bedinvetmab treated dogs versus 29/140* (21.1%) of dogs in placebo group (p = 0.0001). mean pss and pis scores (cbpi) on all other days were significantly different between bedinvetmab and placebo groups (p ≥ 0026). the percentage of dogs that demonstrated improvement in the cbpi overall impression of qol was higher in the bedinvetmab group than in placebo group at every visit during the comparative phase (no data provided). vca improvement versus baseline was significantly different in bedinvetmab versus placebo group (data not shown; p <01). overall improvement based on vca was significantly different in the bedinvetmab group (69.2–91.4%) versus the placebo group (≤ 9%) (p ≤ 0.0002). safety of bedinvetmab most frequently reported ahe was joint pain and lameness (23/146 [15.8%] dogs in the placebo group and 5/141 [3.5%] dogs in the bedinvetmab group). serious ahes: two dogs died during comparative phase; four dogs died during continuation phase. deaths were considered unrelated to treatment. n = 25/146 (17.1%) dogs in the placebo and n = 11/141 (7.8%) dogs in the bedinvetmab group received anti-inflammatory and antirheumatic concomitant medication, which was well tolerated and not associated with ahes in the bedinvetmab group. dogs in the bedinvetmab group showed a decrease in haemoglobin (hb) and packed-cell volume haematocrit (pcv) levels and an increase in aspartate aminotransferase and blood urea nitrogen concentrations compared to baseline and reference ranges and compared to dogs in the placebo group. a mild transient reaction at injection site was observed in one dog and was resolved within 6 and 7 days. a total of four dogs developed treatment-emergent adas during study (two transient and two persistent). 2/138 (1.4%) dogs developed bedinvetmab-associated immunogenicity; clinical manifestation was reduced efficacy of treatment (cbpi treatment success was not achieved at most time points). *these values were generated by the knowledge summary author and based on the back transformed mean proportions reported. limitations: first test cbpi scores were used as baseline group comparison scores in violation of cbpi standard guidance on likely regression effects. thus, subsequent repeated measures comparisons may be systematically distorted. cbpi administration violations may have resulted in initial differences between treatment and control groups. first baseline comparison was significantly different. this produces a high level of uncertainty when associating the reported changes of pain scores in bedinvetmab treated dogs with the clinical meaningful reduction of pain. removing randomised dogs’ outcome data from the efficacy analysis may inflate the estimated treatment effect. randomised dogs’ outcome data were removed from the efficacy analysis but were included in safety analysis, which may lead to biased results of unknown direction. no explanation was provided for why this removal was only considered as treatment failure and not included in the efficacy analysis. statistical management of missing data was not discussed. the authors were employees of zoetis, manufacturers of bedinvetmab, which may have introduced bias. no information on how the study was presented to owners prior to enrollment. no information on whether there was bias about which owners received study information. cbpi was not translated into target languages, which may impact its reliability and validity. vca was not validated, and data was not presented. a decrease in hb and pcv after administration of bedinvetmab was not discussed, and data not presented despite the potential for unexpected haematologic effects associated with mab therapies. the lack of inclusion of a placebo control group in the 6 month continuation phase affects internal and external validity of results (acknowledged by the authors), however, long-term treatment with a placebo of dogs with oa would have been unethical. enrolling a non-randomised subgroup of dogs based on outcome variables obtained in phase 1 of the trial may lead to biased results. no information was provided on how the dispenser’s activity was isolated from veterinary staff or owners to ensure adequate blinding. it is not clear whether randomisation was centralised across the different clinics to minimise selection bias and ensure balance of treatment group factors at baseline. different sections of the paper provide differing numbers of dogs for in comparison groups. it is difficult to determine which numbers are correct and whether p–values cited were based on correct or incorrect numbers of subjects. a treatment success (< 25%) in the placebo group based on cbpi owner assessment was not discussed.   krautmann et al. (2021) population: criteria for inclusion clinically healthy, purpose-bred, mature laboratory beagle dogs; age: 10–12 months old; bodyweight: 5.1–12.7 kg; sexually intact; previously immunised against standard canine pathogens. criteria for exclusion no details provided. sample size: n = 96 dogs. intervention details: overall intervention bedinvetmab (librela, zoetis) 15 mg/ml or 30 mg/ml (refrigerated, 2–8 â—¦c), administered subcutaneously (sc) at marked locations on the lateral neck. control 9% sterile saline solution for injection (hospira, inc.) administered sc at marked locations on the lateral neck and at volume equivalent to the 10 mg/kg dose volume.   three sub-studies study 1 (dose-dependent pre-clinical safety evaluation) maximum intended label dose of bedinvetmab 1 mg/kg. 3 mg/kg and 10 mg/kg overdoses for evaluation of therapeutic and super-saturating overdoses. study 2 (evaluation of t-lymphocyte-dependent immune response of bedinvetmab to keyhole limpet hemocyanin (klh)) klh: an unadjuvanted subunit, good manufacturing practices (gmp) grade klh (stellar biotechnologies) endotoxin-free (0 eu/mg of protein), formulated in 10 mm phosphate–buffered saline at potencies of 0.1 or 1 mg/ml/dose, and administered intramuscular (im) into the hindquarter within 24 hours of formulation. klh was used to examine cellular and humoral immune function by measuring t-cell dependant antibody titres (tdar test) following treatment with bedinvetmab or placebo. study 3 (evaluation of adverse effects of concurrent administration of bedinvetmab and nsaid carprofen) 4 mg/kg carprofen (rimadyl, pfizer) administered sc daily for 14 days. for each separate study 32 dogs were randomly selected and assigned to pens during the acclimation period (prior to study day 0) and to one of four treatments (n = 8; four males, four females per treatment) in pen order. randomisation to pens, treatments, and procedures were generated using sas release 9.4 (sas institute). personnel conducting subjective treatment-phase observations were blinded to group assignments. general, bone / joint, and clinical pathology, and toxicokinetics / ada data were summarised by respective experts unblinded to other study findings. acclimation period approximately 1 month prior to dosing. at conclusion dogs were either released back to the stock colony (study 2) or humanely euthanised (studies 1 and 3) using intravenous (iv) sodium pentobarbital (socumb, henry schein) prior to necropsy. study 1 n=32 split into four treatment groups of n = 8 (four male / four female). three bedinvetmab dose groups (1 mg/kg, 3 mg/kg, 10 mg/kg) and one saline group. treatment was administered sc every 28 days for seven doses (6 months duration). necropsy on days 182/183. four dogs were ‘deemed unsuitable’ (no further explanation was provided) during the acclimation period and were replaced with dogs of the same sex. bodyweights by treatment group and sex [least square mean (lsm), confidence interval (ci) 90%. day 1 pretreatment baseline. study 2 n = 32 split into four treatment groups of n = 8 (four male / four female). two paired groups were allocated to receive 0.1 mg or 1 mg klh intramuscular (im); within each pair, one received bedinvetmab 1 mg/kg and the other received saline sc on day 0. during the acclimation period two dogs (one male and one female) were removed due to thin body condition score and requiring dietary changes. they were replaced with two dogs of the same sex. elisa data was analysed using the average of duplicate background-corrected density data with < 25% coefficient of variation to detect a difference in mean log klh titres of two or four with 80% power at ɑ = 1. least square mean (lsm) ± standard error (se) anti-klh antibody titres after immunisation at two klh antigen doses in adult dogs treated with bedinvetmab. study 3 n = 32 split into four treatment groups of n = 8 (four male / four female). two groups received saline sc and two groups received bedinvetmab (1 mg/kg sc) on day 0, followed by saline or carprofen (4.4 mg/kg sc) daily for 14 days, followed by necropsy. n = 32 dogs survived until scheduled necropsy. for each study all treatments were administered once on the study days indicated. dogs in studies one and three had no significant radiographic evidence of pre-existing joint disease. study design: randomised (stratified by sex), blinded, multi-arm, parallel-group safety study. outcome studied: study 1 primary safety endpoint (objective): pharmacokinetic profile of bedinvetmab: mean bedinvetmab serum concentrations (μg/ml) after doses one and six, at three dose levels (1 mg/kg, 3 mg/kg, or 10 mg/kg sc); n = 8 per dose group). study 2 primary safety endpoint (objective): effect of bedinvetmab on t-lymphocyte-dependent immune function was evaluated by measuring anti-klh immunoglobulin (igg)antibody titers using elisa (t-cell antibody response). study 3 primary safety endpoint (objective): adverse effects in joints of the appendicular skeleton or organs after 2 weeks of concurrent administration of bedinvetmab and carprofen. pretreatment radiographs. objective safety endpoints (studies 1 and 3) serial clinical observations (injection site, neurological and musculoskeletal examinations). clinical pathology: sampling included capillary beds, peripheral nerves, immune and joint tissues of the appendicular skeleton and tissues where bedinvetmab: ngf or anti–drug antibody (ada) complexes might initiate local inflammatory responses. terminal pathology: absolute / relative organ weights. radiography of joints. main findings (relevant to pico question): study 1 bedinvetmab administered sc monthly was well tolerated in healthy laboratory dogs at all dose levels. study 2 the antibody response to klh was unaffected by exposure to bedinvetmab. bedinvetmab concentrations and toxicokinetics indicated that clearing or neutralising adas were not induced. one dog was euthanised approximately 4 weeks after study completion (7 weeks post-treatment) due to vomiting, diarrhoea, lethargy, anorexia, and fever. based on histopathology and clinical evaluation this appeared to be unrelated to treatment manipulation. study 3 daily co-administration for 14 days of bedinvetmab and carprofen was well tolerated: gross and microscopic pathology findings in all tissues were incidental and unrelated to bedinvetmab or carprofen. all joints, ligaments, menisci, bone, and marrow were unremarkable. studies 1 & 3 in selected dogs, local reactions at the injection site (inflammation, heat, swelling) were observed ‘sporadically’ (no semi-quantitative or quantitative evaluation was provided). statistically significant changes compared to controls were reported for selected parameters in blood and urine samples at some time points and categorised by sex (collected after animals were fasted overnight), but no treatment-related effects were identified in clinical pathology parameters. no meaningful treatment-related changes were identified between pretreatment and pre-terminal survey radiographs of major joints. no adas were detected. limitations: enrollment of healthy, mature dogs at a single site: the sample population may not generalise to older dogs with oa. allocation concealment is not described leaving the possibility of selection bias. unclear result reporting. intermittent mild inflammation (swelling, heat, or redness) observed at the injection site was not quantified. multiple concurrent hypothesis testing / pairwise comparison is not detailed. authors are all employees of the manufacturer of the drug, raising conflict of interest. personnel conducting subjective treatment-phase observations were blinded to group assignment, however general bone / joint, and clinical pathology, and toxicokinetics / ada data were summarised by respective experts unblinded to other study findings, potentially introducing bias. limited information on statistical analysis. 10x the recommended treatment dose is twice as much as recommended (emea vich topic gl43, 2008). study 3 lacks internal (duration and number of dogs involved) and external validity (the dogs used in this study were healthy and young). concurrent treatment increases difficulty identifying safety concerns related to intervention. the effect of excluding and replacing dogs from the study on results was not discussed. it is unclear who administered the treatment and whether they were blinded. the significance level set at 10% together with small cell sizes increase the risk of incorrect rejection of the null hypothesis.   appraisal, application and reflection bedinvetmab (librela, zoetis) is a canine immunoglobulin g2 (igg2) monoclonal antibody (mab) intended for the alleviation of osteoarthritis-related pain. its mode of action differs from cyclooxygenase inhibiting nsaids, that block the production of prostaglandins. bedinvetmab modulates nociceptive and neuropathic pathways by targeting and binding to canine nerve growth factor (ngf), blocking ngf / tropomyosin receptor kinase a receptor (trka) signaling (enomoto et al., 2019). species-specific anti-ngf mab treatments may have fewer adverse health events than nsaids due to their high binding specificity and, unlike opiates, may not block protective nociceptive sensation (enomoto et al., 2019). the corral et al. (2021) multi-centre field trial examined the efficacy and safety of 9 monthly subcutaneous injections (sc) of bedinvetmab (0.5–1.0 mg/kg librela, zoetis) in client-owned dogs diagnosed with osteoarthritis (oa). the initial 3 month study was randomised, blinded, and had a placebo control group. the process of randomisation across multiple sites in different countries with different numbers of subjects is unclear. the authors do not describe individual site blinding methodology and do not discuss statistical management of missing data, particularly methods for handling the implementation of rescue medication (donders et al., 2006). furthermore, incomplete follow–up minimised data interpretability. the 6 month, open-label, observational case series study following the 3 month randomised controlled trial (corral et al., 2021) observed efficacy and safety outcome measures without a control group. the study cited ethical concerns with a 6 month placebo comparison group in a clinical sample. a case series study without control can provide suggestive information about treatment and safety outcomes (i.e., potential serious adverse events), but there is an inherent potential for various biases and confounds. the lack of blinding of outcome assessors was an additional issue with this follow-on. no information was provided about demographics, age or weight, or severity of condition for the dogs selected for follow-on (described as ‘responded positively’ previously to treatment with bedinvetmab). corral et al. (2021) neither discuss the implications of selecting the second group on this basis, nor define what ‘responding positively’ means. the study’s primary efficacy outcome measure was owner-assessed oa-related change of pain scores using the canine brief pain inventory (cbpi) (corral et al., 2021). standardisation of the cbpi reports robust statistical power and reliability for  quantifying  owner perception of pain severity and impact of chronic oa-associated pain on dogs’ quality of life (qol) brown et al., 2007; 2008; and 2013). corral et al. (2021) did not adhere to scale administrative guidelines (brown et al., 2008) by collecting data at enrolment and using these as the baseline for comparison with scores obtained at later time points, despite standardisation guidance to avoid using scores collected on the first appointment given concerns about regression (brown et al., 2008; and friedman et al., 2015). a measurable subject variable, like pain, varies over time. pain scores that are 'extreme' by chance tend to 'regress towards the mean' when repeated. the natural variation in repeated in-subject measurements may erroneously infer clinically meaningful change after intervention and affect clinical decisions, while regression to the mean (rtm) confounded the change from baseline (barnett et al., 2005). beginning baseline data collection after the first appointment will allow dogs to be at their 'average' pain level, alternatively taking the mean of two or more baseline measurements before the intervention alleviates rtm effects (brown et al., 2008; and friedman et al., 2015). the study’s relatively small differences between treatment and control may be an artefact of the failure to follow scale guidelines or other test–retest reliability concerns. in addition, there is no discussion of language impacts on reliability and validity (essner et al., 2020). the cbpi was scaled in english, but corral et al. (2021) administered it to owners of various  nationalities. furthermore, no information was provided on the veterinary clinical assessments (vcas) carried out by different veterinarians at different sites and across different countries, raising additional questions about the reliability and validity of the outcome measures of the vcas. a final issue is that numbers reported in charts and in-text descriptions occasionally did not match. due to these concerns, confidence in the results is low. krautmann et al. (2021) investigated the safety of 7 monthly subcutaneous injections with bedinvetmab at different dose levels in healthy, mature laboratory dogs compared to a placebo. this study was randomised, controlled, and blinded. the authors do not describe randomised allocation, and the blinding of outcome assessors was incomplete. sample sizes were small and were further reduced in each of the three studies in this preclinical trial, limiting statistical power and potentially impacting the detection of adverse health effects (ahes). the sample population consisted of healthy, young dogs, limiting generalisability to sensitive subpopulations, such as older dogs with oa. however, this is the statutory safety protocol for licensing new drugs (emea vich topic gl43, 2008). six randomised dogs were removed from the study subgroups during the acclimation period and replaced with dogs of the same sex. four of those dogs were ‘deemed unsuitable’ with no further explanation for their removal or why replacement dogs were ‘deemed eligible’. it is difficult to determine what effect this replacement had on randomisation or magnitude, or direction of effects. krautmann et al. (2021) state that the 2 week trial of short-term co-administration of bedinvetmab and carprofen (nsaid) suggests that (a) a washout period between carprofen and bedinvetmab administration is not needed and that (b) intermittent short-term supplemental pain control via nsaids is possible. study limitations suggest this statement should be viewed with caution. although rapidly progressive oa (rpoa) has not been reported in dogs, evidence from human clinical trials suggests a dose-dependent risk for developing rpoa with humanised anti-ngf mab tanezumab both as monotherapy and when co-administered with nsaids (schnitzer et al., 2015; and hochberg et al., 2021). notably, the food and drug administration (fda) concluded that 2.5 mg tanezumab is not superior to oral prescription strength nsaids for alleviating pain and that adverse events such as accelerated joint destruction and abnormal peripheral sensation are more prevalent with tanezumab than nsaids (fda, 2020; hochberg et al., 2021; and neogi et al., 2022). due to these safety concerns, tanezumab has not been authorised (fda, 2020; and ema, 2021). nsaids are a cornerstone for pain management of inflammatory conditions such as canine oa and demonstrate short-term efficacy (hunt et al., 2015; and hochberg et al., 2021). nsaid therapy can be associated with gastrointestinal, renal, and hepatic complications; their exact incidence rate is, however, unknown and, considering the frequent use of nsaids in clinical practice, likely low (monteiro-steagall et al., 2013; hunt et al., 2015; and gruen et al., 2022). studies by lascelles et al. (2015) and webster et al. (2014) have shown good pain relief with anti-ngf mabs in dogs, and anecdotal evidence reveals a largely positive response of clients and veterinarians to the use of bedinvetmab for pain relief in clinical practice since its launch. this is promising and suggests that anti–ngf mabs may be an additional choice for oa-related pain relief in dogs not tolerating nsaid treatment. however, significant trial design limitations of the two reviewed studies in this knowledge summary mean that they provide only weak / inconclusive evidence for short-term safety and long-term efficacy of bedinvetmab. additional well-designed studies examining the efficacy, effectiveness, and safety of shortand long-term treatment with bedinvetmab for dogs diagnosed with oa and chronic pain are needed. methodology search strategy databases searched and dates covered: cab abstracts on ovid platform (1973–2022 week 33) web of science core collection (1900–25/08/2022) pubmed accessed via ncbi platform (1910–25/08/2022) search strategy: cab abstracts: (dog or dogs or bitch* or canine).mp. (arthrit* or osteoarthrit* or osteo-arthrit* or oa or degenerative joint disease or djd or joint disease).mp. (bedinvetmab or 'monoclonal antibody' or 'nerve growth factor' or ngf).mp. (safety or efficacy).mp. (pain or analgesia).mp. 1 and 2 and 3 and 4 and 5 web of science: (dog or dogs or bitch* or canine) and (arthrit* or osteoarthrit* or osteo–arthrit* or oa or ‘degenerative joint disease’ or djd or ‘joint disease’) and (bedinvetmab or 'monoclonal antibody' or 'nerve growth factor' or ngf) and (pain or analgesia) pubmed: (dog or dogs or bitch* or canine) and (arthrit* or osteoarthrit* or osteo–arthrit* or oa or ‘degenerative joint disease’ or djd or ‘joint disease’) and (bedinvetmab or 'monoclonal antibody' or 'nerve growth factor' or ngf) and (pain or analgesia) dates searches performed: 25 aug 2022   exclusion / inclusion criteria exclusion: pre-defined exclusion criteria: conference articles, review articles, editorial materials, letters. studies not focusing on the safety or efficacy of bedinvetmab for the treatment of canine osteoarthritis. inclusion: clinical trials in which the safety or efficacy of bedinvetmab for the treatment of canine osteoarthritis was studied.   search outcome database number of results excluded – not answering pico question excluded – conference articles, review articles, editorial materials, letters total relevant papers cab abstracts 7 4 2 1 web of science 30 22 6 2 pubmed 18 16 0 2 total relevant papers when duplicates removed 2   acknowledgements the author would like to extend thanks to louise buckley for the introduction to evidence-based veterinary medicine, and to maureen o’mara for her guidance. orcid katrin kronenberger: https://orcid.org/0000-0003-2717-6009 conflict of interest the author declares no conflicts of interest. references barnett, a., van der pols, j. & dobson, a. (2005). regression to the mean: what it is and how to deal with it. international journal of epidemiology. 34(1), 215–220. doi: https://doi.org/10.1093/ije/dyh299 brown, d., boston, r., coyne, j. & farrar, j. (2007). development and psychometric testing of an instrument designed to measure chronic pain in dogs with osteoarthritis. american journal of veterinary research. 68(6), 631–637. doi: https://doi.org/10.2460/ajvr.68.6.631 brown d., boston r., coyne j. & farrar j. (2008). ability of the canine brief pain inventory to detect response to treatment in dogs with osteoarthritis. journal of the american veterinary medical association. 233(8), 1278–1283. doi: https://doi.org/10.2460/javma.233.8.1278 brown, d., bell, m. & rhodes, l. (2013). power of treatment success definitions when the canine brief pain inventory is used to evaluate carprofen treatment for the control of pain and inflammation in dogs with osteoarthritis. american journal of veterinary research. 74(12), 1467–1473. doi: https://doi.org/10.2460/ajvr.74.12.1467 corral, m., moyaert, h., fernandes, t., escalada, m., tena, j., walters, r. & stegemann, m. (2021). a prospective, randomized, blinded, placebo–controlled multi–site clinical study of bedinvetmab, a canine monoclonal antibody targeting nerve growth factor, in dogs with osteoarthritis. veterinary anaesthesia and analgesia. 48(6), 943–955. doi: https://doi.org/10.1016/j.vaa.2021.08.001 donders, a., van der heijden g., stijnen, t. & moons, k. (2006). review: a gentle introduction to imputation of missing values. journal of clinical epidemiology. 59(10), 1087–1091. doi: https://doi.org/10.1016/j.jclinepi.2006.01.014 european medicines agency. (2021). raylumis. [online]. available from: https://www.ema.europa.eu/en/medicines/human/epar/raylumis [accessed september 2022]. emea vich topic gl43. (2008). guidance for industry. target animal safety for veterinary pharmaceutical products. the european agency for the evaluation of medicinal products. emea/cvmp/vich/393388/2006. [online]. available from: https://www.fda.gov/media/70438/download [accessed nov 2021]. enomoto, m. mantyth, p., murrell, j., innes, j. & lascelles, b. (2019). anti-nerve growth factor monoclonal antibodies for the control of pain in dogs and cats. veterinary record. 184(1), 22–23. doi: https://doi.org/10.1136/vr.104590 essner, a., högberg, h., zetterberg, l., hellström, k., sjöström, r., & gustås, p.  (2020). investigating the probability of response bias in owner-perceived pain assessment in dogs with osteoarthritis. topics in companion animal medicine. 39, 100407. doi: https://doi.org/10.1016/j.tcam.2020.100407 fda. tanezumab: fda efficacy review. (2020). u.s. food & drug administration. [online]. available from: https://www.fda.gov/media/146924/download [accessed september 2022]. friedman, l., furberg, c., demets, d., reboussin, d. & granger, c. (2015). baseline assessment. in: l. friedman, c. furberg, d. demets, d. reboussin & c. granger eds., fundamentals of clinical trials, 5th ed. springer international publishing switzerland: cham springer, 201–213. gruen, m., lascelles, b., colleran, e., gottlieb, a., johnson, j., lotsikas, p., marcellin-little, d. & wright, b. (2022). 2022 aaha pain management guidelines for dogs and cats. journal of the american animal hospital association. 58(2), 55–76. doi: https://doi.org/10.5326/jaaha-ms-7292 hochberg, m., carrino, j., schnitzer, t., guermazi, a., walsh, d., white, a., nakajo, s., fountaine, r., hickman, a., pixton, g., viktrup, l., brown, m., west, c. & verburg, k. (2021). long-term safety and efficacy of subcutaneous tanezumab versus nonsteroidal antiinflammatory drugs for hip or knee osteoarthritis: a randomized trial. arthritis & rheumatology. 73(7), 1167–1177. doi: https://doi.org/10.1002/art.41674 hunt, j., dean, r., davis, g. & murrell, j. (2015). an analysis of the relative frequencies of reported adverse events associated with nsaid administration in dogs and cats in the united kingdom. the veterinary journal. 206(2), 183–190. doi: https://doi.org/10.1016/j.tvjl.2015.07.025 krautmann, m., walters, r., cole, p., tena, j., bergeron, m., messamore, j., mwangi, d., rai, s., dominowski, p., saad, k., zhu, y., guillot, m., & chouinard, l. (2021). laboratory safety evaluation of bedinvetmab, a canine anti-nerve growth factor monoclonal antibody, in dogs. the veterinary journal. 276, 105733. doi: https://doi.org/10.1016/j.tvjl.2021.105733 lascelles b., knazovicky, d., case, b., freire, m., innes, j., drew, a. & gearing, d. (2015). a canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain. bmc veterinary research. 30(11), 101. doi: https://doi.org/10.1186/s12917-015-0413-x monteiro-steagall, b., steagall, p. & lascelles, b. (2013). systematic review of nonsteroidal anti-inflammatory drug-induced adverse effects in dogs. journal of veterinary internal medicine. 27(5), 1011–1019. doi: https://doi.org/10.1111/jvim.12127 neogi, t., hunter, d., churchill, m., shirinsky, i., white, a., guermazi, a., omata, m., fountaine, r., pixton, g., viktrup, l., brown, m., west, c., & verburg, k. (2022). observed efficacy and clinically important improvements in participants with osteoarthritis treated with subcutaneous tanezumab: results from a 56-week randomized nsaid-controlled study. arthritis research & therapy. 24(1), 78. doi: https://doi.org/10.1186/s13075-022-02759-0 schnitzer, t., ekman, e., spierings, e., greenberg, h., smith, m., brown, m., west, c., & verburg, k. (2015). efficacy and safety of tanezumab monotherapy or combined with non–steroidal anti–inflammatory drugs in the treatment of knee or hip osteoarthritis pain. annals of the rheumatic diseases. 74(6), 1202–1211. doi: https://doi.org/10.1136/annrheumdis-2013-204905 webster, r., anderson g. & gearing, d. (2014). canine brief pain inventory scores for dogs with osteoarthritis before and after administration of a monoclonal antibody against nerve growth factor. american journal of veterinary research. 75(6), 532–535. doi: https://doi.org/10.2460/ajvr.75.6.532 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use.   veterinary evidence is an rcvs knowledge initiative. issn: 2396-9776 first floor, 10 queen street place, london ec4r 1be resources student awards staff login policies privacy policy accessing information policy cookie declaration terms of use copyright notices stay connected podcasts twitter facebook instagram linkedin back to top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443. erratum to: in horses undergoing volatile anaesthesia, does intraoperative alpha-2-agonist infusion improve recovery? alison bennell bvms certavp(em) certavp(va) msc fhea mrcvs1* 1institute of veterinary science, university of liverpool, chester high road, neston, ch64 7te *corresponding author (alison.bennell@liverpool.ac.uk) vol 7, issue 1 (2022) erratum published: 31 may 2022 original paper published: 20 feb 2021 the original article was published in veterinary evidence vol 6, issue 1 (2021): 10.18849/ve.v6i1.341 doi: 10.18849/ve.v7i2.588 erratum unfortunately the original version of the article had the following error. within the appraisal, application and reflection section the dosage of dexmedetomidine as a bolus changed from: dexmedetomidine as a bolus of 3–8 mcg/kg iv followed by a cri of 75 mcg/kg/hour (marcilla et al., 2012; and risberg et al., 2016) to: dexmedetomidine as a bolus of 3–8 mcg/kg iv followed by a cri of 1.75 mcg/kg/hour (marcilla et al., 2012; and risberg et al., 2016) this error was in the html version only. this has now been updated in the html version.   intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. bracy clark's horse hoof clare boulton rcvs knowledge | head of library and information service vol 1, issue 3 (2016) published: 29 sep 2016 doi: 10.18849/ve.v1i3.60 during the recent reordering of the rcvs headquarters a 6 inch square box was found containing a cardboard model and a folded piece of paper.  further investigation revealed it was something rather exciting – the pasteboard model of a horse’s hoof. colleagues at the royal veterinary college kindly produced a 3d model of the hoof, which you can view in the interactive video below. you can also read more about bracy clark's model hoof on our blog. bracy clark hoof model c1820 by rcvsknowledge on sketchfab erratum to: clinical audit of pom-v / pom prescriptions by remote consultation via a veterinary video telemedicine smartphone application dr sheila mary smith bvms mrcvs1 dr tamsin day bvetmed mrcvs1 dr samantha georgina webster bvetmed mrcvs1 sam davies bsc1 dr trevor peter hardcastle bsc msc phd1 dr adele williams bvsc mrcvs dipeceim phd1* 1vet-ai, ebble house, odstock, salisbury, england, sp5 4jb *corresponding author (adele.williams@vet-ai.com) vol 7, issue 2 (2022) erratum published: 20 jun 2022 original paper published: 08 jun 2022 the original article was published in veterinary evidence vol 7, issue 2 (2022):  10.18849/ve.v7i2.553 doi: 10.18849/ve.v7i2.627 erratum unfortunately the original version of the article had the following two errors. within the results section after figure 6 under the sub-heading complete / expected response to treatment was changed from: complete / expected response to treatment 60.3% (2,135/3,541) of remote consultations which were prescribed a pom-v / pom product resulted in the outcome complete or expected response to treatment. 8% (1,197 /3,541) complete response / resolutions of clinical signs after follow-up appointment or email 5% (938/3,541) expected response to treatment (complete resolution of signs not expected in these cases most requiring chronic ongoing medication e.g., non-steroidal anti-inflammatory drugs (nsaid) for chronic osteoarthritis, or anti-pruritic for atopic dermatitis) of the consults where the outcome was known (when the outcome category ‘no treatment outcome available’ was removed) 89.0% (2,135/2,399) of all treatment outcomes were complete / expected response to treatment. to: complete / expected response to treatment 60.3% (2,135/3,541) of remote consultations which were prescribed a pom-v / pom product resulted in the outcome complete or expected response to treatment. 33.8% (1,197 /3,541) complete response / resolutions of clinical signs after follow-up appointment or email 26.5% (938/3,541) expected response to treatment (complete resolution of signs not expected in these cases most requiring chronic ongoing medication e.g., non-steroidal anti-inflammatory drugs (nsaid) for chronic osteoarthritis, or anti-pruritic for atopic dermatitis) of the consults where the outcome was known (when the outcome category ‘no treatment outcome available’ was removed) 89.0% (2,135/2,399) of all treatment outcomes were complete / expected response to treatment. this error was in both the html and pdf versions. this has now been updated in both the html and pdf versions.   within the results section after figure 6 under the sub-heading no treatment outcome available was changed from: no treatment outcome available of the 3,541 consultations in which a prescription was purchased, 32.3% (1,142/3,541), had no treatment outcome available for the following reasons: 4% (1,078/3,541) no feedback received (lost to follow-up despite multiple attempts) 8% (64/3,541) patients were not administered prescribed medication for reasons including: postal delay / out of stock (those cases were referred into practice) condition deteriorated prior to commencement of treatment and were referred into practice symptoms resolved before medication was administered order cancelled by owner to: no treatment outcome available of the 3,541 consultations in which a prescription was purchased, 32.3% (1,142/3,541), had no treatment outcome available for the following reasons: 30.4% (1,078/3,541) no feedback received (lost to follow-up despite multiple attempts) 1.8% (64/3,541) patients were not administered prescribed medication for reasons including: postal delay / out of stock (those cases were referred into practice) condition deteriorated prior to commencement of treatment and were referred into practice symptoms resolved before medication was administered order cancelled by owner this error was in both the html and pdf versions. this has now been updated in both the html and pdf versions.   intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. can practice-based evidence complement and promote ebvm? steve budsberg dvm, bs, ms, dacvs1* david church bvsc, phd, macvsc, mrcvs2 1university of georgia, college of veterinary medicine, 2200 college station road, athens, georgia 30602, united states 2the royal veterinary college, hawkshead lane, north mymms, hatfield, hertfordshire, al9 7ta, united kingdom *corresponding author (budsberg@uga.edu) vol 1, issue 4 (2016) published: 15 dec 2016 doi: 10.18849/ve.v1i4.80 practice-based research should be performed in all practice settings if the results are to be applied to all practice settings. while the previous statement seems intuitive, that is to have practice-based evidence strengthen evidence-based medicine. the development of such a system of data collection and dissemination has not developed very rapidly. this lecture will describe how the vetcompass programme has grown and evolved to now provide a world-leading platform for unbiased, invisible data collection... this is a podcast of steve and david's talk at the veterinary evidence today conference, edinburgh november 1, 2016. find out more about steve and david. view presentation slides comments: degenerative mitral valve disease in dogs attending uk practices equine vetcompass generating evidence through practice-based equine health surveillance sarah allen, dave brodbelt, josh slater, kristien verheyen collect venom codes, free-text clinical notes and select patient information e.g. age, sex and breed embed venom codes into the electronic clinical records system of participating practices create a set of diagnostic (venom) codes relevant to first-opinion equine practice guiding evidence-based equine healthcare aim: to create an efficient and sustainable practice-based system for equine health surveillance objectives: at each care episode have the attending veterinary surgeon tag the patient record with the venom code that best describes the reason for examination feedback study findings to support ebvm analyse records to estimate frequency of, and identify risk factors for, common equine conditions relevance: electronic clinical records, from first-opinion veterinary practices, represent a valuable yet currently underused source of equine disease information. the development of equine vetcompass will facilitate the use of this data for the monitoring of health in the national horse population. the results of routine disease surveillance can be used to: ● underpin and direct evidence-based veterinary medicine in equine practice ● improve the provision of equine healthcare through the more targeted training of veterinary professionals ● identify priorities for equine research that are relevant to the diseases that affect a large number of uk horses by supporting these activities equine vetcompass will improve the long-term health and welfare of the individual horse and the larger equine population. background: evidence-based veterinary medicine (ebvm) is the conscientious, explicit and judicious use of the current best evidence, when making decisions about the individual patient1. despite being shown to improve patient outcomes2, the application of ebvm in equine practice remains seriously hampered by the lack of reliable data, even for the most common conditions3. accurate prevalence data, needed to guide the diagnostic process, are in short-supply owing to the comprehensive absence of disease monitoring in the uk horse population4. estimates from laboratory submissions, owner-reported surveys and clinical studies, offer some insight but are prone to incompleteness, bias and poor generalisability5. analysis of electronic clinical records (ecrs) from first-opinion veterinary practices, as conducted by vetcompass, can provide a more accurate assessment6. since its launch in 2009, the rvc’s vetcompass project has collected over 10 million ecrs from small animal practices. these have been analysed to quantify the most common disorders affecting dogs and cats7,8 and to establish risk factors for several important conditions9,10. excitingly, vetcompass has now been adapted for use in equine practice, providing enormous opportunity for the study of equine health and the generation of robust disease statistics. references: 1. sackett, d.l., rosenberg, w.m.c., gray, j.a.m. and haynes, r.b. (1996) evidence-based medicine: what it is and what it isn't. br. med. j. 312, 71-72. 2. bahtsevani, c., udén, g. and willman, a. (2004) outcomes of evidence-based clinical practice guidelines: a systematic review. int. j. technol. assess. health care 20, 427-433. 3. marr, c.m. (2003) defining the clinically relevant questions that lead to the best evidence: what is evidence-based medicine? equine veterinary journal 35 (4) 333-336 4. equine sector council [online] available at: http://www.newc.co.uk/law/equine-health-welfare-strategy/ [accessed 27 november 2015] 5. ireland, j.l., wylie, c.e., collins, s.n., verheyen, k.l.p. and newton, j.r. (2013) preventive health care and owner-reported disease prevalence in horses and ponies in great britain. research in veterinary science 95(2):418-24 6. mcgreevy, p.d. (2007) breeding for quality of life. animal welfare 16: 125–128. 7. o’neill, d.g., church, d.b., mcgreevy, p.d., thomson, p.c. and brodbelt, d.c. (2014) prevalence of disorders of dogs attending primary-care veterinary practices in england. plos one. 2014 mar 4; 9(3)e90501 8. o’neill, d.g., church, d.b., mcgreevy, p.d., thomson, p.c. and brodbelt, d.c. (2014) prevalence of disorders recorded in cats attending primary-care veterinary practices in england. veterinary journal. 202 (2) 286-291. 9. stephens, m., o’neill, d., church, d., mcgreevy, p.d., thomson, p.c. and brodbelt, d. (2014) feline hyperthyroidism reported in primary-care veterinary practices in england: prevalence, associated factors and spatial distribution. veterinary record. 175(18):458 10. taylor-brown, f e and meeson, r l and brodbelt, d c and church, d b and mcgreevy, p d and thomson, p c and o'neill, d g (2015) epidemiology of cranial cruciate ligament disease diagnosis in dogs attending primary-care veterinary practices in england. veterinary surgery, 44 (6). pp. 777-83 contact: seallen@rvc.ac.uk http://www.newc.co.uk/law/equine-health-welfare-strategy/ exploring the motivations, challenges, and barriers for implementing evidence-based veterinary medicine (ebvm) in general practice | veterinary evidence skip to main content article keywords: evidence-based veterinary medicine; veterinary practitioners; online learning resource; ebvm exploring the motivations, challenges, and barriers for implementing evidence-based veterinary medicine (ebvm) in general practice laura haddock, bvsc mrcvs pgce1* sarah baillie, bvsc msc phd pfhea mrcvs1 ellie sellers, bvsc mrcvs1 sheena warman, bsc bvms dsam dipecvim edd sfhea mrcvs1 1bristol veterinary school, university of bristol, langford, bristol, bs40 5du, uk * corresponding author email: lil_egan@hotmail.com vol 8, issue 1 (2023) submitted 02 mar 2022; published: 16 mar 2023 doi:https://doi.org/10.18849/ve.v8i1.602 abstract an evidence-based veterinary medicine (ebvm) training resource, ‘ebvm learning’, was created in 2015 and updated in 2019. following feedback from users, it was decided that a more concise practitioner-focused version was needed. seven online focus groups, with a total of 22 veterinary practitioners, explored the motivations of practitioners to engage with ebvm. they considered the challenges and barriers to implementing ebvm in practice, and specific supportive measures they felt would increase adoption of ebvm in practice. participants identified time, support from colleagues and management, and accessing and appraising evidence as being the most important challenges and barriers to the use of ebvm in general practice. however, the value of ebvm was appreciated, and there was an appetite amongst the participants to utilise more ebvm to inform their clinical decision-making. at a workshop attended by experts in ebvm, educators and practitioners, the results of the focus groups were presented and discussed to inform the development of a new online training resource. this study has been used to produce ‘ebvm for practitioners’, to attempt to reduce some of the barriers and challenges faced by practitioners and support them in increasing their use of ebvm. further work by the leaders in the veterinary profession will be needed to expand and improve the quality of the evidence base on which ebvm relies, and to ensure practitioners have the skills, access, and motivation to utilise it. introduction there is a widely held societal expectation that diagnostic and therapeutic decisions made by practitioners are based on evaluation of high-quality scientific literature, a practice known as evidence-based veterinary medicine (ebvm) (shaw, 2001; heneghan et al., 2017; and janicke et al., 2020). ebvm has been defined as the conscientious, explicit, and judicious use of current best evidence to make the best possible decision about a patient (sackett et al., 1996; and dean & heneghan, 2019). practitioners go beyond this to contextualise their decisions and actions within a broader professional framework, considering the individual circumstances of the clinical scenario, patient, and owner (centre for evidence-based veterinary medicine, n.d.). ebvm is becoming increasingly important to veterinary practitioners and is now included within the core competencies defined by some of the accrediting bodies of veterinary education (e.g., american veterinary medical association (avma); royal college of veterinary surgeons (rcvs); and european association of establishments for veterinary education (eaeve)). incorporating ebvm skills within clinical decision-making enables practitioners to be more efficient in their use of evidence-based practice (sackett, 1997; doig & simpson, 2003; and huntley et al., 2017) and helps to build trust with their clients (hauser & jackson, 2017). it is important that practitioners can make judicious use of ebvm as their clients have increasing access to online information (steele et al., 2013; and gibbons et al., 2021). this increased client expectation and knowledge can create a major source of stress for practitioners (gardner & hini, 2006). it is widely recognised that clinicians face several barriers to using ebvm. the most significant of these are time, access to quality evidence, and making evidence relevant and applicable to the clinical setting (sackett, 1997; doig & simpson, 2003; turner & royle, 2015; huntley et al., 2016; hauser & jackson, 2017; gibbons et al., 2021; and sellers et al., 2021). practitioners also need the necessary skills to practise ebvm; effective literature searching, critical appraisal, and the ability to apply the evidence found within the clinical context (vandeweerd et al., 2012; and huntley et al., 2017). these skills are essential to both identify high-quality evidence and ensure evidence gathering is efficient (vanderweerd et al., 2012). veterinary practitioners are confronted with a lot of readily available online information sources (nielsen et al., 2015; and gibbons et al., 2021), and a study in 2012 revealed there were 1139 journals with a significant amount of veterinary content (grindlay et al., 2012). however, research suggests that veterinary practitioners preferred to use online resources such as the veterinary information network (vin, 1991.) and the international veterinary information service (ivis, 1998.), or to ask a colleague for advice (vandeweerd et al., 2012; nielsen et al., 2015; and huntley et al., 2016). a need for improved access to evidence is frequently cited in the veterinary literature (wales, 2000; vandeweerd et al., 2012; hauser & jackson, 2017; and sellers et al., 2021). a decade ago, it was reported that there was significant underdevelopment in the veterinary field across all elements of the information infrastructure that supported ebvm when compared to that of human medicine (toews, 2011). a further report makes a strong case for much-needed funding for research to grow the evidence base (lanyon, 2014) and, more recently, to increase the number and availability of evidence summaries in practice (brennan et al., 2020). in response, and following the lead of human medicine, there have been considerable developments in ebvm. evidence syntheses (e.g. systematic reviews and evidence summaries)rovide an efficient means of accessing succinct syntheses of clinically relevant information in a standardised format (dean et al., 2015; and brennan et al., 2020). an online database listing veterinary systematic reviews has been developed (vetsrev, 2020) and there are increasing numbers of freely accessible online evidence summaries (e.g., bestbets for vets; knowledge summaries; and clinical evidence in equine practice). other initiatives include freely available online databases to search for research papers (e.g., pubmed), open-access journals (e.g., veterinary record open, and veterinary evidence) and evidence-based practice guidelines (e.g., fletcher et al., 2012; sparkes et al., 2015; and carney et al., 2016). veterinary practitioners can subscribe to libraries of resources focused on veterinary science and animal health (e.g., rcvs knowledge library). ventures such as savsnet and venom coding utilise practice-generated data to answer specific clinical questions and act as a form of disease surveillance (kerbyson, 2015). ebvm is gaining interest across the profession, with quality improvement being incorporated as an expected part of regulated practice standards in the uk (rcvs practice standards scheme, 2022). there has been an increase in training in ebvm skills in undergraduate veterinary curricula (arlt et al., 2012; steele et al., 2013; cake et al., 2016; shurtz et al., 2016; dean et al., 2017; sellers et al., 2021; gibbons et al., 2021; and batt-williams & lumbis, 2022), along with the creation of freely available online resources to assist educators e.g. how to include ebvm and research skills in veterinary training (janicke et al., 2020). reports suggest that there are an increasing number of graduates with ebvm skills entering the workforce (hauser & jackson, 2017; and huntley et al., 2017). however, the impact of historically little formal training has led to varying levels of awareness and skills within the profession (sellers et al., 2021). in a recent international survey, 3660/5255 (69%) of veterinarians reported a desire to hear more about ebvm (huntley et al., 2017). in the same research, it was noted that continuing education plays an important role in bringing ebvm skills to those who did not receive formal teaching on ebvm in their undergraduate curriculum. there are postgraduate training opportunities available to develop ebvm skills e.g., the freely available online course ‘ebvm learning’, as well as via formal courses, but these require time investment from busy practitioners. in a previous study, feedback was gathered on the online resource ‘ebvm learning’ from those using it in academia and practice (sellers et al., 2021). the information was used to review and update the resource to ensure it remained relevant and valuable for the range of learners engaged in ebvm. the project also identified challenges, real and perceived, encountered by practitioners in their attempts to embed ebvm into clinical practice e.g., time, access to evidence, and confidence in their own ebvm skills. as a result, it was proposed that a different training resource was needed for practitioners, one that did not cover the same depth and scope as ‘ebvm learning’. it could provide training in the basic principles of ebvm in a manageable concise format, while linking to the ‘ebvm learning’ resource for further detail. practitioners need a concise and focused ebvm tool to support upskillingthis needs to be internationally and freely available to stimulate further interest and engagement in ebvm (vandeweerd et al., 2012; and huntley et al., 2017). the current study aimed to explore the themes identified previously by practitioners in more depth and use the results to inform the development of ‘ebvm for practitioners’: a concise, practitioner-focused version of ‘ebvm learning’. methods focus groups a series of focus groups (krueger & casey, 2014) was used to discuss three topic areas: motivations of practitioners to engage with ebvm; the challenges and barriers to implementing ebvm in practice; and specific needs to support increased adoption of ebvm in practice in the future. the focus group questions are in appendix 1. the study received approval from the faculty of health sciences research ethics committee, university of bristol (reference 99803). participants were recruited using a convenience sampling strategy by approaching veterinary practitioners (veterinary surgeons and veterinary nurses) working in general practice from within the project team’s networks. efforts were made to include those working with different species, from both independent and corporate practices, and from a range of geographical locations in the uk. a recruitment email and information sheet were sent to potential participants and those agreeing to attend a focus group signed a consent form. due to the covid-19 pandemic, the focus groups were undertaken online (using the skype video conferencing platform) and all were facilitated by the lead researcher (author lh, an experienced primary care veterinary practitioner). each focus group was restricted to a maximum of four participants to allow for meaningful contributions in the virtual environment. seven focus groups were undertaken with a total of 22 participants (table 1).   table 1: summary information for the focus group participants focus group demographics age mean 33.6 years range 24–56 years  graduated 2010–2019 14 63.6% 2000–2009 5 22.7% 1990–1999 2 9.1% 1980–1989 1 4.6% before 1990 0 0% mean years graduated: 9.5 years gender male  6  27.3%  female  16  72.7%  geographical location    england  18  81.8%  scotland  1  4.6%  wales  3  13.6%  n. ireland  0  0% practice ownership type independent 13 59.1% corporate 7 31.8% charity 2 9.1% practice type small animal 15 68.2% equine 4 18.2% farm animal 3 13.6% job role veterinary surgeon 20 90.9% veterinary nurse 2 9.1%   the focus groups were audio-recorded, and then transcribed by a university-approved commercial service (university transcriptions). each participant was assigned a number (1–22) and their contributions were labelled with their number prior to analysis to anonymise them. analysis the transcripts were read twice by lh. one transcript was then selected and analysed independently by two researchers (lh and sw) to identify themes and sub-themes within each topic area (1. motivations; 2. challenges and barriers; and 3. future needs). the data were hand coded using a mixture of deductive and inductive thematic analysis (braun & clarke, 2006), identifying codes throughout the transcript where relevant to any of the main topic areas, then grouping these codes into themes and sub-themes. the themes and sub-themes within each topic area were discussed between the two researchers to reach a consensus for an initial thematic framework. this was followed by full coding of each transcript by lh, during which a few additional themes and sub-themes emerged; representative quotes were allocated to each. researcher positioning researcher positioning is an important consideration in qualitative research. the two authors responsible for data collection and analysis have backgrounds as an experienced primary care clinician and secondary school teacher (lh) and an experienced referral clinician, educator and qualitative educational researcher (sw). this ‘insider-outsider’ positioning (dwyer & buckle, 2009) is acknowledged as having potential to influence interpretation of the data; the authors took a reflexive approach to data collection and analysis, using questioning and discussion to critically reflect on the potential impact of researcher positioning and presuppositions on the research findings. workshop a workshop was hosted by rcvs knowledge via zoom where the focus group results were presented. attendees included experts in ebvm, educators and practitioners, some of whom had been focus group participants. breakout rooms were used for small groups to discuss the focus group results and the design of a new online resource specifically to support practitioners in their use of ebvm. the groups were to make suggestions about the structure, content, and key differences between the new resource and ‘ebvm learning’. results the final thematic framework (table 2), was developed and agreed through iterative discussion by lh and sw.   table 2. final thematic framework main themes subthemes 1. motivations: understand what motivates practitioners to engage with ebvm understanding of the concept of ebvm previous experience of ebvm current awareness and use of ebvm perceived benefits of ebvm 2. challenges and barriers: gain a greater understanding of the challenges implementing ebvm in practice time support accessing and evaluating evidence 3. future needs: identify specific needs to support future adoption of ebvm in practice requirements of an online learning resource other ways to remove barriers / challenges   1. motivations: understand what motivates practitioners to engage with ebvm understanding of the concept of ebvm participants across all focus groups agreed that ebvm supported continuous improvement in clinical practice, leading to better outcomes for clients and patients. each participant was assigned a number (1–22) and their contributions were labelled with their number prior to analysis to anonymise them (seen in brackets after each of the focus group quotes below). ‘[ebvm is] best practice, research based, where you’re looking at outcomes and providing good clinical judgements and probably implementing treatment regimes and preventative medicine based on good evidence’. (1) ebvm was seen as something that was often practised by those keen to keep up to date and could be used to provide evidence to support positive change. many participants felt that ebvm was relevant to those working in general practice, although some felt it needed to be used more. ‘i wish it was implemented more […] i think it’s really important to do and i think it just gets overlooked sometimes’. (9) previous experience of ebvm participants who had graduated recently, and those currently involved in teaching or mentoring, were aware that ebvm is now embedded in most undergraduate curricula. however, those who graduated a while ago reported receiving little teaching on ebvm as students. ‘i don’t think [ebvm] was a term when i was studying’. (16) most practitioners who had undertaken postgraduate study felt that it included some exposure to ebvm, but others felt that it was not a priority in the programme of study they had undertaken. ‘it did come up slightly [in my certificate], but i don’t think there was a full lot of learning on that’. (15) it was suggested by several participants that those who studied ebvm at university / college were more likely to want to take part in ebvm-related activities in practice. ‘[…] its use increases as graduates come through the system, because it’s incorporated into the syllabus of the veterinary courses, and the graduates arrive expecting protocols [...]’. (1) current awareness and use of ebvm participants described the sources of evidence that they commonly use; these included discussion with colleagues, or sharing evidence within group settings e.g., journal clubs / rounds. specialist opinion was also mentioned frequently as being highly regarded, with the perception being that such opinions would be backed by evidence but also grounded in clinical experience. ‘[specialist opinion] not only comes with that kind of evidence from the papers but it also comes with that specialist experience as well, which gives you the confidence to go for it […]’. (5) several participants mentioned the value of discussing cases with new graduates and students, along with reflecting on their own previous relevant experiences. other popular sources of evidence were textbooks, continuing professional development (cpd) events, or articles published in veterinary magazines. a few participants mentioned using journals as a source of evidence, either by searching journals for papers on specific subjects, or by browsing a particular journal to keep abreast of developments. ‘i do read journals […] i’ll choose out the bits that are of interest to me and my working life’. (20) searching for research papers by using an online search engine was mentioned by only two participants and accessing published research via a database was mentioned by only one. several participants mentioned that they were aware of the existence of evidence summaries in a variety of formats. the participants widely acknowledged that the quality of evidence from different sources is variable, and the more convenient sources (colleagues, textbooks) could be less reliable. ‘looking up in the books as well, but i think the problem with the books is that sometimes they are a few years old and there isn’t up to date thinking in them’. (22) almost all participants were able to list some specific ebvm activities that they undertook within their practice. there was a clear appetite for the use of evidence-based protocols and clinical guidelines. to maximise the confidence practitioners had in their in-house protocols / guidelines they wanted the method of evidence-gathering to be transparent, and for there to be regular reviews of the evidence. ‘i think probably some of our sops [standard operating procedures], we’ve got a lot of sops, and i think some of them were, once upon a time [evidence-based], whether they still are now […]'. (19) consensus guidelines, such as recommendations on appropriate antibiotic use (protect [bsava & samsoc, 2018]), and mortality and morbidity rounds were mentioned as ways to use ebvm to improve future outcomes. ‘[…] with the mortality and morbidity rounds, that’s really addressing things that have come up. and learning and then developing protocols because of those’. (12)       a commonly mentioned activity was group discussion within the clinical team about cases or research papers (variably termed journal clubs, case discussions, clinical clubs, and clinical veterinary meetings). these group knowledge-sharing activities were seen as an expected part of clinical practice, and most participants felt they were useful and rewarding. ‘we do journal clubs and case discussions with senior clinicians that know a lot more than i do […] i try and get everybody involved in – we have it every week without fail […] it is a planned event, as part of the weekly schedule[…]’. (4) although audits are now an integral part of practice standards, most of the focus group participants were not actively involved in the audit process within their practice. a few mentioned that more of their team were starting to be involved in the audit process, and several felt that it would be used more in the future. ‘[…] all our senior vets and senior [veterinary] nurses have been split into groups and we’ve actually got kind of a clinical audit team now. so, i think […] we will start to use it more in practice’. (21) only a couple of practitioners mentioned using ebvm to make decisions proactively for individual cases. perceived benefits of ebvm overall practitioners felt that there were many benefits to increasing the use of ebvm for individuals, practices and the profession. the perceived benefits included supporting clinical decision-making, improving job satisfaction, reducing stress, improving efficiency, increasing confidence, better outcomes for patients, and improved animal health and welfare. ‘[…] it does feel very good when you get it right and evidence-based vet medicine will help you get that goal’. (18) some of the practitioners also felt that ebvm could lead to a more cost-effective approach for clients, for example; by leading to the correct treatment more quickly, thus improving client-practitioner relationships. ‘[…] you’re doing the best that you can do for the patient and offering the best and most economical outcome for the owner as well’. (11) within farm practice, this was seen as a significant commercial benefit. ‘[…] if you can prove there’s a cost benefit as well, i think that definitely helps’. (2) many of the participants felt that ebvm led to a more consistent approach across the veterinary team, improving the client’s confidence and leading to a more satisfied and cohesive veterinary team. ‘[…] if they go and see two different vets in the same practice within a couple of days and each vet is telling them a different thing, that can be quite confusing, and i don’t think they have enough trust in us then […]’. (22) many of the benefits described within this theme could increase practice profits, along with client retention. ‘client satisfaction will drive increased business’. (8) several practitioners felt that ebvm would enhance the reputation of the veterinary profession by improving the quality of veterinary care, and by stimulating further research. ‘[…] if we want to ask the questions that we want the answers to, that would definitely help to drive research in the right direction […] and it stimulates more studies to be done’. (20) some benefits of ebvm were considered to be broader than just the veterinary profession, in particular the responsible use of antimicrobials. ‘[…] if you’re using things like rational use of antibiotics, you’re protecting the human population as well as other animals […]’. (15) 2. challenges and barriers: gain a greater understanding of the challenges implementing ebvm in practice time the most significant challenge that practitioners identified was the time required to engage in ebvm. the focus group participants often replied simply with the word ‘time’ as a response to queries about challenges and barriers, with many participants feeling no need to provide any further explanation. the most commonly cited time-consuming activities were finding evidence, reading literature, discussing cpd, and generating protocols. some alluded to a sense of the whole process being overwhelming. ‘it is time, i think. that is the main restriction. it’s having time to discuss cpd that’s been learned, to read what other people have written and all the rest of it’. (11) ‘time, without a doubt […] i don’t have time to go reading journal after journal after journal after journal, to make one decision on whether i should do a flank cat spay or a midline cat – those sorts of things, it just takes too long’. (15) support a lack of support presented some challenges, whether related to being allowed paid time to learn more about ebvm or meeting resistance from colleagues who were reluctant to change established practices. ‘i think sometimes people are set in their ways […] people that have been in practice for longer […] they set the protocol, so, it’s harder for you then to make changes’. (12) several participants reported that some colleagues did not like protocols or clinical guidelines, as they felt they restricted clinical freedom. some reported being disheartened after undertaking the initial stages of ebvm, when reluctant colleagues prevented changes being applied in practice. although a few were more optimistic that some activities, specifically audits and journal clubs, would be supported and well received. ‘i think if it was presented in the right way and for the right thing, they might consider it’. (19) accessing and evaluating evidence gaining access to evidence could be challenging, often requiring a journal subscription, and sometimes the evidence required does not yet exist. ‘[…] but also access is a major problem, because access costs money’. (20) many also mentioned that they did not know where to look, or how to gain access quickly and easily. ‘and i think it is quite difficult to actually look up stuff. so, it can be challenging to find the articles, to find the knowledge about certain topics’. (22) whilst inclusion of specific training on the ebvm process varied across the spectrum of postgraduate training the practitioners had undertaken, most who had completed formal postgraduate study had gained additional experience of acquiring and appraising evidence, and so felt more comfortable with these aspects of the ebvm cycle as a result. ‘my knowledge of appraising evidence is based on what i’ve been taught as part of my internship and since working in a referral hospital’. (4) frustration was expressed that some of the evidence available in veterinary medicine was perceived to be of low quality; examples included small, poorly conducted, or biased studies, or articles written based on opinion rather than evidence. additionally, sometimes the evidence was not directly applicable to their own clinical practice. ‘[…] a lot of the case selection of published papers are through referral hospitals and second opinions, so it’s quite hard to find a lot of first opinion data […]’. (15) ‘and particularly in more extensive systems beef and sheep, the amount of peer reviewed papers available to you, to answer a specific question are actually quite few’. (1) another concern related to assessing the impact of evidence when applied in practice, as without feedback mechanisms it was not clear if the associated changes had had a positive impact. ‘i also feel there’s less auditing done in veterinary practice […] so no-one knows really what we’re doing and what the outcome is in general practice. you might have people researching things, but there’s not that much that we feedback as to what worked and what didn’t work’. (12)    it was noted that one of the challenges in veterinary medicine (compared to human medicine) was an insufficient quantity of evidence to draw meaningful conclusions. ‘[…] often the outcome is that, actually, the evidence that we’ve got doesn’t support either way […]’. (14) once evidence had been obtained, participants varied in how confident they felt in their ability to understand or appraise it. consequently, some felt that their lack of skills and previous training in these areas discouraged them from using ebvm. several mentioned relying on the process of peer-review as reassurance that the evidence was of sufficient quality. 3. future needs: identify specific needs to support future adoption of ebvm in practice the final area explored in the focus groups was ways in which future developments, and specifically the planned online learning resource, could assist practitioners in incorporating more ebvm in general practice. requirements of an online learning resource participants were asked to review the existing online ‘ebvm learning’ course prior to the focus groups. their feedback indicated that the resource was very good, but it was too detailed for their needs. ‘[…] i read through the first section, but i didn’t go through the whole thing. i think a shorter one probably for me […] i feel like the five a’s thing is really good, but it is just a lot […]’. (2) they were then asked to consider a new practitioner-focused version. nearly everyone mentioned that the resource needed to be concise, as the main barrier to ebvm use in practice is time. ‘i think it needs to be short and sweet’. (18) the type of content requested varied with the previous experience and current skill level of the participants. for those who had not encountered ebvm as undergraduate or postgraduate students, training in how to acquire and appraise evidence were frequently mentioned. in terms of acquiring evidence, suggestions were to focus on the most relevant sources, preferably with free or affordable access. overall, it was suggested that one way to encourage completion of all five stages of ebvm was to provide a proforma with clinical relevance for each type of ebvm activity e.g., creating a knowledge summary, reviewing practice protocols, performing a clinical audit. participants expressed a desire for visual aids to ease assimilation of the information, and to break up or replace large blocks of text. other requests included starting with the learning objectives and summarising key points at the end of each section. quizzes were a popular feature as was the use of case examples, demonstrating application of the techniques, as the material would be easier to understand and more enjoyable to read. ‘i quite like (quizzes) as a way of making sure you have learned it, you have understood it’. (11) ‘i think sometimes it really helps to go through a case, as well. and if you think of it in terms of a case, you might remember it a bit more than just going through things’. (16) another suggestion was for training to be available in different forms e.g., podcasts and webinars. this was particularly important for farm and equine practitioners who mentioned that time spent driving to calls was useful for catching up on cpd. many of the participants felt that the length of the overall resource was not as important as the ability to break it down into manageable portions. ‘yes, it wouldn’t necessarily matter how long it was overall if it was broken up into hour or half hour chapters […]’. (17) ensuring time spent on the resource would count towards the rcvs cpd requirement was important to many of the participants. in addition, it was felt by several participants that ‘one-size-fits-all’ was not appropriate, given the varying ebvm skills within the profession and the different levels of interest in the subject. a proposed approach was to create a succinct resource to convey only the basic skills and ideas, with additional content provided for those who would like to take their interest further e.g., links to other resources, additional reading materials, and forums for discussion. other ways to remove barriers / challenges some ideas were beyond the scope of this project. for example, developing a nationwide, or even international evidence resource like the cochrane library of systematic reviews available for human medicine. participants mentioned being envious of the quantity, quality, and accessibility of human medical research. further recommendations revolved around ensuring that acquiring the skills to practise ebvm was a compulsory part of becoming a competent veterinary practitioner in the future. there were several suggestions including further increasing the teaching and emphasis on ebvm skills during university courses, requiring the use of ebvm through the rcvs practice standards scheme, and promoting the benefits of ebvm within the veterinary community to encourage greater use and engagement. developing a new online resource: ‘ebvm for practitioners’ as a result of the focus group findings and the discussions at the workshop hosted by rcvs knowledge, a new online resource ‘ebvm for practitioners’ was designed. it is a slim-line resource for busy practitioners, focusing on basic training in the key skills required for ebvm, and offering advice that supports activities practitioners identified as important e.g., clinical audits and journal clubs. it includes signposting to other open-access resources and links to ‘ebvm learning’ for those practitioners seeking to further develop their skills in ebvm. ‘ebvm for practitioners’ is available at: www.ebvmforpractitioners.org discussion this study sought to explore practitioners’ motivations for using ebvm, and the barriers and challenges they encountered. the study findings informed the design of a new online ebvm training resource (‘ebvm for practitioners’) to help practitioners optimise their use of evidence in clinical decision-making. increasing the application of evidence is seen as a key way that ebvm can drive improvements in clinical care (dean & heneghan, 2019). during the focus group discussions, the main reasons cited by the participants for not being able to undertake more ebvm as part of their daily practice were insufficient time, a lack of support for ebvm from colleagues or practice management, inadequate access to evidence, and limited skills in ebvm (particularly acquiring and appraising evidence). these key challenges to implementing ebvm align with those identified by several previous studies (vandeweerd et al, 2012; zwolsman et al. 2013; hauser & jackson, 2017; and sellers et al., 2021). pupport to overcome these challenges should be instrumental in driving an increase in ebvm in the future. the participants were clearly conscious of the value of ebvm in general practice, but greater promotion and overall awareness of these benefits would be helpful. it has previously been shown that support of ebm / ebvm in clinical settings is associated with increased uptake (zwolsman et al., 2013; and sellers et al., 2021). promoting ebvm to veterinary practitioners and the wider veterinary profession could focus on highlighting the benefits e.g., improving clinical outcomes, increasing practitioners’ confidence, building client trust, and increasing employee engagement (hauser & jackson, 2017). the participants identified a need for more accessible, relevant evidence of sufficient quantity and quality, and described their ebvm activities as centring around group knowledge-sharing (e.g., journal clubs) or practice-wide uses of ebvm (e.g., clinical guidelines). it is recognised across the profession that various improvements to the veterinary evidence-base are needed (lanyon, 2014; dean & heneghan, 2019; and sellers et al., 2021), which would allow practitioners to utilise ebvm more in their day-to-day practice e.g., when deciding on treatment of an individual case. greater use of evidence syntheses and published evidence-based clinical guidelines are ways to reduce the time burden on busy practitioners and avoid the need to undertake a full independent evaluation (appraisal) of the primary sources. there have been advances made within the profession to increase the number and accessibility of this type of evidence (as previously outlined in the introduction), but more should be done to expand and promote these to practitioners if their use is to become widespread. primary or secondary sources of evidence were rarely mentioned by the participants as being used in practice, reflecting the findings of vandeweerd et al. (2012). access to evidence databases was limited for those working outside an academic setting, with many relying instead on the convenience of textbooks or consulting with more experienced colleagues. however, there was an awareness of the limitations of the evidence sources being used and a desire to apply higher-quality evidence more often in practice. over two thirds of practitioners (272/403) in a recent study (hauser & jackson, 2017) felt that clinical practice was often based on anecdotal evidence, suggesting that there is significant potential to increase the use of evidence to inform clinical decision-making. raising awareness of the existence of high-quality secondary sources e.g., evidence syntheses, and providing guidance on how to acquire primary research were both incorporated into ‘ebvm for practitioners’, with the aim of improving the quality of evidence that practitioners had access to. it was clear from the focus groups that current veterinary undergraduate curricula in the uk are increasingly providing the basic training on ebvm. however, the participants were still keen to improve their knowledge as having more skills in ebvm was associated with an increased use in practice, even where barriers and challenges were still present (e.g., lack of time, support, or access to evidence). ebvm is a vital clinical skill and requires ongoing development and consolidation (huntley et al., 2017), which can be supported by ensuring ebvm teaching and the promotion of its value continue to be embedded within both undergraduate and postgraduate training (arlt et al., 2012; steele et al., 2013; dean et al., 2017; huntley et al., 2017; gibbons et al., 2021; and batt-williams & lumbis, 2022). the ‘ebvm for practitioners’ resource will be an accessible way to provide a succinct summary of the key skills required for ebvm, as an initial introduction to the subject, or as a refresher course. in the future, the participants hoped that the veterinary profession would follow the medical profession, with widespread access to free, relevant, up-to-date evidence syntheses being seen as key to transforming healthcare (smith & chalmers, 2001). there are many ways in which the wider veterinary profession is rising to the challenge of promoting and supporting the use of ebvm; the production of resources and provision of practical support by several key organisations such as rcvs knowledge and the centre for evidence-based veterinary medicine (cevm), the open-access online training tutorial ‘ebvm learning’, and the inclusion of ebvm in the rcvs day one competences and rcvs practice standards scheme (2022) within the uk. limitations the study was undertaken in 2020, and as such was influenced by the global covid-19 pandemic. practitioners were extremely busy, making recruitment more difficult than originally anticipated, which reduced the sample size for the focus groups. due to limitations of the sampling method and sample size, it was not possible to ensure that the focus group participants reflected the broader demographic of veterinary practitioners in terms of years of experience and type of work undertaken. the selection of practitioners was limited to the network of the research team, so creating a potential bias towards those who had more experience / knowledge of ebvm. the resultant sample was biased towards those who had graduated more recently (63.6% graduated in the past 10 years), and those working as veterinary surgeons (only 9.1% of participants were veterinary nurses). if further research was to be conducted it would be valuable to attempt to recruit a focus group population that more closely represented the veterinary profession as a whole, to ensure that the views of all members of the profession and their needs are heard and considered. however, it is noted that generalisability is not a specified aim within qualitative research; rather enough details are provided so that readers can understand what aspects of the findings might be transferable to their own context. all focus group participants were currently working within clinical practice in the uk, which may limit the generalisability of the findings to an international context. future work there are various opportunities for future research, in particular to investigate the impact of any intervention that aims to promote ebvm. it would be interesting to evaluate ‘ebvm for practitioners’ by measuring the use of ebvm prior to and after accessing the resource, and by gathering feedback on additional support that practitioners would find useful once they have tried to put ebvm into practice. conclusion in conclusion, there are many challenges and barriers to the use of ebvm in general practice; participants identified time, support from colleagues and management, and accessing and appraising evidence as being the most important. however, the potential value of ebvm was clear, and that it could provide benefits to practitioners, practices, and the whole veterinary profession. practitioners are keen for more of their clinical decisions to be supported by robust evidence, to provide better healthcare, and to feel more confident in their clinical work. there are several initiatives within the veterinary profession that are aiming to place ebvm as a central part of clinical practice, but more can be done to expand and improve the quality of the evidence base on which ebvm relies, and to ensure practitioners have the skills, access, and motivation to utilise it. this study has been used to produce ‘ebvm for practitioners’, to attempt to reduce some of the barriers and challenges faced by practitioners and support them in increasing their use of ebvm. supplementary materials supplementary material s1 – focus group topics and questions acknowledgements we would like to thank the practitioners who participated in the focus groups for giving their valuable time, and the project team who attended the workshop and provided contributions to the online resource development. we would like to give particular thanks to clare boulton, rachel dean, joanne ireland, and heather moberly for their contributions to reviewing and editing ‘ebvm for practitioners’, and to rcvs knowledge for supporting and funding the project.  author contributions laura haddock: conceptualisation, methodology, validation, formal analysis, investigation, resources, data curation, writing – original draft, writing – review & editing, visualisation, project administration, funding acquisition. sarah baillie: conceptualisation, methodology, validation, formal analysis, data curation, writing – original draft, writing – review & editing, visualisation, supervision, project administration, funding acquisition. ellie sellers: conceptualisation, writing – original draft, writing review & editing. sheena warman: conceptualisation, methodology, validation, formal analysis, data curation, writing – review & editing, supervision. orcid laura haddock: https://orcid.org/0000-0002-7849-6953 sarah baillie: https://orcid.org/0000-0002-8665-8369 ellie sellers: https://orcid.org/0000-0002-3809-9777 sheena warman: https://orcid.org/0000-0003-0829-2039 conflict of interest the authors declare no conflicts of interest. references arlt, s.p., haimerl, p. & heuwieser, w. 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(2013). barriers to the use of evidence-based medicine: knowledge and skills, attitude, and external factors. perspectives on medical education. 2(1), 4–13. doi: https://doi.org/10.1007/s40037-013-0039-2 intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use.   veterinary evidence is an rcvs knowledge initiative. issn: 2396-9776 first floor, 10 queen street place, london ec4r 1be resources student awards staff login policies privacy policy accessing information policy cookie declaration terms of use copyright notices stay connected podcasts twitter facebook instagram linkedin back to top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443. go slow feeding bowls: how effective are they are getting dogs to eat more slowly? buckley†¹, l. a. and lees¹, j. ¹dept. animal production, welfare & veterinary science, harper adams university, newport, shropshire. tf9 2jw †corresponding author: lbuckley@harper-adams.ac.uk tel: 01952 815147 go slow feeding bowls: how effective are they are getting dogs to eat more slowly? buckley†¹, l. a. and lees¹, j. ¹dept. animal production, welfare & veterinary science, harper adams university, newport, shropshire. tf9 2jw †corresponding author: lbuckley@harper-adams.ac.uk tel: 01952 815147 introduction results conclusion methodology references n = 10 pet dogs ad hoc convenience sample • various ages (1 – 12years), breed types, weights (4.5 – 30kg) and both sexes represented dogs were tested for nine days per feeder type • feed ½ the daily food ration during the test • semi-moist diet familiar to all dogs • tested am (once daily) • green feeder size matched to manufacturer recommendations (<10kg = small, >10kg = standard) • given 10 minutes to consume the ration • data recorded using instantaneous sampling at 1 second intervals outcome measures: 1. latency to consume ration 2. rate of consumption 3. behaviours performed during feeding (not reported here) randomly allocated n = 5 0 50 100 150 200 250 300 350 400 dog bowl go slow feeder l a te n cy t o c o n su m e ra ti o n (s ec o n d s) feeder type this study arose from informal discussions on a vet nursing facebook group in which some vet nurses recommended ‘go slow feeder’ device (gsf) use to slow down feeding and make feeding fun. the gsf feeder used in the study is described by the supplier as a “revolutionary way to turn a dog's meal into a challenging time-consuming game. slowing down eating helps reduce the risk of bloat…” (green slow dog feeder, company of animals, 2016). slower eating rate is linked to improved satiety in humans (andrade et al., 2008; scisco et al., 2011) and may reduce risk of canine gastric dilatation volvulus (gdv) (glickman et al., 2000; but see: elwood, 1998; theyse et al., 1998); therefore, might confer welfare benefits for dogs. thus, we decided to test the bolded claims in this study. we have already reported elsewhere (buckley & lees, 2016) the very limited positive effects of this device on behavioural diversity and time budget during feeding, combined with canine preference for a regular dog bowl. this poster concentrates on: • the effect of feeder device on indices of speed of eating • the effect of experience on device effectiveness at slowing feeding. feeder preference data is also reproduced here to illustrate the canine perspective. figure 1: effect of feeder device on median latency to consume ration (t = 2.0, p = 0.006) andrade, a. m., greene, g. w., melanson, k. j. 2008. journal of the american dietetic association 108: 1186 – 1191 buckley, l. a. and lees, j. 2016. 50th congress of the international society for applied ethology 12-15th july, edinburgh, united kingdom company of animals. 2016. green slow dog feeder. [online]. company of animals. available from: http://www.companyofanimals.co.uk/product/green-slow-dog-feeder (accessed 27/10/2016) elwood, c. m. 1998. risk factors for gastric dilation in irish setter dogs. journal of small animal practice 39: 185 190 glickman, l. t., glickman, n. w., schellenberg, d. b., raghavan, m., lee, t. 2000. 217: 1492 1499 scisco, j. l., muth, e.r., dong, j., hoover, a. w. 2011. journal of the american veterinary medical association journal of the american dietetic association 111: 1231 1235 theyse, l. f. h., van de brom, w.e., van sluijs, f. j. 1998. veterinary record 143: 48 – 50 n = 10 versus two way choice test ten choice tests per dog • one test per day for ten days • side feeder presented on balanced within dog • ½ daily ration offered during the test outcome measures: 1. first feeder approached 2. first feeder eaten from statistical analysis: • wilcoxon matched pairs / one sample tests • reported using medians ± inter-quartile range 0 20 40 60 80 100 120 dog bowl go slow feeder r a te o f co n su m p ti o n ( g/ m in ) feeder type figure 2: effect of feeder device on median rate of consumption (t = 0.0, p = 0.002) 0 20 40 60 80 100 120 140 160 day 1 day 2 day 3 day 4 day 5 day 6 day 7 day 8 day 9 r a te o f c o n su m p ti o n ( g/ m in ) day of testing dog bowl go slow feeder figure 3: effect of experience (days) on median rate of consumption day 1 (inexperienced) versus day 9 (experienced): • experienced dogs were quicker at eating from the go slow feeder (t = 6.0; p = 0.027) nb. there was no effect of day on rate of eating from the dog bowl (t = 9.0; p > 0.05) figure 4: median proportion of choices for the go slow feeder option in a two way choice test nb. dashed line (----) signifies the point of no preference. 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1st feeder chosen 1st feeder eaten from p ro p o rt io n o f ch o ic es f o r th e go s lo w f ee d er choice test parameter ist bowl approached (t = 0.0; p = 0.008) 1st feeder eaten from (t = 0.0; p = 0.002) nb. a version of this data was previously reported at isae, 2016 n = 5 go slow feeding bowls are effective at reducing eating speed and, while dogs become quicker at eating as they develop experience eating from these devices, consumption rate is still slower than that observed when eating from a standard dog bowl. therefore, if slowing down the rate of eating is effective at reducing risk of gdv or confers improved satiety, these bowls may have a role to play in improving the welfare of some dogs. however, we found no evidence that dogs wanted to have their rate of eating slowed down (though feeder colour represents a confound in interpreting these findings) so caution is advised in conflating a slower rate of eating with having fun (a game) and marketing these devices to clients in this way. mailto:lbuckley@harper-adams.ac.uk go slow feeding bowls: how effective are they are getting dogs to eat more slowly?�buckley†¹, l. a. and lees¹, j. �¹dept. animal production, welfare & veterinary science, harper adams university, newport, shropshire. tf9 2jw�†corresponding author: lbuckley@harper-adams.ac.uk tel: 01952 815147 does treatment with clomipramine reduce cat psychogenic alopecia? a knowledge summary by anne-claude griesser rn msc mba 1* 1royal (dick) school of veterinary studies, university of edinburgh, bush estate, midlothian, eh25 9rg *corresponding author (ac.griesser@bluewin.ch) vol 7, issue 2 (2022) published: 29 jun 2022 reviewed by: jacklyn ellis (phd caab), mary fraser (bvms phd certvd macadmed mrescvr cbiol frsb fhea frsph frcvs), conor o'halloran (bvsc msc phd mrcvs) and roberta perego (dmv phd) next review date: 11 dec 2023 doi: 10.18849/ve.v7i2.573 pico question in cats with psychogenic alopecia, is overgrooming reduced by the use of clomipramine compared to untreated cats?   clinical bottom line category of research question treatment the number and type of study designs reviewed one pseudo-randomised controlled study strength of evidence weak outcomes reported effect of clomipramine using owner report of number, intensity, and / or duration of grooming episodes, owner reported clinical improvement, and veterinary measured alopecia, extent of tissue damage, and hair regrowth conclusion the only controlled study found no evidence that clomipramine alone is effective in reducing grooming episodes, alopecia, or improved hair regrowth. further research with randomised, double blind controlled trials and limitation of confounding factors is required to determine the efficacy of clomipramine alone or in addition to behavioural / environmental therapies   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a 6 year old female neutered cat exhibits recurrent episodes of hair pulling and overgrooming without underlying medical cause. a full skin work up has been carried out to exclude fleas or flea allergy. despite environmental changes reducing some stressors the cat continues overgrooming. the cat’s abdominal and inner thigh baldness worries the owner who would like to know if pharmacotherapy might prevent her cat’s overgrooming. the veterinarian knows that clomicalm® by novartis ag has good efficacy and is well tolerated in case of feline urine spraying and wonders therefore if this medication could also be efficacious to treat psychogenic alopecia. the evidence based on the only controlled study comparing clomipramine efficacy with placebo, there is no evidence that clomipramine alone reduces psychogenic alopecia in cats. controlled trial evidence was weakened by small patient numbers and confounded with environmental changes. summary of the evidence mertens et al. (2006) population: cats of any breed, sex, or age with an history of non-inflammatory alopecia, referred to a behaviour or dermatology consultation of the college of veterinary medicine at the university of minnesota. cats should not be sensitive to tricyclic antidepressants (tcas), or having received selective serotonin reuptake inhibitors (ssris) or tcas or monoamine oxidase inhibitors (maois) within the previous 4 weeks, or glucocorticoids within the previous 8 weeks. cats with skin biopsy showing sign of inflammation were tested for food or environmental allergies and were excluded if positive. sample size: 25 cats were included in the study after a skin analysis was performed to confirm self-inflicted alopecia without any dermatologic condition. since data were not completely recorded or treatment not administered properly, two cats were withdrawn from the study. in addition, one cat exhibited urinary obstruction at day 18 resulting in withdrawal from the study. therefore, 22 cats completed the study. intervention details: treatment groups cats were assigned alternatively to either a group receiving placebo (n = 13) or a group receiving clomipramine hydrochloride (0.5 mg/kg po q 24 hours) (n = 12). placebo and clomipramine were in similar gel capsules. investigators and owners were blind to cat treatment condition (i.e., clomipramine vs placebo). neither formal behavioural nor environmental modification plans were implemented in either group. owners were however requested to prevent reinforcement of overgrooming and to stop positive punishment.   experimental timeline treatment either placebo or clomipramine was administered from day 1 to day 56. follow-up phase from day 57 until day 84.   specific role of owners 7 days before starting treatment (day 1–7), owners completed a background questionnaire and performed a baseline assessment. the latter was recorded in a logbook. it encompassed: total number of episodes of licking, chewing, and hair pulling / 24 hours. specific behaviours: anxiousness, calmness, use of cat litter, interactions with human and household pets. special events and environmental changes. this assessment was repeated daily from day 1 until day 84. owners were also asked to record the time of treatment and the occurrence of any adverse events. on day 84, owners were asked to qualitatively assess the overall changes exhibited by their cat from day 1 to day 84.   specific role of the professional team on day 0 (i.e., 1 day before the start of the treatment), day 28, day 56 and day 84: laboratory tests were performed. a dermatologist measured the extent of the alopecia and the degree of hair regrowth. an outline of the dorsum, ventrum and lateral sides of the body were drawn on a graph paper to record the area of alopecia and hair regrowth at each consultation. a behaviourist made a behavioural assessment (no detail is provided on this assessment). on day 0 and day 28, ecg were performed. on day 28 and day 56, the team measured owner’s compliance with treatment administration by checking the logbook, the number of remaining capsules and volume of liquid. study design: double-blind placebo-controlled trial. outcome studied: grooming episodes: daily episodes of licking, chewing, and hair pulling from day 0 to day 84, based on a specific protocol (similar time and duration of daily observations by same observer i.e., owner).   alopecia scores from 1–5, on day 28, day 56 and day 84, in comparison to day 0: score 1 reduced by >75% score 2 reduced by >50–75% score 3 reduced by >25–50% score 4 reduced by < 25% score 5 new areas of alopecia or no change from day 0   mean hair regrowth scores: hair length adjacent to the alopecia area was measured on day 0 and day 28, day 56 and day 84 and the percent reduction between the adjacent area to alopecia and normal hair length was measured. a range score from 1–5 was used to describe these differences in hair regrowth. score 1 reduced by >75% score 2 reduced by >50–75% score 3 reduced by >25–50% score 4 reduced by <25% score 5 no change from day 0   4. adverse events: qualitative owners’ observation, clinical signs, ecg, complete blood counts, thyroxine (t4) and serum biochemicals.   5. general evaluation by the owners. main findings (relevant to pico question): grooming episodes no significant differences in the mean number of grooming episodes between clomipramine and placebo groups (analysis of variance; p = 0.13).   alopecia scores no differences in the mean scores between the two treatment groups (kruskal-wallis test) at day 28 (p = 0.44), day 56 (p = 0.06) and post-treatment at day 84 (p = 0.39).   hair regrowth no differences were found in mean scores between the two treatment groups (kruskal-wallis test) at day 28 (p = 0.18), day 56 (p = 0.48) and post-treatment at day 84 (p = 0.34).   adverse events clomipramine group: no abnormalities were attributed to clomipramine on the ecg or laboratory tests urethral obstruction after 18 days of treatment in one cat lethargy in five cats constipation in one cat reduced appetite in one cat reduced interaction with owner in four cases difficulty in administering medication in two placebo group: intermittent vomiting in two cats increased search for owner attention by one cat during the first 2 weeks of the study.   general evaluation by owners: 7/11 (64%) owners in the clomipramine group reported behaviour and hair coat improvement of at least 50%. 3/11 (27%) owners in the placebo group reported an improvement of at least 50%. limitations: study design: with 25 enrolled cats, the sample size was undersized, and no power calculation was reported. the statistical treatment difference to be detected to conclude that clomipramine was superior to placebo was not specified. no randomisation but rather alternating allocation of the enrolled cats to clomipramine or placebo group, leading to a possible bias in the selection of cases and non-comparability of the two treatment groups. since the paper does not include a table of the cats details for each group, it is not possible for the reader to appraise if the two groups were comparable or if there was any bias in the grouping. while the term ‘investigators’ may include the three authors of the paper only, it is not clear who was specifically blinded to the type of treatment, thus preventing the assessment of possible biases. lack of justification for the recommendations to owners of stopping negative punishment or prevention of reinforcement for grooming in addition to a lack of report on the number of involved cats, prevent the reader from evaluating the impact of this environmental modification on the outcome. no comprehensive measurement of the severity of alopecia including problem duration which might impact outcome. no justification of alopecia reduction and hair regrowth as outcome and whether these two measures were sensitive and specific enough since hair regrowth may differ from one cat to another. no measurement of cat stress with either a validated instrument, or with blood or salivary cortisol level, or both. the authors reported that some enrolled cats may have had dermatologic issues such as demodicosis or cheyletioellosis. no parasiticide response trial was performed for all the cats before inclusion in the study. furthermore, it was possible that some of the enrolled cats had food allergies and/or atopic dermatitis while the histopathological evidence of inflammation in non-affected skin failed to demonstrate food allergies in some cases. lack of details whether postprandial vomiting or spitting out was recorded, as part of measuring owner compliance with clomipramine administration. clomipramine is known to have a bitter taste.   results: lack of information for determining if clomipramine and placebo groups were homogeneous or if some cats’ characteristics were overrepresented in one group or in the other. over representation of exclusively indoor cats and multi-cat households (88%) compared to the general population of domestic cats leading to a potential limit for generalising to the overall household cat population. baseline assessment and results were presented on a graph without explanation nor discussion of 30% higher average number of grooming episodes in the clomipramine versus placebo group at the baseline assessment making difficult for the readers to appraise this difference between both groups. lack of precise mean values and standard deviations of the average number of grooming episodes, alopecia score, and hair regrowth score, prevents the reader from evaluating the variance of results. no information about how alopecia size was factored into interpretation of results. lack of detail about the exhibited grooming behaviours and how they were observed and reported.   conflict of interest: none declared appraisal, application and reflection one pseudo-randomised double-blind, placebo-controlled trial study that fully addressed the pico question was reviewed. the controlled study (mertens et al., 2006) revealed no significant difference between clomipramine and placebo groups, either in the number of grooming episodes throughout the clomipramine treatment period and after its discontinuation or in the score of alopecia and hair regrowth after 28 and 56 days medication and 28 days after stopping the medication. with 25 enrolled patients in the trial by mertens et al. (2006), the sample size was too small to test whether clomipramine is superior to placebo in reducing overgrooming. furthermore, the variability in the pharmacokinetics of clomipramine in cats (lainesse et al., 2007) may also have reduced the ability to detect statistical significance. in addition, the 25 patients were not randomly assigned to the two treatment groups, with a possible selection bias and may have limited the comparison. even if mertens et al. (2006) did not report any differences across the two groups, it is indeed noticeable that the average number of grooming episodes was 30% higher in the clomipramine group (45) than in the placebo group (30) at the baseline assessment. mean grooming episodes decreased by 57% after 56 days of treatment and a rebound after discontinuation of treatment was observed in the clomipramine group, whereas the dynamics in the placebo group did not show the same pattern. it is therefore crucial to ask whether the inclusion of the entire observation period in the calculation of therapeutic efficacy on grooming episodes was relevant since evidence indicates a possible rebound of symptoms when antidepressants are discontinued (henssler et al., 2019). therefore, two separate assessments of the efficacy (1) during the treatment period and (2) its duration after cessation of treatment may have been more appropriate. while the owners were blind to treatment conditions, their ratings may have had unexpected intraand inter-observer variability effects. that said, twice as many owners (7/11) in the clomipramine group found their cat's behaviour and coat improved compared to the placebo group (3/11). since there was no information on how the scoring system was validated, it is debatable whether alopecia and hair regrowth scores were specific enough or sufficient to measure medication efficacy while hair growth can depend on different factors such as season, sex, breed and nutrition (affolter & moore, 1994; and hendriks et al., 1997). in addition, there was no indication for psychogenic alopecia severity such as duration of overgrooming. neither the context of its exhibition nor the size of the area affected was discussed by the authors as a confounding factor. cat psychogenic alopecia is considered a behavioural disorder that may be precipitated by emotional stress triggered by the environment (virga, 2003). therefore, stopping positive punishment may have alleviated the stress-overgrooming cycle, thus limiting the interpretation of results of both groups while it is not reported how positive punishment by owners was distributed across the clomipramine group and the placebo group. it should be noted that one before and after study (seksel & lindeman, 1998), two case series (overall & dunham, 2002; and sawyer et al., 1999) and one case study (talamonti et al., 2017) reported that implementation of a behavioural and environmental modification plan along with clomipramine provided a sustained reduction in overgrooming among cats with psychogenic alopecia. although subjective assessment by owners may have overestimated the positive effects of the treatment combination, these non-controlled study findings suggest mertens et al. (2006) cannot be interpreted without consideration of the environmental changes that may have occurred for some cats enrolled in the study. in mertens et al. (2006), cats were recruited from second-line consultations which constitutes a selection bias. this should be considered but does not constitute an obvious limit to generalisation. psychogenic alopecia is a complex condition that can be challenging to diagnose and treat in a first-line consultation. furthermore, it is good practice that such cases are referred to specialists. multi-cat households (22/25) or indoor cats (23/25) were overrepresented in the sample of the study by mertens et al. (2006), which could limit the generalisation of the results. however, it is known that risk factors for developing a behavioural problem in cats, such as overgrooming include living with other cats or animals (luescher, 2003), or not having access to the outdoors (virga, 2003). the reviewed study (mertens et al., 2006) found that clomipramine alone was not effective in treating psychogenic alopecia in cats. this study was of limited quality and had several confounding factors that may explain the results. therefore, further research with randomised, double-blind controlled trials and limitation of confounding factors is needed to substantiate the efficacy of clomipramine alone or in addition to behavioural / environmental therapies. it should be indeed noted that various non-controlled studies (overall & dunham, 2002; sawyer et al., 1999; seksel & lindeman, 1998; and talamonti et al., 2017) suggested that if a behavioural and environmental modification plan was set up alongside the clomipramine treatment in cats with psychogenic alopecia the exhibition of overgrooming might diminish or even discontinue. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform (1973–2021) pubmed via ncbi website (1900–2021) web of science on ovid platform (1970–2021) search strategy: cab abstracts: (cats or cat).mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (felis catus or feline* or felid*).mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (psychogenic alopecia or over-grooming or hair loss or licking).mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (obsessive-compulsive disorder or compuls*adj$ behavio*).mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (abnormal behaviour or behavior).mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] behaviour disorders/ (skin diseases or pruritus).sh. (clomipramine or clomicalm or anafranil).mp. [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes] (1 or 2) and (3 or 7 or 4 or 5) and 8   pubmed: ("cats"[mesh terms] or ("cat"[all fields] or ("cats"[mesh terms] or "cats"[all fields]))) and ("obsessive compulsive disorder"[mesh terms] or "over-grooming"[all fields] or "grooming"[mesh terms] or ("groomed"[all fields] or "grooming"[mesh terms] or "grooming"[all fields] or "groom"[all fields] or "groomings"[all fields] or "grooms"[all fields]) or "groom*"[all fields] or "alopecia"[mesh terms] or (("psychogenic"[all fields] or "psychogenically"[all fields] or "psychogenicity"[all fields] or "psychogenous"[all fields]) and ("alopecia"[mesh terms] or "alopecia"[all fields] or "alopecias"[all fields])) or ("alopecia"[mesh terms] or "alopecia"[all fields] or ("hair"[all fields] and "loss"[all fields]) or "hair loss"[all fields]) or "itch*"[all fields] or "pruritus"[mesh terms] or "dermatitis/veterinary"[mesh terms] or "bald*"[all fields] or "stereot*"[all fields] or "anxiety"[mesh terms]) and ("clomipramine"[mesh terms] or ("clomipramine"[mesh terms] or "clomipramine"[all fields] or "clomipramine s"[all fields]) or ("clomicalm"[all fields] or "clomipramine"[mesh terms] or "clomipramine"[all fields] or "clomipramine s"[all fields]) or ("clomipramine"[mesh terms] or "clomipramine"[all fields] or "anafranil"[all fields]))   web of science: ((all=(cats or cats or feline* or felis or felid*)) and all=(clomipramine or clomicalm or anafranil )) and all=(compulsive behaviour or compulsive behavior or over-grooming or grooming or hair-loss or itching or stereot* or bald* or licking or alopecia or dermatitis or stereot* or behaviour disorder or behavior disorder) dates searches performed: 11 dec 2021 exclusion / inclusion criteria exclusion: pre-defined exclusion criteria: non-english language, proceedings, book chapter, popular press. inclusion: any comparative (control group utilised) study published in a peer-reviewed journal in which the effect of clomipramine on psychogenic alopecia or overgrooming in cats was studied. search outcome database number of results excluded – not relevant to pico question excluded – not english language excluded – chapter of book or proceedings excluded – duplicate total relevant papers cab abstracts 32 18 3 6 5 0 pubmed 8 6 1 0 0 1 web of science 37 23 6 1 7 0 total relevant papers when duplicates removed 1 conflict of interest the author declares no conflicts of interest. references affolter, v.k. & moore, p.f. (1994). histologie features of normal canine and feline skin. clinics in dermatology. 12(4), 491–497. doi: https://doi.org/10.1016/0738-081x(94)90215-1 hendriks, w.h., tarttelin, m.f. & moughan, p.j. (1997). seasonal hair growth in the adult domestic cat (felis catus). comparative biochemistry and physiology part a: physiology. 116(1), 29–35. doi: https://doi.org/10.1016/s0300-9629(96)00113-2 henssler, j., heinz, a., brandt, l. & bschor, t. (2019). antidepressant withdrawal and rebound phenomena. deutsches ärzteblatt international. 116(20), 355–361. doi: https://doi.org/10.3238/arztebl.2019.0355 lainesse, c., frank, d., beaudry, f. & doucet, m. (2007). effects of physiological covariables on pharmacokinetic parameters of clomipramine in a large population of cats after a single oral administration. journal of veterinary pharmacology and therapeutics. 30(2), 116–126. doi: https://doi.org/10.1111/j.1365-2885.2007.00826.x luescher, a.u. (2003). diagnosis and management of compulsive disorders in dogs and cats. veterinary clinics of north america: small animal practice. 33(2), 253–267. doi: https://doi.org/10.1016/s0195-5616(02)00100-6 mertens, p.a., torres, s. & jessen, c. (2006). the effects of clomipramine hydrochloride in cats with psychogenic alopecia: a prospective study. journal of the american animal hospital association. 42(5), 336–343. doi: https://doi.org/10.5326/0420336 overall, k.l. & dunham, a.e. (2002). clinical features and outcome in dogs and cats with obsessive-compulsive disorder: 126 cases (1989–2000). journal of the american veterinary medical association. 221(10), 1445–1452. doi: https://doi.org/10.2460/javma.2002.221.1445 sawyer, l.s., moon-fanelli, a.a. & dodman, n.h. (1999). psychogenic alopecia in cats: 11 cases (1993–1996). journal of the american veterinary medical association. 214(1), 71–74. seksel, k. & lindeman, m.j. (1998). use of clomipramine in the treatment of anxiety-related and obsessive-compulsive disorders in cats. australian veterinary journal. 76(5), 317–321. doi: http://dx.doi.org/10.1111/j.1751-0813.1998.tb12353.x talamonti, z., cannas, s. & palestrini, c. (2017). a case of tail self-mutilation in a cat. macedonian veterinary review. 40(1), 103–107. doi: http://dx.doi.org/10.1515/macvetrev-2016-0098 virga, v. (2003). behavioral dermatology. veterinary clinics of north america: small animal practice. 33(2), 231–251. doi: https://doi.org/10.1016/s0195-5616(02)00102-x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. evidence-based healthcare: the importance of effective interprofessional working for high quality veterinary services, a uk example tierney kinnison bsc msc phd pgcertveted fhea1 stephen a may ma vetmb phd dvr deo frcvs dipecvs fhea1 1the royal veterinary college, hawkshead lane, north mymms, hatfield, hertfordshire, al9 7ta *corresponding author (tkinnison@rvc.ac.uk) vol 1, issue 4 (2016) published: 29 nov 2016 reviewed by: elizabeth l. jackson (bag (hons) mba phd sfhea) and dr sebastian arlt next review date: 29 nov 2018 doi: 10.18849/ve.v1i4.54 section index:    abstract | introduction | results | discussion | conflict of interest | references | supplementary files abstract objective: to highlight the importance of evidence-based research, not only for the consideration of clinical diseases and individual patient treatment, but also for investigating complex healthcare systems, as demonstrated through a focus on veterinary interprofessional working. background: evidence-based veterinary medicine (ebvm) was developed due to concerns over inconsistent approaches to therapy being delivered by individuals. however, a focus purely on diagnosis and treatment will miss other potential causes of substandard care including the holistic system. veterinary services are provided by interprofessional teams; research on these teams is growing. evidentiary value: this paper outlines results from four articles, written by the current authors, which are unique in their focus on interprofessional practice teams in the uk. through mixed methods, the articles demonstrate an evidence base of the effects of interprofessional working on the quality of service delivery. results: the articles explored demonstrate facilitators and challenges of the practice system on interprofessional working and the outcomes, including errors. the results encourage consideration of interprofessional relationships and activities in veterinary organisations. interprofessional working is an example of one area which can affect the quality of veterinary services. conclusion: the papers presented on veterinary interprofessional working are an example of the opportunities for future research on various topics within evidence-based healthcare. application: the results are pertinent to members of veterinary teams seeking to improve their service delivery, to educators looking to enhance their students’ understanding of interprofessional working, and to researchers, who will hopefully be encouraged to consider evidence-based healthcare more holistically. introduction within this article, the authors seek to highlight the importance of evidence-based research, not only for the consideration of clinical diseases and individual patient treatment, but also for investigating complex healthcare systems. after an exploration of this idea, primarily through human healthcare literature, the article will use the example of veterinary interprofessional working, to explore how evidence can be gained to support the development of high quality veterinary services. evidence-based medicine evidence-based medicine (ebm) emerged as a concept in human healthcare literature in the 1990s, and was defined as: the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. the practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research (sackett et al. 1996). in their article, sackett et al. (1996) were keen to convince their readers that ebm is more than randomised clinical trials and meta-analysis. it involves the integration of best available scientific evidence, with patient needs and individual clinician expertise. however, a systematic review of numerous randomised trials remains their “gold standard” for evaluating the benefits and potential harm of a treatment. evidence-based veterinary medicine literature regarding evidence-based veterinary medicine (ebvm) is a slightly more recent advancement. one of the first instances is an editorial in the journal of veterinary internal medicine in 2000 (keene, 2000). three years afterwards, a ‘handbook of evidence-based veterinary medicine’ was published (cockcroft & holmes, 2003). utilising the same definition of ebm, drivers of ebvm have called for increased patient research utilising individual, randomised, placebo-controlled clinical trials for treatments (keene, 2000). educators have begun to incorporate ebvm into veterinary curricula, and have described teaching ebvm skills utilising critically appraised topics (arlt, haimerl, & heuwieser, 2012) including in the context of online learning (steele et al., 2013). a critique of the definition of ebm/ebvm the definition of ebm/ebvm, and the methodological gold standard to which it is linked, are focused on the care of individual patients. the attention is, therefore, on the diagnosis and treatment of the individual patient’s disease or ailment within the context of the patient’s other needs. the best way to research treatment options, which are often drug trials, is therefore the systematic review of research reports which use randomised patients. in this paper, we argue for consideration of a more holistic view of veterinary services that incorporates the systems involved in their delivery as well as the ebm/ebvm focus on individual patients. this holistic view takes into consideration the healthcare system in which doctors, nurses, veterinarians and other healthcare professions work. successful healthcare depends not just on rational therapy, but also factors such as the skills of those involved in its delivery and client compliance.  many veterinarians might go to the literature and say a horse undergoing surgery for a small intestinal strangulation has an 80% chance of success (proudman, et al. 2002). however, that is relevant only to the surgical team who published that article and their practice team.  the success rate of any other veterinarian and their team might be much less. in the following paragraphs, several prominent authors who use scientific research to generate and deploy an evidence base for healthcare systems will be introduced. much of the focus of these authors relates to the prevention of medical error, and therefore the development of an evidence base for high quality medical services, which could be translated to veterinary services. a systems approach to medical error james reason has been one of the most influential authors on human error in complex organisations (reason, 2000, 2004). reason is a psychology graduate who worked as a research psychologist at the royal air force (raf), a field closely linked to interprofessional working and education, a topic explored later in this article. reason suggests that there are two approaches to the issue of human fallibility – the person and the system. the person approach is historically more prominent. it looks for individuals to blame for their mistake. the system approach on the other hand, recognises that many lapses are actually ‘blameless’ – no one person is wholly responsible for an error. this is explained through the existence of latent conditions (‘organisational’ such as management policies and ‘system’ such as stress in the work environment) added to active failures (during direct contact with a patient) and local triggers (such as time) to create an ‘accident opportunity’ (reason, 2000). therefore, medical errors are not only caused by isolated human incompetence or acts of negligence (kalra, 2004). instead, the swiss cheese model of accident causation (reason, 2004) explains how errors can penetrate several lines of defences, akin to travelling through the holes of swiss cheese, without it being any particular person’s fault. mistakes therefore occur due to the fallibility of humans. it is noted that reporting these mistakes is a contentious issue in healthcare, with fear of litigation following admissions of being sorry. however, this denial has the potential to harm the organisation’s chances of preventing the same mistake from happening again through making changes to the system. a culture which does not seek  individuals with whom to find fault, and instead maintains a no-blame, or ‘just’ culture (wachter & pronovost, 2009), is more aligned to honest reporting and a positive and progressive team. research regarding error disclosure has indeed suggested that patients desire an apology as well as information on the cause of the error, and how the hospital will seek to prevent similar errors (gallagher et al. 2003). in order to establish suitable means to prevent future errors, there is therefore little sense in focusing solely on an individual; whether an individual client or an individual doctor, nurse or any healthcare professional. instead, the use of a systems approach to medical error offers opportunities to actually create solutions that address healthcare delivery holistically. system and cultural effects on the implementation of ebm while the systems approach to medical error can aid in identifying latent conditions and local triggers, and therefore aid development of solutions, it is another thing to implement these solutions in an organisation which has its own historical culture. atul gawande is a surgeon who has written extensively on his experiences of the imperfect science that is medicine. in his books, he explores several low cost methods which have been identified as reducing error, including various protocols, checklists and other systematic methods (gawande, 2007). however, he also describes in detail the difficulty of implementing even simple solutions to improving the care of patients. handwashing is one such example. gawande considers that there would be a greater impact on healthcare if we ensured that services were well delivered, such as the requirement of a physician to wash their hands, rather than spending vast amounts of money on disease-specific research. however, the problem with implementing handwashing in one hospital was that of physician compliance; an obstinacy, blindness and resistance to change. changing the whole culture, through support from traditional leaders and managerial staff for nurses to speak up to physicians, proved significant in increasing compliance. in the definition of ebm, the idea of context, in terms of the patient’s situation and personal choices is considered paramount, alongside the clinician’s own expertise and practice situation. the work highlighted by gawande (2007), as well as syed (2015), helps clarify the full meaning of these other dimensions, in particular the importance of considering the wider situation in which the patient sits – the hospital or veterinary practice – when we consider means to maximise the benefits of ebm and ebvm. systems research on veterinary interprofessional working the term interprofessional is used in a variety of contexts, for example, it is often used in the context of “one health”, where veterinarians work alongside healthcare professionals and environmental professionals. the term could relate to any occupation or profession working together within the veterinary field for the advancement of animal health and welfare, for example, veterinarians working with pharmaceutical companies or pet behaviour councillors. in the current paper, the term is used to relate to the typical uk veterinary practice team. patient care no longer tends to rest solely with one veterinarian. veterinary teams in the current era frequently consist of multiple veterinary surgeons, veterinary nurses, other paraprofessionals, receptionists and administrators in either small animal, equine or mixed practices. all of these professions and organisations have an impact on the care received by the patient and the client; therefore, through researching the veterinary interprofessional team and its culture, it is possible to identify areas of potentially substandard service delivery which could be developed in order to improve the quality of care provided. in the following section, research papers which focus on the systems nature and the culture of veterinary interprofessional working in the uk will be explored. all papers were written by the current author team and their colleagues, and are unique in their empirical focus on interprofessional working within the practice setting. this provides an important first step in the investigation of the systems nature of veterinary service delivery in its entirety. results the culture of knowledge exchange within veterinary teams and its impact on care provision social network analysis (sna), a methodological approach to analysing interactions within a specified network, such as a veterinary practice, was utilised in two recently published papers (kinnison et al. 2015b; kinnison et al. 2015c). it has previously been suggested that the free flow of relevant knowledge around any team creates a pool of shared meaning (patterson, grenny, mcmillan, & switzler, 2001), allowing decisions to be made which are better than any one individual (or individual profession) could have made alone. the two sna papers researched factors which might restrict knowledge exchange interactions within veterinary practices, and therefore impact on service delivery. ‘knowledge interactions’ were defined as: receiving information, receiving advice, problem solving with another and being influenced by another’s work. the two papers identified four key restrictors to the flow of knowledge around a veterinary team. the key restrictors were: the size of the team, the spatial nature of veterinary practices as separate branches (kinnison et al 2015c), the hierarchical nature of veterinary practices, and a link between social and work interactions (kinnison et al. 2015b). as reported in kinnison et al. (2015c), smaller teams were more cohesive for all interaction types. this has implications for practices aiming to expand their team in one location, as protocols may be useful in maintaining levels of interactions.  it was noted, however, that individuals still did not interact with all colleagues for all interactions, and were therefore making choices, as explored below. the nature of the distributed veterinary team across branches, especially those where staff did not rotate across branches, also influenced interactions and created silos of sub-teams within branches. this has implications for practices aiming to expand via incorporating a new branch, and for those corporate practices who claim a benefit of their corporation is sharing best practices across veterinary practices/branches. kinnison et al. (2015b) explored the effect of personal factors on interactions. they identified that for more complex knowledge interactions, like problem solving, individuals more frequently went to their intraprofessional peers, rather than to an interprofessional colleague. a hierarchical nature of interactions was seen between veterinary surgeons and veterinary nurses, whereby veterinary nurses were more likely to ask specific veterinary surgeons for knowledge (information, advice and problem solving) than vice versa. this has implications for creating expert teams, whereby, in an ideal world, knowledge should be sought based on experience and understanding rather than professional status. however, a number of ‘key people’ were identified who were frequently involved in interactions, and these key people did include some veterinary nurses and administrators (such as practice managers), suggesting some evidence of an experienced-based hierarchy in addition to the profession specific hierarchy. additionally, this paper identified a link between the existence of social interactions between a pair of colleagues and work interactions between the same pair. this has implications for practices to actively promote the opportunity for social events between work colleagues to subsequently increase relevant work interactions. veterinary systems’ facilitation and challenge to interprofessional working kinnison et al. (2016) describes the results of two case studies, conducted within veterinary practices which were contrasting in their size, species treated and location. the case studies aimed to explore the systems within veterinary practices which facilitated and challenged interprofessional working. in total, 220 hours of observations were conducted and 12 interviews were held with veterinary surgeons, veterinary nurses, receptionists and administrators (totalling eight hours). analysis of the case study field notes utilised a cultural historical activity theory framework (engeström, 2008) and analysis of interview transcripts followed a thematic analysis (braun & clarke, 2006). this study formed part of a larger study including the aforementioned sna research (kinnison et al. 2015b; kinnison et al. 2015c), and triangulation of the sna results and case study results identified various factors of veterinary practice systems which were facilitators or challenges to interprofessional working. facilitators to veterinary interprofessional working included: trust and value, hierarchy, professionalisation and accountability, different perspectives and formal infrastructure. challenges to interprofessional working included: temporal and spatial nature of work, hierarchy, professional motivation, and error and blame. an interesting dimension exists between utilising different perspectives of professional groups to make decisions that any one profession could not have made on their own, and the contrasting motivation of each of the professions in their daily work. utilising different professions’ perspectives involves having an understanding of their role and their background; however, having different motivations may diminish the understanding that professions have about each other. the veterinary surgeon’s novel perspective and motivation aligned primarily with diagnosing and curing the patient. the veterinary nurse’s perspective and motivation was more focussed on the patient’s welfare. the receptionist’s perspective and motivation was mainly for the client. finally, the administrator’s perspective and motivation was linked to the practice and the practice team. these primary contributions and motivations are not exclusive to any one profession, and all professions expressed contributions and motivations towards all factors. however, making use of the naturally differing foci of the occupational groups within a veterinary practice is a potential way to produce an expert team with distributed cognition (hutchins, 1995) rather than an unintegrated ‘team of experts’ (collin, paloniemi, & mecklin, 2010). system errors in veterinary practices have implications for patients, clients, the practice and the team an unexpected finding from the case studies outlined in the section above was an observation of errors within veterinary practices (kinnison et al. 2015a). once errors were identified as an outcome of the study, a detailed investigation of all field notes was undertaken to identify all errors. the definition of error used in this instance was based on that from mellanby and herrtage (2004), but was more inclusive: an erroneous act or omission resulting in a less than optimal or potentially adverse outcome of any severity for a patient, client or the practice. forty instances were identified as errors and these were categorised as clinical errors (dosing/drugs, surgical preparation and lack of follow-up), team communication errors (records, procedures, missing face-to-face communication and mistakes within face-to-face communication) and a minor group of lost item errors. through the case study observations and interviews, several latent conditions contributing to these errors were identified. these included: a lack of time; frequent handovers between receptionists or between veterinary nurses, with a potential for communication failure; issues with booking in consultations; and branch or veterinary surgeons’ differences, requiring veterinary nurses or receptionists to behave in different ways depending on their context. solutions were often identified by the practices themselves, including encouraging receptionists to go on visits with veterinary surgeons to improve understanding of booking consultations. additional protocols or checklists, as promoted by atul gawande (gawande, 2011), in this case relating to change overs and a reduction of branch differences, could also reduce errors. kinnison et al. (2015a) is the first published report of real-time observed errors within veterinary practices. it follows mellanby & herrtage’s (2004) investigation of recent graduates reporting of errors in practice, and sits well alongside oxtoby et al.’s (2015) investigation of the causes and types of errors through a review of insurance claims with focus groups for in-depth investigation of the identified issues. together, these results call for increased research, at both individual and practice team levels, regarding identification of errors, error reporting, identification of solutions and the results of error management initiatives. discussion ebvm developed due to inconsistent and old-fashioned approaches to therapy being delivered by individuals.  however, a focus purely on diagnosis and treatment will miss many other potential causes of substandard care.  particularly where a patient is handled by multiple people (as is frequent in modern veterinary practices), all participants need to work as an effective interprofessional team. this involves individuals being aware of their own role, the roles of others, the desires of the client and developments in the case. this is in addition to being respectful and supportive of colleagues. these factors may be influenced by the culture of the veterinary practice in which the team works. this paper does not dispute that research on better diagnostic tools and treatments for specific diseases is important.  however, hand-in-hand with these advances, progress must be made on health service delivery as it has been argued that attention to service delivery is likely to be a far more cost-effective way of improving healthcare than further research on individual diseases (gawande, 2007). this paper, therefore, seeks to highlight the potential of evidence-based healthcare for considering veterinary practices as complex systems in order to create an evidence base for high quality veterinary services. the results that are summarised here are intended as an illustration of interprofessional working – one focus for researching of the systems and cultures encompassing the art of veterinary practice. the interprofessional research was initially conducted to develop an evidence base for current interprofessional activities and potential interprofessional issues in practice, which could be used to drive interprofessional education (ipe) initiatives for future veterinary undergraduate curricula. a recent ipe best evidence medical education (beme) review (reeves et al. 2016) identified a total of 46 ipe studies in human healthcare, which suggested that ipe influences learning of knowledge and skills, although it is less influential on changing attitudes or perceptions to interprofessional colleagues. the review also provided evidence that ipe can affect a positive change at different outcome levels, including behavioural, organisational and patient/client outcomes. as highlighted in the results, the focus on ipe is essential as much professional communication in veterinary practice, as in human healthcare systems (zwarenstein et al. 2013), is interprofessional.  so achieving the full potential in terms of accessing summaries of “best practice” and support of their adoption will depend on effective interprofessional dialogues. the research summarised here has not looked at implications of increased specialisation in the veterinary professions and both referral in and between practices.  however, the danger with specialisation is that it leads to greater barriers to interprofessional (irvine et al. 2002; widmark et al. 2011) and intraprofessional (de buck et al. 2002)  working, with less attention to “the patient who has the disease(s)” than “the disease(s) that the patient has” (sweeney et al. 1998).  in addition, this work has demonstrated the barriers to communication caused by geographical and temporal divisions that would apply equally to referral and other centres. therefore, these trends only emphasise the need to pay attention to interprofessional working and communication. the limitations of the depicted articles and therefore this summary, are that the results were based on relatively few veterinary practices in england. eleven practices took part in the sna, and though they cannot represent all of england, or international practices, they did cover a wide range of practice types including independent/corporate, small/large, first opinion/referral, small animal/mixed/equine, and were from across the whole of england. in addition, the sna results were self-reported via a questionnaire, however, observational sna was conducted in two practices and demonstrated a good correlation between reported and observed interactions. the errors reported through the case studies may have underestimated individual cognitive errors; however, they have the previously unseen advantage of an independent observer reporting team-based errors as they occur.  the main argument of this paper is that if ebvm is to be true to the definition provided by the founders of ebm, it must look beyond just an emphasis on randomised drug trials and best treatment evidence to a more holistic evidence-based healthcare approach. as research on veterinary interprofessional working demonstrates, methods to investigate the issues of service delivery will rarely, if ever, include randomised control trials. qualitative methods and mixed methods are far more common and it is a requirement of veterinary practices in the modern era to be able to understand and critique these types of data. this involves an evaluation of their confirmability instead of objectivity, credibility rather than internal validity, transferability instead of external validity and dependability rather than reliability (wigren, 2007). otherwise the danger is that service delivery will be determined by “how to” manuals based on anecdote. in conclusion, this paper aims to encourage the widespread recognition that ebvm, correctly interpreted, embraces evidence-based veterinary healthcare in its broadest sense. this means that ebvm should include the development of an evidence base for high quality veterinary services via researching veterinary practice and identifying areas of substandard service delivery. the papers presented on veterinary interprofessional working are an example of the opportunities for future research on various topics within this valuable area. conflict of interest acknowledgments: the authors would like to thank the veterinary practices and their teams who took part in the sna and case studies.   funding: the veterinary interprofessional papers cited were part of a phd funded by the bloomsbury colleges studentship. competing interests: n/a. references arlt, s. p. haimerl, p. and heuwieser, w. 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(2007). assessing the quality of qualitative research in entrepreneurship. in h. neergaard & j. . ulhoi (eds.), handbook of qualitative research methods in entrepreneurship. cheltenham: edward elgar publishing http://dx.doi.org/10.4337/9781847204387.00026 supplementary files, images & tables all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. ultrasonographic detection of cranial cruciate ligament pathology in canine stifles without craniocaudal instability | veterinary evidence skip to main content article keywords: musculoskeletal ultrasound; sports medicine; cranial cruciate ligament; orthopaedics; arthroscopy; dog; arthrotomy; arthroscopy ultrasonographic detection of cranial cruciate ligament pathology in canine stifles without craniocaudal instability helen tsoi, dvm1* debra a. canapp, dvm ms ccrt cva dacvsmr1 sherman o. canapp jr., dvm ms ccrt dacvs dacvsmr1 1veterinary orthopedic sports medicine group, 10975 guilford road, ste b, annapolis junction, md 20701, usa *corresponding author email: htsoi216@gmail.com vol 8, issue 2 (2023) submitted 28 jun 2022; published: 05 may 2023 doi: https://doi.org/10.18849/ve.v8i2.632 abstract objective explore the value of musculoskeletal ultrasound in detecting canine cruciate ligament pathology. background partial tears of the cranial cruciate ligament (ccl) can be difficult to diagnose due to the lack of instability present on orthopaedic examination. advanced diagnostics would be required for further evaluation. while a common tool in human medicine, magnetic resonance imaging (mri) is of limited use in canines due to cost and the need for general anaesthesia. musculoskeletal ultrasound (msk-us) can be performed without anaesthesia but there are no current studies to date evaluating its usefulness in detecting partial tears of the cranial cruciate ligament. evidentiary value: this is a retrospective case series of 32 dogs that underwent diagnostic msk-us of the stifle who later had a surgical procedure (stifle arthroscopy / arthrotomy) to evaluate the intra-articular space. methods medical records were evaluated between may 2014 – april 2020 for canines with clinically stable stifles that underwent both an msk-us of the stifle followed by stifle surgery. ultrasound findings of the ccl were compared to surgical findings. results compared to surgical findings, ultrasound was a very sensitive test in detecting ccl pathology however it is less specific. its sensitivity (sn), specificity (sp), positive predictive value (ppv) and negative predictive value (npv) were 100%, 58.3%, 81.5%, and 100% respectively. conclusion msk-us is a non-invasive test that can be performed with little to no sedation. using a high frequency 18–5 mhz linear transducer, msk-us is a sensitive test for detecting partial ccl injuries in dogs and may aid in its diagnosis for canines without stifle instability and be useful in guiding treatment. as it is less specific, arthroscopy or arthrotomy would be necessary to further confirm the intra-articular pathology. application diagnostic msk-us is a non-invasive tool that can be used to detect ccl pathology in the canine stifle. its application can help guide treatment recommendations prior to a more invasive diagnostic / therapeutic procedure such as surgery or arthroscopy. introduction it has been well established that cranial cruciate ligament (ccl) disease is one of the most common orthopaedic conditions diagnosed in canines (johnson et al., 1994; and piermattei et al., 2006). diagnosis is typically made by a positive cranial drawer (jerram & walker, 2003; piermattei et al., 2006; de rooster et al., 1998; fossum, 2012; johnson & radasch 1988; and widmer et al., 1994) or cranial tibial thrust test (de rooster et al., 1998; johnson & johnson, 1993; and slocum & slocum, 1993) but may not be overtly evident in cases of incomplete tears which can make diagnosis of a partial ccl tear difficult (piermattei et al., 2006; fossum, 2012; reed et al., 1995; and strom, 1990). there are two bands of the ccl: the smaller craniomedial band, which is taut in both extension and flexion, and the larger caudolateral band which is taut in extension and lax in flexion (de rooster et al., 1998; and fossum, 2012). a tear of the craniomedial band may produce instability in flexion only and an isolated tear of the caudolateral band produces no instability (de rooster et al., 1998; and fossum, 2012). increased periarticular and joint capsule fibrosis from chronic tears, patient size and temperament, location of tear (craniomedial versus caudolateral band), and other factors may contribute to the degree of instability detected on physical examination (fossum, 2012; and johnson & johnson, 1993). in addition, puppies may have a normal stifle laxity present which can be confused as a ‘positive’ cranial drawer sign. this ‘puppy drawer’ typically has a distinct ‘end-feel’ when the ligament reaches the end of their stretch and usually only produces about 4–5 mm of movement (jerram & walker, 2003; piermattei et al., 2006; fossum, 2012; and johnson & johnson, 1993). distinction between what is normal and abnormal may not be intuitive and additional diagnostics are required to bring us closer to a diagnosis. partial ccl tears have the ability to progress to a complete tear and a delay in treatment can lead to persistent lameness, progressive degenerative changes, the development of meniscus tears (piermattei et al., 2006; vasseur, 1984; johnson & radasch, 1988; johnson & johnson, 1993; altarod et al., 2014; and paatsama, 1988). other diagnostic modalities are necessary to help aid in the diagnosis of cranial cruciate ligament tears particularly when instability is not apparent. radiographs of the stifle may reveal displacement or obliteration of the infrapatellar fat pad secondary to increased joint effusion or thickening of the synovial lining, presence of osteophytes and other degenerative changes, and cranial displacement of the tibia in relation to the femur on stressed views in cases of a severe tear (jerram & walker 2003; johnson et al., 1994; vasseur, 1984; de rooster et al., 1998; johnson & johnson, 1993; rubin et al., 1975; and marino & joughin, 2010). radiographs are also useful in ruling out other causes of lameness and instability such as avulsion fractures (johnson & johnson, 1993; and marino & loughin, 2010). they are however non-specific as the cruciate ligaments cannot be directly identified on radiography and stifle effusion and osteoarthritic changes may be present in other conditions affecting the stifle such as infectious disease, other non-infectious causes of arthritis, and neoplasia (marino & loughin, 2010). mri has been shown to be accurate in the diagnosis of partial and complete cranial cruciate ligament disease in dogs (marino & loughin, 2010) but it is costly and requires the use of general anaesthesia, which limits their routine use in companion animals for the diagnosis of ccl pathology (jerram & walker, 2003; fossum, 2012; and johnson & johnson, 1993). in contrast, mri is a common diagnostic tool used to detect anterior cruciate ligament (acl) injuries in humans (johnson & johnson, 1993; and breukers et al., 2019). however, cost, availability, and requirement for the patient to lie still for an extended period of time are factors that still need to be considered (breukers et al., 2019). arthroscopy / arthrotomy has been discussed as the best practice for intra-articular evaluation with the potential for concurrent treatment but they are expensive and invasive (din dar et al., 2010; and little et al., 2014). the use of diagnostic musculoskeletal ultrasound (msk-us) is uncommon in companion animals but it has been reported in the literature as a means of detecting intra-articular (ia) structures within the stifle (reed et al., 1995; kramer et al., 1999; van der vekens et al., 2019; arnault et al., 2009; and gnudi & bertoni, 2001). in the normal stifle, a portion of the ccl can be seen as a hypoechoic band at the point of the tibial attachment (reed et al., 1995; and kramer et al., 1999) however, previous studies in canines have been unrewarding, concluding that tears in the ccl cannot be visualised (little et al., 2014) or that detection rates are quite low (15.4–19.6% of cases) (arnault et al., 2009; and gnudi & bertoni, 2001). these studies primarily evaluated complete tears of the ccl where there is likely a complete loss of fibre pattern in the region where they are typically found. in contrast, the use of arthrosonography in humans has been more rewarding in detecting anterior cruciate ligament pathology with sensitivities and specificities reported to be 88–91.9% and 80–100% respectively (breukers et al., 2019; grzelak et al., 2015; henderson et al., 2015; fuchs & chylarecki, 2002; and ptasznik et al., 1995). skill and experience of an ultrasonographer as well as transducer frequency has been speculated to affect the accuracy and reliability of ultrasonographic findings (van der vekens et al., 2019; and arnault et al., 2009). in the hands of a seasoned ultrasonographer, msk-us can be an invaluable tool for the diagnosis of soft tissue pathology as it is non-invasive and could potentially be performed under light to no sedation (arnault et al., 2009; and gnudi & bertoni, 2001). to our knowledge, there is no published report in canines looking at the use of msk-us in diagnosing partial tears of the cranial cruciate ligament. this retrospective study takes a look at the value of msk-us in detecting cruciate ligament pathologies of canine stifles that display minimal to no instability when compared to arthroscopy or arthrotomy (johnson & johnson, 1993). we hypothesise that by looking at a subset of dogs in which we expect to have at least some intact fibres of the cranial cruciate ligament, that ultrasound would be able to detect pathology if it is present. by detecting partial tears early on, one may be able to intervene with alternative therapy such as regenerative medicine or surgical stabilisation sooner and thus protect the ccl from abnormal mechanical loading leading to further tearing and better preserve joint function (fazio et al., 2018; barker et al., 2016; and canapp et al., 2016). methods case selection medical records of client-owned dogs were reviewed between may 2014 – april 2020 for cases that received diagnostic msk-us of the stifle at a single institution (veterinary orthopedic & sports medicine, annapolis junction, maryland). data was collected for patients that had an msk-us of the stifle which then later had a surgery (arthroscopy or arthrotomy) of the stifle to confirm the diagnosis. information obtained included signalment, medical history, orthopaedic examination findings, diagnostics modalities performed (radiographs, msk-us, etc.), and surgical findings (arthroscopy / arthrotomy). cases were included if physical examination did not reveal the characteristic ‘cranial drawer / cranial tibial thrust’ or only mild instability was present. cases were excluded from the study if there was moderate to severe instability, multi-ligamentous injuries (‘deranged stifles’), previous surgical intervention performed in the stifle, or other diagnoses made (medial patellar luxation, patellar tendon rupture). some cases were evaluated for bilateral conditions or re-presented at a later date due to concerns for the contralateral limb. in these cases, each stifle was included individually. orthopaedic examination data was collected for the limb affected, presence of stifle effusion, and presence of cranial drawer and tibial thrust in flexion and extension. other orthopaedic or neurological exam findings were also recorded (iliopsoas discomfort, back / lumbosacral discomfort, patellar luxation). documentation of additional diagnostics or treatments for the listed co-morbidities were not taken into account as the focus was placed on the ultrasonographic appearance of the cruciate ligaments for the purposes of this study. diagnostic radiography lateral and cranio-caudal radiographs were evaluated for both stifles for the presence of joint effusion and stifle osteoarthritis as an indirect sign of intra-articular pathology. additional images of pelvis and tarsi were present to rule out other causes of lameness. diagnostic musculoskeletal ultrasound msk-us of the stifle was offered to patients in which a preliminary diagnosis of partial cranial cruciate ligament tear was made based on physical examination and radiographs. ultrasonographic images were obtained by 38 mm, high frequency, linear transducer (18–5 mhz) (figure 1). figure 1. ultrasound system (noblus, hitachi aloka medical, twinsburg, oh).   most patients did not require any sedation. light sedation (dexmedetomidine (3 mcg/kg) + butorphanol (0.2 mg/kg) intravenous (iv) was used in those that were too anxious for an awake examination to be performed. patients were placed in lateral recumbency with the stifle of interest on top (figure 2a). the fur on the cranial, lateral, and medial aspects of the stifle were clipped from just proximal to the patella distally to the tibial crest. the skin was cleansed and saturated with 70% ethanol followed by the application of ultrasound coupling gel. the stifle is placed in a fully flexed position to ‘open’ up the joint space and improve visualisation of the intra-articular structures (figure 2b). figure 2. positioning for optimal scan. (a) patients are positioned in lateral recumbency with the stifle being scanned on top. (b) the stifle is placed in a fully flexed position to ‘open’ up the joint space.   with the stifle in deep flexion, the probe is placed longitudinally over the patellar region, with the patella proximal (towards left of monitor) and the tibia insertion distally (towards right of monitor). this position will reveal the patellar tendon and the intra-articular region to evaluate the fat pad, femoral bone margins, tibial crest / plateau bone margins, and cruciate ligament region. this view is used to assess for joint effusion, degenerative joint changes, and the presence of fibrotic / disruptive changes in the mid-body region of the cranial and caudal cruciate ligaments as well as the cranial cruciate ligament at its tibial insertion. to further evaluate the cruciate ligament region and obtain additional views of the cranial cruciate ligament (ccl) from tibial insertion, slightly turn the probe so that the proximal end moves laterally for an oblique approach to the femoral origin. echogenicity and fibre pattern were recorded for the cruciate ligaments and compared to the contralateral stifle. the changes were not categorised and defined into a formal grading scheme as the entirety of the ligaments cannot be fully viewed based on their position within the stifle. from the accessible views, findings were grouped into normal (which includes compensatory and age / work related changes) or abnormal (indicating cruciate ligament pathology). the ultrasounds were performed by experienced ultrasonographers (two american college of veterinary sports medicine and rehabilitation (acvsmr) diplomates and two acvsmr residents). surgical procedures of the stifle joint surgery reports were reviewed for cases that underwent a stifle arthroscopy or arthrotomy. a standard parapatellar approach to the stifle joint was utilised for portal placement during stifle arthroscopy or a routine mini-medial parapatellar arthrotomy was performed to the stifle joint for intra-articular evaluation. data was recorded for the presence of pathology noted in the cruciate ligaments. statistical analysis ultrasonographic and surgical findings of the cruciate ligaments were then compared and analysed to one another. the sensitivity (sn) and specificity (sp), positive predictive value (ppv) and negative predictive value (npv) of msk-us was determined by using surgical findings as the reference standard. the 95% confidence intervals were established using the ‘exact’ clopper-pearson method through an online calculator (medcalc software ltd., 2023). results signalment thirty-two dogs met the inclusion criteria mentioned above. table 1 displays the breeds represented in this study. the most common breed represented were border collie (8/32 (25%)), followed by doberman pinscher (3/32 (9.4%)), labrador retriever (3/32 [9.4%]), mixed breed (3/32 [9.4%]), australian shepherd (1/32 [6.3%]), belgian malinois (1/32 [6.3%]), boxer (1/32 [6.3%]), welsh corgi (1/32 [6.3%]), australian cattle dog (1/32 [3.1%]), belgian tervuren (1/32 [3.1%]), german shepherd (1/32 [3.1%]), great dane (1/32 [3.1%]), greyhound (1/32 [3.1%]), leonberger (1/32 [3.1%]), and samoyed (1/32 [3.1%]). the mean body weight was 27.1 kg (range: 12.5–59 kg) and the mean age was 4.3 years (range: 1.1–10.9 years) at the time of presentation. one patient’s date of birth was missing from the medical records and therefore was not included in the mean age calculation. of these, 53.1% were male (five neutered, 12 intact) and 46.9% were females (10 spayed, five intact). table 1. breeds represented in this study. breed frequency border collie 8 doberman pinscher 3 labrador retriever 3 mixed breed 3 australian shepherd 2 belgian malinois 2 boxer 2 welsh corgi 2 australian cattle dog 1 belgian tervuren 1 german shepherd 1 great dane 1 greyhound 1 leonberger 1 samoyed 1 total 32   physical examination the median duration of lameness was reported to be 2 months (range: 3 days – 2 years) at the time of presentation. all dogs were presented for a unilateral lameness. one of the dogs returned later for issues on its contralateral limb and therefore was counted twice as it met the inclusion criteria. the left hind limb was affected in 19 cases and the right hind limb was affected in 14 cases. two dogs were presented for a unilateral lameness but had concurrent pathology in their contralateral stifles which were further explored during the same time period and therefore the limbs were also counted separately. when counting the evaluated stifles individually, 35 data points were available for analysis. on an awake examination, 24/35 (68.6%) stifles had no clinical signs of cranio-caudal instability as evidenced by a positive cranial drawer or cranial tibial thrust test. of those, two had an increase in internal rotation of the stifle and one had a positive caudal drawer test. eleven stifles exhibited mild instability in flexion only. three of those had concerns for medial instability and one had an abnormal movement of the fibular head. all (35/35 [100%]) of the affected limbs had palpable stifle effusion. the most common concurrent pathology reported was iliopsoas (18/35 [51.4%]) discomfort or tightness on the affected limb. additional examination findings included lower lumber / lumbosacral discomfort (8/35 [22.8%]) and sensitivities over the piriformis region (3/35 [8.6%]) of the affected limb. pelvic limb radiographs stifle radiographs were obtained for all cases. in the affected limb, the most common findings were increased stifle effusion (33/33 [100%]) and degenerative / osteoarthritic changes (8/33 [24.2%]). joint effusion was apparent in (14/33 [42.4%]) of the contralateral stifles and degenerative changes present in (3/33 [9%]). one dog had evidence of mild bilateral hip dysplasia and two dogs had some remodeling seen at the region of the greater trochanter. four dogs had remodeling of the lumbosacral junction on lateral spine radiographs. stifle ultrasound and surgical findings the majority (80%) of the ultrasounds were performed by one individual (dc), the remainder were performed by acvsmr residents. the median time between ultrasound findings and surgery was 1 day (range: 0 –125 days). only a portion of the ccl can be visualised with sonography due to its position within the stifle. this portion is its distal insertion on the tibial tuberosity and is suspected to be approximately 30–60% of the ccl as reported in a previous study (van der vekens et al., 2019). ultrasonographic evaluation determined that there was ccl pathology in 28/35 cases. of these cases, ccl pathology was defined by hyperechoic fibre changes in 96.4% of the cases, fibre disruption in 39.3%, and calcification around the tibial insertion of the ccl in 14.3% of cases (table 2). six stifles were determined to have an intact ccl on ultrasound and the ccl was unable to be visualised in one. the majority of cases had hyperechoic changes, but it was not uncommon to have a mixture of lesions (hyperechoic fibre changes ± fibre disruption ± calcification around the tibial insertion) (figure 3). other stifle lesions documented with ultrasonography were not analysed as this paper was intended to focus on the appearance of cranial cruciate ligament disease. table 2. description of lesions noted on diagnostic msk-us. lesion description number of cases hyperechoic change 27 fibre disruption 11 irregular bony margins / calcification around the tibial insertion of ccl 4   figure 3. (a) ccl deficient stifle. the red arrows represent the regions of disruption to the ccl fibres. there is displacement of the patellar fat pad (fp). (b) normal stifle. the green arrows point to an intact ccl.   thirty-three stifles underwent arthroscopy for joint exploration and two underwent arthrotomy. disruption to the ccl was identified in 22 stifles (partial tear [n = 21] and complete tear [n = 1]). ultrasound detected changes to the ccl (echogenicity, fibre disruption and / or mineralisation) in all 22 stifles (figure 4). stifles that were considered normal or had ‘compensatory / age-related’ changes showed a hypoechoic structure determined to be the intact ccl or mild hyperechoic changes without overt fibre disruption, respectively (figure 5). ultrasound reported a partial tear of the ccl in 5/35 (14.3%) stifles which were not identified intra-operatively, however three of these stifles were reported to have caudal cruciate ligament (cdcl) pathology at the time of surgery. in one stifle, the ccl could not be visualised due to the presence of an echogenic, mass-like structure speculated on ultrasonography which was not confirmed via arthroscopy. this stifle was not included in statistical testing. figure 4. (a & b) the arrows point to regions of ccl fibre disruption and the presence of hyperechoic changes surrounding a hypoechoic structure.   figure 5. (a) hypoechoic structure representing a normal, intact ccl. (b) mild hyperechoic changes without evidence of fibre disruption.   sensitivity (sn), specificity (sp), positive predictive value (ppv) and negative predictive value (npv) of ultrasonography for detecting ccl pathology were 100% (95% ci 84.6%, 100%), 58.3% (95% ci 27.7%, 84.8%), 81.5% (95% ci 69.3%, 89.6%), and 100% (95% ci 100%) respectively. this was calculated using the table below (table 3). in 15/35 stifles, disruption to the cdcl (three complete, 12 partial) was diagnosed on arthroscopy. ultrasound suspected changes to the cdcl in 11 of these cases (figure 6). ultrasound reports did not consistently comment on the cdcl as techniques and experiences of our ultrasonographers have been reported to evolve over time.   table 3. cranial cruciate ligament pathology detected by ultrasound and surgery.      surgery pathology detected not detected ultrasound pathology detected 22 (true positive) 5 (false positive) not detected 0 (false negative) 7 (true negative) figure 6. (a) a region of a hypoechoic structure surrounded by hyperechoic changes seen cranial to the ccl suspected to represent the cdcl. (b) another ultrasound image identifying cdcl pathology.   discussion historically, previous studies have reported that ultrasonographic examinations for the canine stifle have not been rewarding for the diagnosis of cranial cruciate ligament tears in dogs (kramer et al., 1999; arnault et al., 2009; and gnudi & bertoni, 2001). while earlier reports of sonographic examinations of normal stifles report that the cranial cruciate ligament (ccl) can be routinely observed via ultrasound, it can be speculated that once there is a complete tear, visualisation of the ccl is impaired as the ligament is no longer present in its typical location (reed et al., 1995; arnault et al., 2009; gnudi & bertoni, 2001; and cauvin & smith, 2019). in addition, only 30–60% of the total ligament fibre at the distal insertion can be visualised on ultrasonography given its position within the stifle (van der vekens et al., 2019). our study focused on cases in which we did not suspect to have a complete rupture of the cruciate ligament and used a higher frequency transducer (18 mhz) than what was previously reported in the literature (7.5–16 mhz) (reed et al., 1995; kramer et al., 1999; arnault et al., 2009; and gnudi & bertoni, 2001). ultrasound detection of ccl pathology was very high with a sensitivity reported at 100% in this study. this difference compared to previous studies may be due to the fact that the presence of intact fibres in a partial ccl tear makes it easier to observe given its more consistent location within the stifle compared to a complete tear. a previous report describing ccl tears confirm their diagnosis by observing a truncated hypoechoic line near the surface of the cranio-proximal tibial (gnudi & bertoni, 2001). it is possible that they were having a difficult time isolating this hypoechoic structure as the normal hypoechoic structure of the ccl begins to appear more hyperechoic when there is disease present. in our experience, the lack of observable ccl fibres in its usual location coupled with echogenicity changes typically represent a severe or complete rupture of the ccl. however, in the majority of cases, cranio-caudal stifle instability is present, therefore the use of ultrasound to diagnose the rupture is not warranted. the higher frequency probe may also allow us to see finer detail that otherwise may not be detected with a lower frequency transducer. another explanation for this is that our study does have a high selection bias as we selected for patients that had pathology that was suspected to be localised to the knee without obvious instability. if no pathology was detected during ultrasound, arthroscopy was not typically recommended. owners were also less likely to agree to a more invasive procedure (i.e., surgery) if the ultrasound was inconclusive. due to this, we did not have many ‘normals’ that could provide as a control which would have strengthened our data. in our study, msk-us for detecting ccl pathology has a lower specificity (54.5%) as evidenced by the larger number of false positives obtained. changes present in nearby structures such as the synovium or the cdcl may be mis-interpreted to represent changes to the ccl. although surgical assessment of the cdcl were provided in some cases, we did not attempt to interpret the results of the testing as inconsistencies on reporting would make it difficult to draw any valid conclusions. one of the ultrasonographers (dc) report that it was only recently within the past 2 years that they began to notice changes in a certain area, distinct from the ccl insertion on the tibia (figure 6) that appeared to correlate with cdcl changes seen on arthroscopy. earlier examinations were less likely to have scanned this region or provide an interpretation specific to cdcl pathology. previous studies have acknowledged the possibility of visualising the cdcl with ultrasonography (reed et al., 1995; and kramer et al., 1999) while others denote that it cannot be visualised (arnault et al., 2009). reed et al. (1995) described the ultrasonographic location of the cdcl to be seen at the lateral surface of the medial condyle on its point of attachment on the femur while kramer et al. (1999) report that it can only be visualised in larger dogs on a transverse section. in our study, we do not scan the stifles using these methods described above. anectodally, the changes observed (figure 6) are present cranial to the ccl which is inconsistent with its anatomic location within the stifle. however, this may support an indirect sign of cdcl pathology, but further studies would be required to explore this significance. this further denotes that experience and technique of an ultrasonographer plays a large role in the diagnostic value of msk-us. our study design compared ultrasound findings to surgical findings (arthroscopy / arthrotomy) which we considered the reference standard. while surgery provides direct visualisation of the joint, limited views of the stifle anatomy can be seen intra-articularly (fazio et al, 2018; and cauvin & smith, 2019). it has been suggested that since the cruciate ligaments are extra-synovial, arthroscopy provides a limited surface view of the ligament and may underestimate the pathology present even with careful probing (fazio et al., 2018). histology would be required to confirm intra-substance lesions that are not present grossly on visual examination through arthroscopy or arthrotomy (van der vekens, 2019; and doring et al., 2018). unfortunately, histologic evaluation is not possible with this type of clinical study. if ultrasound was detecting some of these earlier changes that is not being visualised during surgery, it could also lead to the number of false positives obtained during this study when comparing ultrasound to surgical findings. however, it is unclear whether these findings are of any clinical significance at this time to warrant surgical stabilisation or treatment, however they may prove useful as a means of monitoring progression of disease in a clinically stable stifle. several limitations are present in this study. this study was retrospective and therefore subjected to variations in technique, reporting, and incomplete documentation. the lack of standardised reporting for arthroscopic / surgical findings for intra-articular structures does have an effect on the results. mild fibre changes, degeneration or disruption to the ligaments may still be translated to the report as intact if torn fibres were not visualised or they were unable to see the entirety of the cruciate ligaments within the joint. as discussed previously, there is a selection bias present due to the nature of cases selected. we also did not have any controls for comparison. surgery would not be recommended if pathology was not detected, contributing to a verification bias which is demonstrated by our high sensitivity and low specificity. this is further confirmed by the 100% confidence interval obtained for the sensitivity and negative predictive value which does not occur. the ultrasounds were performed by four different people which may add to the variability of the lesions detected due to the differences in experience level, although the majority of the scans were performed by one individual (dc). the range of years that we looked at were also quite broad (2014–2020) and the range of technique and confidence of an individual can vary tremendously throughout that time period and affect the findings reported. timing between ultrasound and surgery may also influence the results reported. the majority (24/33 [72.7%]) of patients had surgery performed within 72 hours of their ultrasound date, however some patients were not scheduled for surgery until weeks or months after their ultrasound procedure. the significance of the time gap is unclear at this time although one may expect a progression of the disease process that may be inaccurately represented by earlier diagnostics. to our knowledge, there are no studies looking into this comparison. a previously published study in human medicine reported a high sensitivity and specificity in us imaging for anterior cruciate ligament (acl) tears despite a longer time gap between imaging and surgery (median: 5 weeks; range 0–48 weeks) (breukers et al., 2019). the significance of time on the effect and appearance of the acl was not explored or discussed in this study. what would have strengthened our study is a prospective design in which patients undergoing stifle surgery were enrolled to receive a stifle ultrasound irrespective of suspected stifle pathology. this would decrease or eliminate selection or verification bias in the samples. blinding of the veterinary surgeon to physical exam findings and the results of diagnostic testing would not likely be possible as in clinical practice, veterinary surgeons rely on the use of supporting diagnostics to make recommendations for surgery. the ultrasonographer may be blinded to the physical examination findings and the results of other diagnostic testing. a prospective study would also be able to standardise and minimise the timing between ultrasonography and surgery, reducing the influences of a longer time gap. in humans, ultrasound is capable of detecting partial and complete tears of the acl and they are even incorporating the combination of direct, indirect, and dynamic tests of acl rupture during ultrasonography to strengthen its diagnostic value (breukers et al., 2019; ptasznik et al., 1995; fuchs & chylarecki, 2002; wang et al., 2018; kumar et al., 2018; and palm et al., 2009). the development of additional techniques may also prove valuable in canine ccl detection. in one study, seong et al. (2005) suggested that the use of intra-articular (ia) saline during ultrasonography can improve visualisation of the ccl however these patients underwent general anaesthesia for the procedure. unfortunately, literature on arthrosonography in small animals is lacking. other considerations are to study interobserver variability to look at the influence of experience on the ultrasound findings as it has been reported to be highly operator dependent (coss, 2019; and han et al., 2008). based on the angle and orientation in which one holds the probe, a different image and echogenicity can be created from the same structure (reed et al., 1995) which can contribute to misleading interpretations of the images. this study explored the capability of ultrasound to detect cranial cruciate ligament pathology in dogs. this paper focused on stifle injuries without overt instability as the presence of craniocaudal laxity is pathognomonic for ccl rupture making further diagnostics redundant for diagnosis. ultrasound is a non-invasive tool and the images can be interpreted at the same time of the scan. it can also be performed on an awake patient or with minimal sedation. this is in contrast to an mri which requires general anaesthesia. our study showed that msk-us is a highly sensitive test in detecting partial ccl ruptures in canines. ccl pathology detected on ultrasound warrants further exploration. on the other hand, if ccl pathology is not detected, a more invasive procedure such as surgery may potentially be avoided. author contributions helen tsoi: conceptualisation, methodology, validation, formal analysis, investigation, resources, data curation, writing – original draft, writing – review & editing, visualisation, project administration. debra canapp: conceptualisation, methodology, validation, investigation, resources, data curation, writing – review & editing. sherman canapp: conceptualisation, validation, resources, writing – review & editing. orcid helen tsoi: https://orcid.org/0000-0001-8158-739x sherman o. canapp jr.: https://orcid.org/0000-0002-0271-3413 conflict of interest the authors declare no conflicts of interest. references arnault, f., cauvin, e., viguier, e., kraft, e., sonet, j. & carozzo, c. 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(1994). radiographic and magnetic resonance imaging of the stifle joint in experimental osteoarthritis of dogs. veterinary radiology & ultrasound. 35(5), 371–383. doi: https://doi.org/10.1111/j.1740-8261.1994.tb02057.x contribute to the evidence there are two main ways you can contribute to the evidence base while also enhancing your cpd: tell us your information need write a knowledge summary either way, you will be helping to add to the evidence base, and strengthen the decisions that veterinary professionals around the world make to give animals the best possible care. learn more here: https://veterinaryevidence.org/index.php/ve/guidelines-for-authors licence copyright (c) 2023 helen tsoi, debra a. canapp & sherman o. canapp jr. this work is licensed under a creative commons attribution 4.0 international license. veterinary evidence uses the creative commons copyright creative commons attribution 4.0 international license. that means users are free to copy and redistribute the 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and wales no. 598443. net-bottom cage inserts for water bird casualties jackie belle rvn certsan certfn certvnes dipcabt dipesm dip br dipendv ptlls bsc msc1* 1rcvs knowledge, 62-64 horseferry road, london, sw1p 2af *corresponding author (jackie@rcvsknowledge.org) vol 2, issue 4 (2017) published: 31 oct 2017 reviewed by: jonathan cracknell (bvms certva certzoomed mrcvs), simon girling (bvms (hons) dzoomed dipeczm (zhm) cbiol frsb eurprobiol frcvs) and john chitty (bvetmed certzoomed cbiol mrsb mrcvs) doi: 10.18849/ve.v2i4.66 my bright idea is a net-bottomed cage insert, which is used to support pelagic avian casualties. the idea was designed and modified by the international bird rescue in california (bird rescue). when nursing wildlife casualties there are often challenges in converting existing small animal hospital accommodation to provide appropriate and suitable facilities for triaging wildlife patients before they are transferred to a wildlife facility. as some aquatic birds, such as loons and grebes, are unable to stand on a terrestrial substrates, traditional cat and dog cages are much less suitable for their care. at the bird rescue facility, aquatic species such as the divers, grebes, guillemots and sea ducks were all housed in net-bottomed cages. grebes and divers particularly struggle in captivity as they have long, heavy bodies with legs at the rear (which act as rudders in the water), when on land they move with little jumps and slides. these types of aquatic birds do not spend time on land and are only ever on land during nesting since moving is so difficult on the hard substrate. if these birds are housed in net-bottomed caging they are less prone to pressure sores, injury to their legs and feather rot (prevents urates from building up on the tail feathers). net-bottomed cage design in the net-bottomed cage design, the floor is made of a pvc pipe frame covered with half-inch knotless shrimp  seine (black or white) which is stretched taught then fastened over screws placed on the outside of the frame. the netting provides an even weight distribution and allows faeces and urates to drop through onto newspaper on the cage floor. a heat pad can also be placed above the newspaper to increase the temperature of hypothermic animals.  the gap between the pvc flooring and cage bottom allows air to circulate and ventilate the cage. cages were left prepared (photo 1), with a towel which is used to hang on the inside of the cage door to decrease stress by limiting visual stimulus. photo 1: hospital cage showing raised net-bottom insert we also converted plastic carrier cages for use when transporting pelagic bird. these carriers were converted by placing a net over a pvc frame at the base of the box to prevent injury during transport. the inserts are also easily removed to convert back to a normal pet carrier. these can also be used as haul-outs over water (photo 2 and 3). photo 2: murres (guillemots) on haul-out raft made with pvc and netting photo 3: bird rescue image: common murres feeding on net-bottomed cage insert net-bottom cage inserts materials  pvc piping and elbows (1.5”) nylon netting (¼” – ½”) wood screws instructions  make a rectangle frame out of pvc piping and elbows be sure to measure the desired size of the insert by the “outside” measurement of the frame attach screws to the underside of the frame leave the screw heads with approximately 1/8” exposed, this creates a ‘peg’ to attach the nylon netting space the screws evenly, approximately 3”– 4” apart stretch nylon netting tightly over the frame and secure by looping the netting over the screw heads (peg). the specifications of the netting that bird rescue uses for the net-bottomed pens are at least 1/4" up to ½” knotless nylon netting. this size will stop small birds falling through and evenly distribute the weight of small and medium sized birds (grebe, duck). the photo below of an albatross also demonstrates the diameter of the mesh required. photo 4: laysan albatross in drying cage following wash to remove oil if the nylon mesh becomes damaged or torn it is best to replace the entire net bottom rather than trying to repair a damaged area. a break in the mesh could lead to entanglement or foot abrasion and alter the supportive surface of the netting insert. contact international bird rescue for further information: https://www.bird-rescue.org/ photo 5: example netting (¼” – ½”) photo 6: example netting(¼” – ½”) netting suppliers in usa                            the product is referred to as a delta or ace style netting christenson net works                   4074 sucia dr. ferndale, wa 98248 conflict of interest the author delares no conflict of interest. supplementary files, images & tables all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. is alpha-casozepine efficacious at reducing anxiety in dogs? a knowledge summary by louise anne buckley phd, rvn*1 1harper adams university, edgmond, newport tf10 8nb *corresponding author (lbuckley@harper-adams.ac.uk) vol 2, issue 3 (2017) published: 18 jul 2017 reviewed by: nicola ackerman (bsc(hons), rvn, certsan, certvnecc, vts(nutr), a1 v1 mbvna) and erik fausak (mslis, ma, cvt, lvt, rlat) next review date: 18 jul 2019 doi: 10.18849/ve.v2i3.67 clinical bottom line there is currently no evidence to show that alpha-casozepine is effective as an anxiolytic when administered to dogs shortly (minutes to a few days) before exposure to an anxiety provoking stressor. there is limited and weak evidence to suggest that it may have a role to play in reducing anxiety in dogs over the medium to longer term but the available evidence is of low quality and / or high risk of bias, with confounding variables providing alternative explanations for the findings. more research is needed in this area. question do anxious dogs administered alpha-casozepine show reduced signs of anxiety compared with dogs not administered alpha-casozepine? clinical scenario the veterinary team are reviewing the products that they keep within the practice for use in supporting clients whose dogs are anxious for various reasons. they realise that they have never examined the evidence for the use of alpha-casozepine in relation to canine anxiety. however, they have been widely recommending products that contain it, and have had mixed reports back from clients who have used it, so are curious about its efficacy. thus, they decide to find out how strong the research evidence base is for this biomolecule. the evidence three peer reviewed papers were identified that either partially or fully addressed the pico. two of these studies (palestrini et al., 2010; kato et al., 2012) investigated the use of diets with added alpha-casozepine, though, in the kato et al. (2012) study the diet was also supplemented with another compound (tryptophan) thought to have anxiolytic properties. the remaining study (beata et al., 2007) investigated the use of a daily capsule of alpha-casozepine. the two studies focused on dietary interventions (palestrini et al, 2010; kato et al., 2012) used a placebo-controlled study design, whereas beata et al. (2007) compared alpha-casozepine to another intervention (selegiline) that was already used commercially as an anxiolytic. there is no evidence that alpha-casozepine has any effect on canine anxiety in the short term (e.g. when exposed to fireworks or another short acting stressor) or when administered a few minutes to a few days before exposure to potential stressor. all of the studies focus on the potential anxiety-reducing effects of alpha-casozepine when administered in the medium to long term. there was some evidence that alpha-casozepine may reduce anxiety as, where effects exist, the direction of effect is always a reduction in the level of whatever parameter was used to measure anxiety. however, the evidence available is low quality. despite being clinical trials, experimental design and / or data handling was weak, with confounding variables affecting interpretation of the findings. there is a need for better quality research that specifically investigates the use of alpha-casozepine as an anxiolytic in the scenarios that practices would commonly promote its use for. summary of the evidence palestrini (2010) population: healthy young adult female laboratory-based beagles sample size: 32 dogs: anxious dogs: n = 16 (later reduced to 14, possibly 131), split between two groups (experimental diet versus control diet). non-anxious dogs: n = 16, split between two groups. 1 group (n = 8) received the experimental diet; 1 group received the control diet (n = 8). 1 the authors reporting of this aspect is weak and they report eliminating 3 anxious dogs, but then claim later in the same section to have reduced the anxious treatment group from 16 dogs to 14 dogs. they do not report how this affected numbers of dogs in each group, therefore, the minimum sample size for one of the diet groups could be as low as 6 (if 2 are missing) or 5 (if 3 are missing). intervention details: dogs were split into four groups: anxious dogs fed the control diet anxious dogs fed the experimental diet non-anxious dogs fed the control diet non-anxious dogs fed the experimental diet the two diet treatments compared were: experimental diet: a complete dry dog food that was coated with caseinate hydrolysate (ch) (the milk component containing alpha-casozepine). the authors do not report the inclusion rate of ch. control diet: the same diet as the experimental diet but without the ch. researchers were blinded to which dogs were receiving which treatment. experimental timeline: forty dogs were assessed for anxiety and either included in the study (n = 32) or rejected (n = 8). anxiety assessment used two methods: the evaluation scale of anxiety, and the reactivity evaluation form (ref) (more details below). based on the combined scores, dogs were ranked for level of anxiety. the top 16 dogs were then assigned to the anxious group and the bottom 16 dogs were assigned to the non-anxious group. the intermediary 8 dogs were not used. within group, the dogs were paired-housed such that dogs with the most similar scores were housed together (e.g. the most anxious dog was housed with the second most anxious dog, etc). a randomised block design was then used to allocate diet treatments to the dogs. dogs were blocked according to whether they were anxious or non-anxious (based on the anxiety assessment methods outlined above), and then the 8 pairs of dogs within each block were randomly allocated to receive one of the two diet treatments. both dogs within the pair received the same diet. the dogs included were allocated as described above and then pair-housed. dogs were introduced to their new kennel mate and given 3 days to adjust to this. then, the study commenced. the study lasted either 68 or 69 days (not clear enough to say for certain). baseline period (6 days): baseline parameters were measured for serum cortisol, serum lysozyme, the neutrophil:lymphocyte ratio, and mean heart rate. heart rate was measured telemetrically using a heart rate monitor strapped to the dog’s chest and recorded at 5 second intervals. dogs were fed their normal diet during this period. initial evaluation phase (t1) (2 or 3 days, this is unclear from the paper*): on the first day, the ref was completed and a blood sample taken. on day two, the mean heart rate was determined for ten minutes while the dogs were video recorded for 10 minutes. this video was later viewed by an observer blinded to treatment and group and the frequency or proportion of time spent performing certain behaviours recorded. *in the experimental phase section of the paper, the authors report “after an initial 3 day evaluation phase (t1)” and “each evaluation (t1, t2, and t3) lasted 2 days”. feeding phase 1 (28 days). dogs were given ad libitum access to the food with food replenished once a day (pm), with both dogs in the pen fed the same diet. second evaluation phase (t2, lasted 2 days). data collection as documented in t1. feed phase 2 (28 days). dogs fed as documented in feeding phase 1. third evaluation phase (t3, lasted 2 days). data collection as documented in t1. initial assessment of anxiety (to select dogs): evaluation scale of anxiety: a subjective assessment of anxiety in which dogs were observed and scored from 1 (low) – 6 (high). a two part objective behavioural assessment, comprising an ordinal scale of anxiety level (score 1 – 4) and the presence of various clinical signs of anxiety (e.g. lick lip: yes / no, score 1 point if yes) based on the dogs response to handler presence outside and inside the test pen. both assessment tools were developed by the researchers of this study. two experienced handlers familiar with the dogs independently assessed the dogs using these two assessment methods and then agreed the final score per dog. study design: randomised clinical trial outcome studied: behavioural outcome measures: ref proportion of time spent performing various behaviours in the test pen over 10 minutes (exploration; locomotion, passive behaviour, orientated to the environment, scratching, oral behaviour, vocalisation, play, panting, grooming) frequency of behaviours performed while in the test pen for 10 minutes (yawning, lip – licking, elimination, drinking, eating) physiological parameters: heart rate cortisol neutrophil: lymphocyte ratio lysozyme it is not clear whether plasma or serum cortisol and lysozyme was measured as the authors report the terms interchangeably. main findings (relevant to pico question): no significant differences were found between the baseline period data and the initial evaluation phase (t1) data, so the authors used t1 as their baseline data period. behavioural outcome measures: ref: at the start (t1), anxious dogs had significantly higher ref scores than non-anxious dogs (mann-whitney u test, p < 0.001). at the start (t1), there was no significant difference between anxious dogs fed the control diet and anxious dogs fed the experimental diet. dogs on the experimental diet had significantly lower ref scores by t3 (end of the study) (friedman test, p < 0.01). no further formal statistical comparisons are reported. the figure associated with this outcome measure suggests that anxious dogs fed both the control and experiment diets always scored higher than non-anxious dogs fed either diet. it also suggests that there is no divergence in anxiety scores of non-anxious dogs fed either diet. behaviour: anxious dogs and non-anxious dogs show no significant differences in behaviour at the start of the study (t1). anxious dogs showed less exploratory behaviour at the end of the study (t3) compared to the beginning (t1) (friedman, p < 0.05). there was no change in level of exploratory behaviour between time points in anxious dogs fed the control diet. non-anxious dogs fed the control diet showed less scratching behaviour over time (friedman, p < 0.05) anxious dogs fed the control diet showed increased lip licking over time (friedman, p <0.05). anxious dogs showed a significant increase in orientation to the environment behaviour at t3, compared with t1 (friedman, p < 0.05). physiological outcome measures: heart rate: no significant effects were observed. cortisol: remained within the normal physiological range for anxious and non-anxious dogs during the whole study cortisol level of anxious and non-anxious dogs did not differ at the start (t1). anxious dogs fed the experimental diet showed a significant decrease in cortisol over time (friedman, p < 0.05). post hoc testing indicated that a significant reduction was observed between t1 and t2 (wilcoxon, p < 0.05). non-anxious dogs showed a tendency to have a reduction in cortisol over time (friedman, p < 0.10). neutrophil:lymphocyte ratio: a significant reduction in neutrophils (and increase in lymphocytes) was observed over time in anxious dogs (general linear model, p < 0.05) but not non-anxious dogs. diet treatment had no effect on the ratio for either group of dogs. lysozyme:  no pico relevant significant effects were observed. limitations: the authors fail to report the inclusion rate for caseinate hydrolysate (containing alpha-casozepine) in the diet (g/kg/dry matter). the dogs were fed ad libitum during the study so the dose rate would have varied between dogs. laboratory population in which the breeding life experiences of the dogs were homogenised and tightly controlled. this contrasts to a pet population and may limit extrapolation of the findings to the wider population of dogs. the authors undertook a discriminant analysis to retrospectively (after all the data was collected) eliminate dogs whose ref score did not accurately predict which dogs were identified as anxious through the evaluation scale of anxiety (or vice versa, it is not clear which). as a consequence, 2 or 3 anxious dogs were removed. the authors fail to report how this affected the sample size of anxious dogs in the control diet and experimental diet groups respectively. given the low sample sizes within each group (n = 8), this has implications for the interpretation of any findings or extrapolation to the wider population. this is compounded by the wide degree of variation observed (where standard deviations are reported). retrospective removal of such a large proportion of the sample size for a group should also be questioned. the authors fail to report the measure of central tendency used to report the ref and cortisol data, and do not provide any measure of variation around this central tendency. the authors do not provide enough information to interpret the cortisol findings. they report that anxious and non-anxious dogs’ cortisol levels did not differ at t1, but do not report the findings for the subgroups relevant to the treatments (especially anxious dogs fed the experimental diet versus anxious dogs fed the control diet). eyeballing the figure presented suggests that these two sub-groups might vary at the start and combining this data would have increased the variation associated with the anxious group data and made it more difficult to pick out significant differences. however, the lack of error bars makes it difficult to draw many inferences here. the authors report appears to use the convention of using p < 0.01 (tendency) p < 0.05 (significant), p < 0.01 and p < 0.001 (highly significant). it would have been useful to see the exact p value associated with each finding as most appear to be p < 0.05. the way that they have analysed the behavioural data that they have reported suggests that there may have been many statistical tests performed and this increases the likelihood of a type 1 error (finding a significant finding where one does not exist). the ethogram derived behavioural data is very problematic to interpret: the authors report the findings using mean (± standard deviation) which implies the data is normally distributed. however, they analyse this data using non parametric tests (friedman test, with post-hoc testing via the wilcoxon test) which implies the data is not normally distributed. the error bars suggest that there was a large amount of variation associated with the performance of some behaviours. the authors do not provide enough information for readers to be able to draw their own conclusions about what the behavioural data may indicate. it would have been useful to see the descriptive statistics reported for all the ethogram data, broken down by both treatment diet and anxiety group. the authors appear to have cherry picked which behavioural outcome comparisons to report and key comparisons (e.g. between anxious dogs fed the control diet and anxious dogs fed the experimental diet) are largely missing.  it is not immediately clear that changes between some of the behaviours in the ethogram would represent a change in the level of anxiety. beata (2007) population: pet dogs with anxiety-related disorders the inclusion criteria was as follows: at least 3 months old weigh between 1.5 – 42kg diagnosed with a behavioural complaint related to anxiety at the first visit, the dog scored above 19 (out of a maximum of 45) on the emotional disorders evaluation in dogs scale (eded) (as used by pageat, 1995). dogs were excluded if: the problem had been present for less than four weeks there was any evidence that the problem was caused by disease, illness or injury. any psychotropic medications had been administered in the previous two weeks if the dog scored less than 20 on the eded scale. sample size: forty dogs started the trial, 38 dogs completed it. two dogs died (one per treatment) during the study for unrelated reasons (accidents). intervention details: two treatments (19 dogs per treatment) were compared: behavioural modification therapy (bmp) plus oral alpha-casozepine (15mg/kg/24hrs) bmp plus oral selegiline hydrochloride (0.5mg/kg/24hrs) study design: multi-centre trial that utilised 7 certified veterinary behaviourists. double or triple blind (not clear which) methodology in which the owner, veterinary behaviourist and the supervisors (undefined, researchers?) were unaware which dog received which drug while the study was ongoing. dogs were allocated to treatments using a randomised block design (blocked according to a veterinary behaviourist treating the dog, then randomly allocated to receive a treatment based on a pre-defined randomisation list e.g. dog 1 was given drug 1, dog 2 was given drug 2, and so on). the bmp was tailored to the dog, diagnosis given and how severe this problem was. thus, it varied between dogs but bmp approach did not vary systematically between the two treatment groups. the trial lasted 57 days. experimental timeline: day 0: inclusion visit, owners completed the eded questionnaire. dogs that scored greater than 19 were included. day 14: follow up phone call. day 28: follow up physical visit. day 42: follow up phone call. day 56: follow up physical visit. at each contact, the owner was asked to complete the eded scale again and provide a subjective assessment of improvement on a scale of -10 to +10, with 0 indicating no change, and values higher and lower than this indicating, respectively, an improvement or worsening of the dog’s behavior. the eded score was previously developed by one of the authors for use in investigating the ability of seligiline to reduce anxiety (pageat, 1995, cited  by the current authors), and uses a range of questions to assess the dog’s emotional state on a scale from 9-45. a score of 9-13 is considered to be normal, 14-18 indicative of a dog with a phobia, with dogs that have a score that sits between 18 -30 considered to have an anxiety-related disorder. the authors do not define what a score above 30 means in relation to the dog’s emotional state. they do not state whether this scale is validated for this use. study design: randomised clinical trial outcome studied: the outcome studied at each time point was: eded score owner subjective assessment of improvement the authors also introduced a binomial outcome (success / failure of treatment) “success” measurement. this was based upon the dog achieving two things: an eded score of < 20, and an owner subjective assessment of improvement score of ≥ +6. main findings (relevant to pico question): please note: in reporting the findings, i have included the phase “+ bmp” to each treatment group to improve reader understanding of the treatment group structure. the authors of this paper refer instead only the groups as ‘alpha-casozepine’ and ‘selegiline’ but it is felt that this is misleading. eded scores: the average eded score for both treatment groups decreased between visits 1 (day 0) and visit 3 (day 56) (alpha-casozepine group + bmp: f(4, 18) = 22.20, p < 0.0001; selegiline + bmp: f(4,18) = 26.33, p < 0.0001). at the start of the study (visit one), there was no significant difference between the two treatment groups. the average eded scores on visit 1 were: alpha-casozepine + bmp: 25.0; selegiline + bmp: 24.2 at the end of the study (visit 3, day 56), there was no significant difference between the two treatment groups. the average eded scores on visit 3 were: alpha-casozepine + bmp: 26.3; selegiline + bmp: 16.6. owner subjective assessment of improvement: the data analysed using an anova statistical test are not reported in a clear enough way to precisely define what the researchers think they found. the average improvement score of the apha-casozepine + bmp group increased from 2.7 on day 14 to 5.3 on day 56. the average improvement score of the selegiline + bmp group increased from 3.0 on day 14 to 5.4 on day 56. at the end of the trial (day 56) the improvement score did not significantly differ between the two treatment groups (mann-whitney u test, p = 0.73) success / failure measurement: there was no significant association between treatment received and proportion of dogs that responded successfully to the treatment (χ2 test, d.f. = 1, p = 0.74). the number of successes (failures) in the two groups was: alpha-casozepine + bmp: 10 (9); selegiline + bmp: 9 (10). limitations: the study was funded by ingredia sa (arras, france). ingredia is a company producing milk products and value-added bioactive compounds related to milk. it is not stated whether the funder had input into the study design but its authors report that, during data collection, only the sponsor knew which dog received which treatment during the trial. there was no bmp only treatment group and / or bmp + placebo group. the paper cited by the authors (pageat, 1995) is in french so it is not possible to use this paper to better understand the usage of the eded scale in relation to assessment of selegiline. the authors do not make clear what they mean by average. were they presenting medians or means?  they do not report any measures of variation (e.g. standard deviation, inter-quartile range, standard error of the mean). the authors switch between using parametric and non-parametric tests to study aspects of the same data. they do not report any information to indicate that they considered the underlying distribution of the data. statistical output reported for the between treatment group pairwise comparisons at visit 1 (day 0) and visit 3 (day 56) is unclear as only one p value is reported (p = 0.79) for both results. technically, the authors cannot make the claim reported in the eded scores section (that scores decreased between visits one and three for each treatment group) because they only appear to have carried out an anova. the degrees of freedom indicate that they fitted 5 time points (presumably physical visits 1-3, and telephone calls 1-2). however, no post hoc test has been carried out to identify between which two (or more) pairs of time points the significant difference(s) arises between. eyeballing the graphical data suggests that a significant difference was most likely between visit 1 and 3, but this is complicated by the lack of variation reported. this criticism also applies the anova analysed aspect of the owner subjective assessment of improvement scores. the reporting of the anova analysis for the owner subjective assessment of improvement scores is not clear enough. it is assumed that they are comparing four time points (physical visits 2-3, telephone visits 1 -2 because of the degrees of freedom reported) but they do not include enough information. the claims that are made throughout the research paper are misleading and introduce a potential interpretation bias on the part of the reader with limited research methodology knowledge. the authors consistently refer to the two groups as alpha-casozepine and selegiline, but make limited mention of the fact that these dogs all also received a behaviour modification programme, with no mention at all in the results or conclusion (there is no discussion section). despite this major confounding variable, the authors make statements like: “both compounds were equally efficacious” (results), “both products were efficient to decrease the eded score” (abstract), “due to this efficacy…. alpha-casozepine (zylkene) should be considered an option by the veterinary surgeon for the biological management of anxiety” (abstract), etc. these claims cannot be made given the lack of an adequate control group as each compound could be equally efficacious at having no impact on anxiety (i.e. the bmp was the successful component). kato (2012) population: healthy adult small-medium (1.4 – 12.6kg) pet dogs that scored as ‘anxious’ on the canine behavioural assessment & research questionnaire (c – barq).   both genders were included and a variety of ages and breeds. dogs were excluded if they: were pregnant less than one year of age had had a medical condition (i.e. not necessarily current) were a recipient of behavioural therapy or medications aimed at treating behavioural problems (i.e. psycho-active drugs) sample size: 44 dogs were recruited to the study. 28 dogs completed the study. 4 dogs were lost to follow up during the study; the others withdrew for reasons unconnected to the trial (health issues of the dogs or personal circumstances of the owner). intervention details: the two diet treatments compared for their effects on indices of canine anxiety in a crossover, single-blind, single order trial were: control diet (royal canin select skin care vets plan) experimental diet containing elevated levels of the amino acid tryptophan and alpha-casozepine (royal canin calm canine) the alpha-casozepine inclusion rate was 1.35g/kg dry matter (dm), to provide dogs with a dose of approximately 20mg/kg/day (the recommended dose for dogs under 15kg). the tryptophan content of the experimental diet was 3.04g/kg dm (the control diet contained 2.83g/kg dm). the diets were not identical in all other respects. all the nutritional components reported differed in inclusion rate. the dogs were retained in their home environment throughout the study and fed by their owner (who was blinded to the treatment they were feeding their dog). the experimental timeline is as follows: the owners of potential canine participants completed a c-barq questionnaire. dogs that scored as anxious (n = 44) were included in the trial. dogs received the control diet for 8 weeks. they were fed twice a day. data collection took place in week 7 (see below for outcome measures) and comprised completion of the c barq questionnaire to assess behavioural indices of anxiety and two urine samples collected to assess urinary cortisol levels. one sample was taken in the home environment (baseline, unstressed measurement) and one sample was taken 2hr post vet clinic visit (the ‘stressed’ measurement). dogs then received a 1 week wash out period. the diet fed during this period is not stated and is assumed to be the dog’s normal diet. dogs then received the experimental diet for 8 weeks. all other details are the same as for the control diet phase. further details: the wash out period length was determined by a prior preliminary experiment using high-pressure liquid chromatography which demonstrated that the dietary additives would be entirely removed from the dogs systems within one week. cortisol analysis was carried out in duplicate. urine collection was carried out at the same point of day to reduce the risk of time of day effects on cortisol production. study design: experimental cross-over trial outcome studied: the outcome measures studied were all potentially relevant to answering this pico. the outcome measures included: urinary cortisol:creatinine ratio (uccr) baseline measurement: taken in the dog’s home environment post-stressor measurement: taken 2hrs post vet clinic visit severity of stranger – directed aggression severity of owner – directed aggression severity of stranger – directed fear severity of non-social fear level of touch sensitivity all, bar uccr, were assessed using specific questions within the c-barq questionnaire. this questionnaire asks owners a series of questions to assess each parameter, and owners are asked to score their dog on a scale from 0 (no signs of the behavior) to 4 (signs are severe). the scores for each parameter’s questions (e.g. for stranger-directed aggression there are 10 related questions) are then averaged, to provide a mean score for that parameter. the c-barq questionnaire is a widely used, validated method of assessing canine behavior in a range of ways (not specifically anxiety). main findings (relevant to pico question): uccr: baseline uccr of the dogs was not significantly different between treatments. post stressor uccr was significantly different to baseline measurement, irrespective of treatment (i.e. the dogs were stressed by the veterinary visit) (p < 0.01). the mean (±standard error of the mean, s.e.m.) uccr of the dogs post-stressor was significantly lower (p = 0.04) when they were being fed the experimental diet (32.17 ± 0.21 x 10-6) than when they were being fed the control diet (39.61 ± 0.3-6). questionnaire assessment of the dogs’ anxiety-related behaviours: there was a significant reduction in stranger-directed aggression when the dogs were being fed the experimental diet (t = 2.44, d.f. = 15, p = 0.014). the mean (± s.e.m.) scores were: control: 1.25 (± 0.22); experimental: 0.85 (± 0.20). there was no effect of diet on owner-directed aggression. the mean (± s.e.m.) scores were: control: 0.47 (± 0.07); experimental: 0.43 (± 0.07). there was a significant reduction in stranger-directed fear when the dogs were being fed the experimental diet (t = 3.08, d.f. = 22, p = 0.014). the mean (± s.e.m.) scores were: control: 1.51 (± 0.22); experimental: 1.15 (± 0.14). there was a significant reduction in non-social fear when the dogs were being fed the experimental diet (t = 2.00, d.f. = 17, p = 0.031). the mean (± s.e.m.) scores were: control: 1.44 (± 0.22); experimental: 1.20 (± 0.23). there was a significant reduction in touch sensitivity when the dogs were fed the experimental diet (t = 3.56, d.f. = 25, p < 0.001). the mean (± s.e.m.) scores were: control: 1.34 (± 0.14); experimental: 1.01 (± 0.12). limitations: the study was partially funded by royal canin. the authors do not state whether royal canin had any input into the experimental design. the study was not specifically designed to study the effects of alpha-casozepine on anxiety. rather, it was set up to study the effects of a commercial diet that contained alpha-casozepine and increased levels of tryptophan. thus, there was a complete confounding variable when using this study to address the pico question. the diets used were not identical in all other respects, other than the dietary additives. this was sufficient for a commercial aim (to show the diet was beneficial) but limited interpretation of the effects of any specific additive. the study did not randomise the order in which the dogs received the treatments. therefore, the study is at risk of order effect biases. it is not clear why this was not done as the order that the diets was presented to the dogs was under the control of the experimenters and the experimenters provide no explanation for why this approach was taken. the authors refer to preliminary data to establish that dietary additives to the diet would be fully eliminated from the body within one week, in order to justify the one week washout period. however, it is unclear what dietary additives they are referring to as the experimental diet containing the additional dietary additive (alpha-casozepine) or increased levels of the dietary additive tryptophan was presented to all dogs in the second (post wash out period) phase of the study.  cortisol is a non-specific measure of arousal, rather than a specific biomarker for stress. therefore, it is possible that the dogs were excited or stimulated by a trip to the vets, rather than fearful. the authors fail to determine what the dogs’ normal behavioural response is to a trip to the vets. the c-barq questionnaire assessment of the dogs to determine which dogs were included in the study provides insufficient detail.   the c-barq questionnaire used is not a questionnaire that has been validated to anxiety per se. several of the categories are specifically designed to assess fear, but some are not. or particular relevance here is the aggression-related categories. not all aggression is derived from anxiety. the definition of an ‘anxious dog’ (i.e. that meets the inclusion criteria) was very loosely defined. dogs were only excluded if, on all the questions asked (n = 321), the owner scored the dog as a 0 (no sign) to 1 (mild signs observed). thus, a dog could be included if the owner scored it as a 2 (somewhere between mild and moderate) on just one of the questions. 1assumes mutual exclusivity of the questions. the authors do not clarify whether one question assesses more than one parameter simultaneously. appraisal, application and reflection three peer reviewed papers were identified that either partially or fully addressed the pico. two of these studies (palestrini et al., 2010; kato et al., 2012) investigated the use of diets with added alpha-casozepine, though, in the kato et al. (2012) study the diet was also supplemented with another compound (tryptophan) thought to have anxiolytic properties. the remaining study (beata et al., 2007) investigated the use of a daily capsule of alpha-casozepine. the two studies focused on dietary interventions (palestrini et al, 2010; kato et al., 2012) used a placebo-controlled study design, whereas beata et al. (2007) compared alpha-casozepine to another intervention (selegiline) that was already used commercially as an anxiolytic. all of the studies focus on the potential anxiety-reducing effects of alpha-casozepine when administered in the medium to long term. time from baseline measurement to the first and last assessment of anxiety ranged from 14-56 days (beata et al., 2007), c.30-68/69 days (palestrini et al. 2012) or 7 weeks (one defined timepoint) (kato et al. 2012).  the palestrini et al. (2010) study also undertook an assessment of the dogs at the start of administering the diet (separate to an additional set of baseline measurements taken immediately before starting the diet). however, there is insufficient study detail to define the exact details here and the number of days that comprised this phase is uncertain. furthermore, as no significant differences were identified between this and the pre-diet baseline measurements, it is clear that there are no studies that found a significant effect of alpha-casozepine on indices of anxiety in the short term. further, no studies were identified that looked at the effects of alpha-casozepine to a dog shortly before (e.g. minutes to a few days) exposure to a novel, or intermittent stressor (e.g. fireworks). thus, there is currently no research evidence to support recommending the use of alpha-casozepine to clients seeking a quick acting anxiolytic product to alleviate short term stressors in the dog’s immediate or short term future. all three of the studies that examined the effect of alpha-casozepine administration in the medium-long-term of indices of anxiety were problematic in terms of experimental design. of the studies that looked at the effect of alpha-casozepine, the industry-sponsored study by beata et al. (2007) offered the weakest experimental design and the authors appear unaware of this limitation as the conclusions that they draw are misleading. equivalence and / or non-inferiority type studies in which a new treatment is compared to an existing treatment are increasingly commonplace in medical research and justified as removing the ethical issues of not treating some patients at all (or giving a placebo). beata et al. (2007) adopt this approach, but their study design also includes a behavioural modification programme (bmp) alongside each of the anxiolytic products compared. this represents a confounding variable. as a consequence, even though their findings appear to indicate that alpha-casozepine has a similar efficacy as selegiline, based on their study design, the level of efficacy (from no effect to very effective) cannot be determined for either product as the effect of bmp is also unknown.   this problem is compounded by their exclusion criteria as they systematically exclude any dogs that have already received bmp. thus, it is not possible for the authors to justify their conclusions by the claim that, prior to starting anxiolytic therapy, these dogs had failed to respond to the bmp. though even this appeal would be sensitive to the effects of time spent implementing a bmp on indices of anxiety reduction. any appeal to the efficacy of alpha-casozepine would require appeal to the wider literature demonstrating an effect of selegiline per se on indices of anxiety in the dog and the inherent limitations and problems that entails. thus, this study fails to address adequately the pico posed in the knowledge summary. of the three studies, the palestrini et al. (2010) most successfully set up their treatment groups to address the pico. the two diets compared are identical other than the addition of caseinate hydrolysate (the milk protein isolate containing alpha-casozepine) and the dogs are not undergoing a behavioural modification programme. however, they fail to state the inclusion rate of the caseinate hydrolysate and the dogs were allowed to consume the diet on an ad libitum basis so individual dog exposure to the active ingredient was variable.  one of the strengths of this study is that they also include a non-anxious group of dogs that are also randomly allocated to receive either the experimental or control diets. this potentially allowed them to identify whether any behavioural changes observed were due to other, non-anxiety based, properties of alpha-casozepine. however, the sample sizes utilised in this study were small to start with (n = 8 per sub-group), and they took the further, questionable, step at the end of data collection, of retrospectively removing from the main analysis, three of the dogs in the anxious group. they fail to report which of the treatment groups (experimental versus control diet) these dogs were allocated to and this means that one of these subgroups (crucial to answering the pico) may have had as few as 5 dogs in it. frequently, the paper moves from comparing diet groups (the aim of the study) to comparing the responses of anxious and non-anxious dogs and, therefore, fails to address the pico at many points. there is some evidence (cortisol, reactivity evaluation form) to suggest the experimental diet reduced anxiety in anxious dogs by the end of the study, but most other physiological or behavioural parameters were either not affected by treatment or the findings are unreported. poor data handling and reporting (see limitations) further limit the ability of the reader to draw meaningful inferences from the findings of this study. external validity is also questionable: with a captive-bred, born, reared and studied population of laboratory beagles and a maximum sample size per group of eight dogs (or lower), it is questionable how well any findings could be extrapolated to the pet population, with their varying genetic history and life time experiences. unfortunately, the final study (kato et al. 2012) is also problematic in terms of addressing the pico. in its defence, this industry sponsored study was not set up specifically to study alpha-casozepine but rather the effects of feeding a diet containing both alpha-casozepine and tryptophan on longer term indices of anxiety in the pet dog. thus, the confounding variable of these additives to the diet exists for the purpose of the pico but not for the purpose of the original study. however, the treatment diets were still not tightly controlled with the two diets varying across many dimensions other than the additives thought to reduce anxiety. dogs were used as their own control, with an eventual sample of 28 dogs. data handling was better within this study with relative homogeneity of the treatment effects observed: of the six outcome measures used, only one parameter showed no effect of treatment (owner – directed aggression). the other five parameters (urinary cortisol: creatinine ratio, stranger directed aggression, stranger-directed fear, non-social fear, and touch sensitivity) were all significantly improved when the dogs were fed the experimental diet. however, inclusion criteria for the study was relatively lax. if a dog scored above 1 on any one question out of circa 28 questions selected from the pre-validated c-barq questionnaire for being thought (by the researchers) to be potential measures of anxiety in the dog, they were included in the study. the mean values for each dog on the control diet suggests that dogs were generally scoring low across categories anyway which suggests that, in general these were not necessarily a particularly anxious population of dogs that were studied. furthermore, the experimental design put the findings at a relatively high risk of bias. despite the authors having experimental control over the study population, they chose to undertake an experimental design in which all dogs first received the control diet, followed by all dogs receiving the experimental diet. this makes the outcome particularly sensitive to order effects as dogs may simply have improved over time. for example, the cortisol of the dogs was lower at the second visit to the veterinary clinic. this could be because the dog had habituated to the veterinary practice (though the authors point out these dogs visited the vets regularly). alternatively, if owners chose to participate in a trial testing diets aimed at reducing anxiety, this might alert them to the need to other information that might be used to reduce anxiety in their dogs. furthermore, the researchers refer to a wash out period of 1 week between trials to ensure that additives have been removed, yet it is not clear what additives they are referring to as the ones in question are only included in the second phase. in summary, whilst there is some evidence (through a shared direction of effect where a significant effect exists) across the studies that alpha-casozepine may have a clinically beneficial effect in reducing canine anxiety in the medium to longer term, the current evidence is weak and there is a need for good quality, placebo-controlled, randomised clinical trials that specifically address this compound for common anxiety-causing scenarios that this biomolecule may be promoted as a potential solution for. methodology section search strategy databases searched and dates covered: pubmed (1900 – 2017); web of science (1970 –2017); cab abstracts (1983 – 2016) search terms: (dog or dogs or canine or bitch* or canid or puppy or puppies) and (“alpha casozepineâ€� or alfa1-casozepine or alpha-casozepine or casein or “milk proteinâ€� or zylkene or milk) and (anxiety or anxious or fear or fearful or stress or stressed or stressful or panic or phobi*) dates searches performed: 11 july 2017 exclusion / inclusion criteria exclusion: pre-defined exclusion criteria:  non english language, popular press articles inclusion: any comparative (control group utilised) study in which the effect of alpha-casozepine on anxiety (or similar) in dogs was studied. search outcome database number of results excluded – did not answer pico question excluded – not english language excluded – conference abstract only excluded – duplicates total relevant papers ncbi pubmed 22 22 0 0 0 0 thomson reuters web of science 33 30 1 0 0 2 cab abstracts 46 42 1 1 1 1 total relevant papers when duplicates removed 3 conflict of interest the author declares no conflicts of interest. references beata, c. et al. (2007) effects of alpha-casozepine (zylkene) versus selegiline hydrochloride (selgian, anipryl) on anxiety disorders in dogs. journal of veterinary behaviour: clinical applications and research, 2 (5), pp. 175-183 http://dx.doi.org/10.1016/j.jveb.2007.08.001 kato, m. et al. (2012) effects of prescription diet on dealing with stressful situations and performance of anxiety-related behaviors in privately owned anxious dogs. journal of veterinary behavior: clinical applications and research, 7 (1), pp. 21-26 http://dx.doi.org/10.1016/j.jveb.2011.05.025 pageat, p. (1995) pathologie du comportement du chien. editions du point veterinaire, maisons-alfort: 208 – 224 palestrini, c. et al (2010) efficacy of a diet containing caseinate hydrolysate on signs of stress in dogs. journal of veterinary behavior, 5 (6), pp. 309-317 http://dx.doi.org/10.1016/j.jveb.2010.04.004 intellectual property rights knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. clinical governance and continuous quality improvement in the veterinary profession: a mixed-method study tom ling ma phd1 ashley doorly2* chris gush bsc msc2 lucy hocking bsc msc1 1rand europe, westbrook centre/milton rd, cambridge, cb4 1yg 2rcvs knowledge, belgravia house, 62–64 horseferry road, london, sw1p 2af *corresponding author (ashley@rcvsknowledge.org) vol 6, issue 2 (2021) published: 12 may 2021 reviewed by: jo ireland (bvms cert avp(em) mrcvs phd) and tim mair (bvsc phd deim dests dipeceim assocecvdi mrcvs) doi: 10.18849/ve.v6i2.383 section index:    abstract | introduction | methods and materials | results | the future of qi: what can veterinary stakeholders do to support qi going forward? | discussion | footnotes | conflict of interest | references | supplementary files abstract 96% of the veterinary profession agrees that quality improvement (qi) improves veterinary care. while clinical governance is an rcvs professional requirement, over the last year only 60% spent up to 3 days on the quality improvement activities which allow clinical governance to take place. 11% spent no time on it at all. a lack of time, know-how and organisational support were among the barriers preventing its adoption in practice. rather than being an individual reaction to a problem, quality improvement is a formal approach to embedding a set of recognised practices, including clinical audit, significant event audit, guidelines and protocols, benchmarking and checklists. this framework should be applied within a just culture where errors are redefined as learning opportunities, and precedence is given to communication, team-work and team-morale, patient safety, and distributed leadership. addressing this gap will require evolution – rather than a revolution. persistent packages, given enough time and addressing the whole flow of the patient journey, trump one-off ‘heroic’ and narrowly-focused interventions. creating a rhythm of learning alongside stability of practice allows lessons to be absorbed and improvements routinised. doing good things well is better than doing perfect things sporadically and helps address the widespread concern that there is insufficient time for qi by making the time commitment more predictable and manageable. the research provides a robust, evidence-based, roadmap for the entire sector including professional organisations, educators, those in management positions and care providers.   introduction quality improvement (qi) involves a set of inter-related steps: taking a systematic approach to understanding a problem, measuring its scale, identifying and then testing a potential improvement, reviewing the results and then starting again. within this broad definition there are many varied practices. why might any group of people who work together engage with quality improvement when it involves taking time out of primary tasks? early examples from the car industry, for example, highlight the importance of senior management buying into the approach and subsequently securing buy-in from staff in a top-down way. in human healthcare, the role of senior leadership in delivering improvement is different to the car industry, for example, (where many improvement processes were first formalised); in human healthcare often senior figures learned about improvement from external organisations such as the institute for health improvement, and returned committed, and seeking change in their host organisation. this formalised approach to improving human healthcare quality arose around the turn of the 21st century and was self-consciously a new way of thinking about quality. quality came to be defined as involving six domains (institute of medicine (us) committee on quality of health care in america, 2001): safety patient centeredness timeliness effectiveness efficiency equity alongside this definition of quality, there developed a self-professed ‘science of improvement’ and, reflecting this, a set of practices that became collectively known as quality improvement (qi) with upper case (indicating it is a distinct entity). in this article we use qi to describe this distinctive approach while we will also refer more generally to wider efforts to improve quality as, simply, ‘improving quality’. thus, a whole system approach to embedding recognised techniques[1] would count as qi while singular actions such as attending continuing professional development (cpd), holding a clinical governance meeting, or purchasing new equipment could be ‘improving quality’. it would be wrong to regard qi as either uniformly successful or universally applied in human healthcare, but it involves a set of practices recognised to be different from one-off improvement efforts. rather than being an individual reaction to a problem it is better thought of as a framework within which improvement can be systematically addressed. much of this thinking developed first in the united states and was associated with two studies completed at the turn of the century: to err is human: building a safer health system (institute of medicine (us) committee on quality of health care in america, 2000) and crossing the quality chasm: a new health system for the 21st century (institute of medicine (us) committee on quality of health care in america, 2001). this new framework was multi-faceted but included a movement away from a focus on checking the decisions of individual clinicians and punishing errors, and instead proposed building systems within which teams could work together, peers could support one another, and errors were redefined as learning opportunities (agency for healthcare research and quality, 2013; the health foundation, n.d.). subsequently, people in parts of the veterinary profession in the uk actively engaged with the idea that lessons might be learned and adapted from the improvement framework being developed in human healthcare (as well as qi in other industries beyond healthcare). in particular, in 2017 rcvs knowledge identified a group of practitioners that they considered to be ‘early adopters’ and invited them to form a quality improvement advisory board (qiab). rcvs knowledge sought to become not only a ‘hub’ for improvers to learn and connect, but also a driver of change focused on five areas for action (rcvs knowledge, 2017): clinical audit benchmarking significant event audit guidelines checklists this approach includes a recognition of the importance of ‘top-down’ approaches to establishing and extending clinical audit and so forth, but it was also sensitive to the importance of professionals ‘self-identifying’ as improvers and engaging with it not only in response to demands from above but also as part of a shared identity of veterinary surgeons and veterinary nurses having ‘two jobs’; not only delivering care but also improving the care delivered. it was in this context that rand europe[2] was commissioned by rcvs knowledge to conduct primary research and to work collaboratively with rcvs knowledge to generate insights and learning regarding the current state of qi in the veterinary profession, their appetite for change, and to make recommendations for further progress. this article reports on that research; what was found, and what was recommended, and the future actions for those organisations and people who are involved in animal healthcare. before discussing the findings from the veterinary sector, it is important to briefly reflect on the transferability of lessons from qi in human healthcare. it would be strange if those wishing to support qi in animal healthcare were not interested in learning lessons from human healthcare where, as we have seen, there has been a longer history. however, if lessons are to be learned, it is necessary to also understand the peculiarities that would be relevant for applying lessons to an animal health setting. some implications from human healthcare include: for qi to be successfully embedded, the veterinary sector will need to first understand the quality of care that is already being provided. to do this, it must build data collection systems on a national scale capable of measuring the extent of existing problems and measuring the effects of improvement. this is key to entrenching improvement practice. however, despite recent improvements (for example, in the rcvs practice standards scheme (pss) for hospital accreditation, and in the supporting guidance to the rcvs code of professional conduct for veterinary surgeons and veterinary nurses[3], where there is an emphasis on the importance of collecting data via audits) data collection is not yet standardised, limiting the opportunity to use data to drive improvement (oxtoby and mossop, 2016). the skills regarded as crucial for successful qi in human healthcare are less cultivated in veterinary healthcare than in the nhs (ballantyne, 2016) and this skills gap would need to be addressed. while improvement in human healthcare is undoubtedly helped by top-down elements, it also requires engagement, skills, and confidence building ‘from below’ (hocking et al., 2020b). this might include training, dispersed leadership, client engagement, communities of practice, and networks. these bottom up capacities are not yet formed (at this early stage) in the veterinary sector (hocking et al., 2020a, 2020c). because of these contextual differences, simply transferring lessons wholesale from human healthcare might be unwise. there is a compelling argument that learning how to take qi forward in animal healthcare would need to be based in large measure on evidence collected from that sector. the research presented here intended to begin to address this evidence need. it aimed to address three overarching research questions: what is the veterinary profession[4] currently undertaking in their workplace to improve quality? what shapes, or could shape, the veterinary professions motivations for being engaged and involved with qi? what rcvs knowledge and other stakeholders[5] can do to overcome the barriers, and support the enablers for the veterinary profession, to engage with qi in practice?   methods and materials the methodology was designed to allow the research team to engage with a wide range of stakeholders, within the available resources. in summary, the mixed methods used included: a review of qi documents from the sector 18 semi-structured interviews with key stakeholders a survey of 471 members of the veterinary profession two focus groups with 14 pss assessors a national summit attended by 50 policymakers and influencers from the veterinary profession rcvs knowledge provided support to the researchers, who had no prior experience of working in the veterinary industry, to assist in identifying relevant contacts or groups of contacts, however, it was important to rcvs knowledge and rand europe to minimise the risk of bias with this approach. mitigation strategies to prevent bias included: carrying out focus groups with the pss assessors who were familiar with many and varied practices, with a mandate to assess and assure the standards of clinical governance (among other standards). their remit made them well-placed to understand the current landscape of qi in veterinary practices. interviews up to an hour long were conducted by the researchers. interviewees were a random selection[6] of members of the profession using the databases of members of the rcvs and registered veterinary nurses held and maintained by the rcvs. all registered veterinary surgeons and veterinary nurses in the databases were included in the selection and allocated a unique number. numbers were then randomly selected, and those individuals were invited to an interview. inviting summit attendees through delegation by the leading veterinary organisations and policy makers who represent the breadth of the profession. widely promoting the survey which was open to all those working in a veterinary practice setting in the uk. all research participants were assured that the information that they provided would be used by the research team alone (rand europe), to analyse and report on the findings, and was not directly attributed to named participants. the intention of having an external organisation undertake the research (rather than this being done by rcvs knowledge), was to mitigate the risk that participants might give biased views if they felt that their responses were available directly to an organisation who might be seen as too closely linked to their regulator.    orientation document review to help the research team orientate their work within existing knowledge and research they conducted a short document review of qi-related documents from rcvs, rcvs knowledge, academic literature, large practice groups and professional bodies. this was carried out at the start of the research (january to february 2019). to identify relevant academic literature, rcvs knowledge library and information services conducted a literature search using keywords related to qi:, the research team searched for keywords in the title/abstracts, including ‘quality improvement’, ‘clinical governance’, ‘improvement’ and ‘clinical audit’. articles not in english, books, podcasts, and descriptions of events/workshops without information on results were excluded. this led to nine articles identified as relevant and information extracted. in addition to this, rcvs knowledge made available a list of 36 grey literature documents it identified as being relevant to the research (the full list of the 45 reviewed articles is in the supplementary material appendix 1). this included qi strategy documents and qi reports from rcvs knowledge, large practice groups and rcvs webpages with qi information, such as the rcvs code of professional conduct, among others. each document was reviewed, and information from this has been incorporated throughout the article. in addition to the documents sent by rcvs knowledge, five key systematic reviews covering qi in human healthcare were included (see supplementary material appendix 2). the purpose of this was to explore where progress made within the veterinary sector by rcvs, rcvs knowledge and others sits within the evidence base of human healthcare.   key stakeholder semi-structured interviews eighteen semi-structured interviews were conducted with key stakeholders during march to may 2019 by telephone. the stakeholders, numbers, aims of the interviews and the references used throughout this article are shown in table 1. the interviews were numbered sequentially in the order they were conducted in.   table 1: the number of stakeholder interviews, the aim of interviewing each and the code used to reference interview data throughout the report stakeholder number interviewed aim of the interview code animal charity 1 to understand the current qi initiatives in place within the charity, the barriers and enablers faced by animal charities and how qi can be taken forward in the sector. intx charity animal owner 2 to provide perspectives on where animal owners think improvements can be made in the veterinary sector. intx owner members of the profession 10 to understand the current status of qi across the veterinary sector, the motivations for professionals to engage with qi and the enablers and barriers they face, and how professionals would like qi to be taken forward in the veterinary sector. intx profession large practice groups’ clinical governance leads 2 to understand the motivations and constraints regarding qi for those in practice. intx lpg rcvs knowledge qiab member 1 to gain an understanding of the context of qi in the veterinary sector, the hopes for this project and the role of the qiab in qi now and in the future. intx qiab representatives from organisations who deal with veterinary clients’ complaints 2 to cover the background of qi in the veterinary sector and explore where animal owners think improvements can be made in the sector. intx complaints the interviews were analysed using nvivo[7]; ‘nodes’ were created for each interview question and the transcripts were coded within this template.   survey of the veterinary profession the research team worked closely with rcvs knowledge to design a national survey open to all members of the veterinary profession. through this we explored how professionals working in the veterinary sector (including veterinary surgeons, veterinary nurses, and practice managers, as well as students and researchers/academics) thought about and use qi in their routine work. the survey questions covered: preferred qi terminology; actual and desired time spent on qi activities; use of rcvs knowledge qi tools; qi training; impact of qi on their practice and veterinary care more widely; barriers and challenges in engaging with qi; who is responsible for driving qi; what support is needed to be involved in qi; and awareness, understanding and views of the rcvs code of professional conduct, and the pss. those respondents who did not agree to the consent questions were removed (14 participants) which left 471 responses which were analysed. the survey was administered via the smartsurvey platform and was disseminated by rcvs knowledge through various channels to reach as many of the profession as possible. this included on the rcvs knowledge website, social media channels, e-news and a blog post authored by a member of the research team. a press release was sent and was covered by: veterinary practice ; vetpol; mrcvsonline; vnonline; vet community; vetnurse; and vetsurgeon[8]. it was promoted in rcvs e-news. in addition, several key veterinary organisations were directly invited to participate in the survey and share it within their professional networks (see supplementary material appendix 3 for a list of organisations). the survey was left open for a total of 6 weeks.   focus groups with pss assessors two focus groups with 14 pss assessors were carried out in march 2019. the aim of the focus groups was to understand the motivations of the profession to become involved with qi (including applying and maintaining pss accreditation) and to explore what rcvs and others could do to support qi going forward. each focus group participant completed a consent form ahead of the focus group. each focus group was recorded, transcribed and analysed in nvivo alongside the interview data to identify themes from across the data collection methods. data from the focus groups is referenced throughout this article using similar references as the interviews, either fg1 or fg2.   results the research identified a wide range of evidence regarding the current status of qi in the veterinary sector. here we focused on what the research told us about how, and how far, qi might be taken forward in the veterinary profession. we reported on nine key sets of findings.   1. although the veterinary profession is aware of qi there was variation in the depth of this knowledge qi and its related activities were understood by the survey participants in general, but with variations in how deep this knowledge was (figure 1 and figure 2). it was reported by one interviewee that awareness had increased during the previous decade due to there being a greater focus on it from rcvs and other bodies, particularly large group practices (int9 profession). the introduction of qi activities has increased recently since the push made by rcvs knowledge. for example cvs adopted a strategic approach after attending skills day 2017: quality improvement in veterinary practice, an event held by rcvs knowledge (cvs group plc, 2018). those who have a qi aspect within their role may be more likely to be aware of the types of activities that are used and of the resources available to support this (int9 profession, int10 profession, int13 profession).   figure 1: survey responses to the question: which of the following statements is most applicable to you and your practice about the clinical governance standards set out in the practice standards scheme?[9]   figure 2: survey responses to the question: which of the following statements is most applicable to you about the clinical governance standards of the rcvs code of professional conduct?   2. the veterinary profession views qi as a benefit to practice and to patient care almost all individuals consulted in the survey felt as though qi would improve the care they provided in their own practice (95.97%) and across the uk (98.09%). there is very little resistance to the idea of qi (see figure 3 and figure 4).   figure 3: survey responses to the question: which of the following statements do you agree with regarding the impact of quality improvement on your practice?   figure 4: survey responses to the question: which of the following statements do you agree with regarding the impact of quality improvement on veterinary care across the uk?   many interviewees discussed how they anticipated qi would allow them to provide the best care possible to animals and reduce adverse events (int4 profession, int7 profession, int9 profession, int11 profession, int16 profession, int18 profession). ‘to stop critical events from happening, or try and prevent them as much as possible, and provide the best service that we could.’ (int16 profession) ‘qi means striving to improve our clinical skills and improve a client’s journey through a veterinary practice.’ (int14 profession) interviewees also anticipated that qi might improve the working of veterinary teams (and not just individuals), for example by increasing job satisfaction (int4 profession, int10 profession, int11 profession). ‘qi is trying to make sure that you are doing the right things that you should be doing and not just for the patient but for the client and staff as well.’ (int11 profession) many interviewees also discussed the importance of seeing qi as a journey of constant improvement rather than a one-step change to a better way of working (int1 qiab, int9 profession, int11 profession), including helping to keep up with changes in medicine (int9 profession). ‘it [qi] is a cyclical process rather than a journey from a to b.’ (int11 profession)   3. veterinary professionals view the pss and the rcvs code of professional conduct as beneficial to animal care and to practices, although on their own there were mixed views on the extent to which they would entrench qi in veterinary practice overall, the interviewees held positive views of the pss and felt as though it benefits business and patient care, although there were some concerns that the pss assessment does not necessarily lead to changes in practice. so, although the pss was believed to be a route to introducing qi to those who are not familiar with it (int6 lpg, int11 profession), and advice from the pss assessors during the assessment was helpful for practices in guiding their qi activities, (fg1, int13 profession) it was believed that on its own it was insufficient to entrench qi in veterinary practice. ‘the pss scheme is a good start and is a good guide to get the main [qi] things in place.’ (int11 profession) ‘it [the pss] is a good framework for starting qi.’ (int6 lpg) as with the pss, the survey explored whether members of the profession felt as though the rcvs code of professional conduct supported qi and whether more could be done with the rcvs code of professional conduct to help support qi further. as figure 5 shows, 45.01% of the respondents felt as though the rcvs code of professional conduct supported practices in improving the care they provided and only 6.16% felt it did not. however, 39.07% were unsure as to whether the rcvs code of professional conduct supported qi.   figure 5: survey responses to the question: which of the following statements is most applicable to you about the clinical governance standards of the rcvs code of professional conduct to generate continuous improvement in quality of care?[10]   4. although, as part of clinical governance, quality improvement activities are a professional requirement, many veterinary professionals are spending little to no time on it the survey investigated how much time respondents had spent on qi activities in the last year. as figure 6 shows, almost 60% of respondents spent three days or less on qi over the previous 12 months. of those, 11% reported that they had not spent any time on qi in that time frame. analysis was conducted to explore the differences in time spent on qi across different demographics, including job role, animal species treated, practice type and age. the results were similar across these demographics, although those aged 65 and over appeared to spend more than 10 days on qi (67% of this age group spent more than 10 days). the next closest to this was those aged 55–64 in which 29% spent more than 10 days, which may reflect that those in more senior positions are able to dedicate more time to qi. for age in general, the trend appears to be that time spent on qi increases with age (figure 7). other demographics did not show significant differences in the survey. in addition, all interviewees could speak of at least one qi activity that was used in their practice.   figure 6: survey responses to the question: in the past 12 months, approximately how much time in total have you spent on quality improvement activities?   figure 7: survey responses by age to the question: in the past 12 months, approximately how much time in total have you spent on quality improvement activities?[11]   5. a range of qi activities are used in practice and these are often developed in-house the survey explored which rcvs knowledge qi tools were used by the survey participants over the past 6 months which is when they were launched. in this short time, around one-third of respondents reported having used at least one, with 40% of respondents who had not used these resources indicating they would like to over the next 12 months. only 10% reported that they had not used any of the tools and did not intend to do so in the future. of the responders who had used the rcvs knowledge tools, around one-third had used checklists (34%) and clinical audits (30%). very few respondents reported they had used benchmarking (8%) and 6% of respondents had used other qi tools. when asked what ‘other’ tools were used, responses included both formal qi tools and more generic approaches to improving quality: qi tools developed in-house, including by large practice groups continuing professional development information from colleagues wider literature social media similar tools to those offered by rcvs knowledge but from other sources   6. there are many resources available to support practices in getting started with qi, and creating dedicated qi leads can help embed improvement activities in practice throughout the interviews and review of qi-related documents, the research team identified multiple resources offered to practices to support qi activities. these largely fell into one of two categories: resources to get started with qi creating qi leads within practices interestingly, these were all offered by either rcvs knowledge or developed in-house by large practice groups. the research team did not identify any information on this type of support offered by smaller practice groups.[12] the support provided by large practice groups to implement qi seemed to be more common in practices that have been recently acquired. the types of resources offered are fairly similar to those offered by rcvs knowledge in that they provide veterinary professionals with an understanding of what qi is and provide resources to implement qi in practice. one of the qi leads interviewed outlined initiatives in place in their practices (int6 lpg). this includes creating terms of reference and agenda templates to guide qi-related meetings; qi training to educate professionals on what qi is and how to get started with it; and writing guidance on conducting qi activities, such as significant event audits. this interviewee reported that these resources help veterinary professionals to feel more at ease in getting involved with qi and allow them to feel more comfortable in introducing qi to their work (int6 lpg).   7. our research identified key factors in supporting and challenging qi implementation a range of barriers to engaging with qi were reported by survey respondents and are shown in figure 8. as this shows, the two main barriers identified, with over 50% of respondents, are a lack of time (55%) and difficulty getting others in the practice on board (55%).[13]   figure 8: survey responses to the question: what are the main barriers and challenges you face when engaging in quality improvement activities?   interview and focus group participants were also asked to consider what would support and enable their future involvement in qi. similar themes were identified from the survey. the most frequently identified enablers and barriers from the survey, interviews and focus groups were: lack of time was frequently highlighted as the biggest barrier when trying to engage with qi (int1 qiab, int11 profession, int12 profession, int14 profession, int16 profession). support from colleagues and management was identified as an essential factor in implementing qi activities (int10 profession, int11 profession, int5 animal owner, int6 lpg). the availability of practical and qi-related resources and guidelines can influence the ease at which qi is implemented (int11 profession, int13 profession, int6 lpg, int8 lpg). relevant and helpful training on qi was considered important, although challenges to making this widely available were acknowledged (int6 lpg, int9 profession). variation in barriers and enablers were experienced by different types of practice (int16 profession, int18 profession, int9 profession). for example, more specialised practices may find it easier to implement qi activities (int7 profession, int11 profession, int12 profession, int16 profession, int6 lpg, fg1, int4 charity). when looking at animal species treated, participants indicated that farm and equine vets may face additional barriers to qi (int6 lpg, int10 profession, int13 profession, int16 profession, int7 profession, int15 owner, fg2). finally, smaller practice groups may face additional barriers and fewer enablers than large practice groups (int1 qiab, int4 charity, int6 lpg, int8 lpg, int7 profession, int9 profession, int11 profession, int14 profession, int17 profession, int18 profession).   8. clients are generally not familiar with the complaints procedure, or with qi activities that happen in the practices they visit throughout the interviews with members of the profession, those involved with client complaints and animal owners, it became clear that clients were generally not made aware of the qi activities in the veterinary practices they visit and that these activities are more often seen as internal activities (int3 complaints, int4 charity, int5 owner, int7 profession, int9 profession, int10 profession, int11 profession, int14 profession, int15 owner, int16 profession, int17 profession). a variety of reasons were given as to why qi activities are not communicated to clients. two interviewees commented that they had just never thought to share this type of information with their clients (int7 profession, int11 profession). there was also a concern that clients lack the knowledge needed to understand the care provision for their animal and the reasoning behind the decisions made for their care (int1 qiab, int11 profession, int17 profession).   9. there are mixed opinions as to whether clients should be involved in qi, although feedback was thought to play an important role only 8% (37 out of 471) of the survey respondents felt as though animal owners have a future role to play in qi. the interview with a member of the qiab noted the asymmetries of knowledge that inevitably characterise this area (int1 qiab). however, this would be at odds with the premise of qi as was highlighted by definitions of qi given by some of the interviewees. ‘qi is trying to make sure that you are doing the right things that you should be doing and not just for the patient but for the client and staff as well.’ (int11 profession) ‘qi means striving to improve our clinical skills and improve a client’s journey through a veterinary practice.’ (int14 profession) it may be that the knowledge held by a client on qi activities, such as audits, determines the extent of their involvement in qi activities (int11 profession).   the future of qi: what can veterinary stakeholders do to support qi going forward? the results from this research have so far shown the veterinary professions perceptions and understanding of qi, the current qi activities in use across the profession and the enablers and barriers to the profession engaging in qi. what is important to understand next is, based on these results, what can be done going forward, and by whom, to continue to support qi across the veterinary sector. based on our analysis, our summary conclusions regarding the role of wider stakeholders would be: rcvs could improve qi guidance and signposting to resources for practices, mandating certain aspects of qi (although this received mixed views from the research participants), ensuring there is a focus on improving team wellbeing and continuing to strengthen the qi aspects of the pss. rcvs knowledge could more widely promote the resources and guidance already available, as well as creating new resources and national data collection hubs to encourage improvement, campaign to demonstrate the importance and benefit of qi, and simplify qi language. individual practices, including large and smaller practice groups, could appoint qi leads (which could involve those from both clinical and non-clinical roles) to help implement and sustain qi activities, introduce qi into human resources processes, introduce initiatives to encourage communication across the practice. the practices could create dedicated qi time as well as encourage uptake of the resources and data collection tools available through rcvs knowledge. professional organisations could support rcvs knowledge to develop and promote qi resources, as well as continuing to develop their own resources. universities and educators could introduce a greater focus and unified approach to developing the skill-set required to deliver qi in education and as part of the curriculum, including modules on qi. cpd providers, which includes a range of organisations including individual practices and rcvs knowledge, could incorporate qi into training and cpd to a greater extent. pms providers could incorporate qi tools, such as using venom coding (venom coding, 2020) and api functionality, into their systems. the veterinary client mediation service could support practices to learn from complaints and provide guidance on how to deal with complaints, including partnering with others to help to share lessons learned.   discussion the future progress of qi in animal healthcare will take place and face a variety of challenges that were alluded to during the interviews, survey and focus groups, and which are apparent in wider discussions. qi is clearly not the sole answer to these new challenges but, in our view, should be seen to be part of a coherent response. key challenges within the veterinary sector which will amplify the role of qi include: as animal owners become more informed and often have higher expectations, it becomes more important to have a formal system to show how quality issues are addressed. similarly, there will be strong professional motivations to keep as narrow a gap as possible between the latest and best evidence and ‘treatment as usual’. as veterinary practices grow in size, there are new opportunities to routinise qi, and more risks in not doing so. all of this will happen in the context of growing resource pressures reinforcing the need to identify wasteful practices that do not add value in the care of animals; qi is also concerned with stopping unnecessary procedures and reducing the time between procedures that add unnecessary costs or suffering to the animal. in the light of these challenges, it is therefore perhaps not surprising that the survey results, interviews, focus groups and summit registered a strong appetite for qi. human healthcare is an obvious source of inspiration and ideas to support the embedding of qi in animal healthcare. however, there is a need to carefully tailor qi techniques to the circumstances of the improvement efforts. qi in human healthcare is more mature than in the veterinary sector and this offers the opportunity to use lessons learned, ensuring that from the outset, implementation of qi in the veterinary sector supports both reliable data on the activities and clarity about impacts (oxtoby & mossop, 2016). our survey also showed that support for the idea of qi is greater than the understanding of what qi involves. having engaged with the idea in principle, there is now a need to engage with it in practice. in part, this should be achieved by the careful presentation of evidence. however, the evidence may not be enough to create meaning and to change behaviour. therefore, without it becoming a marketing exercise without substance, by drawing on examples from elsewhere, evidence from the sector, thought leaders and so forth, qi should be branded and communicated, for example through narrative case examples of how and why qi has worked well. the view was expressed in the summit and in a focus group (fg1) that ‘overselling’ qi and giving it a ‘cult status’ would most likely lead to resistance. on the other hand, branding it as ‘the way we do business around here’ and as a helpful and practical way to provide better care within the available resources was seen to be a more likely route to success. professional identity is an important driver of behaviour (godin et al., 2008). medical knowledge is an important driver but so too is knowledge about tools to implement change, to understand the context and to measure results (batalden & davidoff, 2007). in this sense, all those working in animal healthcare have two jobs: one to deliver healthcare and the other to improve it. training has a role to play in shaping professional identity. the research highlighted that qi teaching (at university but also throughout veterinary careers) is patchy and many did not necessarily realise that the qi that they were doing was part of a more formal approach and so did not close the loop in monitoring these activities to ensure they are having the desired impact. where qi is established as part of the expertise and knowledge, professionals need to do their job well and this informs the core curricula (rather than optional extras), new recruits to the veterinary workforce will more readily engage with qi activities. however, throughout the research, the point was made to the research team repeatedly that if qi is to become the routine way of working, it needs to be made easy for those new to qi to engage, and with clear routes to participate. supporting practices to have a package of qi activities and creating a community of practice whereby more experienced improvers can support new starters, could have a high impact. the research unequivocally demonstrates the demand across the industry for rcvs knowledge to support practice teams to embed full-cycle continuous qi for a structured and evidence-based approach to animal care. the organisation aims to lead a harmonised approach to qi that emphasises collaboration and shared learning to advance the delivery of quality care (rcvs knowledge, 2017). the research has shown that rcvs knowledge’s current approach provides a good foundation, and with fidelity to the techniques, and allowing time for veterinary specific evidence to accumulate, rcvs knowledge can play the intermediary role for lessons to be learned and shared across the profession. whatever the merits of a social movement for improvement in the veterinary world, the view from the sector is that there should be evolution not revolution. the reasoning behind this is that there are already in place important parts of an improvement architecture, although they would have to be nudged and reshaped. mirroring findings from the human health sector (ling et al., 2018; and dixon-woods et al. 2012), our survey for this research shows that time is a crucial barrier to engaging with qi. so too is the lack of clarity around how to easily engage with qi. visible and predictable routes should be flagged along with the time commitment they involve. for example, different activities might be offered depending on how much time there is available in any one week. the experience of improvers is that persistent packages, given enough time and addressing the whole flow of patient journey, trump one-off ‘heroic’ and narrowly-focused interventions. creating a rhythm of learning alongside stability of practice allows lessons to be absorbed and improvements routinised. doing good things well is better than doing perfect things sporadically and helps address the widespread concern that there is insufficient time for qi by making the time commitment more predictable and manageable. the benefit of persistence over time is also relevant to the improvement architecture more widely (øvretveit, n.d.; and ham et al., 2016). rcvs knowledge has identified five key areas for action and focusing in this way should help achieve stability (rcvs knowledge, 2017). the example of human healthcare improvement in scotland is instructive in showing that it can take many years for an improvement approach to mature within a healthcare system (the scottish government, 2018). providing a platform to support interpersonal engagement are reported by participants to be very powerful (ling et al., 2018). there is an important exception to the general benefit of consistency and continuity. from time to time there may be issues (perhaps identified through clinical audit) that identify a problem of quality but appear to be immune to merely persisting with existing qi approaches. this is often because they are incompletely understood or because key stakeholders are mis-aligned. under these circumstances, a one-off improvement lab designed to fully interrogate the problem and co-design solutions with key stakeholders has the potential to unlock chronic and deep-set problems (the health foundation, 2019). however, this would require additional resources, including the skills required to deliver such an approach. the evidence presented here suggests that ‘nudging the dial’ to ramp up the role of qi activities is broadly supported, is believed to produce benefits for animals, and is believed to be achievable. we believe that we have presented here some steppingstones for delivering this change but we equally recognise that the engagement and enthusiasm of the veterinary profession will be key to future progress.   footnotes [1] this would include identifying areas for improvement through significant event auditing, clinical auditing and benchmarking. embedding change through checklists, guidelines and protocols. measuring the success of that change through clinical audits and benchmarking. these steps should be repeated continuously. a useful directory of tools for quality improvement can be found here: https://www.hqip.org.uk/wp-content/uploads/2021/01/final-quality-improvement-qi-tools-09-12-20.pdf [2] https://www.rand.org/randeurope.html [3] this will be referred to as the rcvs code of professional conduct throughout the remainder of this article. [4] for the purpose of this research, the veterinary profession includes veterinary surgeons, veterinary nurses and veterinary managers. [5] by other stakeholders, the research team mean any organisation involved in the veterinary sector, such as universities and other educational institutions, individual veterinary practices and team members, professional veterinary organisations, the veterinary client mediation service, cpd providers and practice management system (pms) providers, among others. [6] while these were randomly selected, the researchers ensured that the individuals represented a broad profile of the profession including those who treat small animals; farm animals; equine; pss-accredited practice; non-pss-accredited practice; general practice; hospital; those from corporate or independent practices; veterinary surgeons, nurses; and practice managers. [7] see: https://www.qsrinternational.com/nvivo-qualitative-data-analysis-software/home [8] vetpol, mrcvsonline; vnonline; vet community; vetnurse; and vetsurgeon are online news forums for the veterinary profession. [9] these numbers do not add up to 100% as three individuals (0.64%) did not complete this question and 8.07% (38 people) reported that they were not aware of the clinical governance standards of the pss. [10] these numbers do not add up to 100% as three individuals (0.64%) did not complete this question and 9.13% reported that they were unaware of the clinical governance section of the rcvs code of professional conduct. [11] two participants selected the option ‘prefer not to say’ when asked for their age and these results are not included in this graph. there were 27 people in the 18–24 group, 182 people in the 25–34 group, 150 people in the 34–44 group, 78 people in the 45–54 group, and 29 people in the 55–64 group. the large percentage of those aged 65+ spending more than 10 days on qi is due to the small sample size (only three participants were in this age group). [12] it is important to note that the research team did not explicitly ask this question in the interviews or survey, so participants may not have thought to share information on this. [13] this adds up to more than 100% as participants could select more than one barrier.   conflict of interest the authors declare no conflicts of interest. this was funded in full by rcvs knowledge. acknowledgements: many thanks to all participants who contributed to this research.   references practice facilitation handbook. module 4: approaches to quality improvement. agency for healthcare research and quality. [online] available from: https://www.ahrq.gov/ncepcr/tools/pf-handbook/mod4.html [accessed 1/2/2021] ballantyne, h. (2016).beyond the nursing care plan: an introduction to care bundles.veterinary nursing journal. 31(2), 43– doi: https://doi.org/10.1080/17415349.2015.1127787 batalden, p. b. & davidoff, f. (2007). what is “quality improvement” and how can it transform healthcare? bmj quality & safety. 16(1), 2–3. doi: http://dx.doi.org/10.1136/qshc.2006.022046 cvs group publishes quality improvement and clinical governance report. cvs group plc. 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(2017). safety culture: the nottingham veterinary safety culture survey (nvscs). veterinary record. 180(19), 472. doi: https://doi.org/10.1136/vr.104215 2. burford, j. & brennan, m. (2018). investigating quality improvement methods in equine clinical practice. find a phd. [online] available from: https://www.findaphd.com/phds/project/investigating-quality-improvement-methods-in-equine-clinical-practice/?p96322 [accessed 04 may 2021] 3. cvs group plc. (2018). quality improvement and clinical governance. [online] available from: https://www.cvsukltd.co.uk/wp-content/uploads/2018/12/cvs-group-plc-qi-report-2018.pdf [accessed 29 july 2019] 4. anicura. (2018). quality & sustainability report 2018. [online] available from: https://www.anicuragroup.com/globalassets/group/documents/quality/anicura---quality-and-sustainability-report-2018.pdf [accessed 29 july 2019] 5. rcvs. (2017). strategic plan 2017–2019. [online] available from: https://www.rcvs.org.uk/how-we-work/the-role-of-the-rcvs/strategic-plan/strategic-plan-2017-2019/ [accessed 29 july 2019] 6. rcvs. code of professional conduct for veterinary surgeons. [online] available from: https://www.rcvs.org.uk/setting-standards/advice-and-guidance/code-of-professional-conduct-for-veterinary-surgeons/ [accessed 29 july 2019] 7. rcvs. code of professional conduct for veterinary nurses. [online] available from: https://www.rcvs.org.uk/setting-standards/advice-and-guidance/code-of-professional-conduct-for-veterinary-nurses/ [accessed 29 july 2019] 8. rcvs. about the practice standards scheme. [online] available from: https://www.rcvs.org.uk/setting-standards/practice-standards-scheme/about-the-practice-standards-scheme/ [accessed 04 may 2021] 9. rcvs & work psychology group. (2018). enhancing and supporting veterinary capabilities: a consultation on graduate and professional development phase outcomes. [online] available from: https://www.rcvs.org.uk/news-and-views/publications/graduate-outcomes-consultation/ [accessed 29 july 2019] 10. rcvs. (2017). rcvs facts (2017). [online] available from: https://www.rcvs.org.uk/news-and-views/publications/rcvs-facts-2017/?destination=%2fnews-and-views%2fpublications%2f [accessed 29 july 2019] 11. rcvs (2015) awarding organisation and higher education institution handbook. london: rcvs   12. rcvs. (2016). rcvs news (november 2016). [online] available from: https://www.rcvs.org.uk/news-and-views/publications/rcvs-news-november-2016/?destination=%2fnews-and-views%2fpublications%2f%3fp%3d3 [accessed 04 may 2021] 13. rcvs. certificate in advanced veterinary practice (certavp). [online] available from: https://www.rcvs.org.uk/lifelong-learning/postgraduate-qualifications/certificate-in-advanced-veterinary-practice-certavp/ [accessed 29 july 2019] 14. rcvs. (2018). proposed new framework for post-registration qualifications for veterinary nurses. [online] available from: https://www.rcvs.org.uk/news-and-views/our-consultations/vn-post-registration-qualifications/ [accessed 29 july 2019] 15. rcvs. (2019). advanced practitioner status. [online] available from: https://www.rcvs.org.uk/lifelong-learning/professional-accreditation/advanced-practitioner-status/ [accessed 29 july 2019] 16. rcvs. the role of the rcvs. [online] available from: https://www.rcvs.org.uk/how-we-work/the-role-of-the-rcvs/ [accessed  04 may 2021] 17. rcvs. (2019). advancement of the professions committee. [online] available from: https://www.rcvs.org.uk/who-we-are/committees/advancement-of-the-professions-committee/ [accessed 04 may 2021] 18. rcvs. professional development phase (pdp). [online] available from: https://www.rcvs.org.uk/lifelong-learning/professional-development-phase-pdp/ [accessed 04 may 2021] 19. vet futures project board. (2015). taking charge of our future: a vision for the veterinary profession for 2030. [online] available from: https://www.vetfutures.org.uk/resource/vet-futures-report/ [accessed 04 may 2021] 20. vet futures action group. (2016). vet futures action plan 2016–20. [online] available from: https://www.vetfutures.org.uk/resource/vet-futures-action-plan-2016-20/ [accessed 04 may 2021] 21. rcvs knowledge. (2017). is quality your cup of tea? [online] available from: http://www.rcvskblog.org/is-quality-your-cup-of-tea/ [accessed 04 may 2021] 22. rcvs knowledge. (2017). building a learning culture: how quality improvement can help. [online] available from: http://www.rcvskblog.org/building-a-learning-culture-how-quality-improvement-can-help/ [accessed 04 may 2021] 23. taylor, w. (2017). quality improvement and the nhs: lessons for vets. [online] available from: http://www.rcvskblog.org/quality-improvement-and-the-nhs-lessons-for-vets/  [accessed 04 may 2021] 24. northway, l. (2018). clinical audits – a veterinary nurse’s perspective. [online] available from: http://www.rcvskblog.org/clinical-audits-a-veterinary-nurses-perspective/ [accessed 04 may 2021] 25. rcvs knowledge. (2013). strategic plan 2017–2022. [online] available from: https://knowledge.rcvs.org.uk/document-library/rcvs-knowledge-strategic-plan/ [accessed 29 july 2019] 26. rcvs knowledge. (2019). quality improvement. [online] available from: https://knowledge.rcvs.org.uk/quality-improvement/ [accessed 29 july 2019] 27. rcvs knowledge. oncourse. [online] available from: https://oncourse.rcvsk.org/ [accessed 29 july 2019] 28. rcvs knowledge. vetaudit. [online] available from: https://vetaudit.rcvsk.org/ [accessed 13 july 2019] 29. rcvs knowledge. (2017). skills day: quality improvement in practice. [online] available from: https://knowledge.rcvs.org.uk/quality-improvement/quality-improvement-project/skills-day-quality-improvement-in-practice/ [accessed 04 may 2021] 30. rcvs knowledge. (2018). rcvs knowledge at bsava congress 2018. [online] available from: https://knowledge.rcvs.org.uk/news-and-events/events/rcvs-knowledge-at-bsava-congress-2018/ [accessed 04 may 2021] 31. rcvs knowledge. (2017). quality improvement in veterinary practice. [online] available from: https://www.youtube.com/watch?app=desktop&v=yx-epkdc3pq&feature=youtu.be [accessed 04 may 2021] 32. rcvs knowledge. (2018). complication rates of neutering revealed in national audit. [online] available from: https://knowledge.rcvs.org.uk/news-and-events/news/complication-rates-of-neutering-revealed-in-national-audit/ [accessed 04 may 2021] 33. app advice. the vds vetsafe system. [online] available from: https://appadvice.com/app/the-veterinary-defence-society/1378187997 [accessed 04 may 2021] 34. viner, b. (2010). success in veterinary practice: maximising clinical outcomes and personal well-being. wiley-blackwell. 35. oxtoby, c. & mossop, l. (2019). blame and shame in the veterinary profession: barriers and facilitators to reporting significant events. veterinary record. 184(16), 501. doi: https://doi.org/10.1136/vr.105137 36. rcvs. ten common pitfalls and how to avoid them. unpublished. 37. mosedale, p. (2017).  learning from mistakes: the use of significant event audit in veterinary practice. companion animal. 22(3). doi: https://doi.org/10.12968/coan.2017.22.3.140 38. waine, k. (2017). clinical audit experiences of veterinary surgeons undertaking farm animal work in the uk. veterinary evidence. 2(3). doi: https://doi.org/10.18849/ve.v2i3.137 39. turner, m. (2016). mistakes, errors and foul-ups: practice-based evidence for evidence based practice. veterinary evidence. 1(4). doi: https://doi.org/10.18849/ve.v1i4.69 40. rose, n., toews, l. & pang, d.s.j. (2016). a systematic review of clinical audit in companion animal veterinary medicine. bmc veterinary research. 12(40). doi: https://doi.org/10.1186/s12917-016-0661-4 41. viner, b. (2012). clinical governance. bsava manual of small animal practice management and development. 501–520.  42. oxtoby, c. & mossop, l. (2016). checklists and clinical governance: learning from the nhs. in practice. 38(8), 408–410. doi: https://doi.org/10.1136/inp.i4561 43. ballantyne, h. (2016). beyond the nursing care plan: an introduction to care bundles. veterinary nursing journal. 2016. 31(2),43–46. doi: https://doi.org/10.1080/17415349.2015.1127787 44. oxtoby, c. & mossop, l. (2016). implementing checklists in practice. in practice. 38(9):463–464. doi: https://doi.org/10.1136/inp.i4700 45. clapham, l. (2015). surgical safety: can a checklist really save lives? veterinary nursing journal. 30(7):194–198. doi: https://doi.org/10.1080/17415349.2015.1042415   appendix 2 – five key systematic reviews covering qi in human healthcare reviewed for the study: amaratunga, t. & dobranowski, j. (2016). systematic review of the application of lean and six sigma quality improvement methodologies in radiology. journal of the american college of radiology. 13(19), 1088–1095. doi: https://doi.org/10.1016/j.jacr.2016.02.033 knudsen, v., bering laursen, h.v., ehlers, l.h. & mainz, j. (2017). there is a need for improvement of quality improvementa systematic review of the pdsa method in qi studies. international journal for quality in health care. 29(suppl_1), 45. doi: https://doi.org/10.1093/intqhc/mzx125.72 powell, a., rushmar, r. & davies, h. (2009). a systematic narrative review of quality improvement models in health care. quality improvement scotland. [online] available from: https://www.crd.york.ac.uk/crdweb/showrecord.asp?id=32011000041&id=32011000041 [accessed 04 may 2021] janamian, t., upham, s.j., crossland, l. & jackson, c. (2016). quality tools and resources to support organisational improvement integral to high-quality primary care: a systematic review of published and grey literature. medical journal of australia. 204(57), s22–s28. doi: https://doi.org/10.5694/mja16.00113 wells, s., tamir, o., gray, j., naidoo, d., bekhit, m. & goldmann, d. (2018). are quality improvement collaboratives effective? a systematic review. bmj quality & safety. 27(3), 226–240. doi: http://dx.doi.org/10.1136/bmjqs-2017-006926   appendix 3 – organisations directly invited to participate in the survey: british association of veterinary emergency and critical care (bavecc) companion care/vets4pets veterinary client mediation services (provided by nockolds solicitors) veterinary management group (vmg) british cattle veterinary association (bcva) cvs group plc people's dispensary for sick animals (pdsa) the veterinary defence society (vds) beaumont sainsbury animal hospital department for environment, food and rural affairs (defra) queen mother hospital for animals vetpartners british equine veterinary association (beva) dogs trust royal college of veterinary surgeons (rcvs) veterinary schools council blue cross veterinary evidence rcvs knowledge vetcompass animal surveillance british small animal veterinary association (bsava) the federation of independent veterinary practices (fivp) royal society for the prevention of cruelty to animals (rspca) davies veterinary specialists british veterinary association (bva) goddard veterinary group small animal veterinary surveillance network (savsnet) vetled british veterinary hospital association (bvha) independent vetcare the society of practising veterinary surgeons (spvs) vets now ltd british veterinary nursing association (bvna) infocus stowe veterinary group vn futures centre for evidence-based veterinary medicine (cevm) kernow veterinary group university of liverpool wendover heights veterinary centre city road vets linnaeus group university of nottingham xlvets uk ltd newnham court equine clinic medivet damson house vets   intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in dogs with pyothorax does medical management alone, invasive medical management, or surgical management result in better long-term outcome? a knowledge summary by barnaby dean bvsc, mrcvs 1* sophie adamantos bvsc, certva, dacvecc, dipecvecc, mrcvs, fhea 1 1university of bristol, senate house, tyndall ave, bristol bs8 1th *corresponding author (barneydean@gmail.com) vol 2, issue 2 (2017) published: 05 may 2017 reviewed by: shailen jasani (ma vetmb mrcvs dacvecc) and bruce smith (bvsc ms fanzcvs dacvs) next review date: 05 may 2019 doi: 10.18849/ve.v2i2.87 clinical bottom line currently available literature on canine pyothorax management is low quality, so it is difficult to draw meaningful conclusions from it. with this in mind, however, the literature does suggest that invasive medical management (thoracic drainage and lavage via in-dwelling thoracostomy tubes, and antimicrobial therapy) and surgical management (in conjunction with antimicrobial therapy) of canine pyothorax provide better long-term survival rates compared to non-invasive medical management (antimicrobial therapy, with or without thoracocentesis) alone. more definitive conclusions cannot be made until higher quality evidence (prospective, randomised, blinded) is available on the topic. question in dogs with pyothorax does medical management alone, invasive medical management, or surgical management result in better long-term outcome? clinical scenario a five-year old male neutered english springer spaniel is presented with a two-day history of progressive dyspnea and exercise intolerance. clinical examination reveals tachypnea, bilaterally reduced heart sounds, and pyrexia. basic haematology and biochemistry findings are consistent with infection, thoracic radiography findings are consistent with bilateral pleural effusion, and thoracocentesis findings are consistent with pyothorax. should the patient be treated medically or surgically? summary of the evidence bach (2015) population: nineteen dogs with pyothorax confirmed by either the presence of intracellular bacteria on cytological examination, or a positive bacterial culture of pleural fluid, that underwent medical management, early surgery (less than 48 hours following hospitalisation) or late surgery (more than 48 hours following hospitalisation). sample size: nineteen dogs. intervention details: thirteen out of 19 dogs had bilateral thoracostomy tubes placed (invasive medical management), and intermittent pleural lavage (with 19.0 +/12.1ml/kg warmed crystalloid solution) and drainage was performed two-to-four times daily. five dogs were treated surgically (11 median sternotomies, one lateral thoracotomy). one dog was treated as an outpatient with antibiotics following thoracocentesis. antibiotics used were most commonly enrofloxacin and ampicillin for 10 to 120 days (median 33 days). study design: retrospective single-centre data analysis. outcome studied: overall cost of treatment, survival rate, and duration of hospitalisation. main findings (relevant to pico question): seven patients were in the medical treatment group, five were in the early surgery group, and seven were in the late surgery group. median cost of treatment was £1933 (range £256-2386) for the medical group, £2930 (range £2549-5246) for the early surgery group, and £6059 (range £3783-7208) for the late surgery group. all patients in all patient groups survived to discharge and none had experienced recurrence of pyothorax by six months following discharge. limitations: the study is retrospective, with a small number of cases. the results cover a 10-year study period. the study was performed on data from a single referral teaching hospital. some patients (number not stated) were converted to the surgical group from the medical group which adds bias to the results. the authors’ exclusion criteria excluded dogs that died within 24-hours of hospitalisation. the severity of clinical signs and intensity of each treatment are not discussed or compared between patients groups. little attention is given to specific treatment protocols. boothe (2010) population: forty-six dogs with pyothorax confirmed by either the presence of intracellular bacteria in pleural fluid or tissue, bacteria recovered via culture of pleural fluid, or both, that underwent either non-surgical non-invasive, non-surgical invasive or surgical treatment. sample size: forty-six dogs. intervention details: all dogs were treated with at least one antibiotic, plus thoracocentesis (non-invasive medical, n=7), a thoracostomy tube (invasive medical, 26) with or without pleural lavage and heparin, or a thoracotomy (surgical, 13) and thoracostomy tube with or without pleural lavage and heparin. most commonly used empirical (pre-culture and sensitivity) antibiotics were trimethoprim-sulfonamide (n=30), enrofloxacin (24), amoxicillin (23), ampicillin (20), and penicillin (10). study design: retrospective single-centre case series. outcome studied: short-term (survival to discharge) and long-term (survival to 12 months following discharge) survival rate. main findings (relevant to pico question): treatment was non-surgical non-invasive in sevenpatients, non-surgical invasive in 26 patients, and surgical in 13 patients. overall short-term survival rate was 74% (n=34). short-term survival was 29% (2) for non-surgical non-invasive patients, 77% (20) for non-surgical invasive patients, and 92% (12) for surgical patients. most commonly used antibiotics were trimethoprim-sulfonamide (n=30), enrofloxacin (24), amoxicillin (23), ampicillin (20), and penicillin (10). five dogs received one antibiotic, 13 dogs received two, five dogs received three, 11 dogs received four, 10 dogs received five, and two dogs received seven, in various combinations. overall long-term survival rate was 63% (n=26). long-term survival was 29% (two) for non-surgical non-invasive patients, 71% (17) for non-surgical invasive patients, and 70% (7) for surgical patients. recurrence occurred in three non-surgical invasive patients, and four surgical patients. limitations: the study is retrospective, with a small number of cases. the results cover a 19-year study period. the study was performed on data from a single referral teaching hospital. no criteria for treatment selection are stated. there is significant variation in treatment protocols used between cases within each group. demetriou (2002) population: fifty cases (36 dogs and 14 cats) with confirmed pyothorax were evaluated from five referral institutions in the uk and ireland. sample size: thirty-six dogs and 14 cats. intervention details: seven dogs were treated surgically. thoracostomy tubes (invasive medical management) were placed in 48 of the 50 cases. forty-two of these underwent pleural lavage using 0.5-6l fluid (either isotonic saline, isotonic saline with intrapleural antibiotic solutions (ampicillin and/or metronidazole), or compound sodium lactate. all animals were given antibiotic therapy. most commonly used agents were metronidazole, ampicillin, andenrofloxacin/marbofloxacin. study design: retrospective multi-centre case series. outcome studied: complete resolution of pyothorax following the first treatment after presentation, with no evidence of recurrence at the time of re-evaluation. main findings (relevant to pico question): six dogs died during the study period, of which one was treated surgically and five were treated medically. all remaining canine patients survived without recurrence at the end of the five-year study period. no patients required surgical treatment after medical therapy. two surgically-treated cases from which no foreign bodies could be found did not have chest drains placed. survival beyond 48-hours after presentation is a positive prognostic indicator for canine pyothorax. limitations: the study is retrospective, with a small number of cases. the results cover a five-year period. the study was performed using data from five referral teaching hospitals. data is poorly presented, preventing direct comparisons between medically and surgically managed dogs and cats. frendin (1997) population: nine dogs with thoracic empyema of unknown origin. sample size: nine dogs. intervention details: all dogs were treated with antibiotic therapy and intermittent thoracic drainage. five dogs had surgery performed following unsuccessful invasive medical management. study design: retrospective single-centre case series. outcome studied: patient survival. main findings (relevant to pico question): two dogs were euthanised during the early treatment phase. seven dogs appeared clinically well within two to three weeks following cessation of thoracic drainage. in five dogs (three medical, two surgical cases) there had not been any sign of recurrence three-to-nine (mean five) years following treatment. the remaining two dogs either died despite attempted further management of recurrence, or were euthanised after a thoracic mass was identified. limitations: the study is retrospective, with a small number of cases. the study is 20 years old. cases are from a single hospital. the results cover a five year period, with some cases reported from 29 years ago. there is minimal statistical analysis. johnson (2006) population: fifteen dogs with pyothorax who were treated successfully with medical management and a single thoracocentesis. sample size: fifteen dogs. intervention details: unilateral thoracocentesis (non-invasive medical management) was performed in all 15 cases in conjunction with antibiotic therapy. study design: retrospective single-centre case series. outcome studied: survival and lack of relapse as cessation of antibiotic therapy (six to 16 weeks, mean nine weeks) and long-term follow up (mean 27 months). main findings (relevant to pico question): one patient was excluded because a fluid-filled mass (abscess) was identified and surgery was performed. duration of clinical signs prior to referral was three days to seven months, median four weeks. all dogs were considered clinically normal by owners at cessation of antibiotics. there was no relapse, and all dogs were considered clinically normal at long-term follow up. limitations: the study is retrospective, with a small number of cases. the results cover a seven-year period. the results are from a single referral hospital. only one of the 15 cases had concurrent thoracic pathology identified (adhesions). there is no explanation of how long-term assessment is performed. only seven effusions were culture positive, so antibiotic therapy was empiricalrather than based on culture results in eight cases. lee (2014) population: dogs with pyothorax. sample size: not applicable. intervention details: not applicable. study design: literature review. outcome studied: not applicable. main findings (relevant to pico question): pyothorax in patients treated with antibiotics alone or no treatment is often fatal. the primary complication of various treatments is recurrence of pyothorax. no definitive algorithms are presented by previous studies for management of pyothorax in dogs. there is significant treatment failure in canine pyothorax. no randomised, prospective studies are available. one-hundred percent success has been reported in a case series of 15 canine patients where a single ultrasound-guided thoracocentesis was performed, followed by antibiotic therapy for a minimum of six weeks. repeated thoracic lavage and draining via indwelling thoracic drains is suggested by multiple studies. of six cases of canine pyothorax managed surgically in one study, surgery was indicated as a result of: diagnostic imaging results suggestive of a foreign body in three cases, draining sinus in one case, and pleural or mediastinal masses in two cases. limitations: the review adds nothing new to the literature. very few of the reviewed papers directly compare medical and surgical management of canine pyothorax. macphail (2007) population: dogs and cats with pyothorax. sample size: not applicable. intervention details: not applicable. study design: literature review. outcome studied: not applicable. main findings (relevant to pico question): the prognosis for pyothorax is highly variable, and the argument of medical versus surgical therapy has yet to be decided. mortality rates vary from 0% (in both non-invasive and invasive medical case series) to 42% (in a combined invasive medical and surgical case series. recurrence rates are highly variable, but thought to be higher for actinomyces spp or nocardia spp infections. thoracoscopy should be considered in the future for both diagnostic and treatment purposes. limitations: the review adds nothing new to the literature. very few of the reviewed papers directly compare medical and surgical management of canine pyothorax. meakin (2013) population: fifteen dogs who developed pyothorax following thoracic surgery, confirmed as neutrophilic inflammation within the pleural cavity based on cytological evidence of bacteria within neutrophils and/or a positive bacterial culture of pleural fluid, within 30 days of surgery. sample size: fifteen dogs. intervention details: all dogs received antibiotics and thoracic drainage via thoracostomy drains (invasive medical management). two dogs underwent thoracic lavage. all dogs received broad-spectrum antibiotics prior to culture and sensitivity results, after which appropriate antibiotics were administered as indicated (antibiotics used are not stated). study design: retrospective single-centre case series. outcome studied: prevalence, outcome and risk factors for postoperative pyothorax undergoing thoracic surgery. main findings (relevant to pico question): fifteen dogs (6.5%) out of 232 dogs undergoing thoracic surgery developed pyothorax following surgery. no dogs underwent a second surgical procedure to treat pyothorax. six (40.0%) died, four (26.7%) were euthanised, five (33.3%) survived to discharge. diagnosis of idiopathic chylothorax, preoperative intrathoracic biopsy and preoperative thoracocentesis were identified as independent risk factors for developing postoperative pyothorax. limitations: the study is retrospective, with a small number of cases. long-term follow-up is not available for all cases. patients were suffering from a wide-range of concurrent pathology. there is no mention of the number of cases being treated for pyothorax in the first place. patients were only treated medically so no direct comparison between medical and surgical management can be made. the study is based on data from a single hospital. pyothorax may have been underreported by referring veterinary surgeons after discharge from the referral hospital. mellanby (2002) population: eighty-one dogs with pleural and mediastinal effusions. sample size: eighty-one. intervention details: dogs were treated either with placement of chest drains (invasive medical management) and pleural lavage at least twice daily for five to seven days, and were administered broad spectrum antibiotics (antibiotics used not stated) for between four and eight weeks, or with surgery. study design: retrospective single-centre case series. outcome studied: disease free survival time. main findings (relevant to pico question): thirteen of 81 cases were suffering from pyothorax. treatment was attempted in 11 of the 13 cases. three of these 11 cases died either during the placement of chest drains or within 48 hours of exploratory thoracotomy. seven of the remaining eight cases recovered completely after initial treatment, and one dog died five weeks following surgery. five of the eight dogs who were treated were managed by placement of chest drains which were lavaged at least twice daily for between five and seven days and were administered broad spectrum antibiotics for between four and eight weeks. the three other dogs were treated surgically. limitations: the study is retrospective, with only a small number of cases suffering from pyothorax. cases are taken from a single hospital. cases cover an eight year period. the study does not aim to directly compare medical and surgical management of pyothorax, so data (including details or medical management) and comparisons are limited. piek (2000) population: nine dogs with pyothorax diagnosed through history, physical examination, and radiographic and/or ultrasonographic examination of the thorax. sample size: nine dogs. intervention details: after culture and sensitivity, all dogs were treated with antibiotics: either co-amoxyclav alone (n=6), co-amoxyclav and enrofloxacin (1), metronidazole (1), co-amoxyclav and metronidazole (1). all dogs were also treated with thoracic drains (invasive medical management), and administered thoracic lavage for seven to 12 days (median nine days). study design: retrospective single-centre case series. outcome studied: disease free survival at four week follow up examination, seven week follow up examination, and client telephone contact at least six months following hospitalisation. main findings (relevant to pico question): at a four week follow-up all dogs were free of clinical signs, and clinical examination was unremarkable. thoracic radiography was unremarkable in three dogs at four weeks. in six of the dogs, pleural lines and small amounts of pleural fluid were still evident at four weeks. five of these dogs were available for clinical examination and thoracic radiography three weeks later, which were unremarkable. in eight dogs, follow up client telephone contact revealed no reported relapse. limitations: the study is retrospective, with a small number of cases. the study is 17 years old. cases are from a single hospital. there is minimal statistical analysis. underlying causes are not discussed. robertson (1983) population: twenty-two dogs with thoracic empyema confirmed by radiographic demonstration of thoracic free fluid and bacterial identification by examination of thoracic aspirates. sample size: twenty-two dogs. intervention details: dogs were treated with antibiotics and either thoracocentesis (non-invasive medical management), chest drain placement (invasive medical management), or surgery. study design: retrospective single-centre case series. outcome studied: survival time, up to time of writing. main findings (relevant to pico question): sixteen patients survived to discharge, of which two were euthanised (one treated non-invasive medically, the other treated invasive medically) within four months due to recurrence of signs. survival time ranges from zero days (death during investigations) to seven years (up to time of writing). two patients underwent surgical management, only after medical management alone had failed. limitations: the study is retrospective, with a small number of cases. the study is 23-years old. there is minimal statistical analysis. there is inconsistent data available for all cases. long-term follow-up is not available for all cases. cases only became surgical after medical therapy failed. the study is based on data from a single hospital. rooney (2002) population: twenty-six dogs with pyothorax confirmed by cytological examination of pleural fluid, or by positive bacterial culture of a sample of pleural fluid. sample size: twenty-six dogs. intervention details: seven patients received medical treatment alone (non-invasive medical management), 12 patients were treated medically for 2-to-14 days and then underwent surgery and so were considered surgical patients, and the remaining seven dogs underwent surgery within two days of initial presentation. all dogs received intermittent thoracic drainage and lavage. study design: retrospective single-centre case series. outcome studied: disease-free interval for patients treated medically and surgically up to one-year following treatment. main findings (relevant to pico question): patients were disease-free one year following treatment in 25% of medically-managed cases, and 78% of surgically-managed cases. treatment was 5.4 times more likely to fail in medically-managed cases than surgically-managed cases based on disease-free interval hazard ratio. limitations: the study is retrospective, with a small number of cases. the results cover a 10-year period. the study was performed on data from a single referral teaching hospital. those patients that underwent late surgery should be considered as cases of failure of medical therapy. there is significant variation in treatment administered within patient groups. stillion (2015) population: dogs and cats with pyothorax. sample size: not applicable. intervention details: not applicable. study design: literature review. outcome studied: not applicable. main findings (relevant to pico question): overall survival rate in cases of canine pyothorax is 83% (range 29-100%) in literature published between 2000 and 2015. recurrence rates for dogs and cats range from 0-14%, with risk factors for recurrence including infection with nocardia spp or actinomyces spp, and inhalation and migration of plant material. there is no evidence to suggest reliable characteristics that accurately predict patient outcome or long-term survival at initial presentation. antimicrobial therapy in combination with thoracic drainage is generally accepted as the mainstay of therapy. there is a lack of prospective, randomised research. limitations: the review adds nothing new to the literature. very few of the reviewed papers directly compare medical and surgical management of canine pyothorax. appraisal, application and reflection all relevant studies identified that discuss the outcome of medical or surgical management of pyothorax, or directly compare outcomes of both medical and surgical canine pyothorax cases, are either retrospective case series, or literature reviews that do not add new information to the literature. retrospective case series sit low on the hierarchy of evidence, so meaningful clinical conclusions are difficult to draw. it appears that many cases across these studies are initially medically managed first before escalating to surgical management adding significant bias to their results, and every surgical case appeared to have received medical (either invasive, non-invasive, or both) treatment, therefore it remains prudent to consider that some surgically managed cases may have recovered with medical management alone. further to this, it appears that pyothorax aetiology is often the deciding factor when it comes to choice of treatment modality, and this alone may bring about variations in survival rates. there also appears to be a wide range of treatment modalities applied in all studies, even between cases within the same patient groups, and there is rarely any mention of criteria for treatment selection. it appears from consulting the available literature that invasive medical management (thoracic drainage and lavage via in-dwelling thoracostomy tubes and antimicrobial therapy) and surgical management (in conjunction with antimicrobial therapy) of canine pyothorax provide better long-term survival rates compared to non-invasive medical management (antimicrobial therapy, with or without thoracocentesis) alone. however, until higher quality (prospective, randomised, blinded) research directly comparing standardised medical and surgical management of canine pyothorax is made available, it is difficult to draw meaningful conclusions from the available research. methodology section search strategy databases searched and dates covered: cab abstracts via the ovid platform, covering from 1973 to 2016 week 51. medline via the ovid platform, covering from 1946 to 2017. search terms: (dog or dogs or canine) and (empyema or empyema, pleural or pleurisy or pleuritic or pyothorax) dates searches performed: january 8th 2017 exclusion / inclusion criteria exclusion: articles not available in english, single case reports, book chapters, conference proceedings, articles which were not relevant to the pico question, articles listed on but not provided by the searched databases inclusion: articles available in english which were relevant to the pico. articles had to involve more than one animal. literature reviews were included. search outcome database number of results excluded – non english language publication excluded – single case report excluded – book chapter excluded – conference proceedings excluded – irrelevant to pico excluded – paper not accessible total relevant papers cab abstracts 183 58 2 4 5 98 3 13 medline 139 19 1 0 0 106 1 12 total relevant papers when duplicates removed 13 conflict of interest the authors declare no conflicts of interest. references bach, j.f. balakrishnan, a. (2015) retrospective comparison of the costs between medical and surgical treatment of canine pyothorax. canadian veterinary journal, 56 (11) pp. 1140-1143. boothe, h.w. et al. (2010) evaluation of outcomes in dogs treated for pyothorax: 46 cases (1983-2001). journal of the american veterinary medical association, 236 (6), pp. 657-663. http://dx.doi.org/10.2460/javma.236.6.657 demetriou, j.l. et al. (2002) canine and feline pyothorax: a retrospective study of 50 cases in the uk and ireland. journal of small animal practice; 43 (9) pp. 388-394. frendin, j. (1997) pyogranulomatous pleuritis with empyema in hunting dogs. zentralbl veterinarmed a, 44 (3), pp. 167-178. http://dx.doi.org/10.1111/j.1439-0442.1997.tb01098.x johnson, m.s. martin, m.w.s (2006) successful medical treatment of 15 dogs with pyothorax. journal of small animal practice, 48 (1), pp. 12-16. lee, k.c.l (2014) surgical or medical management of pyothorax in dogs? veterinary record, 174 (24), pp. 605-606. http://dx.doi.org/10.1136/vr.g3817 macphail, c.m (2007) medical and surgical management of pyothorax. veterinary clinics of north america, 37 (5), pp. 975-988. http://dx.doi.org/10.1016/j.cvsm.2007.05.012 meakin, l.b. et al. (2013) prevalence, outcome and risk factors for postoperative pyothorax in 232 dogs undergoing thoracic surgery. journal of small animal practice, 54 (6) pp. 313-317. http://dx.doi.org/10.1111/jsap.12064 mellanby, r.j. villiers, e. herrtage, m.e. (2002) canine pleural and mediastinal effusions: a retrospective study of 81 cases. journal of small animal practice, 43 pp. 447-451. piek, c.j. robben, j.h. (2000) pyothorax in nine dogs. the veterinary quarterly, 22 (2), pp. 107-111. http://dx.doi.org/10.1080/01652176.2000.9695035 robertson, s.a. et al. (1983) thoracic empyema in the dog: a report of twenty-two cases. journal of small animal practice, 24 (2), pp. 103-119. http://dx.doi.org/10.1111/j.1748-5827.1983.tb00419.x rooney, m.b. monnet, e. (2002) medical and surgical treatment of pyothorax in dogs: 26 cases (1991-2001). journal of the american veterinary medical association, 221 (1), pp. 86-92. stillion, j.r. letendre, j.a. (2015) a clinical review of the pathophysiology, diagnosis, and treatment of pyothorax in dogs and cats. journal of veterinary emergency and critical care, 25 (1), pp. 113-129. intellectual property rights knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. prognostic value of haematological indices in sea turtles presenting for cold-stunning (sustained hypothermia) | veterinary evidence skip to main content knowledge summary keywords: sea turtle; blood; haematology; biochemistry; cold-stunning; cold-stun; acidosis prognostic value of haematological indices in sea turtles presenting for cold-stunning (sustained hypothermia) mccaide wooten, dvm mpvm1* 1 uc davis school of veterinary medicine, 1 garrod dr., davis, ca 95616, usa * corresponding author email: caide.wooten.dvm@gmail.com vol 8, issue 1 (2023) submitted 10 dec 2021; published: 01 mar 2023; next review: 06 dec 2024 doi: https://doi.org/10.18849/ve.v8i1.561 pico question in sea turtles presenting for cold-stunning (sustained hypothermia), what blood analytes routinely evaluated at intake provide the most prognostic value? clinical bottom line category of research prognosis. number and type of study designs reviewed ten studies were included in this evaluation including the following study designs: eight retrospective case series, one cross-sectional, and one retrospective cohort. strength of evidence weak. outcomes reported the most consistent finding across all included studies in cold-stunned sea turtles was acidosis (suspected both respiratory or metabolic components) characterised by reduced blood ph, elevated partial pressure of carbon dioxide (pco2), and reduced partial pressure of oxygen (po2). however, this finding was not necessarily linked with failure of rehabilitation. rather, sea turtles presenting for cold-stunning that did not survive rehabilitative therapy were typically in extreme states of homeostatic derangement involving acidosis, but often in conjunction with additional abnormalities (e.g. anaemia, sepsis, organ failure or dysfunction, pneumonia, etc.). conclusion as might be expected, the evaluated literature did not reveal a single or series of blood analytes that were definitively linked with the success or failure of rehabilitation in sea turtles presenting for cold-stunning. however, they did identify analytes that may provide the most clinical value in this clinical situation including packed cell volume (pcv), estimated white blood cell count (wbc), total and / or ionised calcium, ph, potassium (k), and lactate. review of the available studies on the topic provides insightful information that can aid clinicians addressing this syndrome to triage and treat affected individuals most effectively. it also elucidated areas of opportunity for further research. how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. the evidence based on the included studies, the most consistent biochemical finding in the blood of marine turtles presenting to rescue and rehabilitation studies for cold-stunning is acidosis, generally characterised by reduced blood ph, elevated partial pressure of carbon dioxide (pco2), and reduced partial pressure of oxygen (po2). at present, a respiratory or metabolic aetiology of this finding is undetermined, but it was suggested in several studies there are likely elements of both components contributing to the common finding given the nature of the syndrome. it should be taken into consideration that nine of the ten studies (innis et al., 2009; powell et al., 2021; stacy et al., 2013; innis et al., 2007; innis et al., 2019; hunt et al., 2012; mcnally & innis, 2020; keller et al., 2012; and rockwell et al., 2017) evaluated here emanated from the same institution (the new england aquarium, boston, ma, usa), and as such are more subject to internal biases. however, this institution is also one of the most likely to be encountering cold-stunned sea turtles given its location along the northwest atlantic, where juvenile and subadult animals with lower surface area-to-body mass ratios are found to frequent shallower coastal waters that are subject to the effects of rapid oceanic, meteorological, and atmospheric changes. also of note is the variability in study designs, outcomes of interest, and population sizes. these factors varied widely between the evaluated manuscripts and the strict evaluation of blood parameters as they pertained to the survival or death of cold-stunned turtles was infrequently the primary objective. only three of seven known species of extant marine turtles were evaluated here, and of those, the kemp’s ridley sea turtle (lepidochelys kempii) is overrepresented, so blind generalisation of the findings herein is not advised; again, this is likely secondary to these reports primarily emanating from one institution and the nature of the kemp’s ridley sea turtle being the most frequently encountered species succumbing to cold-stunning along the new england coastline. further characterisation of blood parameters in cold-stunned sea turtles is needed in additional geographic regions and among additional species, where applicable, for better understanding of the physiological impacts of this syndrome. given projections for increased cold-stunning events secondary to anthropogenically-influenced warming ocean surface temperatures (griffin et al., 2019), opportunities for study and refinement of clinical methods for rehabilitation will only increase. the overall presented evidence is deemed to be of ‘weak’ strength. however, the author finds the included materials to be of utmost academic, and particularly clinical, relevance. summary of the evidence innis et al. (2007) population: cold-stunned kemp’s ridley sea turtles (lepidochelys kempii) presenting to the new england aquarium (usa) rescue and rehabilitation department oct 29–nov 29, 2005. sample size: 26 sea turtles. intervention details: on the day of admission and multiple times through ‘convalescence’, venous blood gas samples were collected aseptically with heparinised syringes and evaluated for ph, pco2, po2, bicarbonate (hco3), plasma osmolality, sodium, potassium, chloride, ionised calcium, ionised magnesium, glucose, lactate, and blood urea nitrogen. ‘convalescent’ turtles were those documented to be swimming in water at 25°c for at least 10 days, discontinued from parenteral fluid therapy for at least 7 days, and eating voluntarily daily for at least 7 days. 20 turtles were evaluated at each time point. 14 sea turtles provided data at both the initial and convalescent time points. six turtles for which paired data were not available provided data at either the initial or convalescent time points. applicable data were corrected to body temperature using species-specific and general correction methods as indicated. study design: retrospective case series. outcome studied: evaluation of differences between presenting and convalescent blood parameters in sea turtles surviving rehabilitation as compared to previously published data in both healthy and hypothermic turtles. main findings (relevant to pico question): blood samples were only analysed for turtles surviving rehabilitation. samples from turtles that did not survive rehabilitation were not included in this study. the data produced under natural conditions were generally in agreement with blood values that had been experimentally derived in sea turtles exposed to a range of temperatures. there were consistent findings of hypermagnesemia, hypocalcaemia, and mild to moderate respiratory and metabolic acidosis among the turtles evaluated. initial blood urea nitrogen (bun) concentrations were significantly lower than convalescent concentrations. initial lactate concentrations were higher than convalescent concentrations in the full data set, but not among paired individuals. limitations: small sample size. strictly juvenile animals (however, inherently the most likely population given this syndrome, species, and geographic location). single cold-stunning event period. only surviving turtles were evaluated. due to study timing, equipment availability, and animal transfers, only 14/26 turtles had both initial and convalescent samples collected. different therapeutic interventions between individuals could potentially affect serial blood values.   innis et al. (2009) population: cold-stunned kemp’s ridley sea turtles (lepidochelys kempii) presenting alive to the new england aquarium (usa) between 2001–2005. sample size: 176 sea turtles. intervention details: blood samples were collected aseptically with un-heparinised syringes, transferred to heparinised blood collection tubes and submitted for evaluation by a commercial laboratory. blood values were categorised as ‘initial’ values (within 5 days of hospitalisation), ‘clinically convalescent’ values, or ‘calculated convalescent’ values. categorisation was dependent on the time of blood sample collection, the case outcome (survived vs died – if died, had to have died within 1 week of initial blood collection), and the clinical status of each turtle. ‘clinically convalescent’ turtles (n = 15) were those that had no concurrent illness based on physical examination and radiographic findings, had completed treatments of fluids and antimicrobials at least 14 days prior to blood sample collection, had been in room temperatures of 70–80°f for at least 14 days prior to blood sample collection, and had eaten daily for at least 14 days prior to blood sample collection. ‘calculated convalescent’ (n = 176) values were calculated using statistical analysis to define the time at which a variable stabilised during rehabilitation. study design: retrospective case series. outcome studied: evaluated blood analytes included estimated white blood cell count (wbc), manual differential, haematocrit, alkaline phosphatase (alp), alanine transaminase (alt), aspartate aminotransferase (ast), creatine kinase (ck), lactate dehydrogenase (ldh), gamma-glutamyl transferase (ggt), albumin, total protein, globulin, bilirubin, blood urea nitrogen (bun), creatinine, cholesterol, glucose, total calcium, phosphorus, chloride, potassium, sodium, and uric acid. main findings (relevant to pico question): initial total calcium, phosphorus, chloride, potassium, sodium, and uric acid concentrations were significantly greater in turtles that died (n = 34) than in turtles that survived (n = 142). clinically convalescent values of bun and total calcium were significantly greater than initial values among survivors. clinically convalescent values of glucose, sodium, and uric acid were significantly less than initial values among survivors. limitations: strictly juvenile animals (however, inherently the most likely population given this syndrome, species, and geographic location). only 15 turtles met the standards to be considered ‘clinically convalescent’. different therapeutic interventions between individuals could potentially affect serial blood values.   anderson et al. (2011) population: cold-stunned green sea turtles (chelonia mydas) retrieved from the shore or near-shore waters of eastern north carolina (usa) nov 2008, feb 2009, and dec 2009; control blood samples were collected from healthy green sea turtles caught in pound nets in conjunction with a tag-and-release study in core sound and back sound near harker’s island, north carolina in aug 2009, june 2010, and sept 2010. sample size: 34 sea turtles. intervention details: blood samples were collected aseptically with un-heparinised syringes and immediately evaluated for venous ph, pco2, po2, bicarbonate, and ionised calcium; packed cell volume (pcv) / serum total solids (ts) were evaluated after collection; estimated total white blood cell count (wbc), manual differential counts, and a serum biochemistry panel were evaluated by a commercial laboratory. cold-stunned turtles that were included in the study were those that: were recovered with similarly affected turtles following the passage of cold fronts during the periods of study, were comatose or near comatose, had no other evidence of trauma or disease, had a cloacal temperature <14°c, were live stranded, were examined by a veterinarian, and had blood samples collected prior to rewarming on the day of stranding. applicable data were corrected to body temperature using species-specific and general correction methods as indicated. study design: cross-sectional study. outcome studied: evaluation of differences in blood parameters between cold-stunned sea turtles (n = 22) at presentation and a healthy control population (n = 12). main findings (relevant to pico question): all of the evaluated cold-stunned turtles survived to release except for one (21/22 [95.5%]). no significant differences in haematologic parameters were identified between the control and cold-stunned populations. cold-stunned turtles had significantly lower total solids, serum total protein, albumin, glucose, total calcium, ionised calcium, sodium, chloride, and potassium values than control turtles. cold-stunned turtles had significantly higher phosphorous, blood urea nitrogen, and uric acid values than control turtles. cold-stunned turtles were mildly acidotic (uncharacterised as respiratory or metabolic). limitations: control population not sampled in the same season as sample population. small sample size. strictly juvenile animals (however, inherently the most likely population given this syndrome, species, and geographic location). all but one turtle survived, and the individual data for the deceased turtle is not explicitly stated. different therapeutic interventions between individuals could potentially affect serial blood values.   hunt et al. (2012) population: cold-stunned kemp’s ridley sea turtles (lepidochelys kempii) admitted to the new england aquarium (usa) rescue and rehabilitation department. all sea turtles stranded oct–dec on the on the northern shore of cape cod from 2002–2008. sample size: 56 sea turtles, 87 plasma samples. intervention details: multiple times through rehabilitation, venous blood gas samples were collected aseptically with heparinised syringes for analysis. collection days generally ranged within days 0–3 and 18–95 (i.e., ‘admission’ and ‘recovery’ samples, respectively). samples were evaluated for corticosterone and free thyroxine using validated commercial assay kits. glucose was recorded from either the same blood samples as the hormone assays or the nearest collected sample (majority within 7 days). white blood cell count (wbc) was assessed from separate samples attained within 2 days of admission or 7 days of recovery hormone samples. activity and feeding behaviour were assessed daily. turtles were characterised as ‘survivors’ (n = 31) if they lived until release or transfer to another institution. all others were considered ‘non-survivors’ (n = 25). study design: retrospective case series. outcome studied: evaluation of corticosterone, free thyroxine, glucose, wbc, and activity / feeding behaviours in cold-stunned sea turtles and if there were any associations with survival. main findings (relevant to pico question): no significant differences were identified between corticosterone or free thyroxine levels of surviving and non-surviving turtles on admission. corticosterone was significantly lower and free thyroxine was significantly higher in recovery samples of surviving turtles (not assessable in non-survivors). no differences in glucose were noted across groups. corticosterone was negatively correlated with wbc in admission samples, but showed no correlation with wbc in recovery samples. wbc was significantly higher in survivors on admission than in either non-survivors on admission or in survivors during recovery. during recovery, free thyroxine was significantly and positively correlated with grams of food ingested per day during the week prior to sampling. turtles scored as ‘active’ during the week prior to sampling had significantly higher free thyroxine than turtles scored as ‘quiet’. limitations: corticosterone samples were very likely influenced by handling and transport necessitated during admission. no control group. different therapeutic interventions between individuals could potentially affect serial blood values. strictly juvenile animals (however, inherently the most likely population given this syndrome, species, and geographic location). poor availability of normal data for corticosterone and free thyroxine levels in free-ranging healthy sea turtles. inconsistent sampling regimen (influenced by retrospective nature).   keller et al. (2012) population: cold-stunned kemp’s ridley sea turtles (lepidochelys kempii) admitted to the new england aquarium (usa) from oct 2005 to nov 2009. sample size: 64 sea turtles (32 matched pairs). intervention details: turtles were grouped by survivorship with ‘non-survivors’ characterised as dying of natural causes within the first 3 days of hospitalisation (n = 32). ‘survivors’ were paired with each ‘non-survivor’ based on time of hospitalisation (within 2 days) (n = 32). blood was collected by heparinised syringe and evaluated on day 1 of hospitalisation and day of death for ‘non-survivors’ and corresponding hospitalisation days for ‘survivors’. applicable data were corrected to body temperature using species-specific and general correction methods as indicated. study design: retrospective case series (defined in manuscript as case-control, but controls were a subset of identified cases). outcome studied: variables of interest included blood ph, pco2, po2, haematocrit, anion gap, osmolality, ionised calcium, ionised magnesium, sodium, potassium, chloride, glucose, lactate, bicarbonate, and blood urea nitrogen concentrations. main findings (relevant to pico question): po2, ph, and bicarbonate were significantly lower on day 1 in non-survivors than in survivors. pco2 and potassium concentrations were significantly greater on day 1 in non-survivors than in survivors. compared with survivors, there were significantly greater percentage changes for ionised calcium, potassium, and lactate concentrations in non-survivors. compared with survivors, there were significantly lower percentage changes for ph, glucose, and bicarbonate concentrations in non-survivors. limitations: strictly juvenile animals (however, inherently the most likely population given this syndrome, species, and geographic location). different therapeutic interventions between individuals could potentially affect serial blood values. ‘controls’ are defined as a subset of the population of study rather than being an unaffected population.   stacy et al. (2013) population: cold-stunned kemp’s ridley sea turtles (lepidochelys kempii) that were admitted to the new england aquarium (usa) between oct 2010 and dec 2011 and possessed a complete set of blood analytes at admission. turtles that died had to have died within 7 days of admission (n = 25). sample size: 143 sea turtles. intervention details: blood was collected by heparinised syringe and evaluated on admission prior to any treatments. applicable data were corrected to body temperature using species-specific and general correction methods as indicated. three mortality prediction indices (mpi1, mpi2, mpi3) were created to objectively evaluate and quantify the severity of observed biochemical derangements. within the three indices, analytes with receiver operating characteristic (roc) curve area under the curve (auc) values greater than or equal to 0.7 were included in development of three final mortality prediction indices (mpi4, mpi5, mpi6). study design: retrospective case series. outcome studied: variables of interest included blood ph, pco2, and po2; concentrations of sodium, potassium, chloride, ionised calcium, and glucose; osmolality, and anion gap. main findings (relevant to pico question): the final three mpis were not statistically different from one another in predicting mortality with the highest sensitivity and specificity combination (mpi6) reported at 88% and 80.51%, respectively. analytes included in the final mpis were ph, pco2, po2, and potassium (ph and potassium were included in all three). in conjunction with other clinical factors, the developed mpis could aid clinicians in making evidence-based decisions for cold-stunned sea turtles. limitations: strictly juvenile animals (however, inherently the most likely population given this syndrome, species, and geographic location). mortality rate excludes mortalities that occurred prior to admission. limited geographic range of studied population.   rockwell et al. (2017) population: cold-stunned kemp’s ridley sea turtles (lepidochelys kempii) that stranded on massachusetts (usa) beaches in 2012 and 2013. sample size: 202 sea turtles. intervention details: turtles were included that were found alive and were transported for hospitalisation, as well as turtles that were found alive but died prior to transport. blood was collected by heparinised syringe and evaluated on intake. turtles were categorised as an ‘immediate intake’ if the date of their stranding record (date discovered on the beach) and date of their intake physical exam (date admitted to the hospital) matched (n = 120). if the date of the intake physical exam was on the day after their stranding record, they were categorised as a ‘delayed intake’ (n = 82). outcome results were categorised as: dead on arrival (doa) (n = 22), mortality by natural causes while in care (n = 20), mortality by euthanasia while in care (n = 6), and released (n = 154). turtles were also grouped as released or not released, with not released containing all those that were doa, died naturally, or were euthanised. applicable data were corrected to body temperature using species-specific and general correction methods as indicated. study design: retrospective cohort study. outcome studied: overall effect of hospitalisation timing on cold-stunned kemp’s ridley sea turtles. evaluated blood parameters were packed cell volume (pcv), total solids, sodium, potassium, chloride, ionised calcium, ionised magnesium, glucose, lactate, blood urea nitrogen (bun), haematocrit, pco2, po2, and ph. main findings (relevant to pico question): data were analysed from all 202 turtles, regardless of rehabilitative success. pcv, total solids, and potassium concentration were significantly lower in sea turtles that had an immediate intake compared to those that had a delayed intake. there was no significant difference in outcome (released vs. not released) based on intake time. there was no significant difference in any individual outcome between turtles with immediate intake versus turtles with delayed intake. limitations: potential selection bias for immediate vs delayed hospitalisation (i.e., subjectively ‘worse’ cases immediately presented to hospital earlier), although no statistical differences were noted. strictly juvenile animals (however, inherently the most likely population given this syndrome, species, and geographic location). limited geographic range of studied population. different therapeutic interventions between individuals could potentially affect serial blood values.   innis et al. (2019) population: cold-stunned loggerhead sea turtles (caretta caretta) admitted to new england aquarium (usa) after stranding on cape cod, massachusetts (usa) between 2008 and 2016. sample size: 155 sea turtles. intervention details: turtles with blood data from the first day of hospitalisation were sorted into ‘non-survivor’ (death within first week of hospitalisation) (n = 20) and ‘survivor’ (survived to be released into the wild) (n = 135) groups. blood was collected by heparinised syringe and evaluated on intake for all turtles and at least once more for all ‘survivor’ turtles (the most recent blood data for ‘survivor’ turtles was utilised as the convalescent sample). applicable data were corrected to body temperature using kemp’s ridley sea turtle (lepidochelys kempii) species-specific and general correction methods as indicated. study design: retrospective case series. outcome studied: evaluated blood analytes included blood urea nitrogen, ionised calcium, ionised magnesium, chloride, creatinine, glucose, potassium, lactate, sodium, pco2, po2, ph, and bicarbonate. main findings (relevant to pico question): data were analysed from all 155 turtles, regardless of rehabilitative success. non-survivors had significantly higher glucose, potassium, lactate, and pco2 than survivors at admission. non-survivors had significantly lower ph and po2 than survivors at admission. comparison of initial vs convalescent data for survivors indicated that convalescent turtles had significantly higher blood urea nitrogen (bun), sodium, chloride, ph, and ionised calcium, as well as significantly lower glucose, lactate, and bicarbonate. limitations: the inclusion of data acquired using two different blood analyser units was presumed, though not confirmed, to result in significant differences between 4/13 blood parameters (noted by authors to be of minimal clinical significance). variation in timing of acquisition of convalescent samples. limited geographic range of studied population. use of non-species-specific temperature correction methods (although another marine chelonian species). different therapeutic interventions between individuals could potentially affect serial blood values.   mcnally & innis (2020) population: cold-stunned, primarily subadult, loggerhead sea turtles (caretta caretta) admitted to new england aquarium (usa) after stranding on cape cod, massachusetts (usa) between 2008 and 2016. sample size: 133 sea turtles. intervention details: turtles with blood data from the within the first week of hospitalisation were sorted into ‘initial died’ (first sample, death while hospitalised) (n = 4), ‘initial survived’ (first sample, survived to be released into the wild) (n = 129), and convalescent (last convalescent sample prior to release if released from new england aquarium) (n = 24). blood was collected by heparinised syringe and evaluated by a commercial laboratory. study design: retrospective case series. outcome studied: evaluated blood parameters included estimated white blood cell count (wbc), manual differential, haematocrit, alkaline phosphatase (alp), alanine transaminase (alt), aspartate aminotransferase (ast), creatine kinase (ck), lactate dehydrogenase (ldh), gamma-glutamyl transferase (ggt), albumin, total protein, globulin, bilirubin, blood urea nitrogen (bun), creatinine, cholesterol, glucose, total calcium, phosphorus, chloride, potassium, sodium, and uric acid. main findings (relevant to pico question): convalescent wbc count and absolute and relative heterophil counts were significantly lower than initial values, whereas absolute and relative eosinophil counts were higher. convalescent values for ck, ldh, glucose, and uric acid were significantly lower than initial values. convalescent alt, ast, albumin, ggt, total protein, globulin, bun, total calcium, phosphorus, chloride, and potassium were significantly higher than initial values. limitations: convalescent results only available from 24 turtles. statistical comparison of turtles that died and turtles that survived could not be completed due to limited sample size. initial data not collected until day 3 or 4 of hospitalisation, likely skewing results. different therapeutic interventions between individuals could potentially affect serial blood values.   powell et al. (2021) population: cold-stunned kemp’s ridley sea turtles (lepidochelys kempii) that stranded on massachusetts (usa) beaches between 2008 and 2018 and were identified from historical medical records by use of the search terms: osteomyelitis, osteolysis, osteolytic, osteotomy, arthritis, remodeling, lysis, humerus, humeral, tarsus, tarsal, carpus, carpal, tibia, ulna, radius, scapula, femur, enterococcus, mycobacterium, and serratia. sample size: 25 sea turtles. intervention details: blood was collected and sorted according to timing of radiographic diagnosis of osteolytic lesions (‘initial’ median of 10 days prior to diagnosis, ‘convalescent’ of 22 days after cessation of antimicrobial therapy) evaluated by a commercial laboratory. study design: retrospective case series. outcome studied: characterise osteolytic lesions in cold-stunned kemp’s ridley sea turtles hospitalised for rehabilitation and describe methods used for the management of such lesions. evaluated blood parameters included estimated white blood cell count (wbc), manual differential, haematocrit, alkaline phosphatase (alp), alanine transaminase (alt), aspartate aminotransferase (ast), creatine kinase (ck), lactate dehydrogenase (ldh), gamma-glutamyl transferase (ggt), albumin, total protein, plasma protein, globulin, albumin:globulin ratio, bilirubin, blood urea nitrogen (bun), creatinine (cr), bun:cr ratio, cholesterol, glucose, total calcium, phosphorus, chloride, potassium (k), sodium, na:k ratio, total co2, anion gap, and uric acid. main findings (relevant to pico question): compared with convalescent values, haematologic and biochemical data at the time of radiographic diagnosis were significantly higher for wbc, absolute heterophil, absolute and relative monocyte, absolute and relative basophil, and relative eosinophil counts; plasma chloride and cholesterol concentrations; and alkaline phosphatase activity. plasma albumin, total protein, phosphorus, and potassium concentrations were significantly lower at the time of radiographic diagnosis. limitations: small sample size, initial and convalescent data only available for 21 individuals. the primary objective of this study was not to evaluate blood analyte differences between turtles over time, but rather to evaluate osteomyelitis in cold-stunned turtles. potential for skewing of blood data secondary to all affected individuals having some degree of osteomyelitis. blood was evaluated associated with timing of osteolytic lesion diagnosis rather than time of hospital admission / release. different therapeutic interventions between individuals could potentially affect serial blood values.   appraisal, application and reflection for clarity, the most relevant haematological and biochemical parameters evaluated in the included studies are categorised, analysed, and summarised below: haematological indices elevated packed cell volume* (pcv) values at first blood evaluation of affected turtles were observed in multiple studies. in general, this finding was attributed to haemoconcentration given the tendency for convalescent pcv values to decrease in conjunction with other biochemical indicators of dehydration (innis et al., 2009; keller et al., 2012; and rockwell et al., 2017). keller et al. (2012) and innis et al. (2009) also indicate a wide range of presenting pcvs, with several individuals presenting with anaemia. this finding tended to be associated with individuals that presented with one or more chronic comorbidities and was not necessarily found to be directly associated with cold-stunning.1 regarding the leukogram, a common finding was for cold-stunned animals to present with elevated total white blood cell counts (wbc) (innis et al., 2009; powell et al., 2021; hunt et al., 2012; and mcnally & innis, 2020). mcnally and innis (2020) postulated the elevated wbc observed in their study to most likely be linked with stress given the concurrent findings of heterophilia, lymphopenia, eosinopenia, and increased heterophil-to-lymphocyte ratio. as hunt et al. (2012) showed, a component of corticosterone influence appears likely in cold-stunning cases. interestingly, that study also revealed that non-surviving turtles had significantly lower wbcs at admission compared to survivors; although the finding of total leukopenia was likely multi-factorial in origin, this finding may suggest that leukopenia in the context of cold-stunning could be a negative prognostic indicator. *it should also be acknowledged that the evaluated manuscripts use both ‘packed cell volume’ and ‘haematocrit’ to describe the metric derived by determining the percent volumetric contribution of red blood cells to a whole blood sample following centrifugation. by definition, this is a ‘packed cell volume’. ‘haematocrit’ is the terminology given to the metric generated by multiplying mean cell volume and red blood cell count that have been directly measured by an automated haematology analyser. however, since there are currently no haematology analysers calibrated to evaluate avian or herptile blood samples due to the nucleation of red blood cells in these species, it is not necessarily incorrect to use these terms interchangeably in this context. potassium significantly higher potassium (k) concentrations were reported in non-surviving turtles vs surviving turtles on initial evaluation in three different studies (innis et al., 2009; innis et al., 2019; and keller et al., 2012). k values were also included in all mortality prediction indices (mpis) developed by stacy et al. (2013) with higher values associated with higher index values. all of these studies evaluated potassium in kemp’s ridley turtles, and the corresponding findings were consistent with previously reported potassium findings in cold-stunned sea turtles (carminati et al., 1994; and turnbull et al., 2000). conversely, several studies found initially decreased k levels relative to a control population (anderson et al., 2011) and convalescent values in recovered turtles (powell et al., 2021; and mcnally & innis, 2020). these three studies evaluated green (anderson et al., 2011) and loggerhead (powell et al., 2021; and mcnally & innis, 2020) turtles. the observed discord between studies regarding potassium is not fully explained. the observation by anderson et al. (2011) that differences in potassium concentrations ‘may reflect differences in species, environmental conditions, sampling times, and methodology among studies’ (p. 252) remains poignant given the currently available evidence; animal age (juvenile vs subadult), chronicity of hypothermia, renal functionality, and blood ph status (lutz et al., 1989) are other suggested factors at play. however, what does appear to be clear is that there is a negative prognostic relationship with severe hyperkalaemia in the kemp’s ridley. acid-base indices contrary to what is reported in experimental studies of blood ph and hypothermia in sea turtles (kraus et al., 1980; lutz et al., 1989; and moon et al., 1997), the presence of relative physiological acidosis in cold-stunned turtles was noted across multiple papers (with temperature correction) (anderson et al., 2011; keller et al., 2012; innis et al., 2007; innis et al., 2019; rockwell et al., 2017; and stacy et al., 2013).metabolic and respiratory origins for this finding are both supported due to hypoventilation (with secondary hypercarbia and anaerobic metabolic processes), reduced perfusion at lower body temperatures, reduced / exhausted bicarbonate buffering capacity, and reduced renal clearance. keller et al. (2012) reported significantly increased pco2 and significantly reduced po2, ph, and hco3 in non-surviving turtles compared to those that survived cold-stunning. mortalities in the innis et al. (2019) report were also linked with significantly elevated pco2 and significantly reduced ph and po2 relative to surviving loggerheads. ph, pco2, and po2 were also included across all mpis developed by stacy et al. (2013) where decreased ph, elevated pco2, and decreased po2 increased likelihood of mortality. this evidence supports the use of marked blood gas derangements, when corrected for temperature, for inclusion as a negative prognostic indicator in cold-stunned turtles. calcium relative to convalescent values, initial ionised calcium (innis et al., 2007; innis et al., 2019; and keller et al., 2012) or total calcium (innis et al., 2009; and mcnally & innis, 2020) values of surviving turtles were reduced at presentation across multiple studies. anderson et al. (2011) also noted hypocalcaemia (total and ionised) in cold-stunned individuals relative to controls. interestingly, for turtles that did not survive rehabilitation, keller et al. (2012) reported significant increases in ionised calcium over the first few days of hospitalisation relative to survivors; innis et al. (2007) also showed significantly increased total calcium among non-survivors at presentation relative to survivors. the mechanism for this disparity has not been fully described, but for the turtles that died, the authors suggested that compromised renal function, loss of cation homeostatic mechanisms, compensatory homeostatic responses to acidosis, and / or iatrogenic causes could be factoring into the observation. given these observations, the prognostic value of ionised or total calcium are still undetermined. hypocalcaemia appears that it should be an expected finding in cold-stunned turtles, but further investigation into calcium status as it pertains to this syndrome is needed to describe how changes in calcium over time might be associated with mortality. lactate the use of pointand serial-lactate evaluation as a means of identifying the magnitude of anaerobic metabolism occurring in domestic dogs and cats presenting to emergency facilities has become a classic example of a prognostic test in the veterinary literature in recent years (kohen et al., 2018; saint-pierre et al., 2021; and zacher et al., 2010). in the evaluated studies, lactate values in cold-stunned turtles did not exceed levels reported in healthy sea turtles exposed to forced submergence, extended voluntary dives, or trawl net capture (berkson, 1966; lutz et al., 1985; stabenau et al., 1991; and wood et al., 1984). innis et al. (2007) noted that initial lactate concentrations were significantly elevated relative to convalescent values. a later study showed significantly greater lactate levels in turtles that died vs those that survived (innis et al., 2019). keller et al. (2012) demonstrated evidence of significantly different net positive change of lactate values (despite medical intervention) over the first 2 to 3 days of hospitalisation in cold-stunned turtles that died relative to net negative change in turtles that survived over the same period. this latter study showed that there may be a negative prognostic relationship with serially increasing lactate concentrations following hospitalisation for cold-stunning. more recent evidence has shown that serum lactate levels in clinically healthy loggerhead turtles restrained for health exams increase significantly over 15 minutes of restraint (mones et al., 2021). in this context, a clinician must keep in mind the time at which a lactate sample, or series of samples, was taken in order to appropriately interpret the findings. free thyroxine though only evaluated in one of the included manuscripts (hunt et al., 2012) and not necessarily identified as a prognostic indicator for release, free thyroxine (ft4) is identified here given its potential usefulness in connection to return to normal function in sea turtles being rehabilitated for cold-stunning. hunt et al. (2012) showed that in the week prior to sampling, hospitalised turtles that were documented to be eating every day and scored as ‘active’ (vs ‘quiet’) had significantly increased ft4 concentrations over those that were not. this finding shows value for further investigation into thyroid hormone activity in sea turtles and the potential application of t4 supplementation in sea turtles being rehabilitated for cold-stunning. conclusions the summative findings of the reviewed articles most strongly indicate the primary pathological effect of cold-stunning in the studied species of sea turtles, particularly the kemp’s ridley, to be a physiological acidosis (likely both metabolic and respiratory in origin). secondary imbalances in electrolyte status, immune status, and cation balance appear to ensue in a compensatory fashion and anaerobic metabolic processes generally coincide. frequently, sea turtles presenting for cold-stunning may also present with other comorbidities (sepsis, pneumonia, anaemia, etc.). prognostically, total leukopenia, extreme derangements of blood acid-base parameters (increased pco2, decreased po2, reduced blood ph), severe hyperkalaemia, serially increasing blood lactate concentrations, and possibly rapid increases in total or ionised calcium have been identified in association with increased likelihood of death. areas identified for potential research include, but are not limited to, further characterisation of the metabolic processes affected by the speed of rewarming and optimisation to prevent exacerbation of the acidotic state in cold-stunned turtles, description of baseline thyroid activity in healthy sea turtles, implementation of thyroid supplementation in turtles showing reduced activity and / or hyporexia while in rehabilitation, evaluation of serial lactate values across sea turtle species presenting for rehabilitation, and comparative study of blood, gross pathological, and histopathological findings in sea turtles that succumb to cold-stunning. the current recommendations for rehabilitation of cold-stunned sea turtles (innis & staggs, 2017; and wyneken et al., 2006) generally result in favourable outcomes with 50–80% of animals being successfully rehabilitated and released (innis & staggs, 2017). when turtles that succumb to the syndrome within the first 3 days of treatment are excluded, that statistic approaches 90% (innis & staggs, 2017; and wyneken et al., 2006). with continued improvement of the existent protocols designed to remedy this syndrome for the vulnerable species experiencing it, these statistics can only improve. methodology search strategy databases searched and dates covered: cab abstracts via cab direct, 1973–present pubmed via national library of medicine, 1902–present web of science zoological record via clarivate analytics, 1864–present search strategy: cab abstracts: 1) sea turtle* or marine turtle* or cheloni* 2) cold-stun* or hypothermia 3) biomarker* or blood* or hemat* or chemistr* or biochem* or analyte* or plasma or ser* 4) 1 and 2 and 3   pubmed: ((sea turtle* or marine turtle* or cheloni*) and (cold-stun* or hypothermia)) and (biomarker* or blood* or hemat* or chemistr* or biochem* or analyte* or plasma or ser*)   web of science zoological record: ((ts=(sea turtle* or marine turtle* or cheloni*)) and ts=(cold-stun* or hypothermia)) and ts=(biomarker* or blood* or hemat* or chemistr* or biochem* or analyte* or plasma or ser*) dates searches performed: 06 dec 2022   exclusion / inclusion criteria exclusion: non-english-language manuscripts, case reports, abstracts, reviews, book chapters, other non-journal articles, repeat of same relevant result within search. inclusion: relevant journal articles, must include evaluation blood analytes in cold-stunned marine turtle species.   search outcome database number of results excluded – does not include blood analyte evaluation excluded – blood analyte data left unpublished excluded – does not evaluate cold-stunned turtles excluded – evaluates non-biological blood analyte(s) excluded – blood analytes are not routinely evaluated excluded – non-journal article total relevant papers cab abstracts 27 11 1 4 1 1 1 8 pubmed 15 4 1 3 0 1 0 6 web of science 28 10 1 3 1 2 1 10 total relevant papers when duplicates removed 10   orcid mccaide wooten: https://orcid.org/0000-0001-8121-0824 conflict of interest the author declares no conflicts of interest. references anderson, e. t., harms, c. a., stringer, e. m. & cluse, w. m. 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(2006). medical care of sea turtles. in: d. mader, ed., reptile medicine and surgery, 2nd ed. st. louis, mo: elsevier, 972–1007. zacher, l. a., berg, j., shaw, s. p. & kudej, r. k. (2010). association between outcome and changes in plasma lactate concentration during presurgical treatment in dogs with gastric dilatation-volvulus: 64 cases (2002–2008). journal of the american veterinary medical association. 236(8), 892–897. doi: https://doi.org/10.2460/javma.236.8.892 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use.   veterinary evidence is an rcvs knowledge initiative. issn: 2396-9776 first floor, 10 queen street place, london ec4r 1be resources student awards staff login policies privacy policy accessing information policy cookie declaration terms of use copyright notices stay connected podcasts twitter facebook instagram linkedin back to top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443. using evidence: pitfalls, practicalities and positive benefits gillian leng cbe1* 1national institute for health and care excellence, 10 spring gardens, london, sw1a 2bu *corresponding author (nice@nice.org.uk) vol 1, issue 4 (2016) published: 1 dec 2016 doi: 10.18849/ve.v1i4.75 this talk will illustrate the highs and lows of using evidence in the healthcare setting, drawing on experience from the national institue for health and care excellence (nice) relevant to veterinary medicine... find out more about gill. view presentation slides comments: are dogs that are fed from a raised bowl at an increased risk of gastric dilation volvulus compared with floor-fed dogs? a knowledge summary by louise buckley phd rvn1* 1harper adams university, edgmond, newport tf10 8nb *corresponding author (lbuckley@harper-adams.ac.uk) vol 2, issue 1 (2017) published: 16 jan 2016 reviewed by: wanda gordon-evans (dvm, phd, dacvs) and bruce smith (bvsc, ms, fanzcvs, dacvs) next review date: 20 jan 2019 doi: 10.18849/ve.v2i1.57 clinical bottom line there are only two studies that study the effect of raised feeders on the risk of gastric dilatation volvulus (gdv) and their findings conflict. only one study found a significant effect of feeder height, with large and giant breeds fed from a raised feeder being at an increased risk of gdv floor fed dogs. however, these authors found that, where the feeder was raised, the height of the feeder that increased the gdv risk was affected by the size of the dog. large breed dogs were more likely to develop a gdv if fed from a bowl ≤ 1 foot tall, whereas giant breed dogs were more likely to develop a gdv if fed from a bowl > 1 foot tall. no studies found that feeding from a raised feeder reduced the risk of gdv relative to feeding from the floor. therefore, the safest option in the absence of further evidence is to advise that owners of ‘at risk’ dogs feed from a feeder on the floor. this may not reduce the risk of gdv, but there is no evidence to suggest that it will increase the risk.  question are dogs that are fed from a raised bowl at an increased risk of gastric dilation volvulus (gdv) compared with dogs that are fed from a bowl on the floor? clinical scenario raised feeding bowls are available commercially and are sometimes recommended by veterinary nurses to assist elderly arthritic dogs to comfortably access their feed ration. a client with an elderly dog is attending a senior wellbeing clinic and asks for advice on whether they should use one of these feeders. the dog is a large or giant breed dog of the type at increased risk of developing a gastric dilation volvulus. the evidence the literature searches uncovered two papers (glickman et al. 2000; pipan et al. 2012) that directly addressed the pico question. of these, one of the studies (pipan et al., 2012) found no significant effect of feeder height on risk of having a gdv episode. one paper (glickman et al., 2000) found that dogs that were fed from a raised bowl were significantly more likely to present at a clinic with a gdv episode. however, the height of the bowl that increased the risk differed according to whether the dog was a large or giant breed. no studies found a decreased risk of gdv as a consequence of feeding a dog from a raised bowl. summary of the evidence glickman (2000) population: dogs (male, female, neutered and entire) from eleven different large and giant dog breeds (akita, bloodhound, collie, great dane, irish setter, irish wolfhound, newfoundland, rottweiler, saint bernard, standard poodle, and weimaraner), that were located within the usa. dogs were required to be at least 6 months old and not to have a medical history that included an episode of gdv before the study commenced. sample size: 1637 (large breeds: n= 894; giant breeds: n = 743): dogs that developed a gdv during the course of the study: 98 dogs that did not develop a gdv during the course of the study: 1539 nb. this study was derived from a larger prospective cohort study carried out by the authors. 1991 dogs initially enrolled on this study; however, for inclusion in the current study, dogs needed to be 6 months or older, and owners needed to have provided vital status information (undefined in the paper) and have completed the detailed questionnaire initially sent out to owners. intervention details: the study began in june 1994 and ended in february 1999. therefore, the maximum possible period that a dog could be studied for was 58 months. dogs were recruited through breed clubs and dog shows. at the start of the study, owners were asked about the presence of gdv in the medical history of the dog or any of its first-degree relatives. the dog was physically assessed for body condition and temperament, and conformational measurements taken. within thirty days of recruitment, owners were provided with a detailed questionnaire to complete that provided data on the dog’s gdv history (if positive, the dog was excluded), breeding, medical history, reproductive status, personality and temperament, and dietary factors. owners were instructed to notify the researchers if any of the following outcomes occurred: the dog developed a gdv (if so, the researcher confirmed this with the veterinarian who treated the dog) the dog died of another cause the ownership of the dog was transferred to another person owners were contacted in 1997, 1998, and 1999 to find out if, over the duration of the study, their dog had developed a gdv and if so, whether the dog died or survived. this was the methodology for the original prospective cohort study by the authors (referred to above). dogs from that study were included only if: the initial questionnaire had been fully completed there was at least one follow up set of data for that dog 7% of the owners in this study fulfilled both criterion for inclusion (n = 1660) 4% of these owners were excluded because their dog was less than 6 months old at the point of completing the initial questionnaire, leaving 1637 (82.2% of the original sample) available for analysis in this study. of these dogs, the median duration during which the dogs were followed up was 2.4 years (max: 4.8 months; minimum: no stated). the reasons for loss to follow – up (other than death) are not stated. 182 dogs died during this period: 29 died due to the gdv episode, 24 died for unknown reasons. 55 are reported to have died from other medical problems. 74 dogs are not accounted for in the figures reported. study design: prospective cohort study outcome studied: the outcome measure was whether the dog developed an episode of gdv during the course of the study and whether it survived this episode. the study then looked for non-dietary related factors that were associated with an increased risk of developing gdv in the population studied. of relevance to this pico, the authors’ asked owners about the height from which they fed their dog. from this, they derived two specific aspects to assess for risk: was the food bowl raised? yes / no what was the height of the food bowl? not raised / raised ≤ 1 foot / raised > 1 foot in analysing and presenting the data, the authors split the data according to the size of the dog: large breed dogs giant breed dogs main findings (relevant to pico question): feeding from a raised bowl significantly increased the risk of gdv (adjusted relative risk 2.10, 95% confidence interval: 1.4 – 3.30, p = 0.001). large breeds (n = 889): the relative risk posed by feeding from a raised feeder was 2.17 (95% confidence interval: 1.27 – 3.71; p = 0.01). 4% of the cases of gdv could be attributed to the dog being fed from a raised feeding bowl. the incidence (± 95% confidence interval) of gdv per 1000 dog years was 18 (12 – 24), for dogs fed from the floor (n = 625). the incidence (± 95% confidence interval) of gdv per 1000 dog years was 40 (24 – 56) for dogs fed from a raised feeder (n = 264). giant breeds (n = 742): the relative risk posed by feeding from a raised feeder was 1.99 (95% confidence interval: 1.00 – 3.95; p = 0.05). 8% of the cases of gdv could be attributed to the dog being fed from a raised feeding bowl. the incidence (± 95% confidence interval) of gdv per 1000 dog years was 17 (7 – 27) for dogs fed from the floor (n = 341). the incidence (± 95% confidence interval) of gdv per 1000 dog years was 34 (22 – 46 for dogs fed from a raised feeder (n = 401). however, there was an interaction between the height of the feeder that increased the risk and the size (giant versus large breeds) of the dog. if the dog was fed from a raised bowl, the actual height (≤ 1 foot high versus > 1 foot high) of the bowl significantly affected relative risk: large breeds: dogs that were fed from a bowl ≤ 1 foot high (n = 105) were 3.06 times (95% confidence interval: 1.60 – 5.87, p = 0002) more likely than dogs that were not fed from a raised bowl (n = 625) to experience a gdv. the incidence (± 95% confidence interval) of gdv per 1000 dog years was 56 (26 – 86) for dogs fed from a bowl ≤ 1 foot high. dogs that were fed from a bowl > 1 foot high (n = 144) were no more likely to experience a gdv than dogs not fed from a raised bowl (n = 625). the incidence (± 95% confidence interval) of gdv per 1000 dog years was 29 (11 – 47) for dogs fed from a bowl > than 1 foot high. giant breed dogs: dogs that were fed from a bowl ≤ 1 foot high (n = 60) were no more likely to experience a gdv than dogs not fed from a raised bowl (n = 341). the incidence (± 95% confidence interval) of gdv per 1000 dog years was 15 (6 – 36) for dogs fed from a bowl ≤ less than 1 foot high. dogs that were fed from a bowl > 1 foot high (n = 324) were 2.29 times (95% confidence interval: 1.15 – 4.58, p = 0.02) more likely than dogs that were not fed from a raised bowl (n = 341) to experience a gdv. the incidence (± 95% confidence interval) of gdv per 1000 dog years was 39 (25 – 53) for dogs fed from a bowl > 1 foot high. limitations: the authors collect data on feeding height at the start of the study (within 30 days of recruiting dogs). no further attempts were made to collect further data on this at regular intervals. thus, the authors cannot be certain that the dogs were being fed from a height at the time at which it developed a gdv (up to 58 months later). this reduces the ability of the study to detect real effects or meaningfully explain the effects observed. the authors do not examine interactions between: speed of eating and the height of the feed bowl morphometric measurements (particularly height of the dog) and speed of eating the total number of dogs lost to follow up is not reported. the authors exclude dogs from the original study that were lost to follow up before at least one follow up questionnaire was completed. however, this is not the same as saying these dogs were not lost to follow up as, for example, if the study was still in operation, why were further questionnaires not completed by these owners? the authors do not report how many dogs recruited to the study, remained with the study until the study ended. instead they report only median duration of follow up; this is meaningless to assess the number of dogs that remained with the study from recruitment to study end, as the dogs were signed up to the study at different time points. if the dogs that developed gdv and the dogs that didn’t develop a gdv differentially dropped out prematurely, this could introduce a ‘loss to follow up bias’. we know that, by the nature of the recruitment process for the subset of dogs included in this study, that already 13.3% of dogs had been excluded due to lack of follow up data (no follow up questionnaires completed). therefore, it seems likely that total losses to follow up before the study ended would be higher (and possibly considerably so) but the authors fail to give us the information needed to assess this. there is not attempt by the authors to assess whether participant drop out before the study ended was random or whether particular risk factors or characteristics were associated with an increased risk of drop out. furthermore, there are a lot of dogs lost to death that remain unaccounted for in the authors’ reporting. pipan (2012) population: privately owned dogs (any breed or mix, both sexes, neutered and entire) across a wide geographic area. the survey was potentially available to english speaking dog owners with access to the internet in any country worldwide. sample size: 2551 surveys included in the analysis: control group (dogs without a gdv): 1437 respondents gastric dilation-volvulus group (gdv): 1114 respondents intervention details: online survey based study, with ad hoc convenience sampling of dog owners. the questionnaire was divided into three sections: demographic information (year of birth, breed, sex, neuter status, and purpose of the dog; country and postcode of respondent). whether the dog had ever had a gdv that required surgical intervention. this latter question was used to divide dogs into the control group and the gdv group. however, the authors then also included within the gdv group dogs that did not have surgery, or died / were euthanised without surgery but were considered to have a gdv (whether confirmed or presumed). gdv group: a series of 44 questions divided into 4 categories: dog specific factors management factors environmental factors personality factors control group: the same questions were asked of the control group dog owners as were asked of the gdv group, with the exception that they were not asked any questions about the gdv episode (as the dogs had not experienced a gdv). they were asked one additional question (had the dog had a prophylactic gastroplexy?). these changes reduced the total number of questions asked to 32. study design: cross-sectional study outcome studied: the outcome measure was a gdv episode in the dog’s history. the study looked for factors that were associated with an increased incidence of gdv in the population studied. of relevance to this pico, the authors’ asked owners whether the dog was fed from a raised bowl. main findings (relevant to pico question): the findings in relation to raised bowl feeding are not reported within the results section. the authors note in the discussion that feeding from a raised bowl was not significantly associated with the risk of developing a gdv. limitations: the primary limitation is the failure to report their findings (along with numerical data) within the results section as this precludes the reader making an independent assessment of their conclusion. the incidents of gdv were retrospective so owners may have already taken measures to alter their height from which their dog was fed post-surgery, on the basis of veterinary recommendation or lay research. the authors do not outline whether owners were asked to complete the form on the basis of the height the dog was fed from at the time (or preceding) the gdv or, present time, or not directed as to a time frame to use. there was no attempt to match control and gdv cases across other dimensions that may have been relevant (e.g. breed, size, and / or age). the population of dogs studied is not constrained to types of dogs at high risk of gdv (large and giant breed dogs). therefore, if any risk factors identified co-vary with the size of the dog, this would represent a confounding variable in interpreting the data that limits any conclusions that may be drawn. appraisal, application and reflection only two studies were identified that addressed the pico question and these two studies were not in agreement. thus, the evidence base for answering the question is relatively limited. however, it is pertinent to observe that neither study identified feeding dogs from the floor as a risk factor for gdv. it is also pertinent to note that most studies that investigate risk factors for a gdv have found that there are many factors that have been found to be significantly implicated as associated with an increased risk of gdv. it is beyond the scope of this knowledge summary to discuss these but it should be borne in mind by the reader when considering the discussion below and the clinical bottom line provided. of the two studies, the pipan et al. (2012) provides the more impressive sample size for gdv dogs (n = 1114), compared with the glickman et al. study (n = 98). however, despite this, it is difficult to conclude much about the findings by pipan et al. (2012). the authors provide scant information to support either how they investigated feeder height as a risk factor or what they found. the only reference by the authors to their findings in relation to the pico can be found in the discussion section. they provide no numerical information to allow the reader to evaluate this finding (e.g. was there a statistical tendency for the dogs fed from a feeder to have an increased or decreased risk of gdv?).  the study by glickman et al. (2000) provides more comprehensive statistical reporting of the data relevant to the pico question, but provides incomplete reporting of the dogs lost to follow up. follow up losses are likely to be high given that 13.3% of the dogs lost to follow up had already been lost during the primary study that this study data was drawn from. this should be considered as it may severely distort the data if the losses were not randomly distributed across the categories of dogs in relation to this pico question. in this study, feeding from a raised bowl was identified as a risk factor for both large and giant breed dogs. furthermore, there was an interaction between feeder height and whether the dog was a large or giant breed dog. specifically, lower raised feeders (≤ 1 foot) increased the risk for large breed dogs (but not higher raised feeders (> 1 foot), whereas the converse was true for giant breed dogs. the authors provide no explanation for this finding. they do not appear to have examined this finding further in relation to the other data that they collected. for example, does the height of the feeder relative to the height of the dog affect the speed at which the dog is able to consume its ration (fast eating was also identified as a risk factor)? however, caution should be taken in over-interpreting the data as the length of time between owner completing the questionnaire and the dog potentially developing a gdv could be almost five years. therefore, additional interactions sought between the potential risk factors are problematic as owner feed management practices (e.g. feeder used) may have altered over the period studied. furthermore, the small numbers of dogs affected by gdv within each sub-category (e.g. large breed dog fed from a raised feeder) could mean that these findings are simply chance findings. the findings from the glickman et al. (2000) provide an additional possible explanation for the lack of significance identified by the pipan et al. (2012). the glickman et al. (2000) specifically studied eleven ‘at risk’ large and giant breed dogs. both the control dogs and the gdv dogs were therefore drawn from a similar population of dogs. by splitting the data into large and giant breed dogs they further homogenised the dogs in relation to factors such as height of the dog. by contrast, the pipan et al. (2012) study used an ad hoc convenience sample of dogs of any type/breed/etc. this lack of relative homogeneity in the study population may have reduced the ability of the study to detect raised feeders as a risk factor for gdv, if the risk posed by feeding from a raised feeder interacted with morphometric measurements such as height of the dog.  however, by restricting the population studied to eleven breeds, caution should be exercised in extrapolating the glickman et al. (2000) findings to other breeds of dogs. the authors do not extend their analysis to look at whether the relevant risk factors identified are present across each breed studied, but this may be due to the small sample size within in each breed of dogs affected by a gdv. there is a need for additional investigation in these areas. the practical implications of the combined findings are that there is limited evidence in the research area of this pico. the more convincing of the two studies demonstrates a risk associated with using a raised feeder but only for specific height / size of dog (large versus giant breed) combinations. neither of the studies found an increased risk associated with feeding from floor height. consequentially, for the client keen to decrease the risk of their dog developing a gdv, the safest option would be to advise that, in the absence of further research, the dog should be fed from a bowl placed on the floor. if comorbidities exist (e.g. reduced mobility, arthritis) that reduce the ability of the dog to feed from the floor such that feeding from a height is considered beneficial, the practitioner should consider the height of the dog relative to the height of the feeder, and advise accordingly. methodology section search strategy databases searched and dates covered: pubmed (1900 – 2017); science direct (1900 – 2017); web of science (1970 –2017); cab abstracts (1983 – 2016) search terms: (dogs or dog or canine) and ("gastric dilatation" or "gastric dilatation volvulus" or gdv or "gastric torsion" or "stomach volvulus") and (feed* or diet or diets or dietary) dates searches performed: 11th january 2017 exclusion / inclusion criteria exclusion: pre-defined exclusion criteria: non english language, popular press articles, any study lacking a comparator/control inclusion: any comparative (control group utilised) study in which the effect of height of the feeder on development of a gastric dilation (+/volvulus) was investigated. search outcome database number of results excluded – did not answer pico question excluded – not english language excluded – conference abstract only excluded – duplicates total relevant papers ncbi pubmed 25 23 0 0 0 2 thomson reuters web of science 25 22 1 0 2 0 cab direct 46 41 1 2 2 0 science direct 251 251 0 0 0 0 total relevant papers when duplicates removed 2 conflict of interest the author declares no conflict of interest. references glickman, l. et al. (2000) non-dietary risk factors for gastric dilation-volvulus in large and giant breed dogs. journal of the veterinary medicine association, 217 (10), pp. 1492 – 1499 http://dx.doi.org/10.2460/javma.2000.217.1492 pipan, m. et al. (2012) an internet-based survey of risk factors for surgical gastric dilation-volvulus in dogs. journal of the american veterinary medicine association, 240 (12), pp. 1456 – 1462 http://dx.doi.org/10.2460/javma.240.12.1456 intellectual property rights knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. do palliative steroids prolong survival in dogs with multicentric lymphoma? a knowledge summary by clare m knottenbelt bvsc msc dsam mrcvs1* 1college of medical veterinary and life sciences, university of glasgow, bearsden road, bearsden , glasgow, g61 1qh *corresponding author (clare.knottenbelt@glasgow.ac.uk) vol 3, issue 1 (2018) published: 02 feb 2018 reviewed by: simon bate (bvms certsam mrcvs) and adam swallow (bvsc afhea mrcvs) next review date: 02 feb 2020 doi: 10.18849/ve.v3i1.96 pico question in dogs with naturally occurring multicentric b cell lymphoma does treatment with glucocorticoids alone extend survival time when compared to no treatment? clinical bottom line  there is weak evidence, due to insufficient studies with untreated control groups, regarding the impact on survival of prednisolone treatment in dogs with multicentric lymphoma. from the papers identified from the search functions used for the clinical question remission in uncontrolled trials was reported following prednisolone treatment. details of which can be found in other sections of this paper. clinical scenario an eight year old male neutered labrador presents with multicentric lymphadenopathy. he is otherwise well. staging (abdominal and thoracic imaging plus bone marrow aspirates) confirm that he is stage 3a (multicentric lymph node involvement without evidence of systemic illness). routine bloods are normal. the owner does not want to use chemotherapy due to the health and safety implications. you have offered prednisolone treatment and explained the side effects. the owner would like to know the prognosis and average survival time if she opts for treatment with prednisolone alone.  summary of the evidence valli (2013) population: dogs with lymphoma recruited via veterinary cancer society 2006-2008 and with confirmed histopathology sample size: 944 dogs with lymphoma. survival data only available for 456 dogs. intervention details: dogs with lymphoma of varying types (high grade, intermediate grade and low grade) treated with various types of chemotherapy or with prednisolone alone or not treated. drug doses and duration are not specified.  the paper does not state how many dogs were in each of the lymphoma type groups, however there is limited reference to the numbers of dogs in some of the treatment groups. this reflects the focus on survival for the group as a whole rather than in respect of differing treatment regimes. study design: descriptive case series (retrospective) outcome studied: survival in days main findings (relevant to pico question): proportional hazards regression models were used to assess relative risk of death and reported as hazard ratios (hr) and 95% confidence intervals (ci).  the numbers of dogs in each treatment group (chemotherapy including hydroxydaunorubicin, chemotherapy without hydroxydaunorubicin, prednisone alone and no treatment) was not stated for any of the lymphoma types. high grade t and b cell lymphoblastic lymphomas (n= 36) with possible prednisolone only treatment. states that there is no evidence that prednisolone alone is better than no treatment (hr 0.50; 95% ci, 0.064-3.90; p=0.51). centroblastic b cell lymphomas (n= 186). risk of death of dogs treated with prednisolone alone similar to that with no treatment (hr 1.65;95%ci, 0.56-4.87; p=0.36). immunoblastic b cell lymphomas (n= 57). prednisolone only therapy associated with poorer survival than chemotherapy (hr 47.22 ci95% 2.67-834.74 p=0.009) but 0 dogs in this group were were in the no treatment group. this paper also compared treatment to histological grade of lymphoma. the numbers of dogs in this part of the analysis was not stated. survival following the different treatments (chemotherapy including hydroxydaunorubicin, chemotherapy without hydroxydaunorubicin or prednisone alone) was compared to that of dogs that received no treatment. low grade lymphomas (n=81) were treated with chemotherapy including hydroxydaunorubicin, chemotherapy without hydroxydaunorubicin , prednisone alone and no treatment however the numbers in each group were not stated. however those treated with prednisone only had increased risk of death (hr 40.57 6.8-242.09 p <0.001) compared to dogs receiving no treatment. intermediate grade lymphomas (n=242): dogs treated with prednisolone only (hr 1.920.68-5.39 p = 0.22) showed no significant difference from those not treated. dogs treated with chemotherapy including hydroxydaunorubicin or  chemotherapy without hydroxydaunorubicin , showed a reduced risk of death high grade lymphomas (n=103) treated with prednisolone only (hr 1.63 95% ci 0.53-5.03 p=0.39) showed no significant difference compared to chemotherapy including hydroxydaunorubicin, chemotherapy without hydroxydaunorubicin and no treatment) was not stated. based on this study prednisone only showed no advantage over no treatment for dogs with diffuse large centroblastic b cell lymphoma. across all grades of lymphoma (including some t cell lymphoma dogs) treatment with prednisolone alone increased the risk of death but this increase was only significant when compared to chemotherapy treatment with or without hydroxydaunorubicin and not when compared to the no treatment group.  limitations: the paper is a retrospective study assessing a wide variety of aspects of dogs with histologically confirmed lymphoma. these include classification of cell type (t vs b, mitotic rate and histological types.) it aims to show how survival varies in different treatment regimens and relate this to disease variables. cases were recruited through a veterinary cancer society newsletter which could result in loss of patients from veterinary practices without a special interest in cancer treatment which would mean there might be fewer patients in the prednisolone alone or no treatment groups. there was an ongoing study into one treatment regime so this may have been over-represented. the authors state that the majority of cases came from the usa with a few from europe and canada. it is possible that there were variations in treatment choices or histological diagnosis in the cases from europe however there is no detail provided about the patient numbers involved. patients were only included where there was histological confirmation and immunohistochemistry had been performed. again this might reduce recruitment of patients whose owners were unwilling or unable to perform these tests or where a diagnosis was reached by cytology alone. survival time was recorded for all patients and those who remained alive at the time of the study were censored. as this was a retrospective study, patients were allocated to a particular treatment option based on clinician and owners preference. it is not clear from the paper if cases from particular practices or regions had differing treatment regimes. there is no reporting of the dose of prednisolone used for the prednisolone alone group or any reporting of the chemotherapy doses used. similarly there is no reporting of the numbers of dogs in each treatment group within each category. this reflects the focus on survival for the group as a whole rather than in respect of differing treatment regimes. tozon (2006) population: dogs with lymphoma diagnosed by cytology sample size: 39 dogs intervention details: 13 dogs on differing chemotherapy regimes: cop protocol (n=6), copa protocol (n=4) doxorubicin (n=2) and methylprednisolone (n=1). drug doses and duration were not stated study design: descriptive case series outcome studied: occurrence of different cyto-morphological diagnoses and how sex, clinical stage and treatment choice affects first remission time (days) and survival time (days) of patients undergoing differing regimes of treatment. main findings (relevant to pico question): cytomorphological analysis was similar to previous reports with high malignant lymphoma in 25 dogs, intermediate grade lymphoma in 13 dogs and low malignant lymphoma in 1 dog. there is no information on outcome in 26 dogs and it is not clear if they received any treatment. 13 dogs were treated these comprised 6 dogs with high grade, 6 dogs with intermediate and 1 dog with low grade. details on which treatment each dog received are provided but the numbers in each subgroup are two small to draw any further information on the survival times associated with each lymphoma type. however within all grades of tumour  treated  median survivals were: cop-treated dogs (n=6)  160 days, copa treated dogs (n=4) 225 days doxorubicin treated dogs (n=2) were alive at 90 days methylprednisolone alone (n=1) 240 days median first remission was longer in females (n= 6; 215 days) than males (n=7; 159 days) limitations: only one patient out of 39 received prednisolone alone. authors do not state how cases were selected or give any inclusion or exclusion criteria for this study brick (1968) population: dogs and cats with lymphoma examined at ohio state university veterinary clinic 1959-1965 sample size: 32 dogs and 6 cats intervention details: comparison of 4 different treatment regimenscyclophosphamide (n=4 dogs), prednisolone alone (n=6 dogs), chlorambucil (n=9 dogs), chlorambucil combined with prednisolone at the same doses as the individual drugs (n=7 dogs) and no treatment (n= 6 dogs) on mean survival time. the following dosage regimes were used: cyclophosphamide 0.3mg/kg/day for 14 days followed by 14 days with no treatment prednisolone 0.5mg/kg/day for 14 days followed by 7 days without treatment and the schedule then repeated. chlorambucil 0.2mg/kg/day for 14 days followed by 14 days without treatment and the schedule then repeated. prednisolone 0.5mg/kg/day for 14 days followed by chlorambucil 0.2mg/kg/day for 14 days and the schedule then repeated. study design: descriptive case series outcome studied: objective – survival time in weeks main findings (relevant to pico question): 6 dogs were given no treatment and mean survival time was 2.5 weeks and disease was extensive in 4 of the dogs. however grade was not mentioned. prednisolone regime was administered to 6 dogs however one of these also received radiotherapy on one occasion. survival time ranged from 1-7.5 months with a mean of 2.5 months. of the 6 dogs and 2 cats that received prednisolone alone only 7 had a temporary reduction in node size. limitations: the paper is a retrospective study but does not state how patients were identified or if any cases were excluded. diagnosis was based on a combination of clinical signs (anorexia, depression, weight loss, anaemia and generalized lymphadenopathy) haematology results and a biopsy of tonsil or popliteal lymph node or bone marrow which would be acceptable assuming all patients had all three criteria assessed. this is not stated in the paper. furthermore the paper does not state whether dogs had all or some of these symptoms and whether there was a difference in the presentation of dogs and cats.   the paper does not specify the stage/sub stage of the cases reported except to state that the patients that had no treatment had widespread disease. mean survival was reported rather than median which given the low numbers of cases is far from ideal. paper does not state the survival time of 1 dog that also received radiation therapy and does not state which of the 6 dogs and 2 cats did not get a reduction in node size. there is no indication if location or grade of disease affected this finding. regime is not continuous prednisolone as usually recommended in current veterinary practice across the world. squire (1973) population: dogs with naturally occurring lymphoma recruited from local veterinary practices. sample size: 100 dogs. intervention details: comparison of 4 different chemotherapeutic treatment schedules : prednisone 2 mg/kg/day orally for 7 days followed by 1 mg/kg/day thereafter (n=49) prednisone as above plus cyclophosphamide 5 mg/kg/day orally for 7 days followed by 2.5 mg/kg thereafter (n=34) vincristine 0.03mg/kg intravenously on day 1 and 8. prednisone 1 mg/kg/day orally on days 1 and 8 and days 9-21. cyclophosphamide 5 mg/kg/day on days 2-7. regime repeated every 14 days (n=19) vincristine 0.03mg/kg intravenously on day 1 and 8. prednisone 2 mg/kg/day orally on days 1 and 8 followed by 1 mg/kg/day on days 9-21. cyclophosphamide 5 mg/kg/day on days 15-21. 6-mercaptopurine 5 mg/kg/day on days 15-21. regime repeated every 30 days (n=25) dogs that failed to respond to one regime were moved to treatment schedules 2 or 3 and then reported in that group study design: non-randomised controlled trial outcome studied: mean objective remission duration in days (number of days before regime failed to maintain complete remission (cr) or partial remission (pr) despite drug-induced toxicity. survival measured as number of days from initial presentation until natural death or euthanasia in terminal disease. main findings (relevant to pico question): this study excluded 18 dogs that died or were euthanased due to advanced disease or an unsatisfactory response to therapy within 14 days of admission from the survival and remission duration data. of the 49 dogs on prednisolone only 20 (41%) achieved complete remission with a mean objective remission time of 53 days (range 14-210 days). remission induction rapid and usually reached its maximum at 7 days but was often partial within 72h. partial remissions were not reported. in 34 dogs on schedule 2, 13 achieved complete remission with a mean objective remission time of 62 days (range 17-130 days). 25 dogs had previously received prednisolone alone. 7 that that had failed to achieve remission with prednisolone alone showed some sensitivity but the objective remission time is not stated. 2 dogs failed to respond to schedule 2 despite achieving complete remission with prednisolone alone in 19 dogs on schedule 3, 15 achieved complete remission with a mean objective remission time of 184 days (range 30-282 days). 14 of these dogs had previously received prednisolone alone or schedule 2. in 25 dogs on schedule 4, 19 achieved complete remission with a mean objective remission time of 136 days (range 18-300 days). none had received prior treatment no severe side effects reported except in 1 dog which developed a gastric ulcer after several months of treatment. in several patients polyuria and polydipsia necessitated a reduction in dosage to 0.25-0.5 mg/kg/day. increased appetite and mild signs of cushing’s syndrome were noted in several animals (number not stated) 9 dogs that failed to achieve remission on prednisolone alone were then treated with schedule 2. 7 of these dogs responded and 2 of these dogs failed to respond to schedule 2. 14 dogs that failed to respond to prednisolone alone or to schedule 2 were treated with schedule 3. of these 12 achieved complete remission. dogs on prednisolone alone were subsequently given chemotherapy if response was unsatisfactory or when refractoriness developed. limitations: stage of lymphoma was defined as one of 4 stages  (stage 1 = one lymph node or one anatomic location stage 2 = involvement of multiple lymph nodes but limited to one side of the diaphragm stage 3 generalized involvement but limited to lymphoid tissue stage 4 involvement of any non-lymphoid tissue including viscera or blood or bone marrow nervous system etc. viscera would normally be classed as stage 4 on the who system and the other areas would be as stage 5 on the who system definition of stage 3 in this study was generalised involvement but limited to lymphoid tissues i.e. lymph nodes, spleen, tonsils, thymus. in the current staging system this would be a group containing stage 3 and stage 4 patients. only included animals surviving to 14 days. 18 died or were euthanised due to advanced disease or an unsatisfactory response to therapy. doesn’t state which of the prednisolone alone group went on to get chemotherapy and if this was taken into account in the survival times. however as there are no survival times given for this group we assume that most went onto get other treatments. mean remission duration is provided rather than median. given the extremely wide range of 14-210 days this is far from ideal. no data on patients who did not get treatment as patients were recruited to be part of this study and given a treatment regime. appraisal, application and reflection there is limited data on this topic with papers reporting findings in relatively small numbers of dogs. unfortunately the paper that most closely answers the clinical question (mortier et al., 2012)  was only available as an abstract and therefore could not be fully reviewed. this study suggested that dogs could achieve remission for up to 210 days on prednisolone alone (median of 32 days). this is similar to the findings of brick et al. (1968) and their reported survival times of 1-7.5 months with a cyclical administration of prednisolone (0.5 mg/kg/day for 14 days followed by 7 days without treatment and with a schedule repeat). squire et al. (1973) also reported remission times of 14-210 days with administration of 2 mg/kg/d for 7 days, then 1 mg/kg/d thereafter in 20 dogs (41%) who achieved remission for a mean of 53 days (range 14-210 days). in the latter paper they excluded patients who failed to survive 14 days so their median remission time is likely to be lower than their reported mean suggests. in addition squire et al. (1973) do not report overall survival time however it can be assumed that this is longer than remission time. the single relevant case reported by tozon et al. (2006) survived 240 days with stage 3a lymphoma. the most recent publication (valli et al., 2013) suggests that there is no benefit of treatment with prednisolone alone in a number of histological types and grades of lymphoma. clearly more research is required to review survival times of dogs with lymphoma who are given no treatment of any sort and comparing them to those receiving a standardised regime of prednisolone without prior other treatments and no further treatment of any sort being applied at a later date.  methodology section search strategy databases searched and dates covered: cab abstracts (1973-week 32 2017) and pubmed ncbi (1968august 2017) search terms: cab abstracts (lymphoma* or lymphosarcoma*).mp. or lymphoma/ or lymphosarcoma/ (cabi 14164) (dog or dogs or canine).mp. or dogs/ or canis/ (cabi 196531) (glucocorticoid* or prednisolon* or prednison*or steroid* or cortico-steroid* or corticosteroid).mp. or exp glucocorticoids/ or exp prednisolone/ or exp prednisone/ or steroids/ or corticoids/ (cabi 69157) 1 and 2 and 3   pubmed dog or dogs or canine glucocorticoid or prednisolone or prednisone or steroid or cortico-steroid or corticosteroid lymphoma or lymphosarcoma 1 and 2 and 3 dates searches performed: 23/08/2017 exclusion / inclusion criteria exclusion: wrong species, not lymphoma, in vitro studies, t cell lymphoma or wrong location of b cell lymphoma, no treatment reported only chemotherapy or other treatments reported no survival data reported reviews of other reported literature letters to editor conference proceedings with no abstract available available in english inclusion: correct species, b cell lymphoma with group treated with prednisolone alone and survival data reported in any form search outcome database number of results excluded – not relevant to pico question excluded – no survival data reported excluded – reviews and letters excluded – not in english or not available total relevant papers cab abstracts 260 231 1 7 17 4 pubmed 201 194 1 3 0 3 total relevant papers when duplicates removed 5 conflict of interest the author declares no conflicts of interest. references brick j., roenigk, w. and wilson, g. (1968) chemotherapy of malignant lymphoma in dogs and cats. journal of the american veterinary medical association 153 (1) 47-52 mortier,f., daminet, s., vandenabeele, s. et al. (2012) canine lymphoma: a retrospective study (2009-2010). vlaams diergeneeskundig tijdschrift 81 (6) 341-351 squire, r., bush, m., melby, e. et al. (1973) clinical and pathological study of canine lymphoma: clinical staging, cell classification and therapy. journal of the national cancer institute, 51 (2), 565-74 tozon, n., samardzija, p., prijic, s. et al (2006) canine lymphoma: cytologic study and response to therapy. slovenian veterinary research 43 (3) 127-133 valli, v., kass p., san myint, m. et al. (2013) canine lymphomas: association of classification type, disease stage, tumor type, disease stage, tumor subtype, mitotic rate, and treatment with survival. domestic mammal disease 50 (5) 738-748 doi: http://dx.doi.org/10.1177/0300985813478210 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. antiepileptic drugs’ tolerability and safety – a systematic review and meta-analysis of adverse effects in dogs charalambous m1, shivapour sk2, brodbelt d3, volk ha3 1 university college london, uk, 2 iowa state university, ames, usa and 3 royal veterinary college, london, uk background various anti-epileptic drugs (aeds) are used for the management of idiopathic epilepsy (ie) in dogs. their safety profile is an important consideration for regulatory bodies, owners and prescribing clinicians. however, information on their adverse effects still remains limited with most of it derived from non-blinded non-randomized uncontrolled trials and case reports. aim of the study this is the first systematic review and meta-analysis in veterinary medicine which evaluates studies that describe the safety profile of aeds used for the management of ie in dogs, based on objective criteria. material & methods ü electronic searches of pubmed, google scholar and cab direct were carried out (03 january 2016) without date or language restrictions. proceedings of ecvn/acvim annual congresses were searched. peer-reviewed full-length studies describing objectively the adverse effects of aeds in dogs with ie were included. ü studies were selected based on specific inclusion criteria and a two-stage screening process. final studies were evaluated on the grounds of their overall quality of evidence (figure1) as well as outcomes measures (table 1). ca vbh vbl conclusions & discussion ü adverse effects usually appeared mild in all aeds and subsided once doses and/or serum levels were monitored or after the aed was withdrawn. ü although phenobarbital might be less safe than imepitoin and levetiracetam, there was insufficient evidence to classify it as an aed with a high risk of major adverse effects. ü it is important for clinicians to evaluate both aeds’ effectiveness and safety on an individual basis b e f o r e t h e s e l e c t i o n o f t h e a p p r o p r i a t e monotherapy or adjunctive aed therapy. overall number of studies detected total number of studies evaluated after the two-stage screening process number of studies with the highest overall quality of evidence level of evidence provided for each aed safety profile strong weak 368 90 5 ü  phenobarbital, imepitoin, potassium bromide, levetiracetam ü  zonisamide, gabapentin, pregabalin, sodium valproate, felbamate, topiramate, primidone results table 2: level of evidence for aeds’ safety profile figure 3: staircase of aed’s safety profile hierarchy direct comparisons suggested that imepitoin and levetiracetam might have a better safety profile than phenobarbital, whilst the latter might have a better safety profile than potassium bromide. however, none of these comparisons showed a statistically significant difference. comparisons between other aeds were not possible due to lack of relative comparison studies. individual aed assessments indicated that levetiracetam might be one of the safest aeds, followed by imepitoin and then phenobarbital and potassium bromide. the safety profile in other aeds was variable. table 1: criteria for evaluation of aeds’ safety profile proportion of specific adverse effects for each aed prevalence and 95 % confidence interval of the affected population in each study comparative odds ratio of adverse effects for aeds level of evidence provided for the safety profile of each aed calculated for each aed by dividing the number of studies that reported a specific adverse effect by the total number of the studies for this aed. calculated for each study by dividing the number of subjects that developed adverse effects during the specified study period by the total size of the study population. the odds ratio (or) was estimated in order to indicate the increased or decreased odds of observing specific adverse effect(s) in total for an aed compared to its control group (comparison aed or placebo or untreated animals). the or for dichotomous data was calculated using the random-effects model in review manager 5.3. associations were considered to be statistically significant at p < 0.05. ‘strong ’ evidence was provided for the safety profile when at least one brct reported or assessed the adverse effects of an aed; ‘weak ’ evidence was provided for the safety profile when brcts were not available. overall quality of evidence treatment group size quality of subject enrolment study design overall risk of bias figure 1: criteria for evaluation of the overall quality of evidence for each study blinded randomized clinical trials (brcts) with large group sizes, clear inclusion criteria and diagnostic investigations that included clinical signs and thorough test results consistent with the diagnosis of ie, describing outcomes specific for ie and low overall risk of bias were considered to provide the highest available quality of evidence. brct(s); blinded randomized clinical trial(s) figure 2: risk of bias risk of bias assessment presented as percentages across all included studies based on cochrane and syrcle’s ‘risk of bias’ assessment tool. overall high risk of bias in >90% of the studies. evaluation of achilles tendon injuries with findings from diagnostic musculoskeletal ultrasound in canines – 43 cases lauri-jo gamble dvm, ccrp1 debra a. canapp dvm, ccrt, cva, dacvsmr1 sherman o. canapp dvm, ms, ccrt, dacvs, dacvsmr1* 1veterinary orthopedic and sports medicine, 10975 guilford rd, annapolis junction, md 20701, usa *corresponding author (scanapp@vosm.com) vol 2, issue 3 (2017) published: 12 aug 2017 reviewed by: alycen lundberg (dvm) and stephen jones (mvb, ms, dacvs) doi: 10.18849/ve.v2i3.92 section index:    abstract | introduction | methods | results | discussion | conflict of interest | references | supplementary files abstract objective: the objective was to describe clinical and ultrasonographic characteristics of canine achilles tendon injuries. background: even though there have been publications describing characteristics of the normal and injured achilles tendon by diagnostic ultrasound, there has been no previous in-depth ultrasonic evaluation and characterisation of achilles tendon strains. evidentiary value: this is a retrospective case series report of 43 dogs that underwent musculoskeletal diagnostic ultrasound evaluation of their strained achilles tendons, with and without surgical repair. methods: data was collected from medical records of patients from august 2009 to may 2016. inclusion criteria for dogs included a diagnosis of achilles tendon injury based on the presence of fibre pattern modification within one or more components of the achilles mechanism on initial diagnostic ultrasound. results: it was found on the diagnostic ultrasound that achilles tendon injuries were strictly unilateral in 51.2% (n=22/43) of cases and bilateral on presentation in 48.8% (n=21/43) of cases. 18.2% of the unilateral case progressively became bilateral over time (n=4/22). the injury was partial in 90.7% (n=39/43) of the cases and all three components of the achilles mechanism were completely disrupted in only 9.3% of the cases (n=4/43). the partial injuries incorporated changes within the fibre patterns of all 3 components of the achilles in 53.8% (n=21/39) of the cases and alteration of both the gastrocnemius tendon (gt) and common tendon (ct) in 41.0% (n=16/39) of the cases. grade iii strains were predominant (44.3%), followed by grade i (28.6%) and grade ii (27.1%). damage occurred most commonly at the tendino-osseous insertion (77%), with injury occurring less frequently diffusely along the body of the tendon (12.5%) or at the musculotendinous junction (10.5%). conclusion: diagnostic musculoskeletal ultrasound was used to identify lesions of achilles tendon consistent with different grade of strain, as well as identifying the specific region of injury. diagnostic ultrasound findings were correlated to the surgical findings and previous literature. application: diagnostic musculoskeletal ultrasound provides a non-invasive diagnostic modality for patients suspected of having achilles tendon strain. further investigation is needed to establish treatment protocols based on ultrasonographic 3-tier grading scheme for achilles tendon strain injury. abbreviations: common tendon (ct), computed tomography scan (ct scan), gastrocnemius tendon (gt), magnetic resonance imaging (mri), myotendinous junction (mtj), superficial digital flexor tendon (sdft). introduction the achilles tendon, or common calcanean tendon, is made of three components (three separate tendons made of the tendinous insertion of five muscles attaching to the calcaneal tuberosity): (1) the gastrocnemius tendon (gt), (2) the superficial digital flexor tendon  (sdft) and (3-5) the common tendon (ct, combined tendons of gracilis, semitendinosus and biceps femoris) (evans et al., 2013; johnson, 2005). the gt is responsible for tarsal extension and inserts on the proximal dorsal surface of the calcaneus. the sdft inserts collaterally, through the superficial digital flexor retinaculum, at the proximal calcaneus before continuing distally and attaching to the second row of the phalanges. the last component, the ct, inserts at the medial aspect of the calcaneus, but plays a minor role in tarsal extension (evans et al., 2013). although achilles tendon rupture is an uncommon tendon injury, it has been described frequently in dogs (reinke et al., 1993; king et al., 2003; corr et al., 2010; spinella et al., 2010). mature middle-aged, medium to large-breed active dogs seem to be most commonly affected by this type of injury (kramer et al., 2001; harasen, 2006; rivers, 1997). disruption of the achilles tendon can be complete (all components, gt, sdft, ct) or partial (leaving notably the sdft intact). meutstege proposed in 1993 a classification for canine achilles tendon injuries based on the localisation of lesions and gross pathology, where type i is a complete rupture, type iia affects the musculo-tendinous junction, type iib has an intact paratendon, type iic is a gt avulsion with intact sdft and type iii tendinosis and/or peritendinitis (meutstege, 1993). when there is a complete disruption of the achilles tendon apparatus the dog will be initially non-weight bearing and a swelling may be noted at the point of the tarsus (calcaneus) (caine et al., 2009; cervi et al., 2010; spinella et al., 2010). in some cases, a skin lesion/laceration may be evident and there may be a palpable tendon defect (vaughan, 1981). with more chronic lesions, the hock will sink to a hyperflexed position with associated hyperextension of the knee and plantigrade stance with the metatarsals and digits lying flat on the floor (walking on the soles of the paws; flat footed) (johnson, 2005; meutstege, 1993; king et al., 2003). for a partial tear or lengthening of the achilles tendon system, the toes are curled downward (crab claw stance; digital knuckling) (johnson, 2005; meutstege, 1993). dogs with disruption only affecting the gt and ct display a hyperflexed tarsus with contracture of the toes since the intact sdft is placed under considerable tension, which pulls on its insertions on the palmar surface of the proximal end of the middle phalanges of digits ii, iii, iv, and v, contracting the toes (johnson, 2005; meutstege, 1993). achilles tendon rupture in the literature tends to be associated with an acute traumatic episode: either an impact injury resulting in avulsion of the tendon from the calcaneus or a direct sharp trauma to the musculotendinous unit (cut, laceration) (cervi et al., 2010; baltzer et al., 2009). chronic degeneration of the achilles tendon is also possible and is more frequently seen in labrador retrievers and doberman pinschers (harasen, 2006; meutstege, 1993; morton et al., 2015). active dogs can also have an acute on chronic presentation (chronic degeneration exacerbated by an acute injury). degenerative injuries may also be secondary to other causes such as systemic disease (spinella et al., 2010) (i.e. cushing’s disease) or iatrogenic etiologies (shakibaei et al., 2001; lim et al., 2008; hossain et al., 2008; baltzer et al., 2009) (steroid administration, fluoroquinolone treatment) (shakibaei et al., 2001). ultrasound evaluation has become a valuable and practical tool in assessing the achilles tendon. it is used frequently in human medicine for diagnostic evaluation and grading of achilles tendon injuries (griffith, 2014; luscombe et al., 2003; henderson et al., 2015; royall, 2011; maffulli et al., 2004). another advantage of musculoskeletal ultrasound is the possibility to use the contralateral limb as a comparison to evaluate symmetry of the tendon. this comparison may be difficult in the presence of bilateral conditions, but the ultrasonographic findings often differ between limbs and therefore asymmetrical findings within both achilles tendons are notable. sedation and anaesthesia are not necessary which makes it of benefit over ct scan and mri. sonographic evaluation is also less expensive, making it a more viable option for both initial diagnostics and recheck examinations. ultrasonographic evaluation of the normal achilles tendon was first reported in 1997 by kramer (kramer et al., 1997) as part of a report investigating the utility of ultrasonography as a diagnostic imaging procedure in orthopaedic problems in small animals. a more specific study was repeated in 2005 by lamb (lamb et al., 2005) where detailed evaluation of the canine achilles tendon was performed on greyhound cadavers compared to dissected specimens. a few years later, characterisation of the soft tissue structures of the canine tarsus in medium to large breed dogs was obtained by caine (caine et al., 2009). an additional ultrasonic study has been performed by rivers (rivers, 1997) to preoperatively evaluate canine achilles tendon injury in a series of six cases with surgical confirmation of the diagnosis. it was found that ultrasonographic examination could not differentiate partial from complete achilles tendon rupture based on sonographic echotexture pattern (rivers, 1997). however, it was later established in 2001 by kramer (kramer et al., 2001) that ultrasonography allowed identification and differentiation of total ruptures and the differentiation of partial ruptures into deep or superficial ruptures, or those comprising muscular tears. additionally, a few case reports on achilles tendon injury and its treatments in dogs have mentioned successful use of diagnostic ultrasound (baltzer et al., 2009; case et al., 2013; mueller et al., 2009; spinella et al., 2010). the aim of this retrospective case series was to report and characterise the ultrasonic findings of achilles tendon injuries in the general canine population seen at one referral centre. results population sample most of the 43 patients included in this case series were strictly companion animals (n=36/43; 83.7%). the seven other patients had a listed occupation or hobby including field trial/hunting (n=4), police/security (n=1), conformation (n=1), and a combination of multiple activities including agility (n=1). excluding mixed breeds, 18 dog breeds were evaluated. the most common were labrador (n=11; 25.6%), doberman (n=6; 14.0%) and golden retrievers (n=3; 7.0%).  females were overly represented, but this tendency was not significant with 55.8% of the patients being female (22 spayed, 2 intact), and 44.2% being male (13 neutered, 6 intact). the mean and the median age at the time of initial presentation were 6 years and 3 months and 7 years respectively (range 5.6 months to 12 years and 3 months). the mean body weight was 66.0 pounds (30 kg) with a median body weight of 62.4 pounds (28.4 kg) (range of 12.3-150 pounds). the vast majority (n=37/43; 86.0%) of the patients in this case study had a chronic presentation which was defined by a persistence of clinical signs over more than one week. however, the mean estimated time to presentation was 6 months with 6 cases even having a history greater than one year. initial orthopaedic examination visible lameness was reported in 35 of the 43 patients (81.4%) which was subjectively graded on a i to vi scale (table 2) as grade i for 5 patients, grade ii for 14 patients, grade iii for 5 patients, grade iv for 6 patients and grade v for 5 patients. shorter stride was also noted in 2 cases. standing and walking stance were characterised by a hyperflexed tarsus (‘’dropped’’) due to a rupture of the achilles tendon in 34.9 % (n=15/43), whereas the classic contracture of the digits (‘’claw stance’’) was present 41.9% of the time (n=18/43). the reported plantigrade stance (‘’flat footed’’) (spinella et al., 2010; corr et al., 2010; baltzer et al., 2009) was not as frequently expressed; it was only visible in 7.0% of the patients (n=3/43). the most reliable findings on physical examination appeared to be moderate to severe soft tissue swelling at the insertion point of the achilles tendon to the calcaneus (point of the hock) since it was noted 81.4% of the time (n=35/43). perception of generalised or partial thickening of the achilles tendon was not always present with only 37.2% of the patients exhibiting this characteristic (n=16/43). evidence of wounds and laceration was only reported for 2 patients (4.7%). discomfort upon palpation of the achilles tendon and/or during flexion of the tarsus was evident in 32.6% (n=14/43). on physical examination, it was suspected that achilles tendon was injured unilaterally 79.1% of the cases (n = 34/43, 13 right, 21 left) and bilaterally in 20.9 % of the cases (n=9/43). no grading of the strain was attempted only based on physical examination and clinical assessment. radiographs radiographs were unremarkable for two cases (4.7%). radiographs of the affected tarsus of all the other 41 patients revealed soft tissue swelling at the insertion point of the achilles tendon, as illustrated in figure 1. this change was mild in 4 cases (9.8%) compared to moderate to severe in 37 cases (90.2%). mild bone remodeling and periosteal reaction was noted along the calcaneal tuberosity at the insertion point of the achilles tendon in 11 cases (26.8%, see figure 1 a.). calcification or dystrophic mineralisation was noted within 8 achilles tendons (19.5%, see figure 1 a) whereas bone fragment and suspected avulsion of the calcaneus was present in another 8 cases (19.5%, see figure 1 b and c). signs compatible with tarsal degenerative joint disease were seen in 2 cases (4.9%) including changes in shape and opacity of the joint margins, osteophyte formation, ill-defined subchondral bone/cartilage interface. previous implant migration/failure was noted in 2 cases (4.9%). figure 1: tarsal radiographs of different patients affected by achilles tendon injury ahyperextended latero-medial view left tarsus moderate to severe soft tissue swelling was noted at the insertion point of the achilles’ tendon. mild remodeling was present along the calcaneus at the insertion point of the achilles’ tendon, mild calcification was also noted within the tendon. broutine latero-medial view left tarsus avulsion of achilles tendon. moderate soft tissue swelling was present at the insertion point of the achilles tendon on the calcaneus. bone chip presence is indicative of a presumptive avulsion injury.  croutine latero-medial view left tarsus severe soft tissue swelling was observed at the insert point of the achilles tendon on the calcaneus. bone chips and mineralisation were present, indicating a presumptive chronic avulsion injury.  musculoskeletal diagnostic ultrasound compared to the initial physical examination, it was observed on the diagnostic ultrasound that achilles tendon injuries were unilateral in 51.2% of cases (n=22/43, 7 right, 15 left) and bilateral on presentation in 48.8% of cases (n=21/43). this is significantly (p < 0.05) different from the observed clinical signs on physical examination; where lameness, swelling or hyperflexion of the hock were noted unilaterally in 79.1% of the cases (n = 34/43, 13 right, 21 left) and bilaterally in 20.9 % of the cases (n=9/43). during the available follow-up period (6-36 months), 4 of 22 unilateral cases (18.2%) progressively start showing visible ultrasonographic changes on the contralateral achilles tendon. the injury was partial in 90.7% of the cases (n=39/43) and all three components of the achilles mechanism were completely disrupted in the remaining 9.3% of the cases (n=4/43). however, changes within the fibre patterns of all 3 components of the achilles were seen in 53.8% of the dogs affected by partial achilles tendon injury (n=21/39). in some cases (n=4), the sdft was still intact but the fibres were severely affected at the same level of the complete disruption of the gt and ct. the ‘’claw stance’’ posture was significantly more prevalent (p<0.05) with intact sdft, but was also seen in one case with a complete tear of the achilles mechanism. disruption of only the gt and ct was noted in 41.0% of the cases (n=16/39). see table 1 for the complete repartition of the components of the achilles tendon involved within the strain. table 1: achilles tendon injuries localisation noted on diagnostic ultrasound*this table includes only major findings (clinically relevant) for each patient, but may include changes of bilateral achilles tendons. a total of 64 achilles tendons with abnormalities were evaluated. when different components were involved, the grade may have been different for each component. achilles tendon strains were graded on a scale of i-iii (table 3). grade iii strains were predominant (44.3%), followed by grade i (28.6%), and grade ii (27.1%). grade i strains (see figure 2) had intact architecture, but thickening, inflammation, and stretching may be visible. grade ii strains (see figure 3) were characterised by partial disruption of the fiber alignment, laxity and hypoechoic fibres. grade iii strains (see figure 4), or complete disruption, were distinguished by the presence of a hypoechoic band bordered by the retracted hyperechoic tendon ends. see supplementary table 1 for the complete list of the ultrasonic changes noted and refer to figures 2-4 for illustration of those changes. the strain grade was not correlated to sex, breed, age, occupation and level of activity (p < 0.05). figure 2: grade i strain alongitudinal view of grade i strain of common tendon evidence of right ct early disruption with mild hyperechoic/hypoechoic foci noted at the point of insertion. blongitudinal view of grade i strain of common and gastrocnemius tendons there was a generalised hypoechoic fibre pattern to the ct and gt with no disruption noted.  in addition the common tendon bursa also showed chronic hyperechoic changes consistent with bursitis. figure 3: grade ii strain longitudinal view grade ii strain gastrocnemius and common tendons with grade i superficial digital flexor tendon the right sdft appeared slightly thickened but showed overall good pattern. there was a mild amount of periosteal hyperechoic changes noted at the deep margin of the calcaneus.  there was moderate disruption of the gt, mid tendon with normal identifiable pattern at the distal 1/3 of the tendon and more disruption note proximal to that point. the ct was moderately disrupted at the point of insertion with severe hypoechoic fib pattern and hyperechoic foci at the point of insertion at the calcaneus. in addition there were moderate areas of anechoic findings, indicating moderate fluid accumulation within the bursa.  figure 4: grade iii strainalongitudinal view of a grade iii strain of the achilles tendon (all components involved) this achilles tendon was hypoechoic with loss of normal and mottled appearance. there was a significant amount of hypoechoic soft tissue changes with lack of  fibre pattern noted superficially at and just proximal to the calcaneus. the calcaneal tuberosity also had visible periosteal reaction. bcross-sectional view of a grade iii strain of the achilles tendon (all components involved) there was severe disruption of the gt with a minor amount of identifiable fibre pattern at the distal 1/3 of the tendon, attaching to the calcaneus. there were also age/degenerative hyperechoic changes noted within the common tendon bursa. in general the areas of loss of fibre pattern showed hypoechoic tissue with some fibrous tissue.   the vast majority of the injuries evaluated in these cases were chronic, hence hyperechoic foci, mottled or focal hypoechoic core lesions, overall thickening of the tendon, mineralisation, periosteal hyperechoic reaction along the calcaneus in addition to calcified remodelling were noted. in the chronic cases, a significant amount of hypoechoic soft tissue swelling was also noted within the area of the calcaneus insertion making visualisation of the sdft more difficult. more acute injuries would differ by the presence of oedema (hypoechogenicity between the fibres) and/or significant amount of vascularisation in the disrupted area. generalised hypoechoic appearance to the muscle belly indicated a muscle fibre injury and bruising. in comparison, muscle atrophy was characterised by a more hyperechoic fibre pattern. the term laceration was not used in any diagnostic ultrasound report. therefore, this lesion was not characterised in this study.  damage occurred most commonly at the tendino-osseous insertion (77%) with visible hypoechoic fibre lesions and fibre disruption. the mtj was affected less frequently with injury occurring in 10.5% of the cases and was more likely to be observed in animals that exhibited a plantigrade stance. in 12.5% of the cases, the disruption and loss of fibre pattern noted was more generalised and diffuse along the body of the tendon starting at the insertion onto the calcaneus all the way to the mtj. for one patient, this change was accompanied by several hyperechoic fibres ‘’coiled up’’ amongst the altered muscle tissue which was most likely representing retracted tendon fibers in addition to a musculotendinous rupture (see figure 5). those ultrasonographic characteristics were noted in a patient affected by a complete disruption of the achilles mechanism. figure 5: alteration of the musculotendinous junction (mtj)longitudinal view of the musculotendinous junction the musculotendinous junction of both the gt and the sdf were significantly altered with lack of normal muscle of fibre tendon. several hyperechoic fibs were ‘’coiled up’’ amongst the altered muscle tissue which may be representing retracted tendon fibs from a distal rupture in addition to a mtj rupture. evaluation of the bursa was performed while investigating the insertion of the common tendon. mild amount of hyperechoic changes within the common tendon bursa was frequently identified as normal age-related changes (see figure 4 b). minor hyperechoic fibrous changes within the tendons were also typically age-related. a diagnosis of bursitis was indicated by the presence of anechoic fluid at the point of insertion at the calcaneus along with calcification and fibrous changes within the bursa to a greater degree than the contra-lateral side, in addition to no other tendinous insertion fibre changes (see figures 2 b and 3). methods case selection medical records from august 2009 through may 2016 were analysed for canine and feline patients with suspected achilles tendon injury assessed on physical examination (veterinary orthopedic sports medicine group, annapolis junction, md). physical examination, diagnostic findings, ultrasonic findings, surgical findings, and treatment plans were reviewed. data were collected for patients that underwent musculoskeletal diagnostic ultrasound evaluation of their achilles tendons, with and without surgical repair. inclusion criteria for patients included a diagnosis of achilles tendon injury based on the presence of fibre pattern modification within one or more components of the achilles tendon on initial diagnostic ultrasound. patients were excluded from this study due to incomplete medical records, surgical repair performed without initial diagnostic ultrasound (even though follow-up ultrasounds were available), or absence of achilles tendon pathology noted on diagnostic ultrasound. see supplementary figures 1 and 2 for the description of the case selection process. initial orthopaedic examination complete orthopaedic examination, including gait assessment and palpation, was performed by acvs board certified surgeons. lameness was subjectively graded on a modified i to vi scale (millis, 2004) (table 2). physical examination findings and the recognition of the classic gait – increased extension in the stifle with abnormal flexion in the tarsus with or without contracture of the toes or possibly plantigrade stance (meutstege, 1993; corr et al., 2010) associated with achilles tendon injury were the first steps to diagnosing this condition. table 2: lameness numeric rating scale the integrity of the achilles tendon was also tested in lateral recumbency; the tibiotarsal joint was flexed with  the stifle held in an extended position (meutstege, 1993). as previously described by meutstege, when the hock was partially flexed while the stifle was extended and the digits contracted, it was considered consistent with an achilles tendon tear with an intact superficial digital flexor tendon. when the hock was completely flexed while the stifle was extended without tension of the achilles tendon, it was considered consistent with a complete achilles tendon tear. radiographs routine flexed lateral and plantarodorsal radiographsa of the tarsus were performed in all 43 cases and evaluated by a board certified surgeon. radiographs did not specifically aid in grading and characterisation of achilles tendon strain since soft tissue injuries are not well appreciated using this modality, however indirect markers such as thickening or swelling of the tendon, mineralised fragments, or avulsion were noted. swelling along insertion site on the calcaneus was subjectively graded as mild, moderate or severe by the same examiners. although localisation of the injury to a particular soft tissue structure was not possible on radiographs, other tarsal pathologies including bone fractures, luxations (dislocation or misalignments of the tarsus), abnormal opening of a joint when stressed (varus, valgus, extension, flexion) were ruled out. musculoskeletal diagnostic ultrasound musculoskeletal diagnostic ultrasound of the achilles tendon was offered to all patients presenting with suspected achilles tendon injury. if elected, patients were placed in lateral recumbency and the tarsus and achilles tendon were clipped and prepared routinely with the application of isopropyl alcohol and coupling gel to get direct contact and avoid artifact formation. ultrasound of the affected calcaneal tendon was performed first with subsequent assessment of the contralateral unaffected tendon. most examinations were performed by a single experienced practitioner (debra a cannap), except for 9 cases for which findings were all reviewed by dc. sedation was not required to perform ultrasound examinations.  ultrasound was performed using a hitachi-aloka noblus systemb (18mhz linear probe) and sono site systemc (15mhz linear probe) to acquire longitudinal and cross-sectional images of the achilles tendon and musculotendinous region. in static views, the tarsus was placed in a flexed position to provide some tension on the tendon. dynamic ultrasonographic scanning, achieved by examining the tendon during flexion and extension of the tarsus, was also performed for optional diagnosis of complete achilles tendon rupture. the transducer foot-print was a medium length to maintain good contact and proper alignment with the achilles tendon. echogenicity, fibre pattern, and size of each tendon were recorded and compared to the contralateral achilles tendon. every effort was made to keep the ultrasound beam perpendicular to the area of interest to avoid anisotropy. anisotropy can result in the fibres of the tendon appearing hypoechoic when the angle of the tendon is no longer perpendicular to the ultrasound beam. this can occur when the ultrasound transducer is angled as little as 5 degrees off perpendicular (griffith, 2014). the anatomy was grouped into three components when approaching musculoskeletal ultrasound of the achilles tendon: paired tendons of the gastrocnemius muscle (gt), common tendon (ct, combined tendon of the gracilis, semitendinosus and biceps femoris muscle), and tendon of the superficial digital flexor muscle (sdft). identification of tendon injuries was done using a modified 3-tier grading scheme (archambault et al., 1998; takebayashi et al, 1995) (table 3). a partial injury was defined as the fibre pattern modification of one or more components of the achilles tendon in comparison to a complete tear which involved the entire disruption of all three components (ct, gt, sdft). with a partial injury, all three components may have been affected, but they could not all be grade iii strain as this would have resulted in a complete tear. table 3: definition and description of numerical 3-tier grading scheme for tendinous strain injury an evaluation generally began with the probe placed longitudinally on the achilles tendon in caudal/plantar approach. this view allowed for a general approach to the location to assess the anatomy (see figure 7a and 7b). a cross-sectional view was also of importance when evaluating the insertion of the achilles tendon on the calcaneal tuberosity (see figure 7c and 7d). the achilles tendon was assessed for disruption of the fibre alignment, fibre tears, complete disruption, avulsion, mineralisation, or evidence of chronic fibrosis or bursitis. careful evaluation of the region for concurrent tarsal collateral ligaments and retinaculum tear was pursued. the sdft was dynamically assessed for luxation at the level of the calcaneus, as the hock was flexed. following along all components of the achilles tendon, the myotendinous junction (mtj) and belly muscles were then also evaluated with the transducer placed longitudinally and cross-sectionally. with consideration for the treatment performed, diagnostic ultrasound recheck evaluations were typically recommended at 30, 60 and 90 days to assess healing of the achilles tendon. statistics when indicated, non-parametric paired t-test was performedd. significance was established at p<0.05. figure 6a: normal achilles longitudinal and cross-sectional views longitudinal view of a normal achilles tendon in longitudinal images of the distal part of the tendon the gastrocnemius tendon (gt) lies between the superficial digital flexor tendon (sdft) and the common tendon (ct). the insertional bursa (bursa) of the common tendon is visible at proximity of the calcaneal tuberosity (ca) and its acoustic shadowing. figure 6b: cross-sectional view of a normal achilles tendon proximal in cross-sectional view, the appearance of the 3 components of the achilles tendon remains virtually unchanged in the proximal and middle parts of the tendon. figure 6c: cross-sectional view of a normal achilles tendon distal toward the distal part, the superficial digital flexor tendon (sdft) moves to a more superficial position. figure 6d: cross-sectional view of the sdft visualization of the sdft as it courses over the calcaneal tuberosity (ca). table s1: description of every achilles tendon injuries noted on diagnostic ultrasound *the total number of lesions analysed does not correspond to the number of patients included in this study. one patient may have had injuries to multiples components of the achilles tendon which may have been described using diverse characteristics. figure s1: organigram of the case selection figure s2: organigram of the patients included based on the diagnostic ultrasound results*the number of lesions analysed within each grading categories of strain is not additive and does not correspond to the number of patients included in this study. one patient may have had injuries to multiples components of the achilles tendon which were graded separately and changes may have been bilateral. 43 patients were included in this study, 64 achilles tendons had ultrasonic abnormalities but a total of 133 lesions were graded. discussion the population reported in this case series was similar to previous studies, as labradors and dobermans were overrepresented (reinke et al., 1993; meutstege, 1993; rivers, 1997; kramer et al., 2001; harasen, 2006; corr et al., 2010). middle-age, medium to large breed dogs seemed more predisposed to achilles strain. females had the tendency to be more susceptible to achilles tendon injury, but this distinction was not significant. this finding needs to be taken cautiously due to the small sample size enrolled in this retrospective case study.  a total of 130 cases of achilles tendon injuries in five previous studies: kramer: 20 males, 22 females worth: 3 males, 7 females nielsen: 18 males, 10 females baltzer: 3 males, 2 females corr: 22 males, 23 females (kramer et al., 2001; worth et al., 2004; nielsen et al., 2006; baltzer et al., 2009; corr et al., 2010) identified 64 females and 66 males. with previous studies demonstrating overall equal representation of female and male, it is unlikely that any sex predilection exists in dogs. this is an indirect comparison to humans where men outnumber women with achilles tendon injury (silbernagel, 2015; nyyssonen et al., 2008; ganestam et al., 2016; claessen et al., 2014). the level of activity did not seem to predispose dogs to achilles tendon injury in this study. the ten dogs with reported occupation were not more prone to a higher grade of achilles tendon strain or complete rupture. this also seems to differ from injury in humans as it has been suggested that differences between men and women’s achilles tendon injuries might be due to different levels of the sport activities, especially ball-games (nyyssonen et al., 2008). the authors would like to specify that the occupation was listed in the medical report; some patients may have been more active than noted within their file. the level of activity was not confirmed with the owners in this retrospective case study. patients with plantigrade stance on physical examination did not necessarily have a complete achilles tear on diagnostic ultrasound. three of the four dogs with reported plantigrade stance on physical examination were found to have a grade iii strain of the gt and ct but a grade ii strain of the sdft whereas the fourth dog had a grade iii strain of all achilles tendon components. as previously reported, a plantigrade posture was not predictive of involvement of specific tendons of the achilles tendon nor related to the grade of the strain (corr et al., 2010). corr concluded that plantigrade stance was more likely to be observed in animals that had suffered an injury at the musculotendinous junction, which was also observed in our study. thus, physical examination alone may not be sufficient to characterise achilles tendon strain. moreover, 12 patients were subjectively exhibiting clinical evidence of unilateral strain where ultrasonic evidence of grade i-iii strains was found on the contralateral achilles tendon. the ultrasound was able to detect chronic grade i strain on the contralateral limb of 7 of these 12 dogs, and a few clinically more relevant grade ii and iii strains were also noted in the remaining 5 dogs. the authors believe this may be secondary to the increased sensitivity of the diagnostic ultrasound compared to the physical examination. moreover, in 4 cases (of the 21 dogs noted to have changes within all 3 components of the achilles tendon), the sdft was still intact but the fibres were severely affected at the same level of the complete disruption of the gt and ct which brought up the concern for progressive break down and eventual complete rupture of the achilles mechanism. in those cases, ultrasonography findings were essential in determining adequate treatment options. consequently, the physical examination alone is not always sufficient to correctly assess an achilles tendon strain and elaborate treatment recommendations; particularly with regards to individual tendon involvement, severity of strain, and laterality of the disease process. notwithstanding, ultrasonic changes noted within the achilles tendon may not always be clinically relevant and may be strictly incidental. this may be the case for the previously mentioned 7 dogs that presented for unilateral pelvic limb lameness and for which grade i achilles tendon strains were detected on the contralateral limb during ultrasonography.  as previously reported, advanced imaging findings need to be interpreted with the clinical assessment of the patient (rivers, 1997). further research needs to be conducted to evaluate the clinical implication of low grade strain (grade i) and chronic changes noted on the contralateral achilles tendon as these changes may strictly be compensatory and may not require further treatment if the primary lesion is treated on the most affected side. measurement of each component of the achilles tendon could also potentially help characterise the nature and severity of strain as well as objectively establish guidelines for treatment recommendations. however, measurements were not collected in this study. it has been reported that normal gt, ct and sdft each measured 2.4-3.2 mm thick at mid-calcaneal tendon in cross-sectional view (lamb et al., 2005), but this has not been yet investigated in injured achilles tendon. achilles injury occurs anywhere along the tendon, from the mtj through the insertion, but more commonly occurs at/or approaching the insertion. diagnostic ultrasound findings correlated well with surgical findings (except for one case where progression to a higher strain grade was noted from the initial diagnostic ultrasound to the surgical procedure). the sensitivity and specificity of sonographic evaluation of calcaneal tendon injury in humans has been initially reported as 0.72 and 0.83, respectively (kainberger et al., 1990). the kainberger study also reported that the chronicity of achilles tendon tears might impact the sensitivity of diagnostic ultrasound because fibrous scarring and granulomatous tissue can mask the defect. therefore, this could lead to a false negative ultrasonographic study in chronic cases (kainberger et al., 1990). in that study, ultrasonographic examination was performed with a 7.5 mhz where optimal tendon sonographic evaluation is achieved with utilisation of an 10-22 mhz transducer (griffith, 2014). it was later reported that the use of ultrasonography is reliable in diagnosing partial ruptures of achilles tendon with a sensitivity of 0.94, a specificity of 1.00, and an overall accuracy of 0.95 (kälebo et al., 1992). more recent studies in humans suggest that musculoskeletal ultrasound has moderate to high diagnostic values in elucidation of achilles tendinopathy (henderson et al., 2015). such data are not yet available in veterinary medicine. in the authors’ opinion, the use of diagnostic ultrasound is highly dependent on the experience of the ultrasonographer, the ultrasound machine, and the knowledge of the anatomy, but can provide insight during assessment of canine achilles tendon injury. to the authors’ knowledge, even though there have been  publications describing characteristics of the normal (lamb et al., 2005; kramer et al., 1997; caine et al., 2009), and injured (rivers, 1997; cook, 2016; kramer et al., 2001) achilles tendon by diagnostic ultrasound, there has been no previous in-depth ultrasonic evaluation and characterisation of achilles tendon strains. despite limited sample size, the number of patients included in this retrospective study was judged sufficient to describe the most common ultrasonic findings, localisation and grading associated with achilles tendon injury. further study on the utility of ultrasonic assessment, especially in regards to monitoring of lesions through the treatment and recovery process, is warranted. diagnostic ultrasound recheck examinations can potentially be a key component in assessing the structural integrity of the achilles tendon during the treatment process. further investigation is also needed to evaluate the effectiveness of both non-surgical and surgical treatment modalities, to establish treatment protocols based on a grading scheme for tendinous strain injury, and to evaluate the shortand long-term clinical outcome of patients. it is widely thought, that grade i and grade ii strains can be managed conservatively with regenerative medicine, physical rehabilitation, and immobilisation of the tarsus joint in extension. however, surgical correction has been recommended for higher-grade injury such as grade iii strains, avulsions or lacerations of the achilles tendon. as grading of the strain help establish appropriate treatment, and since physical examination and radiographs are not sufficient to establish grading, this exemplifies the value of diagnostic musculoskeletal ultrasounds for achilles tendon strain in dogs.  footnotes a soundeklin, sound™, carlsbad, ca, usa. b hitachi-aloka, aloka, wallingford, co, usa. c sono site, fujifilm sonosite, inc., bothell, washington, usa. d graphpad prism version 6.00, graphpad software, la jolla, california usa conflict of interest acknowledgments:  the authors would like to thank britt j. carr, dvm, ccrt, jennifer g. barrett, dmv, dacvs-la, dacvsmr, and jennifer brown, dmv, dacvs-la, dacvsmr, ccrt for their help obtaining ultrasonographic imaging. furthermore, the authors wish to thank two anonymous reviewers for their helpful and constructive comments which we believe have greatly improved the quality of this manuscript. funding: none competing interests: the authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript. references archambault, j. m., wiley, j. p., bray, r. c., verhoef, m., wiseman, d. a., & elliott, p. d. 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(1995). sonographic findings in muscle strain injury: clinical and mr imaging correlation. journal of ultrasound in medicine, 14(12), 899–905. http://dx.doi.org/10.7863/jum.1995.14.12.899 vaughan, l.c., 1981. the use of carbon fibre implants for the repair of achilles tendon rupture in dogs. the journal of small animal practice, 22(10), pp.629–634. http://dx.doi.org/10.1111/j.1748-5827.1981.tb00565.x worth, a.j. et al., 2004. ability to work and owner satisfaction following surgical repair of common calcanean tendon injuries in working dogs in new zealand. new zealand veterinary journal, 52(may 2015), pp.109–116. http://dx.doi.org/10.1080/00480169.2004.36415 supplementary files, images & tables all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. mistakes, errors and foul-ups: practice-based evidence for evidence based practice mark turner mres student1 1the royal veterinary college, hawkshead lane, hertfordshire, al9 7ta, united kingdom *corresponding author (mturner@rvc.ac.uk) vol 1, issue 4 (2016) published: 23 nov 2016 doi: 10.18849/ve.v1i4.69 in human medicine, the management of care to ensure safety for the service-user constitutes an important element of the patient ‘journey’. the name given to this discipline is patient safety. it is founded upon those elements of good medical practice which help avoid or mitigate human error... this is a podcast of mark turner's talk at the veterinary evidence today conference, edinburgh november 2, 2016. find out more about mark. view presentation slides comments: choice of suture pattern for linea alba closure a knowledge summary by chrissy roberts ba vetmb certsas mrcvs 1* 1hale veterinary group, 19 langley road, chippenham, wiltshire, sn15 1bs *corresponding author (chrissymaskell@yahoo.co.uk) vol 2, issue 3 (2017) published: 25 sep 2017 reviewed by: victoria arbona (dvm, ms) and bruce smith (bvsc ms fanzcvs dacvs) next review date: 25 sep 2019 doi: 10.18849/ve.v2i3.9 clinical bottom line incidence of complications using either a simple continuous or a simple interrupted suture pattern in the linea alba is low if appropriate suture material is chosen and appropriate surgical technique is used.  more, well-planned studies with higher power are required before an evidence-based recommendation for one pattern over the other can be made. question in adult dogs undergoing elective midline coeliotomy, does using a simple continuous suture pattern in the linea alba affect complication rate when compared to a simple interrupted suture pattern? clinical scenario what suture pattern used for linea alba closure following elective ovariohysterectomy in the bitch will result in the lowest complication rate? the evidence canine midline coeliotomy is a commonly performed procedure in first opinion and referral small animal practice. historically, a simple interrupted suture pattern has been employed to suture the linea alba during closure (bellenger, 2003).  standard surgical texts also refer to a simple continuous pattern (smeak, 2012).  a simple continuous pattern has theoretical benefits over a simple interrupted pattern, taking less time and using less suture material, so it is important to know whether the two result in different complication rates, to allow veterinary surgeons to make an informed decision when choosing a pattern for linea alba closure. different types of study provide different strengths of evidence, as illustrated by evidence pyramids (aragon et al., 2003).  an on-line bibliographic search performed in november 2016 identified 186 possible results.  a review of the results identified only five references with data relevant to answering the current question, and these sources provided only weak evidence as summarised below. summary of the evidence crowe (1978) population: dogs and cats ranging in age from 4 weeks to 19 years undergoing midline coeliotomy for any reason at a veterinary hospital in michigan, u.s.a. over a 2 year period. sample size: 469 dogs and 81 cats, of various sizes and ages. intervention details: the aim of the study was to provide evidence that a simple continuous closure of the linea alba using non-absorbable suture material is safe and effective.  following completion of the intra-abdominal procedure(s), abdominal wall closure was performed using polypropylene in a simple continuous pattern (2 metric for animals <2.5kg, 3 metric for animals 2.5-10kg and 3.5 metric for those >10kg).  suture bites were placed 3-5mm from the incised edge and 5-10mm apart. study design: prospective clinical case series. outcome studied: subjective assessment of patient comfort and the gross characteristics of the healing incision, attempting to follow each patient for at least two months post-operatively. main findings (relevant to pico question): one abdominal wall dehiscence recognised out of 550 abdominal wall closures (0.18%), which occurred due to suture breakage. no other wound complications attributed to the closure or suture material were noted in other patients. limitations: no control group. number of surgeons involved and their experience not stated. 65 animals followed up for 10 days or less – insufficient time for all possible complications to develop. precise nature of follow-up after suture removal (veterinary vs owner assessment) not clear. inclusion/exclusion criteria not clearly stated – i.e. not clear if every consecutive abdominal surgery within the study time period (december 1975 to december 1977) was included or whether some were excluded. not clear if animals that had previously had abdominal surgery were excluded or not. multiple patient and surgical variables: two species, large age range, large weight range (1-80 kg), multiple indications for coeliotomy, large range in length of ‘abdominal incision’ from 3-55cm, variation in wound classification on closure. degree of post-operative confinement not stated. kummeling (1998) population: dogs ≥15kg and > 6 months undergoing any surgical procedure via a midline abdominal incision. dogs with a history of previous coeliotomy excluded. sample size: 40 (20 in each of 2 groups). intervention details: the aim of the study was to compare closure of the rectus sheath with a continuous looped suture with simple interrupted sutures with respect to speed, safety and cost. dogs were randomly allocated to one of two groups. following completion of the intra-abdominal procedure(s), abdominal wall closure was performed using simple continuous double-stranded 3.5 metric polyglyconate (group 1) or single-stranded simple interrupted 3.5 metric polyglyconate (group 2). the simple continuous pattern was performed using a double strand of suture so that a loop of suture with both extremities attached to a swaged needle could be used. the looped suture was anchored at the beginning of the incision by drawing the needle through the loop formed after the first stitch. study design: prospective, randomised controlled trial. outcome studied: time taken to close rectus sheath measured. wounds monitored for three days after surgery. owner assessed outcome obtained via telephone call one month after surgery. main findings (relevant to pico question): dehiscence of linea alba recorded in one case (5%) closed with simple interrupted sutures due to knot loosening. time taken to close rectus sheath significantly shorter using simple continuous pattern (mean duration for rectus sheath closure was 5.3 minutes using simple continuous pattern and 8.7 minutes using simple interrupted pattern).  mean length of incision was 18 cm in the group closed with a simple continuous pattern and 17 cm in the group closed with a simple interrupted pattern. limitations: power calculation not performed. follow-up duration (one month) insufficiently long for fascial healing to occur. owner assessed outcome at the one month time point. wound healing only assessed by a vet for three days post-operatively. double strand of 3.5 metric polyglyconate used in simple continuous closure vs single strand of 3.5 metric polyglyconate used in simple interrupted closure. large variation in weight, age, wound classification and duration of surgical procedure, although the differences in these variables was not significant between groups. variation in how the subcutaneous tissues were closed (one or two layers). nine surgeons involved, level of surgical experience not recorded. degree of confinement post-operatively not recorded/standardised. rosin (1985) population: dogs and cats undergoing a variety of abdominal procedures. sample size: 61 dogs and 30 cats. intervention details: the purpose of the study was to provide evidence that a simple continuous suture pattern for single layer closure of the rectus fascia is a safe alternative to a simple interrupted pattern. following completion of the intra-abdominal procedure(s), abdominal wall closure was performed using a simple continuous pattern. various suture materials were used (polyglycolic acid, polyglactin 910, polydioxanone, polypropylene and nylon). 2 metric suture material was used for cats and small dogs, 3 metric for medium dogs and 3.5 metric for large dogs. suture bites were placed 3-5mm from the incised edge and 5-10mm apart. study design: prospective clinical case series. outcome studied: surgical site examined at the time of removal of skin sutures 6-12 days after surgery. owner assessed outcome obtained by telephone call six months after surgery. main findings (relevant to pico question): no incisional hernias recorded in the dogs. one incisional hernia noted in a cat three weeks after surgery. limitations: no control group. size, age, weight and body condition score of animals not recorded. duration of anaesthesia/surgery for each case not recorded. indication for surgery in each case not recorded. not clear if all incisions were median or whether some were paramedian. wound classification on closure not recorded (e.g. presence or absence of peritonitis). suture material not standardised; various different suture materials with different initial tensile strength and absorption profiles used. time scale of veterinary follow-up (6-12 days) insufficient for fascial healing to occur. kirpensteijn (1993) population: adult mature female mixed breed dogs. sample size: 18 dogs in phase ii (three phase study, phase ii experimental trial most relevant to current pico) intervention details: ventral midline abdominal incision made from 5cm cranial to umbilicus and extending 20cm caudally. incision divided into 4x5cm segments. each segment of linea alba closed with either stainless steel fascial staples or 3.5m polypropylene in a simple continuous pattern. closure technique randomly assigned to each segment. subcutaneous tissue closed with 3 metric polyglactin 910 in a simple continuous pattern. skin apposed with 1.5 metric polyglactin 910 in a simple continuous subcuticular pattern. study design: three phase study: phase i – experimental, cadaveric, biomechanical. phase ii – experimental, randomised, controlled.  dogs were randomly allocated to linea alba closure with staples  or simple continuous closure with polypropylene. phase iii – prospective, clinical (only stainless steel staples used to close the linea alba in this phase). ventral midline abdominal incision made from 5cm cranial to umbilicus and extending 20cm caudally. incision divided into 4x5cm segments. each segment of linea alba closed with either stainless steel fascial staples or 3.5m polypropylene in a simple continuous pattern. closure technique randomly assigned to each segment.  subcutaneous tissue closed with 3 metric polyglactin 910 in a simple continuous pattern. skin apposed with 1.5 metric polyglactin 910 in a simple continuous subcuticular pattern. outcome studied: clinical examination including abdominal incision evaluation twice daily until euthanasia. groups of six dogs each euthanised at 7, 14 and 31 days (groups a, b and c respectively). incisions examined at post-mortem. breaking strength was measured by placing tissue samples in tension grips and applying load until failure. histologic appearance was assessed. main findings (relevant to pico question): all group a and b dogs and one group c dog had mild seroma formation in the subcutaneous tissue at post-mortem examination. omental fat was herniated between staples in group a dogs and one group c dog. one group b dog had omental fat herniated in both a stapled and sutured incision. no other complications reported. limitations: surgical technique (e.g. distance of suture bites from incised edge, distance between suture bites) not described. although 5cm segments of linea alba were closed with a simple continuous pattern, this does not fairly represent closure of a whole linea alba incision with a single simple continuous suture. kennedy (2011) population: cats and dogs from animal shelters eligible for ovariohysterectomy by third-year veterinary students at a veterinary school. animals with concurrent illness or a problem that increased risk of anaesthesia/surgery were excluded. sample size: 307 cats and 206 dogs. intervention details: the purpose of the study was to describe morbidity associated with ovariohysterectomy when performed by third year veterinary student as part of a surgical training programme. animals underwent ventral midline coeliotomy and ovariohysterectomy. linea alba was closed with a simple continuous pattern with synthetic absorbable suture material. each student performed two surgeries. study design: prospective clinical case series. outcome studied: anaesthetic time and complications, surgery time and complications, post-operative complications including seroma formation, abdominal wall dehiscence, incisional infection and skin incision dehiscence. animals assessed every 8 hours until discharge 72 hours after surgery. main findings (relevant to pico question): 7/206 dogs (3.4%) developed major complications. the most common major complication was dehiscence of the abdominal wall. 19/206 dogs (9.2%) developed minor complications including seroma formation, incisional infection or skin incision dehiscence. significantly higher number of major surgical complications observed with students performing their first surgery compared to those performing their second surgery. limitations: no control group. all surgeons were students (limited prior surgical experience). precise type and size of suture material not recorded. details of surgical technique (e.g. distance of suture bite from incision, distance between suture bites) not given. variation in subcutaneous tissue closure between cases. very limited follow-up duration (72 hours). number of dogs developing each specific complication not recorded. appraisal, application and reflection only five sources with data relevant to the current question were identified. two of the sources were randomised controlled trials in adult dogs (kirpensteijn et al., 1993; kummeling et al., 1998). neither study design was optimal. the sample size in the experimental kirpensteijn study was very small (18 dogs), the suture material used for the simple continuous sections of linea alba closure (polypropylene) was not a type that is commonly used in linea alba closure in the u.k., and the ‘control’ was sections of linea alba apposed with stainless steel staples. kummeling (1998) used 20 dogs in each group, but a power calculation was not performed to assess whether this sample size would be sufficient to attain statistical significance given that the difference in complication rate between the two groups was likely to be small. another criticism of the kummeling study is that only one strand 3.5 metric polyglyconate was used for the simple interrupted linea alba closures, whereas a double strand of the same suture material was used for the simple continuous closures. the three remaining studies were prospective case series. all three included cats as well as dogs, the feline outcomes not being relevant to the current question. one of the case series studies (crowe, 1978) again used polypropylene suture material while in another (rosin, 1985) a variety of suture materials and sizes were used.  rosin and crowe gave a description of how sutures were placed (bites placed 3-10mm and 3-5mm from incised edge respectively, with both studies placing bites 5-10mm apart). surgical technique was not described in the third case series (kennedy et al., 2011). the number of surgeons involved and surgical experience was not stated in the rosin and crowe studies, but the kennedy study used third year veterinary students in a surgical training programme, which is likely to have adversely affected complication rates. in all three case series studies, veterinary follow-up was of insufficient duration to allow for fascial healing.  histologic assessment of linea alba healing in the kirpensteijn paper suggests that a minimum follow up of 1 month would be appropriate.  anecdotally, chronic incisional hernias can be noted weeks to years post-operatively (smeak, 2012).  on the human side,the european hernia society guidelines on the closure of abdominal wall incisions (in humans) (muysoms et al., 2015) state that a 3 year follow-up should be mandatory in studies evaluating the rate of postoperative incisional hernia after midline laparotomy in humans. taken together, rosin and crowe provide weak evidence that a simple continuous pattern in the canine linea alba carries a low complication rate, with one major complication in 530 canine coeliotomy procedures (0.19%) (large majority of cases followed for at least 8 weeks on owner-assessed basis). this is in line with findings in humans, where the recommendation is to use a slowly absorbable monofilament suture in a simple continuous single layer aponeurotic closure with a small bite technique (5-8mm fascial bites placed every 5mm) (muysoms et al., 2015). the quality of evidence available to answer this question was disappointing. there were very few randomised controlled studies and those identified had significant flaws in methodology and were lacking in power. the strength of evidence provided by case series studies is less than that provided by randomised controlled studies (aragon et al., 2005). the three case series-based studies identified here had inherent major limitations that further compromised the strength of evidence they provided, the most common limitation being insufficient veterinary follow-up duration. factors other than suture pattern are likely to affect healing of the linea alba post-coeliotomy, including (but not limited to) patient variables such as age and co-morbid disease, indication for surgery and surgical technique. in addition, a suture material that will retain a sufficient percentage of its tensile strength for long enough to support fascial healing should be selected (sanz et al., 1988) regardless of which suture pattern is chosen.  knot security has been shown to be affected by suture type, number of throws per knot and surgeon experience (marturello et al., 2014) so these factors should all be considered when performing surgery. there is certainly scope for well-planned and executed studies in this area. a prospective, randomised controlled study comparing two groups of healthy adult dogs matched for age, size and body condition score undergoing elective ovariohysterectomy would be helpful.  a power calculation needs to be performed before the study starts to ensure the groups are an appropriate size.  midline coeliotomy is likely one of the most commonly performed procedures in small animal practice in the uk so an improved evidence base regarding closure technique would be valuable. methodology section search strategy databases searched and dates covered: cab abstracts 1973 to 2016 week 45  pubmed 1910 – november 2016 reference lists for chapter 17 (suture material, tissue staplers, ligation devices and closure methods) and chapter 84 (abdominal wall reconstruction and hernias) in: tobias and johnston (eds) veterinary surgery small animal, missouri, elsevier, 2012. reference list for chapter 18 (suture materials, tissue adhesives, staplers and ligating clips), chapter 29 (abdominal wall) and chapter 32 (abdominal hernias) in: slatter, d (ed) textbook of small animal surgery, philadelphia, elsevier, 2003. search terms: cab abstracts: dog or dogs or canine or bitch* midline or mid-line or median or ‘median line’ or ‘linea alba’ or coeliotom* or celiotom* or laparotomy* interrupt* or continuous suture* or pattern suture* and pattern (1 and 2 and 3 and 4) or (1 and 2 and 5) pubmed: dog or dogs or canine or canines or bitch or canis midline or mid-line or median line or linea alba or coeliotomy or celiotomy or laparotomy suture or pattern dates searches performed: 24th november 2016 exclusion / inclusion criteria exclusion: references written in a language other than english study on species other than dog title not relevant to pico full text not relevant to pico inclusion: studies assessing healing of midline coeliotomy incisions in dogs where either a simple interrupted or simple continuous suture pattern was used for linea alba closure. search outcome database number of results excluded – title not relevant to pico excluded – species other than canine excluded – paper not relevant to pico on reading full text total relevant papers cab abstracts 25 22 0 0 3 ncbi pubmed 161 159 0 0 1 reference list, chapter 17, tobias and johnston 164 163 0 0 1 reference list, chapter 84, tobias and johnston 125 119 4 0 2 reference list, chapter 18, slatter 77 74 2 0 1 reference list, chapter 29, slatter 48 39 4 1 4 reference list, chapter 32, slatter 86 81 3 1 1 total relevant papers when duplicates removed 5 conflict of interest the author declares that there was no conflict of interest in the preparation of this paper. references aragon, c. and budsberg, s. (2005). applications of evidence-based medicine: cranial cruciate ligament injury repair in the dog. veterinary surgery, 34 pp. 93-8 http://dx.doi.org/10.1111/j.1532-950x.2005.00016.x bellenger, c. (2003) abdominal wall. in slatter: textbook of small animal surgery, 405-13.crowe, d. (1978). closure of abdominal incisions using a continuous polypropylene suture: clinical experience in 550 dogs and cats. veterinary surgery, 7 pp. 74-7. kennedy, k., tamburello, k. and hardie, r. (2011). peri-operative morbidity associated with ovariohysterectomy performed as part of a third-year veterinary surgical training program.  journal of veterinary medical education, 38 (4), pp. 408-13. http://dx.doi.org/10.3138/jvme.38.4.408 kirpensteijn, j., fingland, r., boyer, j. et al. (1993). comparison of stainless steel fascial staples and polypropylene suture material for closure of the linea alba in dogs. veterinary surgery, 22 (6), pp. 464-72. http://dx.doi.org/10.1111/j.1532-950x.1993.tb00423.x kummeling, a. and van sluijs, f. (1998).  closure of the rectus sheath with a continuous looped suture and the skin with staples in dogs: speed, safety and costs compared to closure of the rectus sheath with interrupted sutures and the skin with a continuous subdermal suture.  the veterinary quarterly, 20 (4), 126-30. http://dx.doi.org/10.1080/01652176.1998.9694856 marturello, d., mcfadden, m., bennett, a., et al. (2014). knot security and tensile strength of suture materials.  veterinary surgery, 43 (1), pp. 73-9. http://dx.doi.org/10.1111/j.1532-950x.2013.12076.x muysoms, f., antoniou, s., bury, k. et al. (2015). european hernia society guidelines on the closure of abdominal wall incisions.  hernia, 19 (1), 1-24. http://dx.doi.org/10.1007/s10029-014-1342-5 rosin, e. (1985). single layer, simple continuous suture pattern for closure of abdominal incisions.  journal of the american animal hospital association, 21, 751-6. sanz, l., patterson, j., willet, g. et al. (1988) comparison of maxon suture with vicryl, chromic catgut, and pds sutures in fascial closures in rats.  obstetrics and gynaecology 71, 418-22. smeak, d. (2012). abdominal wall reconstruction and hernias. in tobias and johnston: veterinary surgery: small animal, 1353-79 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. full text template title | veterinary evidence skip to main content knowledge summary surgical castration in dogs: does the incision approach influence postoperative recovery? ariel brunn, dvm msc mrcvs 1 london school of hygiene & tropical medicine, keppel street london wc1e 7ht * corresponding author email: ariel.brunn@lshtm.ac.uk vol 7, issue 4 (2022) submitted 01 feb 2022; published: 29 dec 2022; next review: 10 jun 2024 doi: https://doi.org/10.18849/ve.v7i4.587 pico question in male dogs undergoing surgical castration, does a pre-scrotal approach in comparison to a scrotal approach lead to a superior recovery, in terms of duration of postoperative pain and/or reduced post-operative complications? clinical bottom line category of research treatment. number and type of study designs reviewed two prospective clinical trials were critically appraised. strength of evidence weak. outcomes reported woodruff et al. (2015) evaluated postoperative recovery in 206 dogs following surgical castration using a scrotal incision in comparison to 231 dogs using a pre-scrotal approach. complications observed in order of frequency, included: incisional swelling; haemorrhage; pain; and self-trauma, however, apart from self-trauma, complications were not influenced by incision location. dogs castrated using a scrotal approach had reduced odds of self-trauma (or: 0.51, p = 0.04, 95% ci 0.27–0.97). moreover, mean duration of surgery was faster for the scrotal versus the pre-scrotal approach (3.6 minutes, p<0.01, 95% ci 3.38–3.82 versus 5.1 minutes, 95% ci 4.86–5.41). miller et al. (2018) evaluated complication rates following open or closed castration using a scrotal approach in 400 shelter dogs under the age of 6 months. complications involving intra-operative bleeding were not observed, while marginal rates of post-operative events were reported, including peri-incisional dermatitis (2.3%), skin bruising (1.0%), and swelling (0.3%). no self-trauma or rescue analgesia was recorded. in comparing surgical time, the mean duration was 1 minute ± 0.2 minutes in dogs undergoing scrotal surgery, in comparison to canine patients undergoing the same procedure using a pre-scrotal approach, where the mean duration was 3.5 minutes ± 0.4 minutes. conclusion the outcomes of these two studies imply that a scrotal incisional approach in canine castration is at least no worse in the first 24 hours than a traditional pre-scrotal approach and may also reduce mean duration of surgery. however, limitations to the evidence do not permit a firm conclusion and it also remains unclear whether these advantages persist in the longer postoperative period. further research is needed to confirm initial findings suggested here. how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you have agreed to provide elective neutering for a local animal shelter. there are a number of male dogs that need to be castrated prior to their imminent adoption and a colleague suggests you consider using the high-quality high-volume method of scrotal castration. since you want to be certain that the technique you use is based on the best available evidence, you decide to review if postoperative pain and complication rates using a scrotal incisional approach are equivalent to the more familiar method of a pre-scrotal incision that you use on your client-owned patients. the evidence following a literature search in two databases, pubmed and cab abstracts, two papers met inclusion criteria for this summary. both studies evaluated postoperative complications following orchidectomy via direct scrotal access, as well as measuring surgical duration in comparison to traditional castration methods. summary of the evidence woodruff et al. (2015) population: healthy male dogs older than 6 months with a body weight ranging from 3–60 kg (average 17 kg) were selected from five shelters associated with mississippi state university (msu) and the humane alliance (ha) in north carolina. cryptorchid dogs were excluded. sample size: 437 dogs in total. intervention details: random allocation of dogs into two treatment groups: 206 underwent castration with a pre-scrotal incision and 231 underwent castration with a scrotal incision. dogs in each group were anaesthetised with intravenous (iv) butorphanol (0.35 mg/kg); ketamine (3.5 mg/kg); and dexmedetomidine (17.5 ug/kg) combination. preoperative analgesia was given as subcutaneous carprofen (4.4. mg/kg). dogs from both groups underwent identical surgical preparation of the scrotum and pre-scrotal area with a chlorhexidine scrub prior to being moved into theatre. dogs were placed in dorsal recumbency and aseptically draped. dogs in the group with pre-scrotal access had a skin incision made cranial to the scrotum and a closed method used for castration. the incision was closed using an interrupted intradermal pattern (2-0 polyglactin 910 suture). dogs in the group with scrotal access had a midline incision made ventrally in the scrotum and a closed method of castration used, as per the pre-scrotal group. the incision was left open with placement of a single subcutaneous suture (2-0 polyglactin 910 suture). post-operative complications were monitored by shelter employees or private owners. study design: randomised positive control multi-site clinical trial. outcome studied: haemorrhage; pain; self-trauma for 24 hours; swelling at incision site after 2, 4, 6, 24, 48, 72 hours. duration of surgery. main findings (relevant to pico question): self-trauma was observed in 54 dogs in total (pre-scrotal incision group: 34 dogs; scrotal incision group: 20 dogs). the odds of self-trauma were reduced in dogs with a scrotal incision (or: 0.51, p = 0.04, 95% ci 0.27­–0.97). haemorrhage, pain and swelling at any time after surgery were not significantly different between the two interventions. length of surgery was shorter on average for the scrotal approach group (3.6 minutes, p<0.01, 95% ci 3.38–3.82 versus 5.1 minutes for the pre-scrotal group, 95% ci 4.86–5.41) (measured at one site only – msu). limitations: postoperative monitoring was done by shelter staff in mississippi, whereas in north carolina, dogs were monitored by owners. method of pain assessment did not use a validated scale. other than incisional swelling, complications were only monitored for the first 24 hours.   miller et al. (2018) population: shelter-owned male dogs between 2–5 months of age with a body weight 0.9–11.4 kg (median 3.6 kg) were recruited over a 12 month period for castration. sample size: 418 dogs. intervention details: 400 dogs underwent suture-less scrotal castration, and 18 dogs underwent traditional pre-scrotal castration. dogs in both groups were anaesthetised with a combination of midazolam hydrochloride (0.55 mg/kg) and ketamine hydrochloride (5 mg/kg), after preoperative buprenorphine (0.015 mg/kg). gas anaesthesia was maintained with isoflurane and 100% oxygen for the duration of the procedure. scrotal and pre-scrotal areas were prepped with a 4% chlorhexidine solution and alcohol for both groups. a scrotal incision was made ventrally, and open or closed castration was performed at the discretion of the surgeon. the scrotal incision was closed with 1–2 drops of tissue glue. for the pre-scrotal procedure, a midline skin incision was made cranial to the scrotum and either an open or closed castration performed, as per the methods outlined for scrotal incision. skin was closed with a single subcutaneous cruciate suture and the dermis closed with tissue glue. duration of surgery was timed for the 18 dogs that underwent pre-scrotal castration procedures as well as for 18 dogs from the original 400 that underwent scrotal castration. study design: prospective single site clinical trial. outcome studied: post-operative complications were monitored for 24 hours and included haemorrhage, pain, self-trauma, swelling, and dermatitis at the incision site. incisional pain was assessed visually with and without gentle palpation. duration of surgery was measured for two intervention groups. main findings (relevant to pico question): complication rates for open and closed castration methods were not significantly different (p=0.08). post-operative complications reported: 9/400 (2.3%) had peri-incisional dermatitis, 4/400 (1%), had skin bruising, and 1/400 (0.3%) had swelling. mean surgery time for the scrotal procedure was shorter (1.0 ± 0.2 minutes) than for the pre-scrotal procedure (3.5 ± 0.4 minutes) (p <0.001). limitations: complications were only monitored for 24 hours. no randomisation procedures described for the comparative study aspect (duration of surgery outcome). lack of a positive control group to compare complication rates. method of pain assessment did not use a validated scale.   appraisal, application and reflection castration in the male dog is a common surgical procedure with multiple indications including humane population control, modulation of certain undesirable behaviours (mcgreevy et al., 2018), and as an intervention in the control of some health conditions caused by infectious, endocrine, testicular and epidydimal pathologies (hamilton et al., 2014). it is conventionally taught using an incisional approach made cranial to the scrotum that avoids excessive tissue handling of the scrotal skin. some authors have suggested that this approach, which is unique among domestic animal species, is due to a higher infection risk related to the canine scrotum resting on the ground during sitting (wilson, 1975) or that male dogs are ‘scrotal conscious’ and prone to self-trauma (howe, 2006). since canine orchidectomy is widely taught and performed in companion animal practice and variations on the technique exist, evidence review is warranted to further refine a patient-centered approach for this routine procedure. in this critical appraisal of the literature, the evidence supporting the use of a scrotal incision to perform orchidectomy was evaluated against the traditional pre-scrotal approach. two north american studies met the inclusion criteria comparing patient outcomes after castration using the two different incisional access points. post-operative recovery was assessed through observation of incisional swelling, haemorrhage, self-trauma, and pain. since surgical duration is associated with incision infection risk (eugster et al., 2004), the length of each procedure was also recorded and compared. results from a randomised positive control multisite clinical trial conducted in 2015 found that the odds of self-trauma were reduced in dogs undergoing castration with a scrotal incision (or: 0.51, p=0.04, 95% ci 0.27–0.97) in comparison to the positive control group, and that other complications observed were not attributable to differences in location of the skin incision (woodruff et al., 2015). in a subsequent study by miller et al. (2018), post-operative complications were recorded for 24 hours for 400 dogs after undergoing castration using a scrotal approach. complications were reported as peri-incisional dermatitis in 9/400 (2.3%) dogs, as well as skin bruising in 4/400 (1.0%) dogs and incisional swelling in 1/400 (0.3%). in britain, the reported rate of postoperative complications occurring at any time after canine castration is 10.83% (95% ci 8.51%–13.69%) (nasan, 2021). these two studies suggest that the risk of postoperative complications in the first 24 hours is at least no worse when a direct scrotal approach to orchidectomy is used and begin to unpick the assumption that the traditional pre-scrotal technique is safest. the protective effect of a scrotal incision against self-trauma reported by woodruff et al. (2015) conflicts with historic assumptions related to sensitivity of the scrotal tissues. moreover, both studies highlighted a shorter duration of surgery in dogs undergoing a scrotal castration approach. a methodology review suggested that increased surgical efficiency of direct scrotal access results from reduced time required to locate and exteriorise the gonads, as well as less time taken to close the incision, since the incision is normally left to heal by second intention or closed with tissue glue (digangi et al., 2016). the preference for pre-scrotal access may be due to the cosmetic finish of a closed skin incision yielding minimal discharge, as this is generally considered to be more acceptable to pet owners since patients recover from surgery in the home. however, preventive wound management such as scrotal wrapping, adhesive dressing or a wound spray may lessen discharge (digangi et al., 2016), and the imperative to minimise complication risk for elective procedures in animals might one day support a shift in consensus on the most optimal access point for canine castration. currently, however, several limitations prevent firm conclusions from being drawn from this critical appraisal of the evidence. only two studies met the inclusion criteria and both were conducted in the usa, where acceptance of companion animal neutering is generally very high. it is possible that patient outcomes observed in the included studies may not reflect those in other countries. furthermore, use of multiple employees and / or private owners to observe patient recoveries as occurred in the assessed studies could have contributed to inconsistent observations. neither study indicated that validated questionnaires or scoring systems were used in the assessment of subjective parameters, for example, the glasgow composite measure pain scale to evaluate pain scores. alongside inter-observer variability, differences in recovery setting (home recovery versus shelter) could also have influenced the likelihood of complication observation, since patients recovering in a home may receive more attentive care. finally, further research is justified to evaluate postoperative complications that occur more than 24 hours after surgery, as well as trials conducted with larger sample sizes drawn from multiple sites. this review provides support that frequently performed and routine elective procedures warrant periodic and critical review of underlying assumptions. modern surgical techniques and perioperative care may improve outcomes of direct (scrotal) incisional approach in canine castration at least in the first 24 hours, but it remains unclear whether the advantages described in the papers reviewed would be maintained in the longer postoperative period. methodology search strategy databases searched and dates covered: cab abstracts on ovid platform 1973 to 2021 week 47 pubmed accessed via the ncbi website 1920–december 2021 search strategy: cab abstracts: (dog* or canine* or canis).mp. or exp dogs/ (castrat* or neuter* or gonadectom* or steriliz* or sterilis*).mp. or exp sterilization/ or exp castration/ or exp gonadectomy/ ((surger* or surgical or incision* or approach or method).mp. or exp surgery/) adj3 ((pre-scrotal or pre-scrotal or prescrotum or scrotal or scrotum).mp. or exp scrotum/) 1 and 2 and 3    pubmed: #1   dog or canine or canis #2   castrate or castration or neuter or gonadectomy or sterilize or sterilise #3   (surgery or surgical or incision or approach or method) and (pre-scrotal or pre-scrotal or prescrotum or scrotal or scrotum) #4   #1 and #2 and #3 dates searches performed: 10 jun 2022   exclusion / inclusion criteria exclusion: case studies or case series. non-english language. review article. intervention not relevant to pico. inclusion: clinical trial or observational study. english language. canine species. comparative study.   search outcome database number of results duplicates excluded – not english or not accessible excluded – review excluded – other intervention total relevant papers cab abstracts 23 0 5 2 16 0 pubmed 75 4 5 1 64 1 hand search 1 – – – – 1 total relevant papers when duplicates removed 2   acknowledgements the author thanks the rcvs library and knowledge services for assistance with the literature search. the author also gratefully acknowledges insightful discussions with ukrainian colleagues, in particular dr kate lutskevych, which eventually led to the development of this evidence appraisal. orcid ariel brunn: https://orcid.org/0000-0003-2084-6735 conflict of interest the author declares no conflicts of interest. references digangi, b.a., johnson, m.d. & isaza, n. (2016). scrotal approach to canine orchiectomy. clinician’s brief. 5, 87–93. eugster, s., schawalder, p., gaschen, f. & boerlin, p. (2004). a prospective study of postoperative surgical site infections in dogs and cats. veterinary surgery. 33(5), 542–550. doi: https://doi.org/10.1111/j.1532-950x.2004.04076.x hamilton, k.h., henderson, e.r., toscano, m. & chanoit, g.p. (2014). comparison of postoperative complications in healthy dogs undergoing open and closed orchidectomy. journal of small animal practice. 55(10), 521–526. doi: https://doi.org/10.1111/jsap.12266 howe, l. (2006). surgical methods of contraception and sterilization. theriogenology. 66(3), 500–509. doi: https://doi.org/10.1016/j.theriogenology.2006.04.005 miller, k.p, rekara, w.l., detar, l.g., blanchette, j.m. & milovancev, m. (2018). evaluation of sutureless scrotal castration for pediatric and juvenile dogs. journal of the american veterinary medical association. 253(12), 1589–1593. doi: https://doi.org/10.2460/javma.253.12.1589 mcgreevy, p.d., wilson, b., starling, m.j. & serpell, j.a. (2018). behavioural risks in male dogs with minimal lifetime exposure to gonadal hormones may complicate population-control benefits of desexing. plos one. 13(5), e0196284. doi: https://doi.org/10.1371/journal.pone.0196284 national audit for small animal neutering (nasan). (2021). routine neutering complication rates. vetaudit rcvs knowledge. [online]. available at: https://knowledge.rcvs.org.uk/quality-improvement/tools-and-resources/vetaudit/ [accessed september 2022]. wilson, g.p. (1975). surgery of the male reproductive tract. veterinary clinics of north america. 5(3), 537–550. doi: https://doi.org/10.1016/s0091-0279(75)50067-5 woodruff, k., rigdon-brestle, k., bushby, p.a., wills, r. & huston, c. (2015). scrotal castration versus pre-scrotal castration in dogs. veterinary medicine. 110(5), 131–135. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use.   veterinary evidence is an rcvs knowledge initiative. issn: 2396-9776 first floor, 10 queen street place, london ec4r 1be resources student awards staff login policies privacy policy accessing information policy cookie declaration terms of use copyright notices stay connected podcasts twitter facebook instagram linkedin back to top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443. <p><span style="color: #7d0063; font-size: 20px;"><strong>thank you to our 2021 reviewers</strong></span></p> <!-authors --> <!-author 1 --><strong>dr kit sturgess </strong>ma vetmb phd certvr dsam certvc frcvs<sup>1*</sup><br /> <!-affiliations --> <p><span style="font-size: 12px;"> <sup>1</sup>vet freedom ltd brockenhurst, hampshire, so42 7qt<br> <sup>*</sup>corresponding author (<a href="mailto:kit.sturgess@btopenworld.com">kit.sturgess@btopenworld.com</a>) </span></p> <hr> <!-this is an anchor for "back to the top. do not delete" --><a name="index"></a> <!-dates and reviews --> <span style="font-size: 11px;"> <p><strong>vol 7, issue 1 (2022)</strong></p> <p><strong>published:</strong> 21 jan 2022</p> <p><strong>doi:&nbsp;</strong><span class="galley-doi-value" style="color: #0000ff;"><a style="color: #0000ff;" href="https://doi.org/10.18849/ve.v7i1.562" target="_blank">10.18849/ve.v7i1.562</a></span></p> </span> </span> <hr> <p>as 2021 draws to a close i suspect few of us could have foreseen the past year. in the early part of the year, as covid-19 vaccination gathered pace, like many, i was hopeful that we would be seeing coronavirus in the rear-view mirror by the end of the year ― only then to find ourselves in the midst of another wave of cases.</p> <p>despite all the headwinds of coronavirus and the impact of working from home, <em>veterinary evidence</em> has continued to flourish, publishing more papers this year than last. published papers have covered an amazing range of different topics, illustrating not just the wide diversity of questions that are being answered, but the depth and breadth of the team of reviewers that give their time to extend veterinary knowledge, supported by a dedicated group of assistant editors and staff at the journal who coordinate activity, ensure standards, and continue to develop the journal.</p> <p>as a journal, <em>veterinary evidence</em> is maturing with two of the main focuses this year being to further develop our internal journal systems ― which has allowed us to apply for membership of cope (committee on publication ethics) ― and work towards improving the discoverability and accessibility of our published papers. in order to achieve this, the team is working hard to redesign our current website and fulfil the criteria for inclusion in other citation databases beyond cab abstracts, such as medline.</p> <p>we have been delighted this year to expand our editorial board ensuring, as the journal grows, we have the necessary range of skills on the board to maintain high quality, effective reviews delivered in a timely manner. i would like to take this opportunity to thank all our reviewers and everyone who has served on the board this year for their tireless efforts on behalf of <em>veterinary evidence</em> &ndash; without your support the journal could not exist. this year the board has had three online meetings, more than ever before, which have been essential in helping develop the strategy for <em>veterinary evidence</em> over the coming years, expanding the influence and reach of the journal with various strategic initiatives. other key areas have included developing our policy on standard terminology, looking at the best ways to ensure knowledge summaries remain current and working towards making editorial decisions as consistent as possible.</p> <p>and finally&hellip; a huge thank you to everyone who works for and supports <em>veterinary evidence</em>, wishing you all a safe and productive 2022.</p> <p>&nbsp;</p> <p>kit sturgess</p> <p>editor-in-chief</p> <p>&nbsp;</p> <p>&nbsp;</p> <p>adewole adekola</p> <p>jane alexander</p> <p>fergus allerton</p> <p>elizabeth baines</p> <p>simon bate</p> <p>julia beatty</p> <p>jackie brearley</p> <p>jenny brown</p> <p>louise buckley</p> <p>john campbell</p> <p>hilary causer</p> <p>peter cockcroft</p> <p>jacqueline cole</p> <p>francesca compostella</p> <p>rachel conwell</p> <p>claire corridan</p> <p>amanda curtis</p> <p>michael decozar</p> <p>laura dixon</p> <p>sam double</p> <p>tom dutton</p> <p>jacklyn ellis</p> <p>virginia fajt</p> <p>myra forster-van hijfte</p> <p>merran govendir</p> <p>john hird</p> <p>joanne ireland</p> <p>anji jonas</p> <p>theodora k. tsouloufi</p> <p>sarah keir</p> <p>latifa khenissi</p> <p>clare knottenbelt</p> <p>dave leicester</p> <p>zofia lisowski</p> <p>kate loomes</p> <p>panos loukopoulos</p> <p>tim mair</p> <p>tristen merlin</p> <p>andy morris</p> <p>diego moya fernandez</p> <p>john munday</p> <p>malcolm ness</p> <p>constance neville white</p> <p>kazuya oikawa</p> <p>maureen o'mara</p> <p>catherine oxtoby</p> <p>april paul</p> <p>catrina pennington</p> <p>robert pettitt</p> <p>kirstie pickles</p> <p>brian pound</p> <p>david ramey</p> <p>nicki reed</p> <p>david rendle</p> <p>iain richards</p> <p>suzanne rogers</p> <p>rebecca schofield</p> <p>mark senior</p> <p>gon&ccedil;alo serrano</p> <p>tom shaw</p> <p>josh slater</p> <p>lesca sofyan</p> <p>eva spada</p> <p>mike steele</p> <p>adam swallow</p> <p>james swann</p> <p>faye swinbourne</p> <p>sam taylor</p> <p>christopher thom</p> <p>david thomas</p> <p>tom towers</p> <p>nieky van veggel</p> <p>elke van der vekens</p> <p>kate walters</p> <p>richard white</p> <p>adele williams</p> <hr> <br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="open access" /> in dogs with snakebites does the use of antimicrobials compared to no antimicrobials reduce incidence of wound infection? | veterinary evidence skip to main content knowledge summary keywords: dog; canine; snakebite; snake; envenomation; antibiotic; antibiotic resistance; abr; antimicrobial; antimicrobial resistance; amr; one health in dogs with snakebites does the use of antimicrobials compared to no antimicrobials reduce incidence of wound infection? megan ballman, bvmsci(hons) fcggr acmi mrcvs1 davide messina, dvm gclt fhea mrcvs2* 1 scott veterinary clinic, 405 goldington road, bedford, mk41 0ds 2 school of veterinary medicine and science, the university of nottingham, sutton bonington campus, leicestershire, le12 5rd * corresponding author email: davide.messina1@nottingham.ac.uk vol 8, issue 3 (2023) submitted 25 apr 2021; published: 28 jul 2023; next review: 30 mar 2025 doi: https://doi.org/10.18849/ve.v8i3.513 pico question in dogs with snakebites does the use of antimicrobials compared to no antimicrobials reduce incidence of wound infection? clinical bottom line category of research treatment. number and type of study designs reviewed seven case series. strength of evidence weak. outcomes reported three studies looked at the incidence of wound infection in envenomated dogs, three compared antimicrobial use to mortality and one compared other outcomes, such as time in hospital. the incidence of wound infection was low in the studies and overall antimicrobials seemed to have no significant effect on outcomes such as survival or wound infection. therefore, the routine use of antimicrobials for snakebite treatment is not supported by the results, however further studies are required to provide conclusive evidence. conclusion there is currently insufficient evidence from literature to either support or reject the use of antimicrobials in the treatment of snakebites. how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a client has brought in a dog that has a suspected snakebite. you are aware that infection in the wound is possible due to bacteria present on snake fangs, but you want to only prescribe antimicrobials when they are necessary. you want to know whether there is evidence that the use of antimicrobials for this case will improve clinical outcome by reducing incidence of wound infection compared to no antimicrobial intervention. snakebites have long been treated with antivenin, but the therapeutic approach in terms of ideal supportive care remains up for debate. snakes are known to harbour bacteria in their oral cavity, including salmonella, pseudomonas aeruginosa, proteus spp., coagulase-negative staphylococcus spp., clostridium spp., and bacteroides fragilis (peterson, 2006). consequently, many veterinary references recommend the use of antimicrobials following envenomation to prevent wound contamination. comparable research on this topic is lacking in veterinary medicine, nevertheless with the increasing issue of antimicrobial resistance, it is ever more vital for veterinarians to dispense antimicrobials only when they are needed. it is therefore important to consider whether the use of antimicrobials in the treatment of snakebites reduces the risk of wound infection, and therefore whether they are a necessary part of the therapeutic treatment. the evidence there is a lack of evidence available that supports the pico question due to the existence of very few papers that analyse the use of antimicrobials, which are referred to as antibiotics in some papers. at the time of writing there were no studies directly comparing antimicrobial treatment to no antimicrobial treatment. two studies (lervik et al., 2010; and carr & schultz, 2015) were identified that look at the incidence of wound infection following a snakebite. although no statistical analysis was performed, pritchard et al. (2014) reported incidence of infection following snakebite of the dogs in their paper so was also included. the papers by mccown et al. (2009) and kim et al. (2022) were deemed relevant due to the evaluation of the clinical outcome of survival following antimicrobial administration. similarly, witsil et al. (2015) presented data about antimicrobials and rate of mortality, while hackett et al. (2002) compared outcomes such as clinicopathological data, treatment costs and days in hospital, to use of antimicrobials. overall, current study limitations provide insufficient evidence to support or reject the use of antimicrobials. further randomised controlled trials (rct) that directly compare wound infection to antimicrobial administration would greatly help in providing a more reliable proof for this pico. summary of the evidence carr & schultz (2015) population: dogs that were presented following rattlesnake envenomation, at a 24-hour referral hospital in murrieta, california, between march 2012 and may 2013. inclusion criteria: received no antimicrobials. witnessed rattlesnake envenomations. highly suspected envenomations (e.g. rattle was heard, patient yelped and consistent bite wounds evident). suspected envenomations with bite marks, swelling and echinocyte tests that were >90% positive. exclusion criteria: were placed on antimicrobials by referring veterinarian prior to transfer. were initiated on antimicrobials during hospitalisation for conditions unrelated to envenomation. death or euthanasia within 24 hours of presentation. lost to follow-up conducted within 2 weeks by phone or direct inspection of wound. sample size: 102 dogs. intervention details: most (82%) were treated with: intravenous (iv) crystalloid fluids; hydromorphone; antivenom most received crotalidae polyvalent antivenom or received crotalidae polyvalent immune fab (n = 1); release within 24 hours. severe cases (23.5%): diagnosis based on clinical signs combined with either a decreased platelet count, increased prothrombin time, or both, consistent with venom-induced coagulopathy (vic). developed vic was hospitalised for 2 days (n = 1): received crotalidae polyvalent immune fab (n = 1). developed infection (abscess to thoracic limb) suspected to be secondary to compartment syndrome (n = 1): empirical therapy instituted using cefazolin 10 mg/kg iv every 8 hours; aerobic and anaerobic bacterial culture and sensitivity obtained from the abscess; therapy continued with cephalexin 22 mg/kg po every 12 hours for 14 days; abscess surgically debrided and managed with wet-to-dry bandages until the wound could be closed primarily. showed signs of flaccid paralysis and muscle fasciculations consistent with neurotoxic envenomation (n = 1): hospitalised for 3 days. owner declined hospitalisation, (18/102): defined as ‘outpatient’ – hospitalisation for ≤ 4 hours; received antivenin and narcotic analgesics (n = 12); declined all treatment apart from analgesics (n = 6). study design: prospective observational case series. outcome studied: location of bite and head strike. treatment used. mortality. follow-up: direct examination of wound within 2 weeks or; telephone contact with questions regarding: wound healing; signs of infection; need for follow-up care. incidence of wound infection. in one case with an abscess aerobic and anaerobic bacterial culture and sensitivity was obtained. main findings (relevant to pico question): three patients died shortly after presentation from conditions that were clearly not antimicrobial responsive: mortality rate = 2%. of 102 cases, only one developed an infection, that was secondary to suspected compartment syndrome and development of an abscess to the thoracic limb. staphylococcus aureus and pasteurella species were cultured from one case, the anaerobic culture was negative: more consistent with skin contamination of the victim rather than oral flora of the snake. limitations: power of study not calculated. loss to follow-up (n=4). inadequate follow-up techniques as phone calls replaced physical inspection of wound in most cases. cannot confirm subclinical infection develops. did not use a severity scoring system to identify wounds that could potentially become necrotic. treatment and monitoring protocols not standardised.   hackett et al. (2002) population: dogs treated for snakebite at the colorado state university veterinary teaching hospital during a 10-year period (1989–1998). inclusion criteria: contact with a rattlesnake was witnessed or; compatible clinical signs of severe swelling around paired puncture wounds. exclusion criteria: any doubt in the medical record of the diagnosis of rattlesnake envenomation. sample size: 100 dogs. intervention details: hospitalised (n = 94) or outpatient treatment (n = 6). intravenous (iv) fluid therapy consisting of crystalloid fluids (n = 84). one unit fresh whole blood (n = 3). one unit fresh frozen plasma (n = 1). heparin (n = 10). narcotic analgesic drugs (n = 15): morphine, oxymorphone and fentanyl. ketoprofen 1.5 mg/kg (n = 1). antivenin (n = 23). glucocorticoids (dexamethasone sodium phosphate) (n = 87): alone (no antihistamine) n = 32; with antihistamine n = 55. antihistamine (diphenhydramine or pyrilamine) (n = 59): alone (no glucocorticoid) n = 4; with glucocorticoid n = 55. antimicrobial (n = 87): ampicillin alone (n = 54); ampicillin and enrofloxacin (n = 5); amoxicillin alone (n = 9); amoxicillin and enrofloxacin (n = 5); cefazolin (n = 3); cefoxitin (n = 2); gentamicin (n = 1); trimethoprim sulfamethoxazole (n = 1). study design: retrospective case series. outcome studied: patient signalment. geographic location of the snakebite incident. date and time of envenomation. time to reach the hospital. anatomic location of the bite. clinical laboratory abnormalities. treatments. costs of all treatments. duration of hospitalisation. complications and clinical outcome. main findings (relevant to pico question): multiple linear regression was performed to model each response (logarithm of cell counts, cost, or days in hospital) as a function of: variables determined at initial evaluation (age, weight, sex, pcv, and anatomic location of the bite); treatments received (antimicrobials, glucocorticoids, antihistamines, analgesics, and antivenin). for all comparisons, significance was set at a value of p ≤ 0.05. there was no significant association between antimicrobial treatment and any outcome variables. no wound related complications (infections, abscessation, necrosis) were identified in the medical records. limitations: power of study not calculated. retrospective, so limited evidentiary value. large variation in treatment protocols, including type of antimicrobial, and lack of detail with some interventions. the single reported figures for the antimicrobials add up to 80 and not 87 dogs. the study gave no reason for this discrepancy. follow-up of patients beyond discharge was not performed, so possible long-term complications were not identified. hospital stay ranged from <1 day to 5 days so variety in time monitored for complications. some cases were treated as outpatients were not able to be monitored by trained clinicians. small numbers of dogs that did not receive antimicrobials to determine comparison. only outcomes described were duration of hospital stay and mortality so limited analysis of longer-term outcomes. no description of how follow-up was carried out.   kim et al. (2022) population: dogs admitted with snakebites to the kyungpook national veterinary medical teaching hospital, haemaru animal referral hospital, and daegu animal medical center from june 2008 to july 2021. inclusion criteria: dogs in which two fang marks observed at the wound site. exclusion criteria: dogs with bite wounds of unclear origin. sample size: 70 dogs. intervention details: antivenom (n = 53). analgesic: tramadol (n = 29); hydromorphone (n = 10); tramadol, lidocaine, ketamine (n = 8); fentanyl (n = 2); butorphanol (n = 1). fluids: normal saline (n = 29); plasma-lyte (n = 12); hartmann’s solution (n = 6); 5% dextrose water (n = 1); 5% dextrose water (n = 2). chlorpheniramine (n = 51). glucocorticoids (n = 32). antibiotics (n = 62). study design: retrospective case series. outcome studied: signalment. history including witnessed snakebite and time since the snakebite. clinical signs and physical examination records on presentation. routine test results: complete blood count, serum chemical profile, coagulation profile, blood smear evaluation. treatment received. length of hospitalisation. outcomes: ‘survivors’ – discharged alive or referred to another hospital; ‘non-survivors’ – died. main findings (relevant to pico question): the χ2 test was performed to compare categorical data between survivors and non-survivors. statistical significance was set at a p value of < 0.05: among 42 hospitalised dogs with follow-up data, 37 (88%) survived to discharge and 5 (12%) died; the administration of antibiotics was associated with increased survival (p = 0.030); the study could not reveal any benefit or detriment of the use of antibiotics; the study revealed an association of antibiotic use with survival but could not demonstrate that antibiotic use affected survival. limitations: no information regarding how many dogs survived when treated with antibiotics. power of study not calculated. retrospective, so limited evidentiary value. incomplete medical records. many dogs in the study presented to the hospital only for antivenom treatment; thus, the possibility of follow-up and assessment of prognosis was limited. comparing outcomes is difficult without standardised treatment and variation in clinicians. only 42 dogs had follow-up data so cannot assess long-term outcome and means there is a low sample size for statistical analysis. could not confirm snake species so this variation may be confounding. complications could not be evaluated properly because serial laboratory examinations were performed only in a small number of dogs.   lervik et al. (2010) population: dogs bitten by the vipera berus presented at the södra djursjukhuset in stockholm or the university animal hospital in uppsala during the period of april to august 2006. inclusion criteria: strong suspicion of viper bite at the time of presentation based on information from the dog owner (bite was witnessed, or viper seen close to dog); and / or; clinical signs of viper bite (e.g., lethargy or swelling in the suspected bite area). exclusion criteria: ongoing treatment with glucocorticoids for other conditions; known history of liver disease. sample size: 53 dogs. intervention details: fluid therapy consisting of crystalloid fluid at 40–60 ml/kg/h to 40–60 ml/kg/day (n = 53). fluid therapy consisting of colloid fluids at 5–20 ml/kg/10min to 0.8 ml/kg/day (n = 28). glucocorticoids: none (n = 31); pre-admission from referring (n = 7): 1–0.25 mg/kg betamethasone per os, once (n = 5); 6 mg/kg prednisolone injection, once (n = 1); 1 mg/kg prednisolone injection per os, once (n = 1); at admittance (n = 16) (two dogs had additionally been treated by owner): 1–2 mg/kg prednisolone injection, once (n = 11); 2–2 mg/kg prednisone injection, for 2–5 days (n = 2); 1–1.25 mg/kg prednisolone per os, once (n = 3). analgesics (n = 36): buprenorphine, methadone hydrochloride or transdermal fentanyl for 1–6 days – no drug or dosage specified. antibiotics (n = 10): no drug or dosage specified. antiarrhythmic drug (n = 2). study design: prospective case series. outcome studied: blood samples taken at four different times: arrival (n = 53); 24 hours (n = 52); day 4–10 (n = 46); day 9–23 (n = 33). serum harvested and frozen until a time point 1–5 months after presentation. variables recorded: mental status – alert, or slightly, moderately or severely depressed. degree of swelling – minor, moderate or severe. serum biochemistry (n = 34): alanine aminotransferase (alt); alkaline phosphatase (alp); bile acids; glutamate dehydrogenase (gldh); creatine kinase (ck); creatinine. cardiac variables on auscultation. electrocardiogram (ecg) of dogs that had detected arrhythmias (n = 5). main findings (relevant to pico question): no clinical signs of infection in any dog in the study, even though only 10/53 (19%) were treated with antibiotics. limitations: one of the reported values for fluid therapy consisting of colloid fluids (i.e., 0.8 ml/kg/day) seems very small so may not be accurately reported. the reported figures for the baseline group (i.e., the dogs not receiving glucocorticoids, n = 31) and for the exposed group (i.e., the dogs receiving glucocorticoids, n = 7 and n = 16) add up to 54 and not 53 dogs. the study gave no reason for this discrepancy. time points for follow-up were variable with a wide range. small sample size of antibiotic treated dogs reduced statistical power. twenty dogs lost to follow-up and could only collect serum from 34/53 dogs as 19 were not available for all the timepoints, resulting in a reduced sample size. some dogs had concurrent diseases which may have been confounding. variation in veterinarian that examined and non-standardised measurements of variables, such as degree of swelling, meaning reliability of clinical ratings is uncertain. large variation in treatment protocols, with different dosages, routes and measuring timepoints. concluded that no clinical signs of infection were found but these signs were not described so cannot be sure if the diagnoses were correct. no basal value obtained for biochemical parameters used in statistical analysis so difficult to conclude that the changes were significant. lack of, and poorly reported, statistical analysis so unknown if outcomes are significant.   mccown et al. (2009) population: dogs presented to a private referral centre and university teaching hospital in the united states from 1988–2006. inclusion criteria: dogs with puncture wounds combined with presence of clinical signs consistent with crotalid envenomation (including swelling, haemorrhage, or ecchymoses at the site of the bite); treatment with polyvalent igg antivenin; absence of prior history of envenomation; complete medical record (including signalment, body weight, amount of antivenin administered, and outcome). exclusion criteria: treatment with fab antivenin; incomplete medical record. sample size: 218 dogs. intervention details: intravenous (iv) fluids (n = 213). diphenhydramine (n = 150): median dose 2.0 mg/kg; dose not recorded (n = 24). corticosteroids (n = 35): dexamethasone (n = 23); dexamethasone sodium phosphate (n = 2); prednisolone sodium sucinate (n = 7); methylprednisolone sodium succinate (n = 3). antimicrobials (n = 196): β-lactam antimicrobials alone (n = 167); azole antimicrobial alone (n = 1); more than one type: including β-lactam, azole, fluoroquinolone, and other (n = 28). epinephrine (n = 6). heparin (n = 8). blood products (n = 26): plasma (n = 15); whole blood (n = 9); packed red blood cell transfusions (n = 2); infusion of bovine haemoglobin (n = 1). opioid analgesics (n = 178). study design: retrospective case series. outcome studied: patient signalment: breed, sex, age, weight. anatomic area of bite(s) and number of bite(s). species of snake involved in bite (if known). physical examination findings at time of presentation: rectal temperature, pulse rate, respiratory rate, and the presence of swelling, haemorrhage, or petechia / ecchymoses; mentation (bright, alert, and responsive; quiet, alert, and responsive; quiet, depressed, but responsive; or other). clinicopathological data at time of presentation: packed cell volume (pcv), total plasma protein, platelet count, prothrombin time (pt), and partial thromboplastin time (ptt). treatment received. number of vials of antivenin administered. complications of antivenin therapy. length of hospitalisation. cost of treatment. clinical outcome (survival vs death): defined as either natural cardiorespiratory arrest or euthanasia. main findings (relevant to pico question): penalised logistic regression was used to determine the effect of covariates, looking at survivors vs non-survivors, including administration of antimicrobials. 9/218 (4.1%) died: no data on which of these had received antimicrobials. 196/218 (90%) were administered antimicrobials: 167 were administered β-lactam alone; one was administered an azole antibiotic alone; 28 were administered more than one type of antibiotic (including β-lactam, azole, fluoroquinolone, and other). fluoroquinolone administration was associated with an increased likelihood of survival (p = 0.046). not significantly related to survival: β-lactam antimicrobials; azole antimicrobials; other antimicrobials. low mortality rate (n=9). limitations: retrospective, so limited evidentiary value. time period of 18 years, so treatment recommendations have changed. insufficient numbers to achieve adequate power. variety of snake species measured, the bites of which may cause different clinical outcomes. the distribution of cases between the two locations is not described and is therefore a source of potential bias due to possible differences in protocols. no uniform severity scoring, so patients with a broad range of clinical presentations were being compared. lack of uniform treating regime as many clinicians involved. treatment confounded by cost considerations, experience of clinician and reliance on anecdotal reports. several variables were documented in too few dogs to allow statistical evaluation. did not consider interactions of the covariates in any statistical analysis models. the dosage and administration for antimicrobials was not recorded but could be confounding. the prevalence of wound infection was not assessed. no information regarding how many dogs treated with antibiotics survived low mortality rate (n = 9), reliable conclusions cannot be made.   pritchard et al. (2014) population: dogs presented to north carolina state university veterinary teaching hospital from 2004 to 2011. inclusion criteria: dogs residing in wake county that presented within 12 hours of a suspected copperhead bite; ‘confirmed’ cases if owners either saw the copper-head bite the dog or found the dog with fang marks and a snake nearby; ‘suspected’ cases were categorised as those in which an animal had at least one fang mark, clinical signs consistent with snakebite, and a history compatible with the possibility of snakebite. exclusion criteria: had been previously presented for medical treatment at another facility for this presentation. sample size: 52 dogs. intervention details: antimicrobials while hospitalised (n = 35). ampicillin na / sulbactam na (n = 25); amoxicillin trihydrate / clavulanate potassium (n = 6); cefazolin (n = 2); ciprofloxacin (n = 2). with antimicrobials sent home (n = 48): amoxicillin trihydrate / clavulanate potassium (n = 40); cephalexin (n = 6); ciprofloxacin (n = 6). glucocorticoids – dexamethasone (n = 9). analgesia in hospital (n = 48): hydromorphone (n = 20); fentanyl (n = 18); buprenorphine (n = 9); tramadol (n = 4); carprofen (n = 2). with analgesia sent home (n = 49): tramadol (n = 41); carprofen (n = 10); fentanyl (n = 5); meloxicam (n = 5); buprenorphine (n = 1). diphenhydramine (n = 11). famotidine (n = 3). intravenous (iv) fluids (n = 33). study design: retrospective case series. outcome studied: signalment. presenting complaint. ‘confirmed’ vs ‘suspected’ cases. date of presentation. time from presentation to suspected envenomation. vital parameters (temperature, pulse, and respiration) and weight. clinical signs as described by the attending clinician. pain scoring. clinicopathological data: packed cell volume, total solids, blood glucose, complete blood count, serum biochemical analysis, coagulation panel. treatments administered including those prescribed to give at home. bill total for the visit. total hospitalisation time. whether the patients either improved or worsened during their hospitalisation time given the information provided by the record. follow-up phone or e-mail to owner: improvement at home after discharge; if the dog required follow-up medical care at another facility; if the dog developed evidence of bite site necrosis. main findings (relevant to pico question): tissue necrosis at the bite site was reported by 3/27 owners (11%): of those, only one required follow-up care at another veterinary facility and resolved with antibiotic treatment without the need for surgical debridement. self-limiting infection at the bite site was reported by 1/27 owners (4%) that did not require either follow-up treatment at an additional veterinary facility or changes in treatment protocol. no dog bitten by a copperhead was re-presented to the study authors’ emergency facility for snakebite-associated abscess formation. all dogs survived to discharge. limitations: we only know about dogs’ survival to discharge and that owner’s phone or e-mail follow-up survey response was only available for 27/52 dogs (52%), so limited; therefore, we do not know how many were lost to follow-up as the article does not provide this information. power of study not calculated. retrospective, so limited evidentiary value. no statistical analysis performed. information is limited to that which was recorded in the medical record at the time of hospitalisation. comparing outcomes is difficult without standardised treatment and variation in clinicians. could not confirm snake species so this variation may be confounding. follow-up assessment of infection at the bite site relied on owner assessment so is less reliable. no indication of whether the dogs that had complications related to infection had received antibiotics, so cannot determine this significance. interventions included ‘treated with antimicrobials in hospital’ and ‘sent home with antimicrobials’ but there was no indication of the overlap of these groups, though it could be inferred that at least 48 dogs had some antimicrobial treatment (those sent home). outcome of ‘whether the patients either improved or worsened during their hospitalisation time given the information provided by the record’ is subjective. median duration of hospitalisation in dogs was 14.8 hours so no extended period of observation for complications by clinicians.   witsil et al. (2015) population: dogs from six veterinary emergency centres in maricopa county, arizona between 2010 and 2012. inclusion criteria: dogs with witnessed rattlesnake envenomation or clinical signs consisted with envenomation (rapid swelling, pain, puncture wounds) and; dog had access to rattlesnake(s) at time of onset of clinical signs. sample size: 272 dogs. intervention details: antivenom: antivenin crotalus durissus and bothrops asper (‘f(ab′)2 av’) given at the five hospitals: reconstituted using 10 ml sterile 0.9% saline, bacteriostatic water, lactated ringer’s solution, or plasma-lyte fluid. antivenin (crotalidae) polyvalent (acp) (‘igg av’) given primarily at referring clinics prior to transport: reconstitution similar to f(ab’)2 av, but precise methods for administration were not uniformly recorded by referring clinics and could not be described. rattlesnake vaccine (n = 15). antimicrobials (n = 64): β-lactams (n = 48); no antimicrobials (n = 207); unknown antimicrobial (n = 1). glucocorticoids: no number stated. diphenhydramine: no number stated. study design: retrospective case series. outcome studied: patient demographics. age of patient. location of bite. time to presentation. month of envenomation. prior rattlesnake vaccination. canine snakebite severity score (csss) based on the validate human version summation of bite factor scores (swelling, ecchymosis, pain, and drainage) is given a score of either 0 (if absent) or 1 (if noted) and; clinical sign scores (1 point given to each clinical sign noted). treatments received: number of vials of antivenom used; relationship between body weight and vials used; type of antibiotic. length of stay in the hospital. survival. main findings (relevant to pico question): the data were converted into ranks and parametric statistical analyses were performed: 24% cases (n = 64) received antibiotics; mortality was 8/272 (died n = 4, euthanised n = 4): three fatal cases had received antibiotics; five had not received antibiotics. significantly longer duration of hospital stay was found in patients that received antibiotics (p = 0.0004). limitations: no recording or verification of the envenoming crotaline species, which may have been helpful in assessing the outcome. canine snakebite severity score scale has not been validated and individual patient variables are not accounted for, meaning the scale should be narrowly interpreted. challenge of grading animals due to lack of verbal descriptive feedback. cost to owner of measurements the components of csss is confounding as this limited the diagnostics in some cases. treatment was prioritised over acquiring laboratory measurements when finances were a limiting factor. retrospective. administration of treatment depended on severity of clinical signs, patient tolerance of infusion, and clinician preference. low number of fatalities prohibited statistical comparison of the data on survival. specific clinical changes or comorbidities leading up to cardiopulmonary arrest or factoring into decisions to euthanise were not recorded. follow-up of patients beyond discharge was not performed, so possible complications were not identified.   appraisal, application and reflection the literature search performed by the author found seven papers which partially addressed the pico question. apart from carr & shultz (2015) there have been no studies so far evaluating the use of prophylactic antimicrobials in envenomated animals. in the seven papers sample size calculation was lacking and statistical analysis was sometimes poorly reported, thus hindering interpretation of significance. the studies are limited due to a lack of standardised treatment and monitoring protocols, and no consistent assessment regarding severity of envenomation and wound infection. there is wide variation in supportive treatments given in the literature, thus inconsistent protocols were described, which makes direct comparison of the effect of antimicrobials more difficult to assess. notably, steroids were given to a number of dogs in these studies and this may have impacted both the incidence of infection and the response to antimicrobials in these cases. it is also likely that there is variability in clinical outcomes, due to factors such as location of the bite and time to treatment. finally, individual variation in venom profiles has been proven between specimens of the vipera berus, manifesting in a wide range of clinical features (malina et al., 2017). therefore, another confounding factor is the differing venom phenotypes between the range of snake species reported in these studies. firstly, cases of suspected acute rattlesnake envenomation that had received no antimicrobial treatment were enrolled in the study by carr & schultz (2015). within 2 weeks of presentation they were evaluated regarding wound healing, signs of infection and need for follow-up care by direct examination of the wound, or telephone contact when this was not possible. of the 102 cases, only one developed an infection; an abscess to the thoracic limb that was secondary to suspected compartment syndrome. the abscess was cultured and pasteurella and staphylococcus species were found, but these are consistent with skin contaminants, as opposed to the oral flora of the snake (carr & schultz, 2015). this supports the view that incidence of infection in envenomation is low and therefore prophylactic antimicrobials need not be part of a treatment protocol. however, it could not be confirmed that subclinical infections did not develop as there is no accepted way to rule out a sub-clinical infection  other than culture of wounds that had obvious abscessation and necrosis. in addition, patients were lost to follow-up which may have caused selection bias, and there were cases that were included in analysis even though direct examination was not possible. furthermore, there was evident bias due to a large variation in treatment protocols from different veterinarians and non-standardised measurements of variables such as clinical signs. hackett et al. (2002) evaluated 100 cases of snakebite envenomation in dogs at a hospital over a 10-year period. multiple linear regression was performed to model outcomes of cell counts, cost and days in hospital as a function of variables such as treatment with antimicrobials, with significance set as p ≤ 0.05. they found no significant association between antimicrobial treatment and any outcome variable. nevertheless, this method of statistical analysis is limited by low population (n = 100), possible incomplete data and variables may not be independent. in total 87/100 (87%) of dogs received antimicrobials and the authors noted that no wound related complications (infections, abscessation, necrosis) were identified in the medical records which could support use of antimicrobials. but as so few dogs did not receive antimicrobials it is difficult to conclude this due to lack of data for comparison between groups. also, the lack of follow-up after discharge means long-term complications have not been identified, so infections that developed later may have been missed. records of dogs admitted with snakebites to three hospitals between 2008–2021 were reviewed by kim et al. (2022) in their retrospective case series. part of their analysis included performing a χ2 test to compare categorical data between survivors and non-survivors. the administration of antimicrobials was associated with increased survival (p = 0.030) which may therefore support use of antimicrobials in these cases. however, kim et al. (2022) recognised that though the study revealed this statistical association, they could not demonstrate that antimicrobial use affected survival. although 72 cases were included in the study, only 42 had follow-up data to be able to be included in this statistical analysis, meaning a low population is even more limiting. furthermore, assessment of long-term prognosis was impossible due to incomplete medical records and lack of follow-up. limitations of this retrospective study include lack of follow-up, no proof of cause-effect, no treatment standardisation and lack of a control. in the paper by lervik et al. (2010), 53 dogs that presented with a strong suspicion of viper bite and / or clinical signs of viper bite were included in their analysis. no mortalities occurred, however the mortality rate of dogs bitten by the european adder has been reported to be at 4.6% (sutton et al., 2011). therefore, it is possible that the lack of observed difference found in this study is due to small sample size rather than lack of effect. of the population, 10/53 (19%) were given antimicrobials, but clinical signs related to infection were not seen in any of the cases. this could suggest that the administration of antimicrobials does not have an effect on the incidence of wound infection. this finding is consistent with the study by sutton et al. (2011) where 235/422 (56%) of cases received antimicrobials, yet infection was reported in none. nevertheless, despite this conclusion by lervik et al. (2010), the measurements for clinical signs of infection were not described so it cannot be certain that the diagnoses were correct. the lack of objectivity in the study design, such as treatments used and time points for follow-up, along with the confounding effects of concurrent diseases, means that conclusions of the study must be interpreted with caution. in fact, there was a lack of statistical analysis, and where there was it is poorly reported, so it is unproven whether the outcomes of this study are significant. although the study by mccown et al. (2009) does not directly address the pico, it provides some evidence on the clinical effects of antimicrobials and suggests they have no influence on mortality. they found that even though 196/218 (90%) of patients were given antimicrobials, none of these had a significant impact on survival, except fluoroquinolones which increased likelihood of survival (p = 0.046). even though this p value is <0.05, interpretation of this impact should be carried out with reservation due to sampling variation and because the study had a low population (n = 218). in fact, as the sample size (n) is too small, the survival proportions observed in the sample may not be an accurate reflection of the true population proportions due to the effects of random error. once again, there was no standardised severity scoring or treating regime as many clinicians were involved, so a broad range of clinical presentations were compared and may be confounding. the study had too many variables introduced, and the interactions of these covariates were not considered in their statistical analysis models. pritchard et al. (2014) studied clinical records of dogs treated for snakebite at one hospital. reports of follow-up via phone call or email to owners were included, such as if the dog required subsequent medical care at another facility. although no statical analysis was performed, pritchard et al. (2014) presented data relevant to this pico as they reported incidence of cases with signs associated with infection. of the 52 cases reviewed, tissue necrosis at the bite site was reported by 3/27 owners (11%), which is a higher incidence than the other studies in this review. of those, only one required follow-up care at another veterinary facility and no dog re-presented to the hospital in the study for snakebite-associated abscess formation. nevertheless, there is no indication of whether this population had received antimicrobials, so a correlation between their use and outcome cannot be determined. in fact, only 27 cases had follow-up data, so power of study is low. furthermore, the median duration of hospitalisation in dogs was 14.8 hours so clinicians' assessment of long-term complications is limited. the study was limited by poorly described and subjective outcomes, such as ‘whether patients either improved or worsened during their hospitalisation time’ and unreliable follow-up data such as owner assessment of infection. finally, the retrospective cases series by witsil et al. (2015) looking at data from six emergency centres found that there was a significantly longer duration of hospital stay in patients that received antimicrobials (p = 0.0004). however, this may be due to the severity of the clinical picture in these cases and the finding may simply be that overall increased morbidity leads to increased likelihood of antimicrobials being used. thus, caution is required in concluding that the longer hospital stays are directly related to antimicrobials. despite only 64/272 (23%) of cases receiving antimicrobials, there was only a mortality of 8/272. of these, three had been treated and five not treated with antimicrobials. this may suggest that antimicrobials have no effect on the outcome of survival, and the authors conclude that the routine use of antimicrobials was not supported by their results. nevertheless, the paper had many limitations, for example administration of treatment was not standardised and was confounded by severity of clinical signs, clinician preference, cost of treatment and the variations between centres where the data was collected. however, the five hospitals were within a network that shared data capture methods that enhanced the standardisation of analysis. finally, there was loss to follow-up beyond patient discharge, which causes selection bias and meant later complications following envenomation were not identified. in summary, the findings of this review suggest that administration of antimicrobials does not have a significant effect on the incidence of wound infection, nor outcome of survival. the incidence of wound infection following envenomation in canine patients is low, which agrees with human studies, where rate of infection has been found to be 0.08% (august et al., 2018). there remain controversies around all treatment protocols used in canine patients with snakebites, as presented in the review by armentano & schaer (2011). this review drew comparisons between cases of human snake envenomation to advise clinicians on use of antimicrobials, but, as in this paper, they found that due to limitations of the current veterinary literature it is not possible to provide direct conclusive evidence regarding antimicrobial treatment and outcome. armentano & schaer (2011) recommended use of antimicrobials in snakebite cases only when there is clinical and microbiological evidence, extrapolating from human medicine where prophylactic antimicrobials are not indicated as initial therapy because of this low incidence of infection, likely due to the bactericidal effects of the venom itself. interestingly, snakebites are considered a neglected tropical disease in human medicine and the lack of evidence supporting the guidelines for the prevention of wound infections in humans is comparable, making the topic of this review relevant from a one health perspective. however, a cochrane review by bhaumik et al. (2022) is in progress; this intends to inform practice guidelines for antimicrobial treatment of snakebites in humans, the outcomes of which could potentially prove useful for extrapolation to veterinary patients. overall, the available evidence is weak as the studies are case series, meaning they have limited evidentiary power, have a high likelihood of bias and cannot reliably prove causation. the studies had relatively low sample sizes, meaning they all had insufficient numbers to achieve adequate power. in relation to the pico question, these numbers are even lower if considering how many dogs did receive antimicrobials; there are insufficient cases receiving antimicrobials versus those that are not to make a significant comparison. nevertheless, the total population of these studies was 867 dogs which is arguably a powerful sample size to analyse. at least 467 dogs overall received antimicrobials, meaning the antimicrobial treated versus untreated groups were almost proportional, which allows some clinically relevant comparisons to be made. proving the efficacy of treatment is problematic due to the varying degree of effects of venom in each victim and the difficulty in designing a study that can control for all treatments bar the drug of interest, without ethical issues arising. undoubtedly, further controlled prospective studies are needed to provide better evidence-based information. similarly, further evaluation of the incidence of wound infection in canine patients following envenomation would be informative. but until then clinicians must use their own clinical judgment from available evidence to decide on the necessary snakebite treatment for their patient. methodology search strategy databases searched and dates covered: cab abstracts on ovid platform 1910–2023 web of science (clarivate analytics) 1945–2023 scopus (elsevier) 1960–2023 search strategy: cab abstracts: (dog* or bitch* or cani*) and (antibiotic* or antimicrobial* or antibacterial*) and (snake*) web of science: (limited to web of science core collection, veterinary science) (dog* or bitch* or cani*) and (antibiotic* or antimicrobial* or antibacterial*) and (snake*) scopus: (limited to veterinary subject area): (dog* or bitch* or cani*) and (antibiotic* or antimicrobial* or antibacterial*) and (snake*) and (infect* or wound* or bite* or envenomat*) note the terms (infect* or wound* or bite* or envenomat*) were originally included in the search strategy for cab abstracts and web of science, but yielded fewer results than the terms used above and no additional papers. dates searches performed: 30 mar 2023   exclusion / inclusion criteria exclusion: reviews of available treatments. book chapters. case reports. non-english language. papers that could not be accessed by the author or university library. not direct analysis of antibiotic use made. inclusion: studies that cover the use of antimicrobials in canine patients bitten by snakes.   search outcome database number of results excluded – not about snakebites in dogs excluded – not relevant to pico excluded – no english version available excluded – unable to access total relevant papers cab abstracts 77 28 32 9 2 6 web of science 46 31 7 1 1 6 scopus 316 283 23 2 4 4 total relevant papers when duplicates removed 7   orcid megan ballman: https://orcid.org/0000-0002-0746-9368 davide messina: https://orcid.org/0000-0003-3813-5501 conflict of interest the authors declare no conflicts of interest. megan ballman would like to thank martin hawes for their support in this work. references armentano, r.a. & schaer, m. (2011). overview and controversies in the medical management of pit viper envenomation in the dog. journal of veterinary emergency and critical care. 21(5), 461–470. doi: https://doi.org/10.1111/j.1476-4431.2011.00677.x august j.a., boesen k.j., hurst n.b., shirazi f.m. & klotz s.a. (2018). prophylactic antibiotics are not needed following rattlesnake bites. the american journal of medicine. 131(11), 1367–1371. doi: https://doi.org/10.1016/j.amjmed.2018.06.006 bhaumik s., gopalakrishnan, m., kirubakaran, r. & jagnoor, j. (2022). antibiotics for preventing wound infections after snakebite. cochrane database of systematic reviews 2022. 7. doi: https://doi.org/10.1002/14651858.cd015114 carr, a. & schultz, j. (2015). prospective evaluation of the incidence of wound infection in rattlesnake envenomation in dogs. journal of veterinary emergency and critical care. 25(4), 546–551. doi: https://doi.org/10.1111/vec.12337 hackett, t.b., wingfield, w. e., mazzaferro, e.m. & benedetti, j.s. (2002). clinical findings associated with prairie rattlesnake bites in dogs: 100 cases (1989–1998). journal of the american veterinary medical association. 220(11), 1675–1680. doi: https://doi.org/10.2460/javma.2002.220.1675 lervik, j., lilliehöök, i., frendin, j. (2010). clinical and biochemical changes in 53 swedish dogs bitten by the european adder – vipera berus. acta veterinaria scandinavica. 52(12), doi: https://doi.org/10.1186/1751-0147-52-26 kim, d., kim, s., kim, j., lim, j.h., choi, g., bae, s., kwon, y. & jang, m. (2022). clinical features and management of snake bites in 70 dogs in korea. journal of veterinary science. 23(6). doi: https://doi.org/10.4142/jvs.22105 malina, t., krecsák, l., westerström, a., szemán-nagy, g., gyémánt, g., m-hamvas, m., rowan, e., harvey, a., warrell, d., pál, b., rusznák, z. & vasas, g. (2017). individual variability of venom from the european adder (vipera berus berus) from one locality in eastern hungary. toxicon. 135,59–70. doi: https://doi.org/10.1016/j.toxicon.2017.06.004 mccown, j.l., cooke, k.l., hanel, r.m., jones, g.l. & hill, r.c. (2009). effect of antivenin dose on outcome from crotalid envenomation: 218 dogs (1988–2006). journal of veterinary emergency and critical care. 19(6), 603–610. doi: https://doi.org/10.1111/j.1476-4431.2009.00487.x peterson, m. (2006). snake bite: pit vipers. clinical techniques in small animal practice. 21(4), 174–182. doi: https://doi.org/10.1053/j.ctsap.2006.10.008 pritchard, j.c., birkenheuer, a.j., hanel, r.m. & wood, m.w. (2014). copperhead (agkistrodon contortrix) envenomation of dogs: 52 cases (2004–2011). journal of the american animal hospital association. 50(5), 338–344. doi: https://doi.org/10.5326/jaaha-ms-6131 sutton, n.m., bates, n. & campbell, a. (2011). canine adder bites in the uk: a retrospective study of cases reported to the veterinary poisons information service. veterinary record. 169(23), doi: https://doi.org/10.1136/vr.d4695 witsil, a.j., wells, r.j., woods, c. & rao, s. (2015). 272 cases of rattlesnake envenomation in dogs: demographics and treatment including safety of f(ab′)2 antivenom use in 236 patients. toxicon. 105, 19–26. doi: https://doi.org/10.1016/j.toxicon.2015.08.028 contribute to the evidence there are two main ways you can contribute to the evidence base while also enhancing your cpd: tell us your information need write a knowledge summary either way, you will be helping to add to the evidence base, and strengthen the decisions that veterinary professionals around the world make to give animals the best possible care. learn more here: https://veterinaryevidence.org/index.php/ve/guidelines-for-authors licence copyright (c) 2023 davide messina intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, 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warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use.   veterinary evidence is an rcvs knowledge initiative. issn: 2396-9776 first floor, 10 queen street place, london ec4r 1be resources student awards staff login policies privacy policy accessing information policy cookie declaration terms of use copyright notices stay connected podcasts twitter facebook instagram linkedin back to top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443. epileptic seizures versus syncope: pathophysiology and clinical approach marios charalambous dvm, gpcert(neuro), csci, fhea, mrsb, mrcvs1* sergio a. gomes dvm, mrcvs2 stella papageorgiou dvm3 massimo orioles dvm, certavp, mrcvs4 1ucl institute of neurology, faculty of brain sciences, university college london, united kingdom 2queen’s veterinary school hospital, department of veterinary medicine, university of cambridge, united kingdom 3clinique vétérinaire advetia, paris, france 4lida vets, 33 lilac road, cambridge, united kingdom *corresponding author (marios.charalambous.15@ucl.ac.uk) vol 2, issue 1 (2017) published: 28 feb 2017 reviewed by: pete rodgers and nieky van veggel (bsc msc pgcert rsci cbiol mrsb eurprobiol fhea) doi: 10.18849/ve.v2i1.58 section index:    abstract | introduction | pathophysiology | differentiation based on clinical presentation | take-home message | conflict of interest | references | supplementary files abstract generalised epileptic seizures and syncope are two syndromes with similar clinical manifestation and their differentiation can be quite challenging. the aim of this review is to use an evidence-based approach in differentiating these two syndromes through the comprehension of the pathophysiological mechanisms involved and their clinical signs. both syndromes affect regions of the forebrain and consciousness level, although, different mechanisms are involved. syncope is a paroxysmal event secondary to a short-term decrease in cerebral perfusion, oxygenation or essential nutrients delivery. generalised epileptic seizure activity is defined as the clinical manifestation of transient paroxysmal disturbances in brain function secondary to an imbalance between excitatory and inhibitory neurotransmitters. clinical criteria, including precipitating events, clinical signs preceding, during and following the episodes and event duration, can be used to differentiate the two syndromes. although these criteria might be useful for the practitioner, definite conclusions should be precluded due to the lack of original research articles and weak evidence on this specific field. application: the review might be a useful tool for the general practitioner and clinical scientist as it will aid towards the differentiation of two syndromes, i.e. generalised epileptic seizures and syncope, with similar clinical presentation. introduction generalised epileptic seizures and syncope are two syndromes with similar clinical manifestation and their differentiation can be quite challenging. the aim of this review is to provide the clinician with general guidelines on how to differentiate these two syndromes through comprehension of the syndromes’ pathophysiology mechanisms and clinical signs. syncope is defined as a sudden, transient loss of consciousness and postural tone, originating from a short-term interruption of blood perfusion, oxygenation or delivery of essential nutrients to the brain. it is characterised by sudden onset, short duration, and spontaneous recovery (davidow et al., 2001, folino 2005, moya et al., 2009). a dog presented with syncope usually collapses suddenly and may experience transient myoclonus or tonic spasms. micturition and vocalisation may also occur. pre-syncope is defined as a shorter and/or milder cerebral offence in which the animal does not lose consciousness completely, but may manifest incoordination or hind limb weakness (wa, 2007). a more severe presentation of syncope can lead to the occurrence of brief tonic-clonic activity (hypoxic convulsive syncope) and results from a diffuse cerebral hypoperfusion, secondary to severe hypotension, cardiac arrhythmia or asystole (wa, 2007, lewis et al., 1999). generalised epileptic seizures are defined as transient, paroxysmal changes in neurological status or behaviour, secondary to abnormal activity of the cerebral neurons (march, 1998, podell, 1996). seizures can affect sensory, motor, and autonomic functions as well as consciousness, cognition and behaviour. this syndrome might initially occur when the animal’s level of activity is low (e.g. during sleep). generalised seizures consist of three sequential phases: pre-ictus (prodrome and aura), ictus, and post-ictus (berendt et al., 1999). during the pre-ictus, prodromal signs are first seen as subtle manifestations preceding a seizure event and last for minutes, hours or even days or weeks. the prodromal signs consist of behavioural changes and, usually, are not noticed by the owners. the prodrome is followed by the aura, which represents the onset of the seizure (berendt et al., 1999). during this phase, atypical behaviour and autonomic signs are common presentations, including pacing, licking, hiding, attention-seeking, hypersalivation and vomiting. it is followed by the true seizure phase, ictus, which is the most visually impressive event to the owners. ictus is generally manifested by a loss of consciousness, involuntary muscle movements and tonic-clonic activity and its usual duration ranges from 1 to 3 minutes. on the last stage, post-ictus, unusual behaviour such as disorientation, restlessness, and aggression as well as blindness may be present and can last from seconds to days (march, 1998, podell, 1996). differentiation of these two syndromes can be quite a challenging process in daily clinical practice (barnett et al., 2010). they share several clinical features and both are sudden and shocking events to the owners. a thorough anamnesis is the first step into distinguishing the two episodes. the precipitating events, clinical signs preceding, during and following the episodes and main event duration can provide the veterinary surgeon with important clues and initiate a diagnostic protocol. video recording of the event is highly recommended, as it can be a rather helpful tool. however, a relatively recent study showed that video footage should be interpreted with caution (packer et al., 2015). precisely, the study found that there was a low level of agreement among veterinarians who were not always able to interpret, based on the videos, whether they could observe an epileptic seizure or another paroxysmal event. further diagnostic investigation including complete blood count, biochemistry, electrocardiography, holter-monitor, echocardiography, thoracic/abdominal radiographs, brain magnetic resonance imaging (mri) and encephalography (eeg) are usually vital for a definitive differentiation. pathophysiology the main similarity between seizures and syncope is that both affect regions of the forebrain and consciousness level. however, different mechanisms are recruited during each episode that eventually leads to collapse. syncope syncope is a paroxysmal event secondary to a short-term decrease in cerebral perfusion, oxygenation or essential nutrients delivery. these changes result in a decreased function of the brain regions responsible for the level of consciousness (schnipper et al., 2001). even a short-term shortage in oxygen and glucose may lead to syncope, as the brain has the highest energy demands of all body organs (tidwell et al., 2011). syncope can occur when cerebral blood flow (cbf) drops below 50% or 40% of the control value leading to a significant fall of cbf (waelbers et al., 2010). excitement or strenuous exercise are the most commonly associated triggers in animals (wa, 2007). the cbf is determined mainly by the cerebral perfusion pressure (cpp). the cpp is directly proportional to the balance between mean arterial pressure (map) and intracranial pressure (icp). cpp is also inversely proportional to the brain vascular resistance (bvr) (davidow et al., 2001, waelbers, 2010). cbf is kept constant by autoregulatory mechanisms in healthy animals (folino, 2005). usage of formulas can simplify the comprehension of these factors (1). map depends on the cardiac output (co), systemic vascular resistance (svr) and central venous pressure (cvp) (waelbers et al., 2010). so, the formula can be reformulated (1) as follows: it becomes clear that any disorders resulting in an increased icp, cvp, bvr or a decreased co and svr can lead to a decrease in cbf. therefore, syncope may represent an event with multifactorial aetiology (table 1) with several mechanisms being involved. other factors which can affect cbf include arterial oxygenation, venous outflow, metabolic rate and arterial carbon dioxide tension (waelbers et al., 2010). metabolic disorders can trigger a syncopal event, even when cpp is normal (davidow et al., 2001). nonetheless, most aetiologies include brain hypoperfusion which results in the loss of consciousness (folino, 2005). neurocardiogenic reflexes, in particular orthostatic hypotension which commonly occurs in humans, are rare in animals due to their quadruped stance (folino, 2005, wa, 2007). table 1: example of factors that can cause syncope generalised epileptic seizures seizure activity is defined as the clinical manifestation of transient paroxysmal disturbances in brain function which are caused by an imbalance between excitatory and inhibitory neurotransmission (fisher et al., 2005). the brain region, within which seizure activity is triggered, is called epileptogenic zone or area (lüders et al., 2006). in humans, the brain regions that are highly sensitive to develop seizures include temporal lobe structures such as the hippocampus, the amygdala, and the piriform cortex (aroniadou-anderjaska et al., 2008). changes that occur on the epileptogenic zone are poorly understood but are thought to include cell death, axonal growth, reorganisation of neural networks, alterations in the release of neurotransmitters, and neurogenesis (herman, 2006). these changes cause neurons to become hyperexcitable and can lead to spontaneous seizures (herman, 2006). at the neuronal level, seizure activity is characterised by two primary events: hyperexcitability and hypersynchronicity.  the hyperexcitability state, as mentioned above, is responsible for the initiation of the seizures. pathophysiological mechanisms in this state include: 1) altered neuronal membrane function, such as increased permeability, which may occur due to hypoxia or inflammation, 2) decreased inhibitory or increased excitatory neurotransmission mediated, primarily, by gamma-aminobutirric-acid a (gabaa) and glutamate respectively, 3) alteration in number, balance, sensitivity or function of the receptors, such as gabaa or glutamate receptors, and 4) changes in extracellular ions concentration, such as potassium and calcium ions (boothe, 2001, aroniadou-anderjaska et al., 2008, armijo et al., 2002). the hypersynchronicity state is characterised by an increased excitability of neighbouring neurons. the neurons are stimulated by the abnormal electrical activation via non synaptic interactions and activation of collateral fibres (boothe, 2001). once started, the seizure discharge may synchronise with other neurons and spread into the surrounding areas of the brain. normally, the spread of seizure can be prevented by a region of surrounding inhibitory neurons (bromfield et al., 2006). however, this inhibition is surpassed when there is sufficient activation to recruit surrounding neurons (bromfield et al., 2006). the mechanisms recruited for this state include repetitive discharges that lead to different events such as: 1) increase in extracellular potassium ions tending to depolarize neighbouring neurons, 2) accumulation of calcium ions in presynaptic terminals leading to enhanced neurotransmitter release, and 3) depolarisation-induced activation of the n-methyl-d-aspartate (nmda) receptor causing further calcium ions influx and neuronal activation (bromfield et al., 2006). lastly, glial cells play an essential role in buffering functions that balance the uptake of potassium ions and glutamate; alteration of these functions may cause hyperexcitability (rogawski, 2005). there is also evidence that a paroxysmal depolarising shift (pds) can be generated by the release of glial excitatory neurotransmitters. even in the absence of synaptic interactions, glial (astrocytic) release of glutamate can trigger pds-like events (rogawski, 2005). differentiation based on clinical presentation precipitating events precipitating events are those that can often trigger the episodes. in syncope, factors such as exercise, coughing, excitement or various stressful stimuli have been identified as trigger factors of the episode (davidow et al., 2001, bright et al., 1999, calvert et al., 1996, miller et al., 1999). generalised epileptic seizures occur usually spontaneously (davidow et al., 2001), mainly during sleep or rest (carnes et al., 2006). there are, however, factors that have been described as potential triggers of generalised epileptic seizures, such as environmental stress (carnes et al., 2006). signs preceding the episodes both syndromes may show signs prior to the main phase of the episode. in generalised epileptic seizures, there is the pre-ictal period which is not reported in syncope (carnes et al., 2006, wa, 2007, strickberger et al., 2006, ettinger, 1972, davidow et al., 2001). however, sometimes the pre-ictal period may not be noticed in generalised epileptic seizures (davidow et al., 2001). the duration of the pre-ictal period can last from minutes to days (berendt et al., 1999). in syncope, it is quite uncommon to have preceding signs (davidow et al., 2001). if there are any, they might include weakness, ataxia, growling and symptoms derived from the autonomic nervous system such as urination and defecation (davidow et al., 2001, yee, 2010). the duration of these signs is a few seconds only (yee, 2010). signs that animals present during the main phase of the episode a syncopal episode is characterised by flaccid collapse (bright et al., 1999, heaven et al., 2000). in some occasions, though, the animal might not completely collapse (presyncope) (lewis et al., 1999). stiffness of the limbs and opisthotonus might occur, but are quite uncommon compared to generalised epileptic seizures. tonic-clonic movements and rigidity of the limbs might occur during and after the episode (hypoxic convulsive syncope), which might be confounded with generalised tonic-clonic epileptic seizures (ettinger, 1972, folino, 2005, jhanjee et al., 2006, strickberger et al., 2006). in the latter, dogs experience tonic-clonic movements and contractions of the facial muscles, with loss of consciousness (heaven et al., 2000). in addition, urinary and faecal incontinence, as well as hyper-salivation may occur in both syndromes (davidow et al., 2001, skrodzki et al., 2008, yee, 2010). nonetheless, it has been reported that urinary and faecal incontinence (heaven et al., 2000, wa, 2007) and hyper-salivation (yee, 2010) are more often associated with seizures. duration of the main phase of episodes the duration of the two syndromes varies. generalised epileptic seizures (ictus phase) can last from seconds to minutes, whilst syncope lasts only for a few seconds (davidow et al., 2001). generally, syncope occurs for a shorter period of time in comparison to seizures, although this in not always the case (gompf, 2008). signs following the events in epileptic seizures, ictus is followed by signs characteristic of the post-ictal phase. during this phase, dogs might lay motionless for a period of time (usually over ten minutes) appear blind, disoriented, and ataxic (skrodzki et al., 2008). the duration of the post-ictal period might vary from minutes to hours, or even up to some days (podell, 1996, march, 1998). on the contrary, there are no such signs after a syncopal episode (davidow et al., 2001, heaven et al., 2000, wa, 2007). dogs with syncope generally do not experience any signs following the events, have a rapid recovery, and return to their normal pre-syncope stage very quickly (yee, 2010, kenny, 2002, jhanjee et al., 2006, folino, 2005, ettinger, 1972, strickberger et al., 2006). in cases of neurocardiogenic syncope episodes, the period required for the dogs to regain normal consciousness might be prolonged (yee, 2010). rarely, dogs can present signs of confusion or very mild depression for a short period of time (skrodzki et al., 2008). table 2: clinical characteristics of generalised seizures and syncope figure 1: algorithm for the clinical differentiation between generalised seizures and syncope take-home message the clinical differentiation between syncope and generalised epileptic seizures is challenging. same areas of brain affecting the level of consciousness are afflicted, but with different pathophysiological mechanisms being involved. clinical criteria are very helpful for the differentiation of the two syndromes. some of them may be considered more valuable than others as they could provide the clinician with more important clues. the presence of precipitating events (e.g. cough, exercise), motor activity during the episode, duration of the episode and signs following the events might be criteria of greater significance. on the other hand, signs preceding the episodes and autonomous nervous system signs might be considered as criteria of lesser importance. although this review underlines the significance of clinical criteria for distinguishing epileptic seizures from syncope, definite conclusions are precluded due to the current weak evidence on this particular field. therefore, original research studies are vital for establishing clinical criteria for the differentiation of these two syndromes. conflict of interest the authors declare no conflicts of interest. references armijo, j. a. et al (2002) advances in the physiopathology of epileptogenesis: molecular aspects. revue neurologique, 34 (5), pp. 409-29. aroniadou-anderjaska, v. et al (2008) pathology and pathophysiology of the amygdala in epileptogenesis and epilepsy. epilepsy research, 78 (2-3), pp. 102-116. doi: 1016/j.eplepsyres.2007.11.011 barnett, l. et al (2010) a retrospective study of 153 cases of undiagnosed collapse, syncope or exercise intolerance: the outcomes. journal of small animal practice, 52 (1), pp.26-31. http://dx.doi.org/10.1111/j.1748-5827.2010.01013.x berendt, m. and gram, l. 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(2006) an introduction to epilepsy.west hartford (ct), american epilepsy society., viewed 20 september 2016, <http://www.ncbi.nlm.nih.gov/books/nbk2510/> calvert, c. jacobs, g. and pickus, c. (1996) bradycardia-associated episodic weakness, syncope, and aborted sudden death in cardiomyopathic doberman pinschers. journal of veterinary internal medicine, 10 (2), pp. 88-93. doi:http://dx.doi.org/10.1111/j.1939-1676.1996.tb02034.x carnes et al. (2006) management of canine idiopathic epilepsy. standards of care emergency and critical care medicine, 8, pp.1-6. davidow, e.b. woodfield, j.a. (2001) syncope: pathophysiology and differential diagnosis. compendium on continuing education for the practicing veterinarian, 23, pp. 608–620. ettinger, a. j. (1972). cardiac emergencies. veterinary clinics of north america, 2, pp.235-42. doi: http://dx.doi.org/10.1016/s0091-0279(72)50028-x fisher, r. et al. (2005) epileptic seizures and epilepsy: definitions proposed by the international league against epilepsy (ilae) and the international bureau for epilepsy (ibe). epilepsia, 46 (4), pp. 470-472. doi: http://dx.doi.org/10.1111/j.0013-9580.2005.66104.x folino, a. (2005) cerebral autoregulation in neurally mediated syncope: victim or executioner?. heart, 92 (6), pp. 724-726. doi: http://dx.doi.org/10.1136/hrt.2005.069179 gompf, r. e. (2008)the history and physical examination. in: tilley p.l., smith jr w.k.f., oyaman a.m. manual of canine and feline cardiology, saunders elsevier. heaven, d. j. sutton, r. (2000) syncope. critical care medicine, 28, pp. 116-20. doi: http://dx.doi.org/10.1097/00003246-200010001-00002 herman, s. t. (2006) clinical trials for prevention of epileptogenesis. epilepsy research, 68, pp.35-8. doi: http://dx.doi.org/10.1016/j.eplepsyres.2005.09.015 jhanjee, r. et al. (2006) syncope in adults: terminology, classification, and diagnostic strategy. pacing and clinical electrophysiology, 29 (10), pp. 1160-1169. doi: http://dx.doi.org/10.1111/j.1540-8159.2006.00508.x kenny, r. a. (2002) neurally mediated syncope. clinical geriatric medicine, 18, pp. 191-210. doi:http://dx.doi.org/10.1016/s0749-0690(02)00005-8 lewis, d. and dhala, a. (1999) syncope in the pediatric patient: the cardiologist's perspective. pediatric clinics of north america, 46 (2), pp. 205-219. doi: http://dx.doi.org/10.1016/s0031-3955(05)70113-9 lüders, h. o. et al. (2006) the epileptogenic zone: general principles. epileptic disorders, 8 suppl 2, pp. 1-9. doi: http://dx.doi.org/10.3109/9780203091708-114 march, p. (1998) seizures: classification, etiologies, and pathophysiology. clinical techniques in small animal practice, 13 (3), pp. 119-131. doi: http://dx.doi.org/10.1016/s1096-2867(98)80033-9 miller, r. et al. (1999) retrospective analysis of the clinical utility of ambulatory electrocardiographic (holter) recordings in syncopal dogs: 44 cases (1991-1995). journal of veterinary internal medicine, 13 (2), pp. 111-122. doi:http://dx.doi.org/10.1111/j.1939-1676.1999.tb01138.x moya, a. et al (2009) guidelines for the diagnosis and management of syncope (version 2009): the task force for the diagnosis and management of syncope of the european society of cardiology (esc). european heart journal, 30 (21), pp. 2631-2671. doi:1093/eurheartj/ehp298 packer, r. (2015) inter-observer agreement of canine and feline paroxysmal event semiology and classification by veterinary neurology specialists and non-specialists. bmc veterinary research, 11 (1), p. 39. doi: http://dx.doi.org/10.1186/s12917-015-0356-2 podell, m. (1996) seizures in dogs. veterinary clinics of north america: small animal practice, 26(4), pp.779-809. rogawski, m. (2005) astrocytes get in the act in epilepsy. nature medicine, 11 (9), pp. 919-920.doi: http://dx.doi.org/10.1038/nm0905-919 schnipper, j. and kapoor, w. (2001) diagnostic evaluation and management of patients with syncope. medical clinics of north america, 85 (2), pp. 423-456. doi: http://dx.doi.org/10.1016/s0025-7125(05)70321-7 skrodzki, m. and trautvetter, (2008) syncope in dogs-a syndrome, not a disease. veterinary focus, 18 (3), pp. 36-46. strickberger, s. et al. (2006) aha/accf scientific statement on the evaluation of syncope: from the american heart association councils on clinical cardiology, cardiovascular nursing, cardiovascular disease in the young, and stroke, and the quality of care and outcomes research interdisciplinary working group; and the american college of cardiology foundation: in collaboration with the heart rhythm society: endorsed by the american autonomic society. circulation, 113 (2), pp. 316-327. doi: 10.1161/circulationaha.105.170274 tidwell, a. and robertson, i. (2011) magnetic resonance imaging of normal and abnormal brain perfusion. veterinary radiology & ultrasound, 52, pp.s62-s71. doi: http://dx.doi.org/10.1111/j.1740-8261.2010.01786.x yee, k. (2010). syncope. in: ettinger js and feldman e.c. textbook of veterinary internal medicine. 7th ed. st. louis, mo. saunders elsevier. pp. 275-77. wa, w. (2007). syncope or intermittent collapse. in: ware, w. (2007). cardiovascular disease in small animal medicine. london: manson/the veterinary press. waelbers, t. et al (2010). brain perfusion part 1: regulation mechanisms and measurements of brain perfusion. diergeneeskd. tijdschr, 79, pp. 169-177. supplementary files, images & tables all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. the only way is ethics? undertaking research as a practice-based vet/rvn richard mellanby bsc, bvms, phd, dsam, dipecvim-ca, mrcvs1* 1the royal (dick) school of veterinary studies, university of edinburgh, easter bush campus, midlothian, eh25 9rg *corresponding author (richard.mellanby@ed.ac.uk) vol 2, issue 1 (2017) published: 4 jan 2017 doi: 10.18849/ve.v2i1.84 research is essential to provide the evidence-base for veterinary science in order to improve the health and welfare of animals and to improve public health. in this session, dr mellanby will discuss the valuable contribution that practice-based veterinary surgeons and veterinary nurses can make to the future of veterinary knowledge. this is a podcast of richard's talk at the veterinary evidence today conference, edinburgh november 3, 2016. find out more abut richard. comments: in dogs with periodontal disease is feeding a complete raw meat diet more effective than a complete kibble 'dental' diet at reducing periodontal disease? a knowledge summary by nieky van veggel msc, cbiol, fhea1* matthew armstrong bsc, (hons), bvetmed, mrcvs2 1writtle university college, chelmsford, essex, cm1 3rr, united kingdom 2natures menu ltd, watton, norfolk, ip25 6ng, united kingdom *corresponding author (nieky.vanveggel@writtle.ac.uk) vol 2, issue 2 (2017) published: 06 apr 2017 reviewed by: nicola ackerman (bsc(hons), rvn, certsan, certvnecc, vts(nutr), a1 v1 mbvna) and sue badger (med, cert ed, rvn) next review date: 06 apr 2019 doi: 10.18849/ve.v2i2.88 clinical bottom line in light of the absence of evidence, vets and vet nurses should be cautious when recommending raw diets to support periodontal health and advise clients accordingly by relying on their clinical experience rather than the literature until more evidence is generated. question in dogs with periodontal disease, is feeding a complete raw meat diet more effective than a complete kibble 'dental' diet at reducing periodontal disease? clinical scenario you are asked by a client for advice on improving the dental health of their dog after they read on the internet that periodontal disease negatively affects their dog’s wellbeing. they read that raw feeding is better in improving the dental health of their dog than a commercial prescription kibble dental diet and are now asking you if there is evidence to support this. the evidence no published research evidence currently exists regarding the influence of complete raw diets on dental health in dogs. during the literature search some expert opinion papers were found that made reference to dental health and raw feeding. the reference lists of these papers were scrutinised for relevant evidence, however none of the sources retrieved this way were relevant to the research question for this paper. appraisal, application and reflection although raw feeding in carnivores has been discussed for many years (see e.g. fagan (1980) and bond and lindburg (1990)), it has become an increasingly popular concept in companion animals in recent years (schlesinger and joffe, 2011; freeman et al., 2013) and owners regularly seek feeding advice from veterinarians. however, the evidence-base for raw feeding-related issues in dogs, and companion animals in general, is underdeveloped. the majority of research relating to raw feeding to date has focused on nutritional risk/benefit to the animal and public health and consumer safety.schlesinger and joffe (2011) argue that although some high level evidence based on mainly north american studies is available regarding the latter, the evidence base for the former is weak. in all literature search strategies, the balance between sensitivity and precision of the literature search is key (o’connor et al., 2014). due to the nature of the evidence regarding raw feeding, the search strategy for this paper was deliberately on the sensitive side so that no potential relevant papers would be missed. as a result, the authors believe the outcome of this paper to be representative of the lack of research on raw feeds and feeding, rather than it being related to the specificity of the literature search strategy. during the inclusion/exclusion stage of the literature review 18 unique records were excluded for reporting on complementary feeds rather than complete feeds. these records included both raw and non-raw feed types. this shows there is merit in a critical evaluation of the current literature for evidence regarding complementary raw feeds and dental health in dogs. in addition, as the current systematic scrutiny of existing knowledge clearly highlights a gap in the evidence, a strong justification for further research is present (lund et al., 2016). the authors therefore recommend original research into dental health and complete raw feeding is undertaken. methodology section search strategy databases searched and dates covered: cab abstracts (1973-2017) pubmed (1950-2017) – veterinary science filter applied web of science (1970-2017) search terms: (dog or dogs or canine or canines or bitch or bitches) and (periodontal disease or gingivitis or gingiva or tartar or plaque or stomatitis or periodontitis or gum disease or dental disease or calculus) and (feed or diet or food or pet food) dates searches performed: 3rd january 2017 exclusion / inclusion criteria inclusion and exclusion criteria were determined in advance of the search phase. papers were initially screened by title and abstract and included for analysis if they met the inclusion criteria below. where there was doubt, papers were included. subsequently, full-text articles were obtained and a second inclusion/exclusion phase based on the criteria below was performed. where there was doubt about the suitability of a full text paper, an independent party was consulted and a majority vote applied. exclusion: non-dietary dental hygiene treatments dental hygiene complementary feeds (e.g. treats, chews, etc.) review papers non-peer reviewed material inclusion: primary research papers systematic reviews (sr) dental hygiene complete feeds complete raw feeds search outcome database number of results excluded – not related to pico excluded – not primary research/sr excluded – non-dietary treatment excluded – not complete feed excluded – kibble feed only total relevant papers cab direct 186 113 37 8 16 12 0 ncbi pubmed 210 181 9 3 10 7 0 thomson reuters web of science 185 151 5 0 0 0 0 total relevant papers when duplicates removed 0 conflict of interest nieky van veggel declares no conflict of interest. matthew armstrong declares the conflict of interest that he is an employee of natures menu, a producer of commercial raw pet food. the authors would like to gratefully acknowledge clare boulton (rcvs knowledge) for her help with finalising the search strategy and retrieving full-text papers. references bond, j. c. and lindburg, d. g. (1990) carcass feeding of captive cheetahs (acinonyx jubatus): the effects of a naturalistic feeding program on oral health and psychological well-being. applied animal behaviour science, 26 (4), pp. 373-382. https://doi.org/10.1016/0168-1591(90)90036-d fagan, d. a. (1980) diet consistency and periodontal disease in exotic carnivores. in: proceedings of the american association of zoo veterinarians, pp. 34–37. available at http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.462.6411 freeman, l. m., chandler, m. l., hamper, b. a., et al. (2013) current knowledge about the risks and benefits of raw meat–based diets for dogs and cats. journal of the american veterinary medical association, 243 (11), pp. 1549-1558. doi: 2460/javma.243.11.1549 lund, h. brunnhuber, k. juhl, c. et al. (2016) towards evidence based research. british medical journal, 355, october, i5440. doi: 10.1136/bmj.i5440 o’connor, a. m. anderson, k. m. goodell, c. k. et al. (2014) conducting systematic reviews of intervention questions i: writing the review protocol, formulating the question and searching the literature. zoonoses and public health, 61, 28-38. doi: 10.1111/zph.12125 schlesinger, d. p. and joffe, d. j. (2011) raw food diets in companion animals: a critical review. the canadian veterinary journal, 52 (1), pp. 50-54. available at https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3003575/ intellectual property rights knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. building a business case for ebvm elizabeth l. jackson bag (hons) mba phd sfhea1 sarah hauser bsc (hons) mpa mpp1* 1royal veterinary college, 4 royal college st, london, nw1 0tu *corresponding author (shauser@rvc.ac.uk) vol 1, issue 4 (2016) published: 24 nov 2016 doi: 10.18849/ve.v1i4.70 the clinical benefits of ebvm are clear however the business case for ebvm requires development. we aim to expand the adoption of ebvm amongst uk veterinary practices by identifying its improvement to practice performance... this is a podcast of elizabeth jackson and sarah hauser’s talk at the veterinary evidence today conference, edinburgh november 2, 2016. find out more about liz. view presentation slides comments: when treating canine diabetic ketoacidosis, do balanced crystalloids provide superior outcomes compared to 0.9% saline? a knowledge summary by sara marella dvm mrcvs 1* 1vets now hospital glasgow, 123–145 north street, glasgow g3 7da *corresponding author (sara.marella93@gmail.com) vol 7, issue 3 (2022) published: 24 aug 2022 reviewed by: dominic barfield (bsc bvsc mvetmed dacvecc decvecc fhea mrcvs) and amanda curtis (rvn) next review date: 01 mar 2024 doi: 10.18849/ve.v7i3.599 pico question when treating canine diabetic ketoacidosis, do balanced crystalloids provide superior outcomes compared to 0.9% saline?   clinical bottom line category of research question treatment and prognosis the number and type of study designs reviewed zero strength of evidence zero outcomes reported there is currently a lack of studies looking at comparing 0.9% saline to a buffered crystalloid solution (such as hartmann's) in dogs with diabetic ketoacidosis conclusion in view of the strength of evidence and the outcomes from the analysed studies, there is currently no evidence that the use of 0.9% saline or the use of a buffered crystalloid affects the outcome in dogs with diabetic ketoacidosis   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a dog presents with a history of lethargy, polyuria, polydipsia, vomiting and anorexia. the physical examination is consistent with hypovolaemic shock. initial diagnostics reveal hyperglycaemia, glycosuria, ketonaemia, a metabolic acidosis with high anion gap, hyponatraemia and hyperlactatemia. this patient has diabetic ketoacidosis (dka) and hypovolaemic shock. is it better to use 0.9% saline or a balanced crystalloid solution as a replacement fluid therapy, and which fluid is better as maintenance fluid therapy? should we give importance to the ph, to the dysnatraemia, to the risk of cerebral oedema or to the risk of hyperchloraemia? the evidence no peer-reviewed scientific papers were identified that addressed the pico question. summary of the evidence there was no peer-reviewed evidence that met the inclusion criteria to be summarised. appraisal, application and reflection diabetic ketoacidosis (dka) is one form of complicated diabetes mellitus. as these patients can have severe fluid losses, with electrolyte loss depending on the fluid composition, most of the patients with dka show differing degrees of acid-base and electrolyte imbalances and alterations in effective osmolarity. as a consequence of these alterations, restoring an appropriate fluid balance, before starting insulin treatment, remains one of the cornerstones in the treatment of these patients (boysen, 2008; connally, 2002; wolfsheimer, 1989; chastain, 1981; and hess, 2013). electrolyte imbalances and severity of acidosis influences the prognosis in patients with dka (hess, 2013; hume et al., 2006; efstathiou et al., 2002; ueda et al., 2015; agarwal et al., 2016; and ahuja et al., 2019). a variety of crystalloid fluids are currently available but they differ in buffer composition and ion concentration. in selecting the most appropriate fluid therapy for dka patients, there are two key elements to consider; sodium content in the fluid, and the alkalising / acidifying property of the fluid. of course, these two characteristics need to be related to the patient’s serum osmolarity, serum sodium concentration and acid-base status. in contrast to human medicine, where cerebral oedema is described as a complication of dka, particularly in paediatric medicine, cerebral oedema is rarely a reported complication of dka in veterinary medicine. multiple mechanisms are responsible for its development, with the patients initial natraemia and osmolarity playing a key role, alongside the correction of these abnormalities associated with the pathogenesis of the condition (boysen, 2008; and long & koyfman, 2017). one mechanism that results in alterations in sodium levels relates to the patients hyperglycaemic state; accumulation of glucose in the extracellular space leads to intra-cellular dehydration and dilutional hyponatraemia (pseudohyponatraemia). secondary to the hyperglycaemic osmotic effect, it is sodium concentration (total body sodium content relative to extracellular water content) rather than total body sodium content that changes. mathematical formulae have been extrapolated in order to estimate the natraemia (corrected sodium) in a normoglycaemic state, excluding the fluid shift caused by hyperglycaemia (katz, 1973; and hillier at al., 1999). however, other mechanisms, such as osmotic diuresis, excretion of ketoacids and gastro-intestinal losses, may result in total sodium depletion, all contributing to patient dysnatraemia (connally, 2002; wolfsheimer, 1989; tabor, 2019; and panciera, 2006). neurons are the most sensitive cells to alteration in osmolarity and in order to counter the extra osmolality of plasma during these episodes of hypertonicity, they accumulate intra-cytoplasmatic osmoles (connally, 2002; wolfsheimer, 1989; and tabor, 2019). the aim of initial fluid therapy in dka is to improve hyperglycaemia along with patient natraemia without significant changes in osmolarity, or cerebral oedema and further neurologic dysfunction may occur (connally, 2002; wolfsheimer, 1989; panciera, 2006; nelson, 2015; harris et al., 1990; hoorn et al., 2007; hale et al., 2008; durward et al., 2011; and schermerhorn & barr, 2006). this requires normal kidney function and a fluid therapy that aims to correct both the patient’s sodium and water deficits. replacement fluid therapy reduces blood glucose and ketone concentrations through different mechanisms, such as dilution, increased glomerular filtration rate, decreased circulating catecholamines and reduction in antidiuretic hormone (adh) and renin-angiotensin-aldosterone system (raas) activation. in addition to dysnatraemia, dka patients often have profound metabolic acidosis secondary to multiple mechanisms: overproduction of ketoacids, hypovolaemia (lactic acidosis, volume-responsive azotaemia) and hyperchloraemic metabolic acidosis. the latter occurs mainly as a result of chloride retention when keto-anions are excreted in the urine with sodium and potassium and / or secondary to administration of chloride-rich fluids (0.9% saline) (boysen, 2008; thomovsky, 2017; semler et al., 2018; and self et al., 2018). it is known that, due to its high chloride content, 0.9% saline can cause a non-anion gap metabolic acidosis with a reduction in serum strong ion difference; this acidosis is generally considered transient and of low impact (wolfsheimer, 1989). nevertheless, a causal link between hyperchloraemia and renal vasoconstriction has been hypothesised, which clinically may translate into a higher risk of acute kidney injury (boysen, 2008; williams et al., 2020; and semler et al., 2018). in comparison to chloride-rich saline, buffered crystalloids (such as hartmann’s solution, plasmalyte 148, ringer’s acetate) have a more physiologic chloride concentration and contain anion buffers that avoids hyperchloraemic metabolic acidosis.  these balanced crystalloids are on average more expensive than 0.9% saline and some studies also argue that infusion of ringer’s lactate solution may cause an elevation in serum lactate levels that may accumulate in cases of liver insufficiency, or may be converted into glucose, exacerbating hyperglycaemia (boysen & dorval, 2014). finally, from experimental studies and theoretical conceptions it seems that the acetate present in plasmalyte 148 and ringer’s acetate may be associated with alterations in myocardial activity and patient hemodynamics (boysen, 2008; connally, 2002; and ellekjaer et al., 2019). from a pathophysiological point of view, it is evident that in dka, the choice between 0.9% saline and buffered crystalloids is not straightforward; given their different compositions each fluid has advantages and disadvantages. in veterinary medicine no clinical trials evaluate outcome for dogs with dka that received 0.9% saline compared to a buffered crystalloid (such as hartmann's). from the search strategy applied, no papers met the inclusion criteria for this knowledge summary. some veterinary opinion articles, not directly addressing the pico question but reviewing the topic of fluid therapy in dka, suggest 0.9% saline as the fluid of choice because this is the fluid recommended by most of the human dka guidelines, the acidosis due to chloride-rich fluids is minimal and self-limiting, and its higher sodium content avoids rapid variation in osmolarity, reducing the risk of cerebral oedema. moreover, the use of buffered crystalloids may lead to overshoot alkalosis when keto-anions and lactate are metabolised, negatively charged lactate can promote further sodium and potassium loss in the urine, and finally in the presence of severe dehydration or shock, a lactic acid may contribute to the already existing acidaemia (boysen, 2008; connally, 2002; wolfsheimer, 1989; hess, 2013; nelson, 2000; panciera, 2006; nelson, 2015; and macintire, 1995). on the other hand, articles have questioned the use of 0.9% saline because of its acidifying effect and the lack of association between lower sodium concentrations in buffered crystalloids and a greater risk of cerebral oedema (long & koyfman, 2017). finally, other veterinary opinion articles advise modification of the fluid therapy toward 0.9% saline or a balanced crystalloid on the basis of the acid-base and electrolyte status of the single patient, using a personalised approach in the choice of the fluid therapy (wolfsheimer, 1989; chastain, 1981; gant, 2019; tabor, 2019; brown, 2009; nelson, 2000; and nelson, 2015). human medicine studies about development of cerebral oedema in dka found that the type of fluid rarely plays a role; it seems that dka cerebral oedema is mainly due to reperfusion of ischaemic brain tissue and increased vascular permeability, rather than shifting of water into brain cells, making fluid therapy rarely, if ever, a contributing factor (chastain, 1981; hume et al., 2006; higgs, 2013; gant, 2019; and long & koyfman, 2017). in human medicine, the incidence of new or progressive acute kidney injury (aki) and resolution of aki was not different between patients in dka that received 0.9% saline versus a balanced crystalloid (williams et al., 2020). furthermore, human medicine trials have compared outcomes in patients with dka that received 0.9% saline versus a balanced crystalloid. no significant difference in outcomes (time to normalise ph or glycaemia, time to receive subcutaneous insulin, sodium alteration, duration of hospitalisation, resolution of dka) has been found in most of the studies (williams et al., 2020; yung et al., 2017; chua et al., 2012; chiasson et al., 2003; van zyl et al., 2012; fayfman et al., 2017; and self et al., 2020).whilst this was not a primary outcome, one controlled trial found that patients that received hartmann’s solution, in comparison to 0.9% saline, had a statistically significant shorter length of hospitalisation (yung et al., 2017). a secondary analysis of two cluster randomised clinical trials found that treatment with balanced crystalloids resulted in more rapid resolution of dka, compared with 0.9% saline (self et al., 2020). based on several recent human randomised clinical trials comparing buffered crystalloids vs 0.9% saline, buffered solutions are increasingly recommended as first-line replacement fluid. despite this, most of the dka human guidelines suggest the use of 0.9% saline as the first fluid of choice (jayashree et al., 2019; tran et al., 2017; fayfman et al., 2017; and nice, 2015). as already mentioned, there is currently no evidence in veterinary medicine if any particular type of crystalloid fluid is superior to another in hyperglycaemic emergencies. however, veterinary opinion articles and human studies represent a starting point in the analysis of which type of fluid therapy is better in a patient with dka, highlighting the importance in evaluating certain elements of a fluid’s composition (sodium content and alkalising / acidifying property) that may change the outcome in patients with dka and also may shorten hospitalisation time, potentially reducing the cost of treatment and mortality associated with euthanasia. in conclusion, there is zero evidence if one particular isotonic crystalloid fluid confers a clinical outcome benefit over others in the treatment of dka in veterinary medicine. a personalised fluid therapy plan that considers the patient’s specific acid-base balance and electrolytes and re-evaluates these values during the treatment may be the best solution in this complex pathology. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform–1973 to 2022 week 08 pubmed accessed via the ncbi website 1920–february 2022 hand search search strategy: cab abstracts: (dog or dogs or canine or canines).mp. or exp dogs/ (diabetic or diabetes).mp. or exp diabetes/ (dka or ketoacid* or acidosis or complicat* or emergenc*).mp. (saline or 'sodium chloride' or nacl or 'non buffered crystalloid').mp. ('buffered crystalloid' or 'balanced crystalloid' or 'balanced fluid' or hartmann* or ringer* or 'sodium lactate' or isotonic or 'balanced salt' or plasma-lyte or plasma lyte or normosol or 'fluid therapy') 1 and 2 and 3 and (4 or 5) pubmed: dog or dogs or canine or canines diabetic or diabetes dka or ketoacid or acidosis or complication or emergency saline or 'sodium chloride' or nacl or 'non buffered crystalloid' 'buffered crystalloid' or 'balanced crystalloid' or 'balanced fluid' or hartmanns or ringers or 'sodium lactate' or isotonic or 'balanced salt' or plasma-lyte or plasma lyte or normosol or 'fluid therapy' 1 and 2 and 3 and (4 or 5) dates searches performed: 01 mar 2022 exclusion / inclusion criteria exclusion: not relevant to pico. no full text available. non-english language publications. duplicate papers. conference proceedings. articles involving the wrong species. inclusion: article relevant to the pico question. full text available. papers relevant to veterinary medicine. search outcome database number of results excluded – not relevant to pico excluded – inaccessible excluded – non-english language publications excluded – duplicates excluded – conference proceedings total relevant papers cab abstracts 56 27 2 7 0 20 0 pubmed 60 60 0 0 0 0 0 hand search 4 4 0 0 0 0 0 total relevant papers when duplicates removed 0 conflict of interest the author declares no conflicts of interest. references agarwal, a., yadav, a., gutch, m., consul, s., kumar, s., prakash, v., gupta, a.k. & bhattacharjee, a. (2016). prognostic factors in patients hospitalized with diabetic ketoacidosis. endocrinology and metabolism (seoul, korea). 31(3), 424–432. doi: https://doi.org/10.3803/enm.2016.31.3.424 ahuja, w., kumar, n., kumar, s. & rizwan, a. (2019). precipitating risk factors, clinical presentation, and outcome of diabetic ketoacidosis in patients with type 1 diabetes. cureus. 11(5). doi: https://doi.org/10.7759/cureus.4789 boysen, s.r. (2008). fluid and electrolyte therapy in endocrine disorders: diabetes mellitus and hypoadrenocorticism. veterinary clinics of north america: small animal practice. 38(3), 699–717. doi: https://doi.org/10.1016/j.cvsm.2008.01.001 boysen, s.r. & dorval, p. (2014). effects of rapid intravenous 100% l-isomer lactated ringer's administration on plasma lactate concentrations in healthy dogs. journal of veterinary emergency critical care (san antonio). 24(5), 571–577. doi: https://doi.org/10.1111/vec.12213 brown, v. (2009). dealing with complex and unstable diabetic conditions in small animals. veterinary times. 39(5), 23–24. chastain, c.b. (1981). intensive care of dogs and cats with diabetic ketoacidosis. journal of the american veterinary medical association. 15;179(10), 972–978. chiasson, j-l., aris-jilwan, n., bélanger, r., bertrand, s., beauregard, h., ekoé, j-m., fournier, h. & havrankova, j. (2003). diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state. canadian medical association journal. 168(7), 859–866. chua, h.r., venkatesh, b., stachowski, e., schneider, a.g., perkins, k., ladanyi, s., kruger, p. & bellomo, r. (2012). plasma-lyte 148 vs 0.9% saline for fluid resuscitation in diabetic ketoacidosis. journal of critical care. 27(2), 138-145. doi: https://doi.org/10.1016/j.jcrc.2012.01.007 connally, h.e. 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(1989). fluid therapy in the critically ill patient. veterinary clinics of north america: small animal practice. 19(2), 361–378. doi: https://doi.org/10.1016/s0195-5616(89)50035-4 yung, m., letton, g. & keeley, s. (2017). controlled trial of hartmann's solution versus 0.9% saline for diabetic ketoacidosis. journal of paediatrics and child health. 53(1), 12–17. doi: https://doi.org/10.1111/jpc.13436 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. in canine cranial cruciate ligament disease, are conservative treatment and lateral fabellotibial suture recoveries comparable? | veterinary evidence skip to main content knowledge summary keywords: cranial cruciate ligament disease; surgical treatment; lateral fabellotibial suture; extracapsular suture; nonsurgical treatment; conservative treatment; dogs in canine cranial cruciate ligament disease, are conservative treatment and lateral fabellotibial suture recoveries comparable? tafara mapuvire, bvsc pgcertacp savc1* 1 surgivet veterinary consultancy, 123 bram fischer drive, randburg, johannesburg 2194, south africa * corresponding author email: tafara@surgivetconsultancy.co.za vol 8, issue 2 (2023) submitted 15 apr 2022; published: 31 may 2023; next review: 20 sep 2024 doi: https://doi.org/10.18849/ve.v8i2.612 pico question in dogs with cranial cruciate ligament disease, is conservative non-surgical treatment as effective as surgical treatment with the lateral fabellotibial suture technique in reducing time to recovery? clinical bottom line category of research treatment. number and type of study designs reviewed one retrospective study. strength of evidence zero. outcomes reported there is no evidence that surgical treatment with the lateral fabellotibial suture (lfts) reduces time to recovery compared to conservative treatment in dogs with cranial cruciate ligament disease. conclusion in dogs with cranial cruciate ligament disease there is no statistical evidence to support recommendation of surgical treatment with the lfts technique compared to conservative treatment in reducing time to recovery. how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are presented with a 7-year-old labrador retriever with a confirmed complete rupture of the left cranial cruciate ligament. you offer the treatment options available to the client. the client explains that finances are constrained, and you offer either conservative treatment or surgery with the lateral fabellotibial suture (lfts) technique, both as cost effective options. the client is willing to go with the cost effective surgical option of the lfts technique if it will result in a quicker recovery than conservative treatment with non-steroidal anti-inflammatories (nsaids) and restricted exercise for 6–8 weeks. you look for evidence comparing the rate of recovery of the two treatments in order to be able to advise the client appropriately. the evidence there is no evidence that dogs treated with the lfts technique to address cranial cruciate ligament disease recover quicker than dogs treated conservatively with nsaids and exercise restriction. summary of the evidence chauvet et al. (1996) population: dogs weighing more than 22.7 kg with cranial cruciate ligament ruptures managed with fibular head transposition (fht), lateral fabellar suture (lfs) or conservative treatment presented at the university of illinois veterinary medical teaching hospital between 1986 and 1991. sample size: 61 dogs, 72 stifles. intervention details: 22 stifles (19 dogs) were treated with fibular head transposition (fht) technique. time between intervention and evaluation mean 26.7 months, median 28.5 months, range 3–66 months. 39 (36 dogs) stifles were treated with lateral fabellotibial suture (lfts) technique. time between intervention and evaluation mean 20.4 months, median 13.5 months, range 6–60 months. 11 (10 dogs) stifles were treated with conservative treatment (ct). time between intervention and evaluation mean 7.1 months, median 3 months, range 3–24 months. study design: retrospective study. outcome studied: subjective: owner evaluation outcomes. investigator physical examination evaluation. investigator radiographic evaluation. objective: investigator force plate evaluation. main findings (relevant to pico question): mean owner evaluation score for conservative treatment was lower than that for lfts technique but not statistically different. no significant differences in investigator evaluation scores. no statistical difference in force plate peak vertical forces. limitations: clinical evaluation is subjective. no preoperative force plate evaluation was carried out to provide a reference for comparative purposes. comparison of force plate evaluation of affected limb with contralateral limb is validated. however, several dogs presented with lower ground reaction forces in the contralateral limb, suggesting possible injury. ideally comparison should be with an unaffected limb. although a power analysis was not performed, the sample size could be too small for proper statistical inference. there was no presurgical evaluation of affected limbs to provide a reference for postsurgical evaluation. sample only included large dogs weighing more than 22.7 kg. it is difficult to conclude whether the results of this study can be applied to a heterogeneous dog population including those weighing less than 22.7 kg. cranial drawer sign, joint crepitus and capsule thickening are of little value as sole methods for evaluating stifle recovery and may not correlate to functional outcomes. the choice of surgery or conservative treatment was made by mutual agreement between the owners and respective veterinary surgeons. this means that interventions were neither blinded nor randomised. owner compliance was not evaluated.   appraisal, application and reflection cranial cruciate ligament (ccl) disease is a leading cause of hindlimb lameness in adult dogs (ness et al., 1996). surgical management of ccl rupture (cclr) is often recommended with a variety of surgical techniques described. surgical techniques to address cclr in dogs can be broadly classified into three categories. one category of techniques aims to provide dynamic stabilisation of the ccl deficient stifle by eliminating cranial tibial thrust (ctt). another category of techniques aims to provide a temporary static fixation by extracapsular stabilisation. the third category of techniques aims to provide a static fixation by replacement of the failed ccl with an intra-articular graft. evidence based assumptions are difficult to make regarding the preferred surgical treatment option for patients. however most recent reviews appear to support the tibial plateau levelling osteotomy (tplo) technique (tikekar et al., 2022; krotscheck et al., 2016; and bergh et al., 2014). the tplo procedure can be considered an advanced procedure with a significant learning curve and the necessity for additional equipment and expense. extracapsular suture (ecs) techniques such as the lateral fabellotibial suture (lfts) technique can often be performed with less expensive surgical equipment and implants, and less overall cost to owners. this makes the ecs a viable option for many patients. the goals of surgery to manage cclr are to provide immediate stifle stability, allow a quick return to optimal function and slow the development and progression of osteoarthritis in the affected joint. a 1984 study by vasseur demonstrated that small dogs weighing less than 15 kg can do well without surgery. the same study showed that outcomes after conservative treatment were poor for dogs weighing more than 15 kg. considering this, it remains unclear what the expected outcomes would be in a heterogeneous population of dogs. clients often opt out of surgery for various reasons including, but not limited to, financial constraints, increased surgical and or anaesthetic risks due to age, and / or presence of other medical, orthopaedic and / or neurologic disease. in these cases, clients might seek to gain more insight into the expected outcomes associated with conservative treatment compared to surgical intervention with ecs in order to decide whether surgical intervention would be worth the accompanying expense and / or risk. the 1996 prospective experimental study by jevens et al. compared functional outcomes between modified retinacular imbrication technique (mrit) and conservatively treated dogs with experimentally induced rupture of the ccl. they demonstrated that dogs that underwent mrit did significantly better than dogs that received conservative treatment according to the results of force plate analysis, although the recovery was prolonged. however, mrit and lfts are distinct procedures. the former was first described by flo in 1975 while the latter appears to be a hybrid of the lateral retinacular imbrication technique first described by de angelis & lau in 1970, the mrit as described by flo (1975), and the lateral suture technique as first described by gambardella et al. in 1981. both the mrit and lfts fall under the extracapsular technique classification. the study by jevens et al. (1996) therefore, may not be relevant to the clinical question. a 1996 retrospective study by chauvet et al. demonstrated that there was no statistical difference in outcomes for dogs treated for ccl disease, between conservatively and lfts treated stifles according to investigator evaluation. although owner evaluation demonstrated that lfts had higher functional scores than conservative treatment, the difference was not statistically significant. owner evaluation is subjective and difficult to use as a basis for scientific conclusions. the results of owner evaluation could be attributable to the placebo effect in the surgically treated group as the owners were not blinded as to which treatment their dog had received. the only objective method of outcome analysis in this study was force plate analysis, which showed no statistical difference between the two interventions. the comparison of force plate evaluation of the test limb with the contralateral limb is validated (o’connor et al., 1989). however, there is no evidence that the contralateral limbs were evaluated before the interventions to ensure that they were normal and therefore, acceptable as bases for comparison. the study also excluded dogs weighing less than 22.7 kg, making it difficult to determine whether the results can be applied to dogs weighing less than 22.7 kg. the recent availability of client based validated metrology instruments such as the bologna healing stifle injury index (bhsii [pinna et al., 2019]), canine orthopaedic index (coi [brown, 2014a; 2014b; and 2014c]) and the liverpool osteoarthritis in dogs (load [walton et al., 2013]), can help address the limitation of lack of objectivity in owner evaluation. however, they would be more relevant if used in prospective, randomised and blinded studies. the paucity of such studies renders these instruments less useful. the significance of this when applying the evidence to a heterogenous population of dogs is difficult to determine. owner compliance in the study by chauvet et al. (1996) was also not evaluated. this is an important factor affecting outcome and evaluation of compliance should therefore ideally form an integral part of any study aiming to compare outcomes of two interventions. the time from intervention to evaluation also varied widely in the study, making it difficult to determine and compare the extent of reduction of time to recovery of the two interventions under comparison. the pico question specifically aimed at comparing the reduction in time to recovery. therefore, time between intervention and evaluation should be standardised in order for the study to be able to address the pico question. the retrospective nature of the study makes it difficult to address this shortcoming. there is no evidence that points towards shorter recovery times with lfts. however, evidence can be obtained by using prospective, randomised, blinded and controlled clinical trials with large sample sizes representing a heterogeneous population of dogs with naturally occurring cranial cruciate ligament disease. there is paucity in such studies. the rcvs knowledge canine cruciate registry aims to plug this evidence base gap by collecting data from practitioners in the uk performing surgery to address cruciate ligament disease in dogs. this initiative may provide the much lacking, albeit needed, evidence to inform treatment choices for practitioners and owners alike (www.caninecruciateregistry.org). although participation in the initiative is limited to dog owners and practitioners registered and performing cruciate surgery in the uk, results from data collected can, hopefully, be extrapolated to any heterogenous population of dogs worldwide. methodology search strategy databases searched and dates covered: cab abstracts on ovid platform 1973–week 39 2022 pubmed accessed via the ncbi website 1910– september 2022 search strategy: cab abstracts: (dog or dogs or canine or canines or bitch or bitches) or exp dogs/ or exp canis/ or exp bitches/ (cranial and cruciate) (lateral or fabellar or fabello-tibial or tibiofabella or extracapsular or extra-capsular or lfts or de angelis or 'modified retinacular imbrication' or mrit ('non operative' or 'non surgical' or conservative or nonoperative or nonsurgical or non-operative or non-surgical or ('anti$inflammatory drug* and analgesi*) or nutraceutical* or 'dietary management' or 'prescription diet*' or 'weight loss' or physiotherapy or 'exercise restriction' or rest) 1 and 2 and (3 or 4)   pubmed: dog or dogs or canine or canines or bitch or bitches cranial and cruciate lateral or fabellar or fabello-tibial or tibiofabella or extracapsular or extra-capsular or lfts or de angelis or 'modified retinacular imbrication' or mrit. conservative or nonoperative or nonsurgical or non-operative or non-surgical or (antiinflammatory drug* and analgesi*) or nutraceutical* or 'dietary management' or 'prescription diet*' or 'weight loss' or physiotherapy or 'exercise restriction' or rest 1 and 2 and (3 or 4) dates searches performed: 20 sept 2022   exclusion / inclusion criteria exclusion: irrelevant to the pico. articles not in english. inclusion: articles in english. articles comparing outcomes of relevant interventions.   search outcome database number of results excluded – article not in english excluded – article irrelevant to pico total relevant papers cab abstracts 428 45 382 1 pubmed 280 5 274 1 total relevant papers when duplicates removed 1   orcid tafara mapuvire: https://orcid.org/0000-0002-7170-0624 conflict of interest the author declares no conflicts of interest. references bergh, m.s., sullivan, c., ferrell, c.l., troy, j. & budsberg, s.c. 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(2022). retrospective comparison of outcomes following tibial plateau levelling osteotomy and lateral fabello-tibial suture stabilisation of cranial cruciate ligament disease in small dogs with high tibial plateau angles. new zealand veterinary journal. 70(4), 218–227. doi: https://doi.org/10.1080/00480169.2022.2052992 vasseur, p.b. (1984). clinical results following nonoperative management for rupture of the cranial cruciate ligament in dogs. veterinary surgery. 13(4), 243–246. doi: https://doi.org/10.1111/j.1532-950x.1984.tb00801.x walton, m.b., cowderoy, e., lascelles, d. & innes, j.f. (2013). evaluation of construct and criterion validity for the ‘liverpool osteoarthritis in dogs’ (load) clinical metrology instrument and comparison to two other instruments. plos one. 8(3), e58125. doi: https://doi.org/10.1371/journal.pone.0058125 contribute to the evidence there are two main ways you can contribute to the evidence base while also enhancing your cpd: tell us your information need write a knowledge summary either way, you will be helping to add to the evidence base, and strengthen the decisions that veterinary professionals around the world make to give animals the best possible care. learn more here: https://veterinaryevidence.org/index.php/ve/guidelines-for-authors licence copyright (c) 2023 tafara mapuvire intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right 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or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use.   veterinary evidence is an rcvs knowledge initiative. issn: 2396-9776 first floor, 10 queen street place, london ec4r 1be resources student awards staff login policies privacy policy accessing information policy cookie declaration terms of use copyright notices stay connected podcasts twitter facebook instagram linkedin back to top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443. are dogs that eat quickly more likely to develop a gastric dilatation (+/volvulus) than dogs that eat slowly? a knowledge summary by louise anne buckley phd rvn1* 1harper adams university, edgmond, newport tf10 8nb *corresponding author (lbuckley@harper-adams.ac.uk) vol 1, issue 4 (2016) published: 13 dec 2016 reviewed by: gillian monsell (ma vetmb phd mrcvs) bruce smith (bvsc ms fanzcvs dacvs) next review date: 13 dec 2018 doi: 10.18849/ve.v1i4.53 clinical bottom line the available evidence is mixed and of variable quality. most evidence indicates that rate of eating has no effect on risk of gastric dilatation – volvulus (gdv). where significant effects occur, fast eating was implicated as a risk factor. no studies found that slow eating was significantly associated with an increased risk of gdv.  slowing the rate at which a dog consumes a meal will not increase risk of gdv but it may possibly reduce the risk. based on the limitations and unreliability of the current relevant literature there is not enough evidence to make a conclusion either way. question are dogs that eat quickly more likely to develop a gastric dilatation (+/volvulus) than dogs that eat slowly? clinical scenario a client approaches the clinic for advice on reducing the risk of their dog developing a gastric dilatation volvulus (gdv) as they have heard that their particular breed of dog is particularly at risk from this condition. they have read on the internet that they should buy a go slow / anti-gulp feeding bowl to slow down the speed at which their dog eats because eating quickly is a risk factor for developing this condition. they want to know if there is any evidence that slowing down a dog’s rate of eating does reduce the risk of the dog developing a gdv. the evidence the literature searches uncovered six papers (glickman et al., 1997; elwood, 1998; theyse et al., 1998; glickman et al. 2000; raghavan et al., 2004; pipan et al. 2012) that directly addressed the pico question. of these, four of the studies (elwood, 1998; theyse et al., 1998; raghavan et al., 2004; pipan et al., 2012) found no significant effect of speed of eating on risk of having a gdv episode. one paper (glickman et al., 1997) found that dogs that ate quickly were significantly more likely to present at a clinic with a gdv episode. the final paper (glickman et al., 2000) found that large breed dogs (but not giant breeds) were significantly more likely to develop a gdv if they ate fast, but the 95% confidence intervals associated with the relative risk value that the authors report suggests that the true risk may not differ from that of slow eaters. summary of the evidence pipan (2012) population: privately owned dogs (any breed or mix, both sexes, neutered and entire) across a wide geographic area. the survey was potentially available to english speaking dog owners with access to the internet in any country worldwide. sample size: 2551 surveys included in the analysis: control group (dogs without a gdv): 1437 respondents gastric dilatation – volvulus group (gdv): 1114 respondents intervention details: online survey based study, with ad hoc convenience sampling of dog owners. the questionnaire was divided into three sections: demographic information (year of birth, breed, sex, neuter status, and purpose of the dog; country and postcode of respondent). whether the dog had ever had a gdv that required surgical intervention. this latter question was used to divide dogs into the control group and the gdv group. however, the authors then also included within the gdv group dogs that did not have surgery, or died / were euthanised without surgery but were considered to have a gdv (whether confirmed or presumed). gdv group: a series of 44 questions divided into 4 categories: dog specific factors management factors environmental factors personality factors control group: the same questions were asked of the control group dog owners as were asked of the gdv group, with the exception that they were not asked any questions about the gdv episode (as the dogs had not experienced a gdv). they were asked one additional question (had the dog had a prophylactic gastroplexy?). these changes reduced the total number of questions asked to 32. study design: cross-sectional study outcome studied: the outcome measure was a gdv episode in the dog’s history. the study looked for factors that were associated with an increased incidence of gdv in the population studied. of relevance to this pico, the authors’ asked owners to rate, on a scale of 1 to 5, the speed with which their dog consumed its food ration. main findings (relevant to pico question): the findings in relation to speed of eating are not reported within the results section. the authors note in the discussion that speed of eating was not significantly associated with risk of gdv. limitations: the primary limitation is the failure to report their findings (along with numerical data) within the results section as this precludes the reader making an independent assessment of their conclusion. the measurement of speed of eating on a scale of 1 -5 will be sensitive to owner subjectivity in assessment. the authors do not provide any information on how owners were guided (if at all) to select the number that most represented their dog. further, the incidents of gdv were retrospective so owners may have already taken measures to reduce their dog’s speed of eating post-surgery, on the basis of veterinary recommendation or lay research. the authors do not outline whether owners were asked to complete the form on the basis of the dog’s feeding behavior at the time of (or preceding) the gdv, or present time, or not directed as to a time frame to use. there was no attempt to match control dogs and gdv dogs across other dimensions that may have been relevant (e.g. breed, size, and / or age). the population of dogs studied is not constrained to types of dogs at high risk of gdv (large and giant breed dogs). therefore, if any risk factors identified co-vary with the size of the dog, this would represent a confounding variable in interpreting the data that limits any conclusions that may be drawn. glickman (2000) population: dogs (male, female, neutered and entire) from eleven different large and giant dog breeds (akita, bloodhound, collie, great dane, irish setter, irish wolfhound, newfoundland, rottweiler, saint bernard, standard poodle, and weimaraner), that were located within the usa. dogs were required to be at least 6 months old and not to have a medical history that included an episode of gdv before the study commenced. sample size: 1637 (large breeds: n= 894; giant breeds: n = 743): dogs that developed a gdv during the course of the study: 98 dogs that did not develop a gdv during the course of the study: 1539 nb. this study was derived from a larger prospective cohort study carried out by the authors. 1991 dogs initially enrolled on this study; however, for inclusion in the current study (which used data from the larger study), certain criteria needed to be met and this reduced the sample size. further details are outlined in the intervention section. intervention details: the study began in june 1994 and ended in february 1999. therefore, the maximum possible period that a dog could be studied for was 58 months. dogs were recruited through breed clubs and dog shows. at the start of the study, owners were asked about the presence of gdv in the medical history of the dog or any of its first-degree relatives. the dog was physically assessed for body condition and temperament, and conformational measurements taken. within thirty days of recruitment, owners were provided with a detailed questionnaire to complete that provided data on the dog’s gdv history (if positive, the dog was excluded), breeding, medical history, reproductive status, personality and temperament, and dietary factors. owners were instructed to notify the researchers if any of the following outcomes occurred: the dog developed a gdv (if so, the researcher confirmed this with the veterinarian who treated the dog) the dog died of another cause the ownership of the dog was transferred to another person owners were contacted in 1997, 1998, and 1999 to find out if, over the duration of the study, their dog had developed a gdv and, if so, whether the dog died or survived. this was the methodology for the original prospective cohort study by the authors (referred to above). dogs from that study were included only if: the initial questionnaire had been fully completed there was at least one follow up set of data for that dog 7% of the owners in this study fulfilled both criterion for inclusion (n = 1660) 4% of these owners were excluded because their dog was less than 6 months old at the point of completing the initial questionnaire, leaving 1637 (82.2% of the original sample) available for analysis in this study. of these dogs, the median duration during which the dogs were followed up was 2.4 years (max: 4.8 months; minimum: no stated). the reasons for loss to follow – up (other than death) are not stated. 182 dogs died during this period: 29 died due to the gdv episode, 24 died for unknown reasons. 55 are reported to have died from other medical problems. 74 dogs are not accounted for in the figures reported. the authors converted the raw data into number of gdv cases per 1000 dog years in order to present the data as incidence of gdv (± confidence interval) among the large and giant breed dog population. study design: prospective cohort study outcome studied: the outcome measure was whether the dog developed an episode of gdv during the course of the study and whether it survived this episode. the study then looked for nondietary related factors that were associated with an increased risk of developing gdv in the population studied. of relevance to this pico, the authors’ asked owners to rate, on a scale of 1 (slow) to 10 (fast), the speed with which their dog consumed its food ration. the authors did not direct the owners further as to what constituted e.g. a rating of ‘3’, but, instead, the owner was left to use their judgement and experience. in analysing and presenting the data, the authors’ merged speed ratings to form three categories: slow: speed rating of 1 – 3 average: speed rating of 4 – 6 fast: speed rating of 7 – 10 and then, further split the data into: large breed dogs giant breed dogs main findings (relevant to pico question): large breeds: large breed dogs that ate quickly were 2.36 times more likely to develop a gdv during the study than dogs that ate slowly. the incidence (± confidence interval) of gdv episodes per 1000 dog years was: slow eaters: 13 (2-24) average eaters: 23 (13-33) fast eaters: 30 (19-41) 8% of gdv cases could be explained by the dogs eating fast.   giant breed dogs: no statistically significant association was found between speed of eating and risk of gdv in giant breed dogs. the incidence (± confidence interval) of gdv episodes per 1000 dog years was: slow eaters: 36 (12-60) average eaters: 29 (15-43) fast eaters: 22 (12-32) limitations: the authors use the proportional hazards model to calculate the risk of having a gdv, as a function of speed of eating score, and include an interaction between breed size (large versus giant). however, the population attributable relative risk of gdv that they report for fast eating in large breed dogs (2.36 times more likely) is drawn from their univariate analysis. the 95% confidence interval for this is 0.91 – 6.12, which is both a wide range (giving less confidence in the 2.36 value reported) and overlaps an odds ratio of 1.0 (awarded to the slow eating group to which the other groups are compared), indicating that, based on the univariate analysis, the true relative risk may not differ between slow and fast eaters. the authors collect data on eating speed at the start of the study (within 30 days of recruiting dogs). no further attempts were made to collect further data on this at regular intervals. thus, unless speed of eating is an unchanged behavior of the individual dog and not influenced by other factors (e.g. diet change, age, etc), this reduces the ability of the study to detect real effects or meaningfully explain the effects observed. the measurement of speed of eating on a scale of 1 -10 will be sensitive to owner subjectivity in assessment. the total number of dogs lost to follow up is not reported. the authors exclude dogs from the original study that were lost to follow-up before at least one follow up questionnaire was completed. however, this is not the same as saying these dogs were not lost to follow-up as, for example, if the study was still in operation, why were further questionnaires not completed by these owners? the authors do not report how many dogs recruited to the study, remained with the study until the study ended. instead they report only median duration of follow-up; this is meaningless to assess the number of dogs that remained with the study from recruitment to study end, as the dogs were signed up to the study at different time points. if the dogs that developed gdv and the dogs that didn’t develop a gdv differentially dropped out prematurely, this could introduce a ‘loss to follow-up bias’. we know that, by the nature of the recruitment process for the subset of dogs included in this study, that already 13.3% of dogs had been excluded due to lack of follow-up data (no follow-up questionnaires completed). therefore, it seems likely that total losses to follow-up before the study ended would be higher (and possibly considerably so) but the authors fail to give us the information needed to assess this. there is not attempt by the authors to assess whether participant drop out before the study ended was random or whether particular risk factors or characteristics were associated with an increased risk of drop out. furthermore, there are a lot of dogs lost to death that remain unaccounted for in the authors’ reporting. theyse (1998) population: great danes. sample size: 109 dogs: 38 dogs that had presented at the authors’ vet clinic with a gdv 71 dogs owned by members of a great dane breed society intervention details: clinic records were retrospectively searched for cases of acute gdv in great danes presented to the clinic over a 14 year period (january 1981 – december 1994). no information is provided on the fate (survived or died) of the dogs that attended the clinic. control dogs were obtained by contacting a great dane breed society. owners of both groups of great danes were asked to complete a questionnaire that asked owners about their feeding and exercise regime. demographic information was also recorded (age, sex, neuter status, and, for gdv dogs only, type of food eaten before the gdv episode). study design: a cross sectional study (based on the rcvs knowledge’s knowledge summary guide); the authors describe it as a case-control study. outcome studied: of relevance to this pico, the authors assessed speed of eating by asking owners whether their dog took more than, or less than, five minutes to consume its feed ration. main findings (relevant to pico question): a significant association between food intake time and development of a gdv was not observed. no further information is provided. limitations: the use of a binary less than, or more than, five minutes to consume a feed ration is a crude assessment tool: owners were not specifically asked to measure length of time taken so it probably represents a variable and subjective assessment the authors also ask owners whether they feed their dog once, twice or more often per day. dogs that consume several meals will have smaller portions per feeding session and so be more likely to consume a ration within five minutes. therefore, there may be a partial confound in the findings between size of portion and time taken to consume the ration. this weakens its use as a measure to assess speed of eating. there is no evidence that the authors tried to control for this statistically (e.g. by only analysing the dogs that were fed once daily). the authors provide no numerical data to support their assertion that there was no significant effect of food intake time. the authors retrospectively searched clinic records for gdv cases in great danes between 1981 and 1994 and owners of affected dogs contacted to complete a questionnaire that retrospectively assessed feeding and exercise regime. thus, owners were often being asked to recall information about their dog’s exercise and diet regime many years after the gdv episode and / or likely death of their dog. factual recall is likely to be poor under these circumstances. whereas, control group owners were probably being asked about an existing, current dog that they own (not enough information is provided to say this for certain). alternatively, dietary and exercise regime modifications may have been implemented post-acute gdv episode (in the dogs that survived) and these reported by the owner as their regime. this would prevent accurate measurement of risk factors associated with gdv development. there is not enough detail provided by the authors to allow this possibility to be evaluated. glickman (1997) population: owned dogs within the usa. sample size: 202 dogs (101 matched case-control pairings). intervention details: several veterinary practices were contacted to complete a clinical data sheet for dogs that were presented at the clinic, diagnosed with gdv, and whose owners were willing to be contacted by researchers. vets were asked to also identify a similar dog (matched for age and breed if pure breed, or age and weight if cross bred). researchers provided their own case control dog through the university veterinary hospital if vets were unable to. all owners (gdv, and case-matched control) were interviewed by phone. data on the following areas were collected: the owner of the animal environmental factors clinical history physical activities dietary factors personality and temperament two types of questions were asked: those designed to evaluate the dog in the 8 hours preceding the gdv episode (gdv dogs) or telephone interview (case – control dogs) those designed to evaluate the dog’s behavior. diet, etc more generally over the preceding year. of particular importance to this pico was rate of eating. this is mentioned in the abstract and results section but the authors fail to mention in the methods section either rate of eating per se or how this was assessed by the owners or quantified by the researchers. in the results section, the authors refer to slow, moderate, and fast groupings in relation to rate of eating, but how dogs were allocated to these groupings remains unclear. study design: a cross sectional study (based on the rcvs knowledge’s knowledge summary guide); the authors’ describe it as a case-control study. outcome studied: of relevance to this pico, owners were asked about rate of eating. however, the authors fail to provide any information about whether this was objectively quantified or represented a subjective impression of the dog’s feeding behavior. main findings (relevant to pico question): dogs that have a moderately fast (p = 0.05) or fast rate of eating are significantly more likely (p = 0.005) to have presented at the clinic with a gdv than dogs that ate slowly. compared with slow eaters, dogs that ate moderately fast were 2.59 (1.01 – 6.79, 95% confidence interval) times more likely to have developed a gdv. fast eaters were 4.72 (1.57 – 14.24, 95% c.i.) times more likely to have developed a gdv, than slow eaters. limitations: failure to report any information about how speed of eating was assessed represents a failing in this study as it is difficult to critique the approach used or draw any conclusions as to the validity or otherwise of the method. it is not clear how many dogs (total; gdv; case-controlled pairs) were represented within each of the groups (slow, moderate, and fast). it is not clear whether the gdv group included dogs that were deceased as a consequence of the first gdv episode. it is possible that referring veterinarians would not approach owners of dogs that died or, alternatively, that owners whose dogs died were more or less willing to be interviewed. this may have introduced bias into the data set if survival rate from a gdv is associated with speed of eating. elwood (1998) population: irish setter dogs (both sexes, neutered and entire) owned by members of uk irish setter breed clubs sample size: 669 dogs: 75 dogs that had had an episode of gastric dilatation and / or volvulus 594 control dogs intervention details: a questionnaire was sent to members of uk irish setter breed clubs, and owners requested to complete one form per irish setter that they had owned in the last ten years. demographic information included age, sex, neuter status and whether the dog had ever had an episode of bloat/gdv. owners were requested to complete the answer by providing data for the dog that applied at the time of the first gdv episode (gdv dogs) or current data (control dogs). a range of questions were asked about potential risk factors. these included a range of dietary, environment, temperament and exerciserelated factors. study design: cross-sectional study outcome studied: of specific relevance to this pico, the owners were asked to rate their dogs speed of eating from 1 to 10 (1 = very slow, 10 = very fast). in the statistical analysis of this, the authors gender-and age-matched control dogs to those of the gdv group. there is insufficient information as to whether this was objectively quantified (i.e. authors provided a descriptor for how fast each dog should eat in order to be awarded a given score). or, whether this represented a subjective impression of the dog’s feeding behavior. main findings (relevant to pico question): speed of eating was not identified as a risk factor for gdv. the median (1st quartile – 3rd quartile) score for speed of eating was 6 (5 – 8) for the gdv dogs, and 7 (2.1 – 8) for the control dogs. limitations: the questionnaire was asking owners to complete a form for every irish setter dog that they had owned in the previous ten years. this poses a number of related issues for the data: the dogs may not still be alive. thus, it is not clear how the owners of the dogs not affected (the control dogs) could complete the questionnaire as per the instructions as the dogs may have been dead at the time of completion. do the owners then complete the form based on the management, exercise, feeding, etc routines of the dog shortly before it died, or when it was younger/fitter/healthier? if the owners all elect for the form (as the closest point to ‘current’) this could introduce significant biases into the data set. up to ten years ago, is a long time to expect owners to accurately reflect back and recall their dogs feeding, exercise, housing regime, and so on. as the gdv group owners were asked to recall this information from the time the dog had its first episode of gdv, the length of time the owners were required to reflect back could be even longer. there is not enough information supplied regarding the speed of eating score to allow further criticism of it. raghavan (2004) population: dogs (male, female, neutered and entire) from eleven different large and giant dog breeds (akita, bloodhound, collie, great dane, irish setter, irish wolfhound, newfoundland, rottweiler, saint bernard, standard poodle, and weimaraner), that were located within the usa. dogs were required not to have a medical history that included an episode of gdv. sample size: 318 dogs were included: 106 dogs that developed a gdv 212 dogs that did not develop a gdv intervention details: this study used dogs drawn from a larger study. the methodology for this study is detailed above (glickman, l. et al. 2000). at the end of that prospective study, there was sufficient information on diet and ‘vital status’ (not defined by authors, presumed to be gdv development and other demographic information matched for in the current study), for 1634 dogs to be potentially included in this study. of these, all dogs that developed a gdv (n = 106) were included. a nested case control study design was used so dogs that developed a gdv were placed in one of six groups (corresponding to the year – 1994 – 2000 they experienced the episode of gdv). the dogs that made up the control group (n = 212) were placed into one of six groups according to the year they joined the study (i.e. the year they completed the detailed questionnaire about diet, etc). from each of these year groups, for every gdv case that occurred in that year group, two dogs were randomly selected to act as controls. this was done to ensure that the diet related information (including the estimation of how fast the dogs ate) was collected at a similar time for both gdv dogs and control dogs. study design: case-control study outcome studied: the outcome measure was whether the dog developed an episode of gdv during the course of the study and whether it survived this episode. the study then looked for breed related factors that were associated with an increased risk of developing gdv in the population studied. of relevance to this pico, the authors asked owners to rate, on a scale of 1 (slow) to 10 (fast), the speed with which their dog consumed its food ration. the authors did not direct the owners further as to what constituted e.g. a rating of ‘3’, but, instead, the owner was left to use their judgement and experience. to analyse the data, dogs from each group were split into two groups: slow eaters (score: 1-3); moderate speed eaters (4-6); fast eaters (7-10) and odd ratios calculated based on difference from moderate eating. thus, both slow and fast rates of eating were evaluated as a risk factor for gdv. main findings (relevant to pico question): there was no significant effect of how quickly (or slowly) a dog ate, on risk of developing a gdv. limitations: the measurement of speed of eating on a scale of 1-10 will be sensitive to owner subjectivity in assessment. the authors collect data on eating speed at the start of the study (within 30 days of recruiting dogs). no further attempts were made to collect further data on this at regular intervals. thus, unless speed of eating is an unchanged behavior of the individual dog and not influenced by other factors (e.g. diet change, age, etc), this reduces the ability of the study to detect real effects or meaningfully explain the effects observed. appraisal, application and reflection this knowledge summary aimed to identify whether eating quickly increased the risk of gdv in dogs. it was concerned with being able to advise clients, who wish to use a device to slow down their dog’s rate of eating in order to reduce the gdv risk, whether the use of these devices was warranted. the literature searches uncovered six papers (glickman et al., 1997; elwood, 1998; theyse et al., 1998; glickman et al. 2000; raghavan et al., 2004; pipan et al. 2012) that directly addressed the pico question. of these, four of the studies (elwood, 1998; theyse et al., 1998; raghavan et al., 2004; pipan et al., 2012) found no significant effect of speed of eating on risk of having a gdv episode. one paper (glickman et al., 1997) found that dogs that ate quickly were significantly more likely to present at a clinic with a gdv episode. the final paper (glickman et al., 2000) found that large breed dogs (but not giant breeds) were significantly more likely to develop a gdv if they ate fast, but the 95% confidence intervals associated with the relative risk value that the authors report suggests that the true risk may not differ from that of slow eaters. the approaches used to assess speed of eating varied in both type and quality. the weakest of these studies in relation to the pico question was the study by theyse et al. (1998). the questionnaire asked owners to identify whether their dog consumed its meal in less than five minutes or more than five minutes. this apparently arbitrary cut off point may have been prone to ceiling effects (unpublished data by the author of this knowledge summary suggests most dogs will consume their ration within five minutes). furthermore, it seems likely (based on the study methodology), that the authors were asking the owners to estimate ‘time taken to consume meal’ on the basis of recall of a dog that may have had a gdv episode as 10 years or more previously. finally, the authors fail to provide any numerical data to support their finding so further examination of the results is impossible. where the studies provided information on the methodology used to assess speed of eating, most authors (elwood, 1998; glickman et al., 2000; raghavan et al. 2004; pipan et al. 2012) used a ratings scale approach to evaluate this. this approach was preferable to the theyse et al. (1998) study as this removed the partial confound present between time taken to consume ration and size of the ration. most of the scales were between 1-10 (elwood, 1998; glickman et al., 2000; raghavan et al. 2004), but pipan et al. (2012) used a scale of between 15. none of the authors report providing descriptors to accompany each ratings score, but glickman et al. (2000) reports leaving it to the owner’s own judgment and experience (as raghavan et al. 2004 also used a sub-section of this data this point will also apply to this study as they are not truly independent studies). this may have reduced the ability to find a true effect as owner judgement may be subjective and partially dependent upon other dogs owned and utilised as a comparator. it is not clear how, in the absence of a definition/descriptor to accompany each rating, the 110 scale was any more useful than a 15 scale.  the pipan et al. (2012) authors fail to report the speed of eating findings within the results section. the authors then note in the discussion that there was no significant effect. however, this failure to report their finding adequately reduces the clinical and research value of this study. a failure to case match against potentially relevant dimensions (e.g. breed, size) may also have reduced the ability of this study to identify significant effects in at risk breeds as there may be many low risk breeds or size dogs that also eat fast. however, conversely this may also have reduced the risk that other causal factors that might correlate with speed of eating in high risk breeds and do cause increase risk of gdv, may wrongly lead to speed of eating being implicated a risk factor. the elwood (1998) study into risk factors for gdv specifically focused on irish setters and found no significant effect. however, the methodology employed in this study limited its ability to detect meaningful differences. control dog owners were asked to provide current data for speed of eating; gdv dog owners were asked to provide speed of eating data that pertained to when the dog had its first episode of gdv. thus, there is likely to be a difference in how long ago owners were being asked to reflect back and remember accurately their dog’s speed of eating. this may be reflected in the data: median values did not differ between the two groups, but the variation around this median was much wider for control dogs, and much less (clustered relatively tightly round the median) for gdv dogs. the glickman et al. (2000) study focused on 11 large and giant breed dogs known to be high risk for gdv. this study reported that eating fast significantly increased risk in large, but not giant, breeds. however, the 95% confidence interval for the relative risk that they report for eating fast overlaps the odds ratio of 1.0 for slow eaters, indicating that the relative risk may not differ between the two groups. the giant breeds appeared to show the converse relationship when plotted graphically but this was not statistically significant. it cannot be discounted that it was underpowered to detect this effect statistically as the confidence interval associated with each speed of eating parameter (both large and giant dogs) was wide; however, given the number of giant breeds included (n = 738) this seems unlikely for any biologically important effect. another issue surrounded dogs lost to follow-up as the authors failed to report this figure, but, from the information they do report, it seems likely that the loss to follow-up was high enough to severely risk invalidating the findings if participant losses were not random. the authors do not evaluate whether losses were random or systematically related to one of more of the participant characteristics or potential risk / protective factors for a gdv episode. the other main issue with this study was that it asked owners to rate their dog’s speed of eating at the start of the study and then followed the dogs’ outcome for up to 58 months. however, there is no evidence that speed of eating is a fixed behaviour trait that is unchanging over time. interestingly, the raghavan et al. (2004) study utilised a subset of data (all gdv cases, and twice as many controls, matched by year of gdv episode) that was collected and analysed for the glickman et al. (2000) study and found no significant effect of speed of eating in either large or giant breed dogs. the authors report that the control and gdv dogs did not differ across dimensions such as age, breed or size. the use of a subset of the same data set and the failure to find a similar significant effect weakens the confidence that one might have in the findings of glickman et al. (2000). finally, the glickman et al. (1997) used dogs that presented at participating veterinary clinics with a gdv and case matched them with dogs of a similar age and breed (or size) that did not have an episode of gdv. this study found that, compared with slow eaters, eating as a moderate or fast speed, both significantly increased risk of gdv occurrence. however, the authors fail to mention in the methods section anything about collecting data on speed of eating, thus it is impossible to evaluate their methodology further in relation to this specific issue. this was a definite study weakness. furthermore, the case matched dogs were (where needed), drawn from the authors’ own university veterinary hospital. this was a source of bias in one other dimension (rural living), but is potentially a source of bias in other areas. it is not clear how rural living might affect speed of eating; however, it cannot be excluded as a potential risk for bias. in conclusion, the evidence that eating fast is associated with an increased risk of gdv is mixed and inconclusive. the current studies that address this question are of variable quality and sometimes fail to report sufficient detail about either their methodology or results to facilitate adequate interpretation of the findings. however, it is worth noting that none of the studies found that eating slowly significantly increased the risk of gdv; where a significant effect was found, the increased risk of gdv was always associated with a faster rate of eating. thus, if owners wish to slow down the rate at which their dog consumes it’s meal, the veterinarian practitioner may advise that there is no evidence that this will increase the risk of gdv (though it may have no effect at all anyway). methodology section search strategy databases searched and dates covered: pubmed; science direct; web of science; cab abstracts (1973-2015) search terms: (dogs or dog or canine or bitch) and ("gastric dilatation" or “gastric dilation "gastric dilatation volvulus" or gdv or "gastric torsion" or "stomach volvulus") and (feed* or diet* or food*) dates searches performed: 28th september 2016 exclusion / inclusion criteria no limitations regarding study design, setting, sample size or study population were imposed. exclusion: pre-defined exclusion criteria: non english language, popular press articles inclusion: any comparative (control group utilised) study in which the effect of rate of feed intake on development of a gastric dilatation (+/volvulus) was investigated. search outcome database number of results excluded – did not answer to pico question excluded – not english language excluded – conference abstract only excluded – duplicates total relevant papers ncbi pubmed 32 26 0 0 0 6 thomson reuters web of science 33 26 1 0 6 0 cab direct 58 49 1 2 6 0 science direct 337 259 0 0 0 0 total relevant papers when duplicates removed 6 conflict of interest the author declares no conflicts of interest. references elwood, c. (1998) risk factors for gastric dilatation in irish setter dogs. journal of small animal practice, 39 (4), pp. 185 – 190 http://dx.doi.org/10.1111/j.1748-5827.1998.tb03627.x glickman, l. et al (2000) non-dietary risk factors for gastric dilatation-volvulus in large and giant breed dogs. journal of the veterinary medicine association, 217 (10), pp. 1492-1499 http://dx.doi.org/10.2460/javma.2000.217.1492 glickman, l. et al (1997) multiple risk factors for the gastric dilatation-volvulus syndrome in dogs: a practitioner/owner case-control study. the journal of the american animal hospital association, 33 (3), pp. 197-206 http://dx.doi.org/10.5326/15473317-33-3-197 pipan, m. et al (2012) an internet-based survey of risk factors for surgical gastric dilatation-volvulus in dogs. journal of the american veterinary medicine association, 240 (12), pp. 1456-1462 http://dx.doi.org/10.2460/javma.240.12.1456 raghavan, n. et al (2004) diet – related risk factors for gastric dilatation – volvulus in dogs of high risk breeds. journal of the american animal hospital association, 40 (3), pp. 192-203 http://dx.doi.org/10.5326/0400192 theyse, l. et al (1998) small size of food particles and age as risk factors for gastric dilatation volvulus in great danes. veterinary record, 143 (2), pp. 48 – 50 http://dx.doi.org/10.1136/vr.143.2.48 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. full text template title | veterinary evidence skip to main content knowledge summary does high-intensity laser therapy speed return to primary function in horses with suspensory ligament desmopathy? james b. rushing, ba mba msc candidate1* 1 royal (dick) school of veterinary studies, university of edinburgh, bush estate, midlothian. eh25 9rg * corresponding author email: j.b.rushing@sms.ed.ac.uk vol 8, issue 1 (2023) submitted 03 jan 2022; published: 12 jan 2023; next review: 06 sep 2024 doi: https://doi.org/10.18849/ve.v8i1.564 pico question in horses with a suspensory ligament branch injury, does high-intensity laser therapy (energy output greater than 500 mw) combined with conservative management, compared to conservative management alone, result in a faster return to primary function? clinical bottom line category of research treatment. number and type of study designs reviewed the number and type of study designs that were critically appraised were two peer-reviewed studies: a non-randomised controlled clinical trial and a randomised controlled experimental study. strength of evidence weak. outcomes reported the outcomes reported are summarised as follows: the two appraised studies report positive effects of high-intensity laser therapy (hilt) on equine tendon and ligament injuries as measured by pain to palpation, lameness, swelling and ultrasonographic and magnetic resonance imaging (mri) evaluation of hilt-treated lesions. conclusion in view of the strength of evidence and the outcomes from the studies the following conclusion is made: the two appraised studies provide only weak evidence to show that horses treated with high-intensity laser therapy (hilt) and conservative management return to primary function sooner than horses treated with conservative management alone. issues of design, methodology, statistical analysis and reporting reduce the reliability and external validity of these studies. how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario your client competes in amateur-level show jumping with her trakehner (warmblood) gelding, aged 12 years. your clinical examination of the horse indicates an acute injury to the medial branch of the right forelimb suspensory ligament, confirmed by ultrasound. you advise a course of conservative treatment to include rest, icing, cold-water hosing and controlled exercise. that evening, your client sends you an internet article on hilt and asks if that could accelerate the timeline for her horse's return to competition. before responding, you want to know if evidence exists to support the use of hilt to treat equine desmopathy and how it compares to conservative management with the goal of returning a horse to competition.   list of abbreviations: at after hilt treatment bt before hilt treatment csa cross-sectional area ddft deep digital flexor tendon dt during hilt treatment hilt high-intensity laser therapy iqr interquartile range mlmm multivariate linear mixed model mri magnetic resonance imaging pico patient/population, intervention, comparison, outcome sdft superficial digital flexor tendon sl suspensory ligament body slb suspensory ligament branch the evidence there is little evidence that high-intensity laser therapy (hilt) is effective in treating soft tissue injuries in horses. only two peer-reviewed controlled studies address the pico question: a non-randomised controlled clinical trial (zielińska et al., 2020) and a randomised controlled experimental study (pluim et al., 2020). two pico-relevant studies were excluded from appraisal due to a lack of control groups: a retrospective case series examining hilt treatment of tendon / ligament injuries and the return to function of 150 sport horses (pluim et al., 2018) and a case report describing hilt treatment of ligament injuries and the return to function of two horses (quiney et al., 2020). other excluded papers were a conference paper reporting hilt treatment of equine tendinopathy / desmopathy in clinical and experimental settings (fortuna et al., 2002), an equine orthopaedic application of hilt (zielińska et al., 2015), an examination of the effects of hilt on the surface temperature of equine skin (zielińska et al., 2021), and a potentially pico-relevant paper with insufficient methodological and reporting detail to appraise (jaafar et al., 2021). also excluded from review was pluim et al. (2022), which examined histological properties of tissues from pluim et al. (2020), supporting the conclusions of the earlier study. neither appraised paper (pluim et al., 2020; and zielińska et al., 2020) considers the return to function of hilt-treated horses and provides only low-quality evidence to answer the pico question; the quality of evidence is reduced by issues of study design, methodology, and data analysis and reporting. summary of the evidence pluim et al. (2020) population: horses recruited to a veterinary hospital (method not reported). inclusion criteria: healthy horses without lameness and normal results from ultrasound examination of the suspensory ligament branches of all four limbs. sample size: 12 warmblood horses. group characteristics: five geldings, seven mares. age: 4–12 years (mean and standard deviation not reported). intervention details: surgical protocol: 48 lesions of the lateral branch of the suspensory ligament were surgically induced under general anaesthesia (one lesion in each limb of each horse). phenylbutazone administered for 5 days post-surgery (dosage not reported). treatment and control groups each comprised of 24 lesions. for each of the 12 horses, the right or left diagonal limb was randomly assigned to the treatment group; the other diagonal limbs assigned to the control group. the horses were equally divided into a short-term post-treatment evaluation group (4 weeks) and a long-term evaluation group (6 months). the horses in both groups were euthanised at the end of the evaluation period. lameness evaluations were performed by a veterinarian and a motion analysis system (device not reported) weekly for four weeks, then monthly. general clinical signs and lesion heat, swelling and pain were recorded daily for each horse. high-intensity laser therapy (hilt): laser device: touch life rehab prototype with custom software, maximum output 15 w, four simultaneous wavelengths between 635 nm and 980 nm. each horse was treated with hilt 1x daily for 20 minutes commencing day one post-surgery for 4 weeks. the laser handpiece was held perpendicular to the skin at a distance of 0.5 cm. controlled exercise protocol: each horse was lunged daily at trot (10 minutes increasing to 30 minutes, direction change every 5 minutes) commencing day one post-surgery for 1 week or until an obvious lameness occurred; this was done to stimulate an inflammatory response in the surgically induced lesions. short-term group: 20 minutes hand-walk daily on hard surface for weeks 2–4. long-term group: 20 minutes hand-walk daily on hard surface from week 2 to month 3. trot (2–20 minutes) added in months 3–6. canter (2–4 minutes) added in months 5 and 6. ultrasound and colour doppler: examination and evaluation by the same veterinarian. video recording and images evaluated by a second, blinded veterinarian. a total of ten ultrasound and doppler evaluations were performed (admission, weeks 1–4 and months 2–6. magnetic resonance imaging (mri): mri was performed on cadaver limbs after the horses were euthanised (short-term group at 4 weeks; long-term group at 6 months). mri scoring was performed by three blinded evaluators, each repeating the measurements three times. statistical analysis (treatment vs control): independent t-test used to compare lesion transverse size and ligament transverse size. multivariate linear mixed model (mlmm) used to compare lesion cross-sectional area (csa) and circumference. mlmm with post-hoc scheffé test used to compare echogenicity. logistic regression used to compare binary doppler signal. mlmm used to compare changes in lesion csa, circumference and transverse size between week 1 and week 4 and week 1 and month 6. mlmm used to compare mri measurement of csa and mean lesion signal. details of the mlmm and binary logistic models were not provided. ethics approval: ethical commission of the university of ghent, belgium. study design: prospective, randomised, within-subject controlled experimental trial. outcome studied: general clinical signs including lesion heat, swelling and pain recorded daily for each horse. subjective measures: lesion heat, swelling and pain evaluation (subjective; scoring scales not reported). lameness assessment (subjective; scoring scale not provided); motion analysis system (objective; device not reported). lesion csa, circumference and transverse size. colour doppler signal: subjective; ordinal scale (0–5; 0 = no signal, 5 = strongly increased signal). converted to a binary outcome: scores 0 or 1 = ‘no signal’; scores 2–5 = ‘increased signal’. objective measures: echogenicity percentage: objective, software-aided pixel count; calculated as lesion pixel intensity divided by pixel intensity of the non-injured portion of the ligament branch. main findings (relevant to pico question): all horses: no heat, pain on palpation or swelling at lesion sites on day 1 post-surgery; mild to moderate heat, pain on palpation and swelling after week 1 (lunging at trot). no lameness at the walk (duration of the study). no skin burns or other adverse effects of hilt. ultrasound: ten ultrasound measurements taken (day 1–week 4, n = 12 horses; months 2–6, n = 6 horses). no significant difference between treatment and control for mean lesion csa and mean lesion circumference (day 1–month 6). csa enlargement at week 4 (week 4 csa minus week 1 csa) was significantly smaller (p = 0.01) in the treatment group compared to control. additionally, circumference enlargement (week 4 circumference minus week 1 circumference) was significantly smaller in the treatment group compared to control (p = 0.016). this was depicted in figure 5 of the paper; actual values not reported. treatment group mean lesion transverse size was significantly smaller than control at month 2 (3.5 mm, standard deviation (sd) = 0.9 mm vs 4.3 mm, sd = 1.9 mm; p = 0.026) and month 3 (4.2 mm, sd = 1.0 vs 4.6 mm, sd = 1.9; p = 0.015). in six ultrasound measurements (week 4 to month 6), treatment and control mean echogenicity scores were significantly larger than their respective scores at week 3 (p < 0.001). treatment group colour doppler signal was significantly higher than control during the treatment period (day 1–week 4; p < 0.001). mri: no significant differences between mri scores of the three blinded evaluators. mri results were consistent with the ultrasound and colour doppler evaluations. in shortand long-term treatment groups, mean lesion csa was significantly smaller (p = 0.002) and mean mri signal was significantly lower (p = 0.006) than control. limitations: no follow-up beyond 6 months, no consideration of return to function (horses were euthanised). selective reporting of significant differences of ultrasound measurements (treatment vs control) may result in reader interpretation bias. for example, in table 2, 28/30 (93%) ultrasound measurements (treatment vs control) were not significant; however, there was no discussion of this. the healing properties of surgically induced suspensory branch lesions may differ from lesions occurring naturally due to injury. the authors do not state their reasons for choosing a surgical design rather than treating naturally-occurring lesions. no explanation was provided for having shortand long-term post-treatment evaluation groups. the length of time required to create the 48 surgically-induced lesions and the number of veterinary surgeons involved was not reported. the authors do not report the variance within the surgically-induced lesions to the parameters stated in the surgical protocol. the authors refer to supplementary file 1 for details on ultrasound measurements; however, this file does not show echogenicity scores and the scores for csa, transverse size and swelling do not match those in the paper. the description of statistical tests used to analyse ultrasound and mri data was insufficient to appraise the suitability of the tests. it is unclear how many different mlmms were used and how they differed. confidence intervals are not reported. the lameness detection motion-analysis system was not specified. power calculations were not reported. the study may be underpowered to detect differences in the measured outcomes; however, increasing the sample size would likely be unethical. the laser device software was custom to this study (details not provided); no information was provided regarding the testing or validity of the software. mean and sd not reported for the ages of the 12 horses. the authors report no significant difference between the scores of the mri evaluators but do not state the protocol for resolving scoring differences. the method of randomised assignment to treatment and control groups was not reported. the method of assignment to shortand long-term evaluation groups was not reported.   zielińska et al. (2020) population: horses admitted to a single-centre veterinary hospital in poland. inclusion criteria: clinical diagnosis of tendinopathy or desmopathy with at least two of; pain on palpation, limb swelling or lameness. tendon or ligament injury confirmed by ultrasound. injury not previously treated. sample size: twenty-six horses with 29 tendon and ligament lesions. group characteristics: warmblood performance horses of both sexes (details not reported). age = 5–24 years; mean = 11.5 years (sd not reported). lesions: superficial digital flexor tendon (sdft) (n = 12; 41%), deep digital flexor tendon (ddft) (n = 8; 28%), suspensory ligament branch (slb) (n = 6; 21%), suspensory ligament body (sl) (n = 3; 10%). intervention details: treatment and control groups: treatment (n = 23) and control (n = 6) group sizes were predetermined (details not reported). one horse had a sl injury in both forelimbs; the left limb was assigned to the treatment group; the right limb was assigned to the control group. twenty-two tendon and ligament injuries were randomly assigned to the treatment group; the remaining five injuries were assigned to the control group. clinical assessment: three clinical assessments, including ultrasound performed by the same veterinarian, measured pain response, degree of lameness, relative swelling, degree of lesion echogenicity and lesion size: before treatment (bt; day 0), during treatment (dt; days 13–15), after treatment (at; days 38–40). rehabilitation: all horses (treatment and control) received the same conservative rehabilitation (days 1–40): twice daily 20 minute walks on a hard surface followed by 20 minutes of cold-water hosing of the lesion. high-intensity laser therapy (hilt): laser device: astar polaris hp s class 4 laser, maximum power 18 w, simultaneous 808 nm and 980 nm wavelengths. horses in treatment group received 15 treatments (same veterinarian) beginning day 1. the time between successive groups of treatments was increased: four treatments (24 hours apart), four treatments (48 hours apart), four treatments (72 hours apart), three treatments (96 hours apart). the laser handpiece was held perpendicular to the skin (distance from the skin not reported). the laser device software calculated the duration and total energy dose of each treatment which varied according to lesion location (details not reported). sedation was not required for hilt treatment. ethics approval: ethical committee for experiments on animals, wroclaw university, poland. study design: prospective, non-randomised, non-blinded, controlled clinical trial. outcome studied: clinical measurements were taken three times: bt, dt and at. measurements taken: pain on palpation: subjective ordinal scale (0–3; 0 = no pain, 3 = severe pain). lameness assessment: subjective ordinal scale (0–3) using the american association of equine practitioners (aaep) scale; 0 = lameness not perceptible under any circumstances, 3 = lameness is consistently observable at a trot under all circumstances. relative swelling: objective calculation of the percentage difference between the circumference of the injured limb at the lesion location and the circumference of the healthy limb at the same location. lesion echogenicity (ultrasound): subjective ordinal scale (0–3; 0 = isoechoic, 3 = anechoic). lesion percentage (ultrasound): subjective measurement, objective calculation (lesion percentage = lesion cross-sectional area / tendon or ligament cross-sectional area x 100). main findings (relevant to pico question): statistically significant differences reported between treatment and control at the end of hilt treatment for each outcome measured (pain, lameness, relative swelling, lesion echogenicity and lesion percentage). pain (pearson’s chi-square test): treatment vs control: treatment group had significantly lower at pain scores than control (p = 0.023); 22/23 (95.7%) of treatment at pain scores were (0 or 1) compared to 3/6 (50.0%) for control. intra-group (bt vs at): treatment group at pain scores significantly lower than bt scores (p < 0.001). lameness (pearson's chi-square test): treatment vs control: treatment group at lameness scores were significantly lower than control (p = 0.04); 19/23 (82.6%) of treatment at lameness scores were (0 or 1) compared to 3/6 (50.0%) for control. intra-group (bt vs at): treatment group at lameness scores significantly lower than bt lameness scores (p < 0.001). mean relative swelling (one-way anova, post-hoc tukey test): treatment vs control: treatment group dt mean relative swelling significantly lower than control (4.2% vs 7.8%; p = 0.024). treatment group at mean relative swelling significantly lower than control (2.4% vs 6.8%; p = 0.008). intra-group (bt vs at): treatment group at mean relative swelling significantly lower than bt mean relative swelling (2.4% vs 6.4%; p < 0.001). lesion echogenicity (pearson's chi-square test): treatment vs control: treatment group at echogenicity scores significantly lower than control (p = 0.001); 18/23 (78.3%) of treatment lesion echogenicity scores were (0 or 1) compared to 0/6 (0%) for control. intra-group (bt vs at): treatment group at lesion echogenicity scores significantly lower than bt lesion echogenicity scores (p < 0.001). lesion percentage (mann-whitney u test): treatment vs control: treatment group at mean lesion percentage significantly lower than control (15.7% vs 35.5%; p = 0.02). intra-group (friedman anova): treatment group: dt mean lesion percentage significantly lower than bt (20.7% vs 24.1%; p < 0.001). at mean lesion percentage significantly lower than dt (15.7% vs 20.7%; p = 0.001). at mean lesion percentage was significantly lower than bt (15.7% vs 24.1%; p < 0.001). control group: at mean lesion percentage significantly lower than bt (35.7% vs 39.7%; p = 0.04). data variability: control group interquartile ranges (iqrs) at bt, dt and at were larger than those of the treatment group by factors of 4.0, 3.8 and 2.4, respectively. treatment group maximum lesion percentage values at bt, dt and at were 3.7, 3.7 and 4.4 times their respective third quartile (q3) values. control group maximum lesion percentage values were 1.1, 1.0 and 1.1 times their respective q3 values. hilt safety: horses treated with hilt did not experience skin burns, pain reactions or other adverse effects. limitations: internal validity threatened by questionable methodology related to treatment / control group sizes, allocation randomisation, lack of blinding and statistical mistakes. treatment and control groups: treatment and control group sizes were predetermined, likely resulting in allocation bias (details not reported). questionable method of randomisation to allocate lesions to treatment and control. power calculations were not reported; this study may have been underpowered to detect clinically meaningful effects. the distribution of lesions by type in treatment and control groups was not reported; the number of slb injuries in the treatment group is not known. selection bias is likely as all horses were performance horses (breed and discipline not specified). the type and severity of lesions may not represent the general population. standard deviation (sd) of horses' ages not reported. methodology: all hilt treatments and clinical and ultrasound assessments were performed by the same unblinded veterinarian, increasing the risk of observer and confirmation bias. the majority of outcome measures were subjective. the laser device software determined the duration and energy dose of each hilt treatment (not reported). information regarding the testing or validity of the laser device software was not reported. no post-treatment follow-up. the authors do not state how relative swelling percentage was calculated for the horse with sl lesions on both front limbs (no healthy limb to compare). data analysis and reporting: confidence intervals not reported. risk of reader interpretation bias: relative swelling: table 2 in the paper shows the median, iqr and min-max values for percentage relative swelling, whilst figure 2 shows boxplots of relative swelling percentage with mean, mean ± standard error (se; boxplot body) and mean ± 1.96 x se (boxplot whiskers). se values not reported. lesion percentage: figure 5 in the paper shows boxplots (median, iqr, min-max) of treatment and control lesion percentage at periods bt, dt and at. the authors do not discuss the large visual differences between treatment and control iqrs and maximum values (same y-axis scale), leaving interpretation to the reader.   appraisal, application and reflection high-intensity lasers, also known as high-power, class iv and nd:yag lasers, are characterised by an energy output greater than 500 mw and the ability to penetrate tissue to a depth of 5 to 15 cm (ahmad et al., 2021). human and veterinary medical applications of high-intensity laser therapy (hilt) include pain management and the treatment of tendinopathy, desmopathy and osteoarthritis (zielińska et al., 2015; fortuna, 2017; ahmad et al., 2021; and mongkolrat et al., 2021). two peer-reviewed controlled studies utilising hilt to treat equine tendon and ligament injuries were appraised; however, each study has design, methodological, statistical analysis and reporting issues that reduce reliability and external validity. additionally, the lack of standardised protocols for hilt treatment of equine soft tissue injuries complicates comparisons of study methodologies (fortuna, 2017). for example, each appraised study used a different commercial high-intensity laser device running custom software that determined the laser energy output and other treatment parameters based on lesion location. importantly, the total energy administered during each hilt treatment was not reported, making it impossible to compare the treatment doses administered in the two studies. further, the number of treatments and the time between treatments varied between the two studies; zielińska et al. (2020) administered a total of 15 hilt treatments over 40 days (increasing time between successive treatments), whilst pluim et al. (2020) administered one hilt treatment daily for 4 weeks. the appraised studies differed in their implementation of conservative management. for example, in zielińska et al. (2020), horses in both the treatment and control groups received twice-daily hand-walking on a hard surface (20 minutes) followed by cold-water hosing of the hilt-treated lesion (20 minutes). this protocol was administered for the 40 days of hilt treatment; however, it is unknown whether rehabilitation continued post-hilt. in the four-limb surgical model of pluim et al. (2020), one diagonal limb pair (right front / left hind or left front / right hind) was randomly assigned to the treatment group, and the other diagonal limb pair was assigned to the control group. a progressive exercise programme commenced 2 weeks after the start of hilt, consisting of 20 minutes of hand-walking on a hard surface progressing to incrementally increasing trot and canter work. dyson (2007; and 2018) reports that horses with suspensory ligament branch (slb) injuries may require 9–18 months of conservative management depending on lesion severity before returning to primary function; however, neither appraised study achieved this guideline or considered return to function. zielińska et al. (2020) did not follow their subjects post-hilt, whilst the horses in pluim et al. (2020) study were euthanised 4 weeks post-hilt (short-term group) and after 6 months (long-term group). design decisions likely reduced the internal validity and potential clinical relevance of the two appraised studies. for example, the four-limb surgically-induced lesion model of schramme et al. (2010), modified by pluim et al. (2020) to create slb lesions, may be of questionable validity. estrada et al. (2014) found significant differences in the healing properties (tendinous and biochemical composition) between surgically-induced forelimb and hindlimb superficial digital flexor tendon (sdft) lesions, suggesting additional research is needed to validate the four-limb model. although the conclusions of estrada et al. (2014) were based on surgically-induced tendon lesions, their findings may apply to surgically-induced ligament lesions and suggest the results of pluim et al. (2020) be carefully considered. additionally, the four-limb surgical model may present welfare concerns (ribitsch et al., 2020). neither appraised study reported power calculations; therefore, these studies may be underpowered to detect clinically meaningful effects of hilt treatment. further, zielińska et al. (2020) do not explain why the treatment (n = 23) and control (n = 6) group sizes were predetermined. additionally, the allocation method employed by zielińska et al. (2020) likely resulted in a non-randomised allocation of lesions between treatment and control, increasing the risk of selection bias (christley & french, 2018). zielińska et al. (2020) reported results that conflated lesion types, making it impossible to consider the effects of hilt on slb injuries. reporting results by lesion type may have increased the relevance of this study to the pico question. pluim et al. (2020) treated slb lesions exclusively; however, their reported results may bias reader interpretation. for example, the differences between treatment and control mean transverse lesion size were significant in months 2 and 3; however, the authors fail to discuss the implications of the 28/30 (93%) other lesion measurements, including cross-sectional area (csa), circumference and transverse size that were not significant. further, two reporting errors were found in zielińska et al. (2020) table 1, column ‘degree of lesion echogenicity’. first, the chi-square test p-value for treatment vs control for at lesion echogenicity was incorrectly reported as p = 0.70; the authors incorrectly concluded there was no significant difference between lesion echogenicity for treatment vs control (type ii error). using the data provided in table 1, the knowledge summary author calculated the chi-square test statistic and p-value using the ‘chisq.test’ function in r (version 4.1.1; r core team, 2021) and an online chi-square calculator (preacher, 2001). the results from r and the online calculator were identical (p = 0.001), indicating a significant difference between treatment and control. all other reported p-values in table 1 are correct. second, for the control group, the at frequency count and percentage for scale value = 1 was incorrectly reported as '0 (50.0)'; it should read '0 (0.0)'. in summary, the two appraised studies provide insufficient evidence to show that horses treated with hilt and conservative management return to primary function sooner than horses treated with conservative management alone. the non-randomised controlled trial (zielińska et al., 2020) showed significant effects of hilt; however, results were conflated by four different lesion types and return to function was not considered. the randomised controlled experimental trial (pluim et al., 2020) selectively reported significant effects of hilt; however, overall results were inconclusive and return to function was not considered. finally, there is limited understanding of the temperature effects of hilt on pigmented and non-pigmented equine skin; additional research in this area may have clinical relevance to hilt treatment of slb injuries (zielińska et al., 2021). therefore, there is only weak evidence to show that hilt treatment of equine soft tissue injuries hastens lesion healing and return to primary function compared to conservative management alone. methodology search strategy databases searched and dates covered: cab abstracts on ovid platform (1973–2022 week 35) pubmed on ncbi platform (1910–2022 week 35) web of science core collection (1900–2022) embase on ovid platform (1980–2022 week 35) search strategy: cab abstracts: exp horses/ or horse* or equine* ((high* adj4 laser) or (class* adj4 laser) or hilt or nd:yag or "nd yag") tend* or ligament* or desmopath* 1 and 2 and 3   pubmed: (horse* or equine*) and laser and (high* or "high intensity" or "high power" or class* or nd:yag or "nd yag") and (tend* or ligament* or desmopath*)  note: a non-truncated version of the above pubmed search string (all search words spelled out) returned only four papers; therefore, the pubmed search was conducted using the truncated version of the search string.   web of science: (horse* or equine*) and laser and (high* or "high intensity" or "high power" or class* or nd:yag or "nd yag") and (tend* or ligament* or desmopath*)   embase (horse* or equine*) and laser and (high* or "high intensity" or "high power" or class* or nd:yag or "nd yag") and (tend* or ligament* or desmopath*) dates searches performed: 06 sep 2022   exclusion / inclusion criteria the pico question considers equine suspensory ligament branch injuries treated with high-intensity laser therapy (hilt). the initial literature search (restricted to equine ligament injuries) returned only four papers; consequently, the search was broadened to include studies that treated equine tendon or ligament injuries with hilt. exclusion: non-english language, non-equine studies, studies using high-intensity laser therapy to treat other than equine tendon / ligament injuries, conference proceedings, non-systematic reviews, papers published before 1985, abstract-only papers, studies without a control group, papers lacking sufficient details to appraise. inclusion: controlled studies in which high-intensity laser therapy was used to treat equine desmopathy or tendinopathy, systematic reviews.   search outcome database number of results excluded – not directly related to pico question excluded – no control group excluded – insufficient details to appraise excluded – papers published before 1985 excluded – non-systematic review or conference proceedings excluded – abstract only excluded – not english language total relevant papers cab abstracts 11 2 2 0 0 2 0 3 2 pubmed 28 22 2 0 2 0 0 0 2 web of science 31 19 2 0 0 3 1 4 2 embase 8 2 2 1 0 1 0 0 2 total relevant papers when duplicates removed 2   acknowledgements the author would like to thank dr louise buckley and maureen o’mara phd for their guidance and encouragement. orcid james rushing: https://orcid.org/0000-0002-7451-5707 conflict of interest the author declares no conflicts of interest. references ahmad, m., hamid, m. & yusof, a. (2021). effects of low-level and high-intensity laser therapy as adjunctive to rehabilitation exercise on pain, stiffness and function in knee osteoarthritis: a systematic review and meta-analysis. physiotherapy. 114, 85–95. doi: https://doi.org/10.1016/j.physio.2021.03.011 christley, r. & french, n. (2018). validity in epidemiological studies. in: m. thrusfield & r. christley, eds., veterinary epidemiology, 4th hoboken, nj, usa: john wiley, 383–396. dyson, s. (2007). diagnosis and management of common suspensory lesions in the forelimbs and hindlimbs of sport horses. clinical techniques in equine practice. 6(3), 179–188. doi: http://dx.doi.org/10.1053/j.ctep.2007.08.004 dyson, s. (2018). suspensory branch injuries in sports horses and racehorses. uk-vet equine. 2(3), 90–96. doi: https://doi.org/10.12968/ukve.2018.2.3.90 estrada, r., van weeren, p., van de lest, c., boere, j., reyes, m., ionita, j., estrada, m. & lischer, c. (2014). comparison of healing in forelimb and hindlimb surgically induced core lesions of the equine superficial digital flexor tendon. veterinary and comparative orthopaedics and traumatology. 27(5), 358–365. doi: http://dx.doi.org/10.3415/vcot-13-11-0136 fortuna, d. (2017). highâ€�intensity laser therapy for the equine patient. in: r. riegel & j. godbold, jr., eds., laser therapy in veterinary medicine: photobiomodulation, 1st chichester, west sussex, uk: john wiley and sons, 415–421. fortuna, d., rossi, g., paolini, c., magi, a., losani, f., fallaci, s., pacini, f., porciani, c., sandler, a., torre, r., pinna, s. & venturini, a. (2002). nd:yag pulsed-wave laser as support therapy in the treatment of teno-desmopathies of athlete horses: a clinical and experimental trial. laser florence 2001: a window on the laser medicine world. spie. 4903, 105–118. doi: http://dx.doi.org/10.1117/12.486622 jaafar, s., al-bayti, a. & abdullah, s. 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[online]. available at: https://www.r-project.org/ [accessed december 2021]. ribitsch, i., baptista, p., lange-consiglio, a., melotti, l., patruno, m., jenner, f., schnabl-feichter, e., dutton, l., connolly, d., van steenbeek, f., dudhia, j. & penning, l. (2020). large animal models in regenerative medicine and tissue engineering: to do or not to do. frontiers in bioengineering and biotechnology. 8, 972. doi: http://dx.doi.org/10.3389/fbioe.2020.00972 schramme, m., hunter, s., campbell, n., blikslager, a. & smith, r. (2010). a surgical tendonitis model in horses: technique, clinical, ultrasonographic and histological characterisation. veterinary and comparative orthopaedics and traumatology. 23(4), 231–239. doi: http://dx.doi.org/10.3415/vcot-09-10-0106 zieliå„ska, p., kieå‚bowicz, z. & paczuska, j. (2015). high intensity laser therapy (hilt) in the treatment of orthopedic diseases in horses. medycyna weterynaryjna. [online]. 71(6), 373–376. available at: http://www.medycynawet.edu.pl/images/stories/pdf/pdf2015/062015/201506373376.pdf (in polish, english abstract). [accessed december 2021]. zieliå„ska, p., nicpoå„, j., kieå‚bowicz, z., soroko, m., dudek, k. & zaborski, d. (2020). effects of high intensity laser therapy in the treatment of tendon and ligament injuries in performance horses. animals. 10(8), 1327. doi: http://dx.doi.org/10.3390/ani10081327 zieliå„ska, p., soroko, m., howell, k., godlewska, m., hildebrand, w. & dudek, k. (2021). comparison of the effect of high-intensity laser therapy (hilt) on skin surface temperature and vein diameter in pigmented and non-pigmented skin in healthy racehorses. animals. 11(7), 1965. doi: http://dx.doi.org/10.3390/ani11071965 intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and 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top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443. clinical audit of pom-v / pom prescriptions by remote consultation via a veterinary video telemedicine smartphone application dr sheila mary smith bvms mrcvs1 dr tamsin day bvetmed mrcvs1 dr samantha georgina webster bvetmed mrcvs1 sam davies bsc1 dr trevor peter hardcastle bsc msc phd1 dr adele williams bvsc mrcvs dipeceim phd1* 1vet-ai, ebble house, odstock, salisbury, england, sp5 4jb *corresponding author (adele.williams@vet-ai.com) there is an erratum to this paper published in veterinary evidence vol 7, issue 2 (2022): 10.18849/ve.v7i2.627 vol 7, issue 2 (2022) published: 08 jun 2022 reviewed by: sarah allen (bvetmed certavp[em] msc[vetepi]) and danitza pradelli (dmv phd eumsc gp-cert pm&a) doi: 10.18849/ve.v7i2.553 section index:    abstract | introduction | methods | results | discussion | footnotes | conflict of interest | references abstract objective: to assess outcomes of a limited period (7 months) of remote video consultation with prescribing of prescription-only (pom) or prescription-only-veterinary (pom-v) medications by royal college of veterinary surgeons (rcvs) registered veterinary surgeons to uk clients via a veterinary telemedicine smartphone application. background: objective evidence is needed to inform the veterinary profession on the impact that remote prescribing, without physical examination in person, has on animal health and welfare. during the covid-19 pandemic, the rcvs allowed remote prescribing temporarily. methods: clinical records from all veterinary video consultations from 1 april–31 october 2020 were reviewed. details were assessed pertaining to: signalment, body system / disease categories managed, referrals into practice, medication classes prescribed and outcomes following pom-v / pom medications. records of adverse events and antimicrobial prescribing were reviewed. results: 16.6% (3,541/21,383) of video consults had a pom-v / pom prescribed; with a (mild) adverse event rate of 0.8% (30/3541). antibacterials were prescribed in 5.88% of all consultations (1,258/21,383), 99.3% (1249/1258) being first line. follow-up on prescribing was available in 67.7% (2,399/3541) of cases. 89% (2135/2399) of all known treatment outcomes were complete or had an expected response to treatment. dermatological disease was the most common body system / disease category seen and prescribed for. conclusion: low prescribing rates (including antibacterials) were recorded, treatments were efficacious and no harm was done by prescribing remotely via a veterinary video consult app. application: veterinary surgeons and governing bodies are invited to use the information provided in this clinical audit to inform decisions on the suitability of remote consultations and prescribing in veterinary medicine.   introduction this manuscript is a clinical audit from a uk-based virtual veterinary telemedicine provider. this audit examines prescribing of prescription-only (pom) and prescription-only-veterinary (pom-v) medications that occurred as a result of veterinary-led video consultations undertaken during a 7 month period (april–october 2020) when remote prescribing without physical examination was permitted under royal college of veterinary surgeons (rcvs) emergency measures due to the covid-19 pandemic.   background on the smartphone application and remote veterinary telemedicine service provision the uk-based company producing this clinical audit (vet-ai) has a smartphone veterinary telemedicine application (joii petcare (2021), available on ios and android). dog and cat owners are able to download the app for free on their smartphones, sign up to the app, agree to terms and conditions, and register their pet(s). the functions within the app include options for a client to directly choose to connect to a video consultation with a veterinary surgeon, or to check symptoms via a symptom checker. the symptom checker, designed and developed by veterinary surgeons, directs clients through a series of questions to triage the presenting complaint and direct appropriately depending on the severity of the presenting complaint. if there is an emergency, urgent or serious problem identified, the client is directed to contact a physical veterinary practice, and location services within the app highlight veterinary practices within the local area. if a non-serious / non-urgent problem is identified that still warrants veterinary advice, a veterinary video consultation is suggested. there is the option for owners to have video consultations with registered veterinary nurses if that is the appropriate course of action. there is also the facility for video consultation with a ccab qualified behaviourist, but only after an initial video consultation with a veterinary surgeon. veterinary video consultations are available 24/7. clinicians interact with clients via video link on a bespoke practice management software system where clinical notes are recorded. clinical records and data are stored in the company’s secure database. the company has a dedicated data protection officer ensuring gdpr compliance and confidentiality of client and pet data (joii pet care, 2021). all of the veterinary surgeons providing consultations via the app are registered with the rcvs to practice in the uk, and have been qualified and in practice for at least 3 years before joining vet-ai. all veterinary nurses are qualified and registered with the rcvs. the veterinary surgeons are predominantly part-time and work variable shift patterns. during the period of prescribing, under the temporary rcvs guidance, from april–october 2020 there was no physical practice associated with the company and the clinicians all worked remotely.    follow-up and sharing of clinical information all clients are provided with an in-app treatment plan at the end of a video consultation. clinical records are also kept for every consultation, and are provided to a client’s local registered veterinary practice when appropriate.  clinical record keeping includes the mandatory selection of veterinary nomenclature (venom, 2022) codes to indicate top differential diagnosis / diagnoses at the time of consultation, with the purpose of aiding to identify disease classification types within clinical records.  all clients that had video consultations that resulted in prescription of a pom-v / pom within the app were booked a follow-up veterinary video consult appointment via the app to assess response to treatment and identify any problems arising, or if alternatives needed to be pursued. if clients failed to engage in a follow-up video consultation then they were emailed requesting follow-up information; any follow-up information provided by email was entered into the clinical notes. clinical history from a patient’s physical veterinary practice was sought (with owner permission) for any animal prescribed a pom-v / pom; chronic medication prescriptions were refused if a full and accurate clinical history could not be obtained. in emergency situations where acute medication was needed to be prescribed for animal welfare reasons, prescribing occurred and a history was sought (or several attempts made to obtain the history) from the registered veterinary practice (following guidance set out in the rcvs code of conduct 5.7). when a patient treated with pom-v / pom remotely was referred into a physical veterinary practice, clinical history was forwarded to that practice (with owner permission).   telehealth excellence and clinical monitoring vet-ai has an internal telehealth excellence team of clinicians, joii scientific advisory committee (the authors), dedicated to monitoring clinical practice standards and auditing of clinical data to help produce structured clinical guidelines for the veterinary team to maximise the quality of remote consultation. they also collaborate evidence from the veterinary and human medical communities to develop best practice telemedicine guidelines. robust literature reviews govern and underpin all clinical decision-making and guide regular clinical meetings. best practice and gold standard is the level aspired to, monitored and achieved. pharmacovigilance data is collected, assessed and reported to the veterinary medicines directorate (vmd, 2022). the company has a proactive approach to assessing follow-up and adverse event data after all prescriptions. the team ensures that all clinicians have a structured format for their video consultations and that a full and thorough remote video consultation is performed.   remote prescribing rules in the veterinary profession the rcvs provide the following information in their code of professional conduct regarding the use of telemedicine (rcvs, 2021): 2.29 specific advice provided remotely, for example via phone or video-link or without additional physiological data (commonly referred to as telemedicine or telehealth), should only be given to the extent appropriate without a physical examination of the animal. the more specific the advice, the more likely it is that the animal’s owner should be advised to consult a veterinary surgeon in person for a physical examination. in this scenario, the animal owner should be asked to provide the veterinary surgeon carrying out the physical examination with a copy of any advice given remotely. 2.30 veterinary surgeons should ensure as far as possible that the provision of specific advice provided remotely does not compromise welfare, since the animal has been examined and there is no ability to monitor the animal.  under normal circumstances, a veterinary surgeon can only prescribe pom-v / pom medications for a pet animal under their care in the uk if they have physically examined the individual animal in person.   emergency measures during the covid-19 pandemic as an emergency measure during the covid-19 pandemic, the rcvs released temporary guidance regarding prescription of pom-v / pom medications by veterinary surgeons, due to the extenuating circumstances that emerged with the requirements for en masse public isolation (rcvs, 2020). this time period provided the ideal opportunity to assess the impact of remote prescribing on animal health and welfare. this can be examined in this clinical audit by detailing the percentage of veterinary video consultations that resulted in pom-v / pom prescriptions, which medications were prescribed, the common body system / disease categories (grouped by the veterinary nomenclature venom codes within the clinical records) that resulted in prescriptions, and what the outcomes were for those treatments where follow-up was available. recording of any adverse events could be reviewed, as can the use of antimicrobials to examine antimicrobial prescription trends and frequency.   remote prescribing company policy pom-v / pom medications were only prescribed if the following criteria could be met, as per rcvs guidance (rcvs, 2020): enough information could be obtained to assess the pet sufficiently without a hands-on physical exam there was no suitable alternative medication of a pom-vps, nfa-vps (non-food animal – veterinarian, pharmacist, suitably qualified person) or avm-gsl (authorised veterinary medicine – general sales list) category the benefit to the animal and / or public health risk outweighed the risk immediate / un-delayed action was required in the interests of animal welfare the client was fully informed of any risks associated with remote prescribing for the given condition detailed notes were made for any decision to remotely prescribe and the reasoning behind it. any consultation resulting in medication being prescribed was booked in for a follow-up consultation at the time of recommending the product. the interval between initial and follow-up consultation was determined on a case-by-case basis by the clinician involved. if the client had not returned for their follow-up appointment, an email was sent to their registered email address. the email made a general enquiry into the state of the pet having been treated, as well as asking the following three questions: are the symptoms still present? are you satisfied with the outcome? has your pet experienced any adverse events in relation to the medication prescribed?    evidence around telemedicine and remote prescribing vet-to-vet telemedicine has existed since the 1980’s, when telecardiology was utilised to allow general practice veterinarians to seek support from specialist colleagues (robertson, 1999). with the advent of digital technologies and live video streaming, veterinarian-to-client telemedicine is a new and emerging service within the veterinary sector globally.  there is controversy within the profession regarding the suitability of this method of vet-pet-client contact for maintaining professional standards and protecting animal health and welfare, given the inability to perform a physical examination on remote animals (cary & massecar, 2017; and cushing, 2017).  objective evidence, which up to now has been in short supply due to the legal limitations on remote prescribing, is needed to inform this debate, so that rational judgements can be made for the benefit of animal health and welfare based on fact rather than subjective opinion. a recent literature review on the subject (teller & moberly, 2020) suggests that the few published reviews of direct to consumer (dtc) telemedicine have been favourable, and that if human paediatrics is used as an analogy to veterinary medicine, studies in paediatric telehealth can lead to cautious optimism for veterinary medicine to observe similar outcomes.   the aim of the audit was to: perform an initial data exploration to assess if any harm was caused and the efficacy of remote prescribing (pom-v / pom) medications via remote video telemedicine veterinary-led consultations by looking at outcomes.   the objectives of the audit were to assess: the outcome of remote prescribing (pom-v / pom) in terms of complete / expected response to treatment, partial response to treatment with referral into a physical practice, no response, or adverse event; grouped into separate subcategories according to body system / disease categories; the prescribing of antibacterial medications.   methods a clinical audit was performed on veterinary-led video consultations via a dedicated smartphone veterinary telemedicine application (app.). the audit involved a single veterinary telemedicine company, with (at the time period of the audit) 50 rcvs registered veterinary surgeons licensed to practice in the uk, all of whom participated in video consultations remotely. the number of veterinarians fluctuated during the audit period; all veterinarians worked part-time hours on a flexible and varied rota basis. there is no physical veterinary practice associated with the company. the audit involved review of medical records but did not involve review of consultation video recordings. this was a retrospective analysis of data from clinical records and client communications via emails stored in the company’s secure cloud storage. all records that had a remote consultation via the app. between 1 april–31 october 2020, whilst the rcvs temporary remote prescribing guidance period was active, were retrieved. all consultations consisted of both a visual video and audio link with the client and pet. a remote consultation was only considered ‘completed’ if internet connectivity / audio and visual quality was sufficient to allow for history taking and assessment of the pet. descriptive details of all pets having a veterinarian video consult were retrieved and assessed pertaining to: signalment (species, age, breed, gender) body system / disease categories managed remotely classified into 15 sub-categories according to primary veterinary nomenclature (venom) code presumptive diagnosis selected by consulting veterinarian: integument musculoskeletal parasitic ophthalmic gastrointestinal cardiorespiratory trauma / external factor urinary & renal reproductive general / systemic / metabolic dental neurological behavioural neoplastic & miscellaneous masses[1] non-specific[2] every consultation resulting in a pom-v / pom prescription was pulled from a mysql relational database and tracked to resolution. mysql is a relational database management system that is based on structured query language (sql) (mysql, 2022). these consultations were identified through the product ordering system, allowing for identification of the client, product purchased and date of purchase. every 2 weeks the consultation was assessed in the company’s practice management system to ensure that the client had returned for their follow-up, and to note the outcome of the given treatment and condition. for consults where pom-v / pom medications were prescribed the following data was collected: details of different prescription medication (pom-v / pom) classes prescribed: oral antimicrobial topical containing antimicrobial analgesics (nsaids, paracetamol ± codeine, gabapentin, tramadol) parasiticide antipruritic[6] other[3] outcomes of treatments with pom-v / pom medications were classified into one of the following mutually exclusive categories: complete / expected response to treatment partial response to treatment – (all pets referred into a physical practice) no response to treatment* adverse event no treatment outcome available (no follow-up available / prescription medication not administered) *sent to clinic for physical examination or for further diagnostics / procedure, or followed-up with further remote care with a change of treatment plan. data was aggregated and anonymised so that no person or pet could be identified from the presentation of results in this publication. descriptive data was then prepared and presented in graphical format to understand the clinical outcomes and inform the veterinary and wider business team. descriptive statistics were produced using data extracted from our data warehouse (google bigquery, 2022) using sql programming language (mysql, 2022; google bigquery, 2022) and visualised through a combination of microsoft excel and python seaborn. all queries were saved as views enabling them to be audited and re-run as required. the data extracted for this paper included consultation random universally unique identifier (uuid), consultation date, consultation type, outcome, pet uuid, species, gender, pet age at time of consultation, presenting problem, diagnosis, product name, product uuid, product legal category, product class, product european medicines agency (ema) classification, product antibacterial active ingredient, product oral / topical grouping, product antifungal / antibacterial grouping, and date product shipped.   results number of consults and prescriptions 21,383 veterinary video consults were undertaken via the app. during the study period. 78.1% (16,695) were dogs and 21.9% (4,688) were cat consults. the mean age for dogs was 4.9 years (median 3.8 years). the mean age for cats was 5.6 years (median 5 years). the male:female ratio was 10:7 for dogs and 2:1 for cats. of the total 21,383 vet-led video consults completed in this timeframe, 16.6% (3,541) had a pom-v / pom prescribed during the consultation (figure 1). figure 1: total completed video consultations with and without pom-v / pom prescriptions for the audit period   a pie chart depicting the completed remote veterinary led video consultations via a dedicated veterinary telemedicine smartphone app. between 1 april–31 october 2020, showing the split of consultations that resulted in remote prescribing of pom-v / pom medication, and those that had ‘other’ outcomes (follow-up consultation with remote veterinary team; recommend in person veterinarian visit [physical exam required]; alternative product recommendation [nfa-vps, avm-gsl]; no concern noted; monitor at home; recommend in person veterinarian visit [emergency]; laboratory testing). the other 17,482 consultations that did not have a prescription medicine prescribed had the following individual or combination of resolutions assigned (total of 22,131 resolutions): follow-up consultation with remote veterinary team: 6,421 recommend in person veterinarian visit (physical exam required): 4,852 alternative product recommendation (nfa-vps, avm-gsl): 4,216 no concern noted: 3,151 monitor at home: 2,313 recommend in person veterinarian visit (emergency): 959 remote laboratory testing (samples collected by owners at home and analysed by external laboratory): 219   breakdown of prescriptions of the 3,541 vet-led video consultations that had a prescription, some consultations resulted in more than one medication being prescribed.     there were 4,282 pom-v / pom medications prescribed in total between 1 april–31 october 2020; 96.1% (4,117) were pom-v, and 3.9% (165) were pom (prescribed following the prescribing cascade). pom-schedule medications (7) have been included in the pom / pom-v totals above. [5] for consults where pom-v / pom medications were prescribed, prescription medications divided into the medication classes described in the methods can be seen in figure 2. figure 2: pom-v / pom medication classes prescribed remotely during the audit period   a pie chart depicting the pom-v / pom medication classes prescribed as a result of completed remote veterinary led video consultations via a dedicated veterinary telemedicine smartphone app. between 1 april–31 october 2020, showing the grouping into broad medication classes. 4,282 pom-v / pom medications were prescribed, from 3,541 vet-led video consultations. medication broad classifications included oral antimicrobials, topicals containing antimicrobials, analgesics, parasiticides, antipruritics and other / miscellaneous. [3] antibacterials were classified using the traffic light (red / yellow / green) system utilised by the bsava / samsoc protect me guidance as recommended by the rcvs and bsava (bsava, 2018) (figure 3). of the 1,258 antibacterial prescriptions (five antimicrobial products were not included due to them being anti-fungal); 99.3% (1249) were ‘green’ first-line antibacterials, 0.7% (nine) were ‘yellow’ highest priority critically important antibacterials, all of which were topical, and no ‘red’ restricted antibacterials were prescribed. the nine yellow, critically important antibacterials were topical fluoroquinolone ear medications (eight marbofloxacin, aurizon; one orbifloxacin, posatex). 66.7% (six) of these were prescribed after culture and sensitivity was performed on an ear swab. 33.3% (three) were prescribed first line after no culture and sensitivity. 33.5% (422/1258) were oral antibacterials and 66.5% (836/1258) were topical antibacterials, (five oral antifungals included as antimicrobials in figure 2 are not counted here as they are not antibacterial). figure 3: antibacterial pom-v / pom medications prescribed remotely during the audit period   a bar chart depicting the antibacterials prescribed as a result of completed remote veterinary led video consultations via a dedicated veterinary telemedicine smartphone app. between 1 april–31 october 2020, and the application route (topical or oral). (green = first line antibacterials, yellow = highest priority critically important antibacterials, red = antibacterials with restricted use in human medicine [none prescribed]).   co-prescribing of medications co-prescriptions are best visualised across product families by a heatmap of the row signatures as displayed in figure 4, where each row represents the number of consultations (count) in which a particular combination of medications was prescribed. the heatmaps, separated out for dogs and cats, include both pom and pom-v prescriptions, showing a large variation in prescribing patterns. figure 4: counts of the number of consultations in which combinations of pom-v / poms falling into product broad classification were prescribed   medication broad classifications included oral antimicrobials, topicals containing antimicrobials, analgesics, parasiticides, antipruritics and other / miscellaneous. [3]   body system / disease category conditions managed remotely that had a remote prescription were classified into 15 body system / disease category presumptive diagnosis subsets according to primary veterinary nomenclature (venom) code selected by consulting veterinarian (figure 5): integument musculoskeletal parasitic ophthalmic gastrointestinal cardiorespiratory trauma / external factor urinary & renal reproductive general / systemic / metabolic dental neurological behavioural neoplastic & miscellaneous mass[1] non-specific[2] figure 5: remote consultations with and without pom-v / pom prescriptions, grouped into body system / disease category   a graph depicting all body system / disease categories managed remotely by completed remote veterinary led video consultations via a dedicated veterinary telemedicine smartphone app. between 1 april–31 october 2020; showing the number of consults grouped into 15 body system / disease category presumptive diagnosis subsets according to primary veterinary nomenclature (venom) code selected by the consulting veterinarian at the time of video consultation. blue segments show the proportion of cases for each category that were treated with a pom-v / pom via remote consultation (percent figure of prescriptions for that body system / disease category shown numerically at end of line). grey segments had alternative outcomes that did not involve the prescription of pom-v / pom medication via remote means; veterinarians were able to allocate multiple venom codes per consult to the non pom-v / pom consults. the top five body system / disease categories appointed during all consultations between 1 april–31 october 2020 in descending order were integument, non-specific[2], gastrointestinal, musculoskeletal and cardiorespiratory (figure 5). the top five body system / disease categories from all consultations across all body systems that were prescribed a prescription medication in descending order were integument, parasitic, non-specific[2], musculoskeletal and ophthalmic (figure 5).     dermatological disease (integument) was the most common body system / disease category that was seen through the app. and had the greatest volume of prescription medications. however, when looking at the percentage of prescriptions for each specific body system consultation (figure 5) it was second most prescribed for (21.1% = 1,765 prescriptions / 8,367 dermatology consults), with parasitic being the highest with a 84.5% prescription rate for all parasitic consultations (1166 prescriptions / 1380 parasitic consults). non-specific[2] body system / disease categories made up the second most common consultation seen and third most prescribed for during this time. the non-specific[2] sub-category includes rechecks and consultations where no body system / disease category was applicable. gastrointestinal cases were the third most common consultation seen but with a relatively lower prescribing rate (6.9% = 333 prescribed / 4,845 gastrointestinal consults).   outcomes of treatment following remote prescription outcomes, based on analysis of clinical notes and/or response to client feedback email, of treatments with pom-v / pom medications were classified into one of the below categories (figure 6): complete / expected response to treatment adverse event no response to treatment partial response to treatment (with all pets referred into a physical practice) no treatment outcome available figure 6: treatment outcomes for consultations with remote prescriptions   a graph depicting outcomes of treatment for patients managed remotely that had a pom-v / pom prescription as a result of completed remote veterinary led video consultations via a dedicated veterinary telemedicine smartphone app. between 1 april–31 october 2020; showing the outcomes of treatments with pom-v / pom medications separated into the following outcome categories: complete / expected response to treatment; partial response to treatment with referral into a physical practice; adverse event; no response to treatment; and no treatment outcome available.   complete / expected response to treatment 60.3% (2,135/3,541) of remote consultations which were prescribed a pom-v / pom product resulted in the outcome complete or expected response to treatment. 33.8% (1,197 /3,541) complete response / resolutions of clinical signs after follow-up appointment or email 26.5% (938/3,541) expected response to treatment (complete resolution of signs not expected in these cases most requiring chronic ongoing medication e.g., non-steroidal anti-inflammatory drugs (nsaid) for chronic osteoarthritis, or anti-pruritic for atopic dermatitis) of the consults where the outcome was known (when the outcome category ‘no treatment outcome available’ was removed) 89.0% (2,135/2,399) of all treatment outcomes were complete / expected response to treatment.   partial resolution – referred to clinic 4.0% (140/3,541) of remote prescriptions needed to be referred to a clinic for reasons including; further diagnostics (radiography, blood tests, eye examination) procedures (ear flush, abscess lance) injectable or topical treatments requiring veterinary administration   no response to treatment 2.7% (94/3,541) of remote prescriptions did not respond to treatment. these patients were then either: sent to clinic for physical examination sent to clinic for further diagnostics / procedure followed-up with further remote care with a change of treatment plan   no treatment outcome available of the 3,541 consultations in which a prescription was purchased, 32.3% (1,142/3,541), had no treatment outcome available for the following reasons: 30.4% (1,078/3,541) no feedback received (lost to follow-up despite multiple attempts) 1.8% (64/3,541) patients were not administered prescribed medication for reasons including: postal delay / out of stock (those cases were referred into practice) condition deteriorated prior to commencement of treatment and were referred into practice symptoms resolved before medication was administered order cancelled by owner   adverse events assessment for possible adverse events was undertaken at follow-up examination or by follow-up email (if a second consult was not attended). there were 30 adverse events (0.8%, 30/3,541) identified following pom-v / pom medication remote prescription, from use of 11 suspected products (with three further products used concomitantly) within the reporting period. overall, the signs seen were mild and predominantly associated with the gastrointestinal tract, 29/30 reactions involved vomiting or diarrhoea. all adverse events were reported to the vmd. from our body system / disease categories groupings 33.3% (10/30) were prescribed for the musculoskeletal system, 30% (9/30) for parasitic disease, 26.7% (8/30) for the integument system, 6.7% (2/30) for gastrointestinal disease and 3.3% (1/30) for cardiorespiratory disease. from our prescription medication groupings, 43.3% (13/30) of adverse events were seen after nsaids, 30.0% (9/30) after an anti-parasitic product, 10.0% (3/30) after an oral antimicrobial, 10% (3/30) after an antipruritic, and 6.7% (2/30) after oral steroids[4]. 6.7% (2/30) were sent into practice for examination and treatment. 93.3% (28/30) were confirmed resolved during follow-up consultation or email. we were unable to attain follow-up information for two patients (6.7%). over half (56.7%, 17/30) the adverse events reported were identified by follow-up email for people that had failed to attend a follow-up consultation. if this process had not been followed, we may not have been informed of these mild adverse events.   further breakdown of prescribing outcomes and medication classes outcomes of consultations where medication was prescribed divided into body system / disease category (figure 7) and patient outcomes per prescription medication class (figure 8) show that the majority of the prescribing outcomes in every category was expected / complete response to treatment, with a fairly even distribution across the sub-categories. figure 7: patient outcomes for consultations with remote pom-v / pom prescriptions for the audit period grouped by body system / disease categories   a graph depicting outcomes of treatment for veterinary patients (cats and dogs) managed remotely that had a pom-v / pom prescription as a result of completed remote veterinary led video consultations via a dedicated veterinary telemedicine smartphone app. between 1 april–31 october 2020; grouped into 15 body system / disease category presumptive diagnosis subsets according to primary veterinary nomenclature (venom) code selected by the consulting veterinarian at the time of video consultation. the outcomes of consultations with pom-v / pom medications separated into the following outcome categories: complete / expected response to treatment; adverse event, no response to treatment; partial response to treatment with referral into a physical practice; and no treatment outcome available. figure 8: patient outcomes for remote pom-v / pom prescriptions for the audit period grouped by medication class   a graph depicting outcomes of treatment for veterinary patients (cats and dogs) managed remotely that had a pom-v / pom prescription as a result of completed remote veterinary led video consultations via a dedicated veterinary telemedicine smartphone app. between 1 april–31 october 2020. outcomes grouped by the following prescription medication class groups: oral antimicrobial; topical containing antimicrobial; nsaids and paracetamol with codeine; parasiticide; antipruritic[6]; and other[3]. the number of prescriptions issued for each body system / disease category broken down into medication classes prescribed is shown in figure 9. the majority of prescriptions issued for the: integument body system / disease categories were distributed between the anti-pruritic, topical antimicrobial and parasiticide medication classes musculoskeletal body system / disease category were for the nonsteroidal / paracetamol medication class parasitic body system / disease category were for the parasiticide medication class ophthalmic body system / disease category were for the topical antimicrobial medication class non-specific body system / disease category were for the parasiticide medication class figure 9: medication class subsets for remote pom-v / pom prescriptions for the audit period grouped by body system / disease categories   a graph depicting different classes of pom-v / pom medication prescribed (oral antimicrobial; topical containing antimicrobial; nsaids and paracetamol with codeine; parasiticide; antipruritic (oclacitinib, anti-histamines, topical hydrocortisone spray, topical steroids without antimicrobial, oral steroids); miscellaneous[3]) grouped into 15 body system / disease category presumptive diagnosis subsets according to primary veterinary nomenclature (venom) code selected by the consulting veterinarian at the time of video consultation, as a result of completed remote veterinary led video consultations via a dedicated veterinary telemedicine smartphone app. between 1 april–31 october 2020.   discussion big picture: what gaps does our research fill? why is this important? peer-reviewed evidence examining whether remote prescribing by a dedicated veterinary telemedicine route can be efficacious and safe for patients, is currently not available in the veterinary literature. a recently published comprehensive review of veterinary telemedicine concluded that most information regarding direct-to-consumer telemedicine, although favourable, was gleaned from human healthcare, and therefore more relevant evidence was needed from the veterinary sector (teller & moberly, 2020). our hope with this audit is to begin the process of presenting real data, so that the rcvs and other legislative bodies will be able to develop best practice for the future of veterinary telemedicine based on evidence. looking to the human medical sector, where telemedicine is a topic of significant discussion, teleconsultation appears to work well for both acute and chronic disease management (burke et al., 2015). shigekawa et al. (2018) deemed human telehealth to be equivalent to in-person care. another study in paediatrics, which are deemed most close to animals due to restricted communication, suggested that the assessment of febrile children by remote assessment was as reliable as bedside assessment (siew et al., 2016). mcswain et al. (2017) suggested that children under 2 years of age are not appropriate candidates for telemedicine, due to the higher risk nature of children of that age, and not due to their lack of ability to communicate. therefore, extension of this statement to animals on the basis of their lack of communication is a false conclusion to draw (teller & moberly, 2020). remote prescribing, as part of direct-to-consumer telemedicine provision, may prove valuable to clients, pets and veterinarians in certain situations for reasons including earlier intervention, reduced stress and anxiety both for patient and client, enhanced continuum of care, clinically vulnerable people, accessibility, affordability, convenience, time management, and safety of the veterinarian. pet owners have indicated that they would prefer to be able to continue to obtain pom-v / pom medicines via remote teleconsultation (yougov, 2021). the current rcvs definition of ‘under your care’ (currently under review) which governs the right to prescribe and limits it to in-person physical examination, is ambiguous and there is disparity between prescribing for a herd of farmed animals and individual pets. it does not currently allow for remote prescription to pets without a physical in-person examination. we hope that the data provided in this audit will help to guide the rcvs (and other professional bodies) in their decision-making regarding future governance of remote prescribing, that there are certain situations, in well-structured and governed telemedicine, where remote prescribing does not cause harm and may even be of benefit to animal health and welfare.   critical analysis of the major findings, additional findings and literature comparison assessment of the data gathered during our audit prescribing period has shown the following: a low prescribing rate per number of video consults prescription medications were only issued in 16.6 out of every 100 app. based veterinary video consultations. a third of the consultations that did not result in a prescription being issued were referred into practice or had further laboratory testing, whilst the other two thirds were either recommended a non pom-v / pom product, were monitored, had a follow-up veterinary telemedicine appointment or were not of concern. there is limited data to show the percentages of in-practice consultations that lead to a pom-v / pom prescription in small animal general practice in the uk. a vetcompass study (elkholly et al., 2019) of primary care records of uk dogs found a systemic glucocorticoid prescribing rate of 6.2% (28,472/455,557 dogs in a 1 year period). a second publication examining systemic glucocorticoid prescriptions in three uk veterinary practices found a systemic glucocorticoid prescribing rate of 15.3% (4790/31,273) of dog and cat consults, but with a great deal of inter-practice variation in prescribing patterns (o’neill, 2012). our systemic (oral) glucocorticoid prescribing rate was 0.8% (177/21,383). however, this may in part reflect the disparity between telemedicine vs in practice case loads, and the fact that no injectable medications were administered by nature of the remote means of consultation. ours is also a smaller case load, from just one ‘practice’ and over 7 months rather than a year’s duration. therefore, it is currently impossible to compare prescribing rates directly between a dedicated telemedicine provider and a general practice. we would welcome an audit of a general practice’s prescribing rates to see how these compare. we suspect that there is a critical difference in the case presentation population for a smartphone veterinary telemedicine app. when compared to that of general practice, and so granularity of data on case types would need to be available for a robust comparison. some prescribing data from small animal practice has been published that can be used for comparison. a small animal veterinary surveillance network (savsnet) study by singleton et al. (2018), examined medical records from 457 companion animal practices over a 2 year period for prescribed pharmaceutical agents, finding 65% of dog and 69% of cat consultations had a prescription. one major difference with that study was that it included vaccines, which we did not administer by telemedicine. they found a pom (human-only use authorised medicine) prescribing rate of 5.1% of all prescriptions in dogs and 2.1% for cats. our pom prescribing rate was comparable to these figures at 3.9% (165/4,282). they used a novel mapping method to examine differences in prescribing patterns by species, based on presenting complaint, as well as looking for groups of drugs commonly co-prescribed which is something that we could further do with our data. we examined co-prescription and found a large variation, but in the future, we could also examine the differences more closely by examining presenting complaints along with this. we have not generally separated our data in cats and dogs as the numbers would have been smaller and our aim was to gather an overall picture in general for this audit. summers et al. (2014) found a prescribing rate of 97% (659/683) for antimicrobials alone in 683 presenting cases of canine pyoderma out of 54,600 dogs presented to 73 participating practices in the uk in 2010. of all dermatological cases presenting in the audit period, only 21.1% (1,765/8,367) received any form of prescription treatment. singleton et al. (2019) found the most common prescription medication provided to a cohort of canine acute diarrhoea cases to be systemic antimicrobials, given to 49.7% of cases in their study population of 3,189 cases (3,159 dogs) collected from 179 volunteer veterinary practices between april 2014 and january 2017. this compares with 6.9% (333/4,845) of gastrointestinal cases presenting during the audit period being prescribed any pom / pom-v medication in our app. as previously suggested, it may be that the reason for our apparent difference in prescribing patterns is that our case population differs from that seen in general practice, in that we see cases earlier and we see cases that otherwise would not have been presented for veterinary examination. the relative proportions of consultations resulting in pom-v / pom prescriptions vs those that did not for the different subsets of body system / disease categories managed remotely cannot be easily compared across categories because they are likely to be influenced by a category-dependent selection bias. this is simply because certain disease categories are more amenable to remote assessment. this is borne out in the numbers and appeals to common sense: skin conditions are more easily assessed because the clinician can see the affected area clearly and perform a satisfactory clinical examination, despite being remote from the patient. as for the absolute proportions, without data from an in-clinic setting, there is no distribution on which to base a null hypothesis for a standard hypothesis test.   categories of types of cases seen although not the main aim of this audit, it is worth briefly considering the broad types of cases seen through our app., that were categorised into body system / disease category subsets to gain insight into the types of cases in a remote video consultation practice. the largest caseload, which also had the largest number of prescriptions across all body systems, was dermatological cases. the second most common consultation reason category was ‘non-specific’ cases, including consultations where no body system / disease category was applicable, 45% (432/951) of which were for parasite prophylaxis. gastrointestinal cases were the third most common consultation seen yet prescribing for gastrointestinal cases was low. musculoskeletal, cardiorespiratory and ocular cases were the next three most common categories. a paper presenting the common presenting conditions in uk small animal practice found skin to be the most commonly affected body system, followed by non-specific problems, then gastrointestinal problems (robinson et al., 2015). this is similar to our caseload for the most common body system / disease category, however the case presentations in the less frequent categories differed slightly, with a notable higher prevalence of dental, respiratory, cardiovascular and renal cases compared to our data. they also examined low numbers (2,158 dogs and 881 cats), so data from a larger dataset from physical companion practice would be an insightful comparison. we plan to further thoroughly examine this data in detail with our growing dataset and publish our findings as a subsequent audit, to aid better understanding of case types managed by our telemedicine app.   antibacterial stewardship the majority of literature on prescribing rates in general practice relate to antibacterial use. it is a major concern within the profession that prescription via teleconsulting will result in overuse of antibacterials and fuel a selection bias for increased antibacterial resistance (magalhães-sant'ana et al., 2020). this concern is valid considering the evidence that ray et al. (2019) produced showing increased antimicrobial prescribing rates in human telemedicine via remote means. some multicentre studies have examined antibacterial prescribing rates in uk companion animal practice. a savsnet study by singleton et al. (2017) recorded an antibacterial prescription was dispensed for 18.8% of dogs and 17.5% of cats seen in first opinion practices across england and wales over a 2 year period (2014–2016) from 457 veterinary practices. a vetcompass 2 year study of 374 uk companion animal practices revealed an antibacterial prescribing rate of 25% (242,736/963,463) in dogs and 21% (122,594/594,812) in cats receiving at least one antibacterial, with 42% of those receiving a further antibacterial (buckland et al., 2016). radford et al. (2011) recorded rates as high as 35.1% (5,519/15,727) in dogs and 48.5% (2,708/5,587) in cats for uk pets, assessing data over a 3 month period from 16 small animal practices in england and wales. our data showed that during the audit period, antibacterials were prescribed in 5.9% (1,258/21,383) of all veterinary consultations (2.0% (422/21,383) oral preparation / 3.9% (836/21,383) topical containing antibacterial). the majority of the topical antibacterials prescribed were for dermatological cases and ophthalmological cases. the majority of the oral antibiotics were prescribed for dermatological cases (predominantly allergic skin disease) and trauma cases (bites, burns or infected wounds). there were low numbers of urinary or respiratory case numbers, which in clinical practice may be expected to result in a higher rate of oral antibacterial usage. deeper understanding of any differences in case loads between remote consultations vs a traditional veterinary setting would make an interesting and useful comparison. our antibacterial prescribing rate is significantly lower than the prescription rates in physical uk first opinion small animal practice. again, the apparently lower rates of antibacterial prescribing we are reporting could be a reflection of a different caseload, or due to increased clinician vigilance on remote prescribing of antibacterials, or a combination of both. prescribing patterns have changed over the recent years with the increasing awareness of antibacterial prescribing best practice and antimicrobial resistance. as use of antimicrobials is a key driver for development of antimicrobial resistance, it has been highlighted as vital that the veterinary profession embraces the responsible use of antimicrobials, to safeguard human and animal health, and to preserve the right to prescribe certain antimicrobials that are important in human medicine (singleton et al., 2021). companion animal veterinary practitioners have been shown to respond to involvement in structured antimicrobial stewardship programmes (singleton et al., 2021). during the audit period we prescribed 1,258 antibacterials. the joii antibiotic prescribing policy utilises the traffic light (red / yellow / green) system based on the bsava / samsoc protect me guidance as recommended by the rcvs and bsava (bsava, 2018) and additional support from internal medicine specialists at the royal veterinary college. of the 1,258 antibacterial prescriptions; 99.3% (1,249/1,258) were green first-line antibacterials, 0.7% (9/1,258) were yellow highest priority critically important antibacterials, all of which were topical, and none were red restricted antibacterials. 33.5% (422/1,258) were oral antibacterials and 66.5% (836/1,258) were topical antibacterials. bsava / samsoc guidance advises that ‘topical preparations reduce selection pressure on residential intestinal flora (microbiome)’ so this route was utilised preferentially when it was clinically indicated. as a result of this audit, our antibiotic prescribing guidelines will ensure to highlight the importance that first line topical ear preparations are prescribed first, ideally after culture and sensitivity, and critically important antibacterials are reserved for those cases which have not responded to first line treatment or have been shown to require these antibacterial classes on culture and sensitivity. the european medicines agency (ema) classifies antibacterials into four categories; a (red) avoid, b (orange) restrict, c (yellow) caution, and d (grey) prudence; slightly different to the traffic light system of the bsava / samsoc protect me guidance that we employed. the categorisation of polymixin b by the ema (ema website) as a category b restricted antibacterial is different to the bsava / samsoc protect me guidance, where polymixin b topical ear medication is a recommended first line treatment for otitis externa. during the audit period polymixin b (surolan) was our first line topical ear medication following the guidance and also taking into account there was a stock issue with fusidic acid and framycetin sulphate (canaural). the classification of polymyxin b is something we will monitor within the uk guidance and alter our antibacterial prescribing protocols accordingly. as it has been classified as restricted in europe we will guide our veterinarians to utilise other first line topical ear medications as a priority.   efficacy of treatment complete and expected response to treatment accounted for 89% (2,135/2,399) of consultations where prescription medication was prescribed where follow-up information was available (60.3% (2,135/3,541) of all consultations where prescription medication was prescribed, if those where no treatment outcome was available are included). a low rate (2.7%, 94/3,541) of consultations where prescription medication was prescribed had shown the medication was not effective in treating the patient. the majority of the remainder were lost to follow-up and a small proportion had a partial response but were referred into practice. there was no pattern in terms of condition type that resulted in poor remote outcome after prescribing. in terms of medication type, prescribed pain relief appears to have marginally higher figures of partial response to treatment than other medication types. further analysis of the cases would be needed to determine the exact cause of this. we suspect that, due to the nature of remote prescribing during covid-19, that a significant number of these cases were prescribed nsaids purely as a temporary measure until the patient was able to be seen at their local veterinary practice and assessed for further diagnostic tests or medication.   follow-up engagement was high follow-up was achieved for the majority of prescription medications issued in this audit. we were unable to attain follow-up in 32.3% (1,142/3,541) of cases despite multiple attempts to contact owners. therefore, we are blinded to the outcome of those cases and it is not possible to infer or extrapolate what may have happened with those cases – this is a limitation of this study. there is no comparison available in the literature to show how this measures up to general practice. we were proactive in encouraging follow-up for pom-v / pom prescribed cases as we are aware that remote prescribing is unchartered territory and we wanted to ensure a high clinical standard of care for our patients. follow-up via a video link, or failing that an email exchange with owners, may be a less frictional way of attaining follow-up data than requesting re-examination at a physical practice. therefore, it is probable that we have a higher follow-up attainment compared to clinical practice, though this is purely speculative.       no harm caused we had a low rate (0.8%, 30/3,541) of adverse reactions to remotely prescribed pom-v / pom medications reported, which was an adverse event rate of 0.14% (30/21,383) from total remote consultations during the audit period. all adverse reactions were reported to the veterinary medicines directorate (vmd). all were mild in severity, in most cases vomiting or diarrhoea that fully resolved[4]. our data shows 30.0% (9/30) adverse events occurred after parasiticides and 43.3% (13/30) occurred after anti-inflammatories. these medication groups were in the top five groups accountable for all adverse events in all animals reported to the vmd in their latest pharmacovigilance summary report (vmd, 2019). the vmd online dashboard (vmd, 2019; vmd, 2020) shows that 14.6% (6,369/43,619) of all clinical signs reported with adverse events in cats and dogs in the uk were due to anti-parasiticides and 6.7% (2,910/43,619) due to anti-inflammatories. gastrointestinal signs were commonly seen and from all reports submitted to the vmd in 2019, emesis (1st for anti-inflammatories, 2nd for anti-parasitics) and diarrhoea (4th for anti-inflammatories, 7th for anti-parasiticides) ranked within the top ten signs reported for both classes of medication. the clinical signs and medications we have reported here fit with those commonly reported to the vmd. a vetcompass study examining side effects of glucocorticoids reported within 31 days of treatment, over a 1 year prescribing period, found 4.9% of patients to have side effects of polyuria, polydipsia, diarrhoea and or vomiting following glucocorticoid administration (elkholly et al., 2020).  the risk of side effects was increased with use of oral glucocorticoids either alone or in combination with injectable, compared to use of injectable alone. our own oral glucocorticoid prescribing rate was low, with a lower adverse event rate (1.1%) than that reported in the vetcompass study. we did not have reports of polyuria or polydipsia as adverse events in this audit. our follow-up times were in most circumstances much sooner than 31 days (typically within 1–4 days of the end of a treatment course), therefore we could have missed some patients developing these signs. thus highlighting that we need to change company policy to include asking questions around these clinical presentations and also to pursue longer-term adverse event and side effect reporting on follow-up of remote prescribing cases. it is hard to find comparable figures for adverse events from general veterinary practice. evidence relating to oral and topical medications is not readily available, most likely due to the under-reporting of adverse events to the vmd.  the vmd are currently funding a phd project and a masters project in collaboration with savsnet (small animal veterinary surveillance network (savsnet) – university of liverpool, 2021) which may in future help answer questions on how many adverse events get reported compared to the number that occur in practice. we were proactive in enquiring about adverse reactions to every client where a pom-v / pom had been issued. over half (56.6%, 17/30) the adverse events reported were identified by follow-up email for people that had failed to attend a follow-up consultation. if this process had not been followed, we may not have been informed of these mild adverse events. it is probable that in physical veterinary practices, owners do not always inform the practice about a mild gastrointestinal upset after a medication has been given. adverse events in the veterinary and human world are under reported due to many reasons including: level of awareness of reporting obligations length of time the product has been on the market increased reporting rate in the first 2 years reporting environment social media publicity / news coverage de briyne et al. (2019) conducted a survey of 3,545 veterinary surgeons to gain a better insight into the adverse event reporting habits of veterinary practitioners. the findings indicated marked under-reporting. in order to increase spontaneous reporting, there is a need to make reporting easier and to make veterinarians better aware of the importance of reporting and the added value it may bring. it is estimated that less than 10% of serious adverse events and 2–4% of non-serious adverse events are reported (personal communication, veterinary pharmacovigilance course, 2014, management forum). since we discovered over half of our adverse events, albeit a low number and mild, by proactive owner engagement following prescription, it would seem sensible that this approach be adopted and encouraged by the wider veterinary profession to ensure high standards of pharmacovigilance.     the relative proportion of outcomes of pom-v / pom remote prescription grouped by body system / disease category subsets, and for medication class groups is subject to selection bias in a similar way to prescribing vs not prescribing. the bias in this instance results from the different medications administered across the various categories. it is therefore impossible to extract any statistically significant differences between the proportions of adverse / non-adverse outcomes that is attributable solely to the remoteness of the clinician. the absolute proportions of adverse / non-adverse outcomes within each category are also difficult to assess quantitatively without in-clinic data for a null hypothesis distribution. however, it is not unlikely that adverse events are equally likely to result from data derived from in-clinic consultations, because, critically, our clinicians used their discretion in each case and used a level of caution commensurate with conducting an assessment remotely.   limitations of our data what we are currently unable to demonstrate? case sample and comparison to general practice we can say that our prescribing rate seemed to be low across different body systems / disease categories, that our reported adverse events were mild and very low, that our use of antibacterials was conservative and more frequently topical than systemic. we can say that remote prescribing, in our hands, does not appear to cause harm, but this is not the same as concluding that remote prescribing is safe, per se. there were cases that were directed into practice for further examination and diagnostics, and it would likely have been unsafe to prescribe to those cases. what we cannot say is how any of this data compares to physical veterinary practices. we also have not presented a more in-depth breakdown of disease types and presentations, since that was not the focus of this audit; however, it is clear that that information is also needed to help to inform the profession on the types of cases typically encountered by a dedicated veterinary telemedicine app.     it would have been useful to analyse information pertaining to owner demographics and characteristics in order to investigate influences on outcome of therapy. however, given the retrospective nature of this study and our ethical consideration of gdpr and sensitive data regarding people, we unfortunately lack some of this information and cannot include it in this manuscript. it is likely that clients turn to alternative options (friends / the internet / paraprofessionals) before seeking care at their local practice. what we may be seeing here is the opportunity, via a dedicated veterinary smartphone app., to intervene earlier in the process of a given disease, and therefore significantly and positively impact animal health and welfare.   data set limitations the limitations to our dataset is that it was a sample from less than a year of in-app. consultations, and during that year our caseload was growing, so may not be reflective of a typical year on year in an established online veterinary practice. we were limited to this time by the limited time period of remote prescribing relaxed rules set out by the rcvs. the audit time was also undertaken during the occurrence of a global pandemic, and so people’s behaviours and indeed prescribing decisions may have been altered due to the nature of the extenuating circumstances of a lockdown. it would be ideal to perform this audit annually on an ongoing basis, but the right to prescribe remotely would need to be approved by the rcvs in order for us to gather and then present this data. study design and data capture was aided by our practice management system, allowing us to collect multiple comparative data points for every case seen remotely. we have a structured clinical notes section with drop down selections and limited free text written records, to streamline our data, make it easier to explore our data, and ultimately to reduce human error. the need for any prescription medicine sale to pass through our sales system means there is no error in terms of missing cases for the audit. clinical staff were informed of data gathering but it was not at that time used to directly monitor performance so there should be little room for conflict of interest, although this is always possible in an audit setting. it should be borne in mind that this review was on data from a dedicated smartphone app, where a secure video and audio link was essential for a consultation to happen, and therefore no conclusions can be drawn about remote prescribing by other means, such as email and photo exchange, or telephone conversations.   future directions at this time, we have ceased remote prescribing in line with the rcvs’s temporary guidance. this means that we are unable to complete the cyclical nature of a true clinical audit, and cannot implement any learnings to better inform our prescribing protocols. if we did begin prescribing again, then stricter policy re provision of nsaids would need implementation, since we saw some adverse reactions predominantly to those. we would also review antibacterial prescribing and set evidence-based guidelines (where evidence available) for best practice to reduce use and use alternatives. we would also continue to record treatment outcomes in our clinical records, and proactively engage owners for follow-up after pom-v / pom prescribing, both immediately and at longer time points following prescription, reporting adverse events to the vmd.     to really make use of our data set, we need comparative studies from other practices, both remote and in person.   overall conclusion and impact: take home message in summary, through this audit we have found that remotely prescribing via our dedicated smartphone veterinary telemedicine app, we had an overall low prescribing rate, including a low antibacterial prescribing rate; our treatments were on the whole efficacious and no harm was done by prescribing remotely. we have a low rate of systemic (oral) glucocorticoid prescribing compared to physical practice. we are currently unable to compare much of our findings directly with clinical practice, due to a lack of published evidence. it is likely that the virtual practice case population is different to a physical clinic population, which could in part explain the favourable results for lack of harm by remote prescribing in our hands. more data is needed examining the case presentation types for both remote consults and physical practices, for direct comparisons to be made.     we can also conclude that proactive follow-up, both immediately during / at the end of treatment and longer term, to find out about adverse events needs to be encouraged and maintained both within our virtual practice and, we suggest, across the profession. we invite the rcvs and other veterinary governing bodies to consider that there is a place for prescribing remotely for certain cases under certain conditions, such as a secure video and audio link via a dedicated app with clinical record keeping and pharmacovigilance practice, and that a blanket ban is not appropriate with the advance of modern technology. the future of veterinary medicine should include remote consultations with remote prescribing where appropriate, to be able to reach as many owners and provide professional advice and appropriate treatment on pet health so that those animals that do not necessarily currently receive veterinary care do so, and to bridge the gap wanted by clients.   footnotes [1] includes – lump / swelling, polyp – rectal, nasal (nose) disorder (unspecified), wart, skin (cutaneous) cyst, granuloma (site unspecified), mass lesion – skin (cutaneous), mass lesion – anal gland / sac, mass lesion – conjunctival, mass lesion – ear (aural), mass lesion – eyelid, mass lesion – nail bed, mass lesion – nose (nasal), nasal cavity, mass lesion – perianal, mass lesion (site unspecified), haematoma – other, abscess (site unspecified), congenital disorder mass lesion – vaginal, mass / swelling – skin, papilloma, solitary.   [2] non-specific conditions include the following assigned venom codes – no diagnosis, not presented for problem investigation, diagnosis unchanged from last visit, not presented for a complaint, problem not identified, re-examination appointment.   [3] miscellaneous / other medication includes the following – propentofylline, dexmedetomidine 0.1 mg/ml oromucosal gel for dogs, estriol tablets, chlorhexidine gluconate miconazole nitrate shampoo, cimetidine, bromhexine, pimobendan, frusemide ,omeprazole, selegiline hydrochloride, maropitant, phenylpropanolamine hydrochloride, cyclosporine a ophthalmic ointment, fluoxetine capsules, silver sulfadiazine cream, 1% w/v prednisolone acetate eye drops, lactulose, famotidine, ranitidine, cabergoline oral solution, carbimazole tablets, hypromellose ph.eur. 0.5% w/v. drops, levothyroxine sodium, thiamazole.       [4] six cats had adverse events to prescribed medications. one cat reacted to sarolaner and selamectin (stronghold plus, zoetis) in combination with emodepside and praziquantel (profender, vetoquinol) showing signs of vomiting and lethargy. two cats reacted to meloxicam (metacam, boehringer ingelheim) showing vomiting and diarrhoea respectively. three cats also developed diarrhoea after medication with clindamycin (antirobe, zoetis), ciclosporin a (atopica, elanco) and amoxicillin and clavulanic acid (synulox, zoetis) respectively. of the six reactions, five resolved fully and for one, we tried but were unable to attain follow-up information. twenty-four dogs had adverse events to prescribed medications. seven reactions were seen after a meloxicam product (five with metacam, [boehringer ingelheim] of which one had amoxicillin and clavulanic acid, [synulox zoetis], concomitantly. two with meloxidyl, [ceva]). of these seven, two showed diarrhoea, two showed vomiting and two showed both vomiting and diarrhoea. one showed inappetance after an overdose. five showed reactions to moxidectin, pyrantel and sarolaner (simparica trio, zoetis), one with oclacitinib (apoquel – zoetis, concomitant). three vomited, one had diarrhoea and one had an upset stomach. four showed reactions to robenacoxib (onsior, elanco) three vomited and one had diarrhoea. prednisolone (prednicare, animalcare – 1, prednidale, dechra – 1) caused diarrhoea and lethargy respectively in two dogs. omeprazole caused vomiting and vomiting and diarrhoea in two dogs. diarrhoea was seen in a further four dogs, two after imidacloprid and moxidectin (advocate, bayer) one after spinosad a/d 85:15 (comfortis, elanco) and one after amoxicillin and clavulanic acid (synulox, zoetis). of the 24 reactions, 23 resolved fully and for one we tried but were unable to attain follow-up information.   [5] pom-schedule (7) were included in the pom / pom-v totals: pardale-v (schedule five pom-v), tralieve (schedule three pom-v), diazepam rectal solution (pom human schedule four), gabapentin (pom human, schedule three).   [6] 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[online] available from: https://yougov.co.uk/topics/overview/survey-results [accessed 2 jun 2021]. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. box rest and analgesia compared to arthroscopic debridement for lame horses with hindlimb subchondral lucencies | veterinary evidence skip to main content knowledge summary keywords: subchondral; lucency; cystic; equine; stifle; tibia; condyle; horse; arthroscopic debridement box rest and analgesia compared to arthroscopic debridement for lame horses with hindlimb subchondral lucencies charlotte taylor, bvsc mrcvs pgcert1 julia dubuc, dmv des m.sc dacvs-la fhea mrcvs2* 1 hoermann equine ltd, wrights lodge east, oakham road, whissendine, rutland, le15 7ha 2 oakham veterinary hospital, ashwell road, oakham, rutland, le15 7qh * corresponding author email: julia.dubuc@nottingham.ac.uk vol 8, issue 2 (2023) submitted 06 mar 2022; published: 19 apr 2023; next review: 28 feb 2025 doi: https://doi.org/10.18849/ve.v8i2.603 pico question in lame horses, caused by osseous cyst-like lesions in the proximal hindlimb, is box rest and analgesia administration more effective at returning the horse to previous level of performance in comparison to arthroscopic debridement? clinical bottom line category of research treatment. number and type of study designs reviewed two relevant publications were found, both were retrospective case series. strength of evidence weak. outcomes reported the success rate of horses returning to previous level of competition following arthroscopic debridement varies widely in the literature available, from 25–86%. while a study reports 64% return to soundness following rest, it is not clear which horses received strict box rest or paddock rest, the duration of the rest period, and whether non-steroidal anti-inflammatory drugs were also prescribed. it is also worth noting that all horses which undergo surgery will also undergo a period of box rest – which makes the two treatment options difficult to compare. conclusion newer techniques with better success rates are now available and should be considered in lieu of box rest or arthroscopic debridement. across all treatments available, age remains an important factor with regards to return to soundness, with older horses having a poorer prognosis. thorough examinations should therefore be performed to rule out concurrent conditions before deciding upon treatment options. how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are presented with a 5-year-old recently retired thoroughbred which is now being retrained for eventing. the owner is concerned that the horse is becoming disunited at canter on the right rein and it has refused to jump yesterday, which it had never done before. following regional diagnostic anaesthesia, you identify the left stifle as the source of lameness. indeed, the owner’s complaint under saddle has resolved after blocking the left medial femorotibial joint, while a previous femoropatellar block left the horse unchanged. the evidence the quality of evidence available for this clinical question is low. the authors only found two publications relevant to the question, all were retrospective case series, with no randomised trials comparing treatment with arthroscopic debridement and box rest. the authors found one publication directly comparing the two treatment options (textor et al., 2001), although all lucencies involved the proximal tibial plateau and only two horses were treated with rest. a more recent publication (santschi et al., 2020) includes lucencies of the femoral condyles and the proximal tibial plateau but there was only one horse in the arthroscopic debridement group. summary of the evidence textor et al. (2001) population: horses (nine males, three females), mixed breeds, aged 6 months to 12 years old. sample size: 12 horses with tibial plateau lucencies: two with bilateral lesions. intervention details: horses divided in two groups: young (6/12): considered osteochondrosis (mean age 12 months); older (6/12): considered osteoarthritis (oa) (mean age 9 years). two treatment categories: arthroscopic debridement for lesions in cranial third of the plateau (7/12); other treatments (5/12). study design: retrospective case series. outcome studied: lameness. main findings (relevant to pico question): duration of lameness: mean 6.4 months (range: < 1 month to > 2 years). lameness grade from 0–3 (on 0–5 scale). 7/12 horses (58%): arthroscopic debridement (four young, three older): of the four young, three performed athletically, one was euthanised; of the three old, one sound, two returned to lower level. 5/12 horses (42%): other treatments: horse 1 (young): stall rest for 8 weeks, anti-inflammatory for 2 weeks, intramuscular pentosan polysulphate for 4 weeks (3 mg/kg, every 7 days). had surgical debridement at 1 year of age as persistent lameness, in training at 2 years old. horse 2 (young): stall rest for 8 weeks, weekly intrasynovial injections of polysulphated glycosaminoglycans in both femorotibial joints (bilateral lucency), had an 8 year racing career with intermittent hindlimb lameness. horse 3: transcortical debridement open. euthanised. horse 4: non-steroidal anti-inflammatory drugs (nsaids). lost to follow-up. horse 5: no treatment. euthanised. limitations: follow-up information hard to follow. outcome is unclear as sometimes presented as soundness versus return to exercise. management of all five horses in other treatment group was different. no cases of femoral lucencies.   santschi et al. (2020) population: horses (seven females, 10 males, aged 4 months to 15 years, mixed breeds). sample size: 17 horses with proximal tibial lucency. intervention details: stifle radiographs (at least caudoproximal 15°-craniodistal) one of four treatment options: 6/17 horses (35%) – limited exercise (box rest) or round pen confinement for 90 days + nsaids based on lameness (variable amount of time). 1/17 horses (6%) – arthroscopic debridement. 8/17 horses (47%) – screw placement transcondylar or tibial. 2/17 horses (12%) – no treatment. study design: retrospective case series. outcome studied: radiographic healing. resultant lameness. level of exercise reached following procedure. main findings (relevant to pico question): all but one were unilateral. 11/17 horses (65%): primary (no other subchondral lucencies [scl]), all except one in lateral tibial plateau (tp): 9/11 horses (82%) diagnosed < 1 year old. no lameness to lame at the walk. follow-up for nine primary horses: one euthanasia (debrided arthroscopically, after rest failed). six horses without lameness (three rest and three screws). two horses lame broodmares (rest). 6/17 horses (35%): secondary to medial femoral condyle (mfc) scl, all in medial tp, two bilateral: all ≥ 3 years old. all either lame at trot or walk. all but one had lag screws (tibia only or tibia + mfc). follow-up for five secondary horses: three with tibial and mfc screws: lame at flexion or trot only; two with tibial screws (one had mfc before): one lame at walk and one sound (ranch rodeo horse). limitations: little information on analgesia treatment (length, nsaids used). only one debridement case, which also had stem cells. small numbers for rest group. rest included round pen, not only.   appraisal, application and reflection subchondral lucencies are areas of reduced bone density on radiographs, often surrounded by sclerosis and usually located over weight-bearing surfaces (stewart & reid, 1982). in equine hindlimbs, the medial femoral condyle (mfc) is most commonly affected but lucencies of the proximal tibia have also been described concurrently or not, to femoral lesions (jeffcott & kold, 1982; verschooten & de moor, 1982; textor et al., 2001; bonilla et al., 2016; and santschi et al., 2020). histopathologic examinations of lucency linings have revealed an upregulation of inflammatory cytokines, namely il-1 and il-6, and an increased production of prostaglandin e2, which laid the foundation for the inflammatory theory (von rechenberg et al., 2004). the origin of subchondral lucencies is still debated today and has in the past fallen under the osteochondrosis umbrella. work from ray et al. (1996) suggested that trauma to the weight-bearing surface could contribute to the development of these lucencies. in addition, more recent work on juvenile equine femoral condyles (lemirre et al., 2021) failed to identify chondronecrosis, a hallmark of osteochondrosis, within these subchondral lucencies, which reinforces the argument in favour of the traumatic origin for these lesions. subchondral lucencies of the proximal hindlimb have historically been treated through rest with or without anti-inflammatories. while a success rate of 64% (16/28) for return to soundness has been reported (jeffcott & kold, 1982; and stewart & reid, 1982), the number of horses box rested compared to rested in a small paddock or a round pen remains unclear. the duration of the rest period also differs between studies from unknown (stewart & reid, 1982; and verschooten & de moor, 1982) to 90 days (santschi et al., 2020), 8 weeks (textor et al., 2001) and 6 months (jeffcott & kold, 1982). there is no established protocol for the use of nsaids during box rest or light work with variable dose range, frequency and duration of administration retrieved from the different papers: none (jeffcott & kold, 1982), as needed with light work (stewart & reid, 1982), unknown (santschi et al., 2020) or 4.4 mg/kg of phenylbutazone orally during the rest period (bonilla et al., 2016). while there are recent publications including horses treated with rest, the numbers of horses treated conservatively is always very small and the lack of standardised treatment does not allow any extrapolation of the results. while the oldest publications often include a large number of conservatively treated horses, their outcome is not always presented clearly, often with no difference made between soundness and return to previous level of exercise. in all the studies, soundness is either evaluated by their referring veterinary surgeons or the owners, which could make the follow-up data less reliable. this is important as the degree of lameness in relation to the size of the lucency remains poorly understood. recently, a longitudinal radiographic follow-up of shallow mfc lucencies (≤ 3 mm) in young racing thoroughbreds showed these can resolve on their own (6.1%; 15/248), decrease in size (23.6%; 59/248), or increase in size (8.2%; 20/248). while 40.7% (101/248) of the lucencies did not change in size and only 3.6% (9/248) developed into a cyst, those horses still had less race starts as 2-year-olds than their maternal siblings free of stifle pathology (pérez-nogués et al., 2021). surgical management has been historically recommended with presence of lameness, persistent joint effusion and for horses destined to athletic use (ortved, 2017). the surgical debridement of subchondral lucencies has been developed in order to reduce the inflammation present within the cavity and the arthroscopic technique was first described by lewis in 1987. it then remained the favored treatment for these lesions for the following 20 years. four publications were found looking at arthroscopic debridement of the medial femoral condyles and one for proximal tibial plateau lesions. there is no consistent approach to arthroscopic debridement of the lucencies. for example, some authors used osteostixis with a 3.2 mm drill bit within the lucency cavity following its debridement (howard et al., 1995). others have enlarged the lucency opening at the level of the joint space to 1 cm diameter (schneider et al., 1997) possibly to decrease intraosseous or intracystic pressures which has been hypothesised as one cause of pain in these cases (ortved, 2017). this is an interesting modification of the technique considering that medial meniscal injuries were later recognised following debridement of some medial femoral condyle lucencies (hendrix et al., 2009). four of these meniscal lesions were graded 3 according to walmsley et al. (2003), indicating a tear of the cranial horn of the medial meniscus and its cranial meniscotibial ligament which extends underneath the femoral condyle (caudal limit not visible). the success rate across the debridement studies varies between 25% and 86% (schneider et al. (1997). schneider et al. (1997) described a much better success rate with focal lucencies (86%; 6/7) compared to diffuse ones (25%; 1/4), but all the horses included in that publication had normal radiographic findings pre-operatively. this could be due to radiographic technique or positioning or the fact these 11 cases had only a small defect or flattening in the medial femoral condyle (grade 1: flattening or small defect in the subchondral bone of the central mfc, santschi et al., 2015). the success rate in the study employing osteostixis was low at 56% (22/39) (howard et al., 1995) with almost half the horses (44%; 17/39) having had drilling. it is unclear from the results how many of the successful horses had osteostixis compared to the ones which only had debridement. interestingly, 68% of that horse population was aged 1–3 years old. this is in direct contradiction to several other studies which have reported a better outcome in younger horses with 3 years old advanced as a non-official cut off (jeffcott & kold, 1982; stewart & reid, 1982; and smith et al., 2005). smith et al.’s publication is extremely thorough in terms of follow-up and reported a 69% (27/39%) return to previous level of exercise in horses < 3-years-old compared to 29% (13/45) for horses > 3 years of age, in a population mainly composed of thoroughbreds. it is possible that the added osteostixis is not beneficial to treatment of the subchondral lucency but this cannot be determined with certainty based on this data only. the presence of other anomalies within the femorotibial joint also comes into play with older horses. indeed, enthesiophytosis of the intercondylar eminence of the proximal tibia (seven horses) and the intercondylar fossa of the distal femur (eight horses) was detected on pre-operative radiographs with more than 70% (5/7) of these being > 3-years-old (smith et al., 2005). in addition, cartilage lesions other than at the lucency site were noted in 24% (20/85) of horses, 80% (16/20) of which were aged over 3-years-old. following the report of concurrent meniscal lesions following lucency debridement (hendrix et al., 2009) and a 67%  (35/52) success rate following arthroscopic intralesional injection of medial femoral condyle lucencies with corticosteroids (wallis et al., 2008), the arthroscopic debridement technique fell out of fashion, especially if the subchondral bone plate was considered stable by the surgeon. interestingly, the return to racing following intralesional corticosteroid administration in a recent study remains unchanged (68%; 21/31 [klein et al., 2022]) as first described by wallis et al. in 2008. newer techniques, such as the transcondylar screw placement across the subchondral lucency have shown more promising results (santschi et al., 2015; and ravanetti et al., 2021). the original technique reported a 75% (15/20) return to soundness 120 days after insertion of a single screw across medial femoral condyles lucencies and decreased the lucency size as visible on radiographs (santschi et al., 2015). that original study comprised 13 racehorses and it was later found that 77% of these went on to race successfully (santschi, 2021). most recently, a 73% (16/22) successful return to racing was also reported following insertion of an absorbable implant inserted in medial femoral condyle lucencies (ravanetti et al., 2021). it should be noted that any surgical procedure will entail a certain amount of box or paddock rest with the administration of analgesia and the contribution of these to lucency healing and lameness remains unknown. the authors of this knowledge summary search failed to find even one single study comparing box rest with arthroscopic debridement including a decent number of cases in each group. the evidence in the literature at present is weak and does not allow recommendation of box rest and analgesia over arthroscopic debridement nor vice versa. the latest return to racing data reported for arthroscopic debridement was 72% (42/57), with no conservative management group in that study either (klein et al., 2022). there is, however, substantial evidence that other / newer techniques are now available and should be considered as treatment for these lesions possibly in lieu of box rest and arthroscopic debridement. indeed, reported success rates for return to racing are higher with the transcondylar screw technique (77% return to racing; 10/13 [santschi, 2021]) and intralesional mesenchymal stem cells (84% raced after surgery; 16/19 [klein et al., 2022]). as with other techniques, the age factor (< 3-years-old having better odds) has also been reported with the transcondylar screw technique (santschi et al., 2015). in the authors opinion, subchondral lucencies in older horses should be evaluated carefully for the presence of other lesions within the femorotibial joints and clinical decision making done taking these factors into consideration, along with response to intra-articular diagnostic analgesia. while return to soundness is a desirable outcome, not regaining soundness does not preclude return to previous level of exercise and follow-up information should be considered carefully in light of this. methodology search strategy databases searched and dates covered: cab abstracts on ovid platform 1973–week 08 2023 pubmed on the ncbi interface platform 1920–february 2023 search strategy: cab abstracts: (horse* or equine* or pony or ponies or mare* or colt* or filly or fillies or stallion or racehorse or thoroughbred).mp. or exp horses/ or exp mares/ or exp colts/ or exp stallions/ or exp thoroughbred/ or exp racehorses/ (occl or 'osseous cyst-like lesion*' or 'osseous cyst like lesion*' or 'subchondral bone cyst*' or 'subchondral cystic lesion*' or scl).mp. (stifle* or 'proximal hindlimb*' or 'femoral condyle*' or 'medial femoral condyle' or mfc or femur or tibia or ('medial condyle' and femur*)).mp. (rest or 'box rest' or (conservative and (management or treatment or approach))).mp. (arthroscop* or curettage or ((arthroscopic or surgical) and debridement )).mp. 1 and 2 and 3 and (4 or 5)   pubmed: horse or equine or pony or mare or colt or filly or stallion or racehorse or thoroughbred occl or 'osseous cyst-like lesion' or 'osseous cyst like lesion' or 'subchondral bone cyst' or 'subchondral cystic lesion' or scl stifle or 'proximal hindlimb' or 'femoral condyle' or 'medial femoral condyle' or mfc or femur or tibia  (rest or 'box rest' or (conservative and (management or treatment or approach))) arthroscopy or  curettage  or ((arthroscopic or surgical) and debridement) 1 and 2 and 3 and (4 or 5) dates searches performed: 28 feb 2023   exclusion / inclusion criteria exclusion: proceedings, distal limb subchondral lucencies (scl), other osteochondral lesions, concurrent ostechondritis dissecans (ocd), surgical debridement through open technique or transcortical, other language than french or english, case reports, narrative reviews, opinion pieces. inclusion: subchondral lucencies of proximal tibia and distal femur.   search outcome database number of results excluded – proceedings, case report, reviews, book chapters excluded – not published in french of english excluded – not directly relevant to pico question excluded – duplicate excluded – duplicate from cab total relevant papers cab abstracts 39 6 3 25 3 – 2 pubmed 31 0 0 24 2 5 0 total relevant papers when duplicates removed 2   orcid julia dubuc: https://orcid.org/0000-0003-0552-9117 conflict of interest the authors declare no conflicts of interest. references bonilla, a.g., bertone, a.l., brokken, m.t. & santschi, e.m. (2016). concurrent or sequential tibial subchondral cystic lesions in 4 horses with medial femoral condyle subchondral cystic lesions. journal of the american veterinary medical association. 249(11), 1313–1318. doi: https://doi.org/10.2460/javma.249.11.1313 hendrix, s.m., baxter, g.m., mc ilwraith, c.w., hendrickson, d.a., goodrich, l.r., frisbie, d.d. & trotter, g.w. (2009). concurrent or sequential development of medial meniscal and subchondral cystic lesions within the medial femorotibial joint in horses (1996–2006). equine veterinary journal. 42(1), 5–9. doi: https://doi.org/10.2746/042516409x454556 howard, r., mcilwraith, c. and trotter, g. (1995). arthroscopic surgery for subchondral cystic lesions of the medial femoral condyle in horses: 41 cases (1988–1991). journal of the american veterinary medical association. 206(6), 842–850. jeffcott, l.b. & kold, s.e. (1982). clinical and radiological aspects of stifle bone cysts in the horse. equine veterinary journal. 14(1), 40–46. doi: https://doi.org/10.1111/j.2042-3306.1982.tb02333.x klein, c.e, bramlage l.r, stefanovski d., ruggles a.j., embertson r.m. & hopper s.a. (2022). comparative results of 3 treatments for medial femoral condyle subchondral cystic lesions in thoroughbred racehorses. veterinary surgery. 51(3), 455–463. doi: https://doi.org/10.1111/vsu.13782 lemirre, t., santschi, e.m., girard, c.a., fogarty, u., janes, j.g., richard, h. & laverty, s. (2021). microstructural features of subchondral radiolucent lesions in the medial femoral condyle of juvenile thoroughbreds: a microcomputed tomography and histological analysis. equine veterinary journal. 00(1–13). doi: https://doi.org/10.1111/evj.13486 lewis, r. (1987). a retrospective study of diagnostic and surgical arthroscopy of the equine femorotibial joint. in: proceedings of the american association of equine practitioners. ortved, k.f. (2017). surgical management of osteochondrosis in foals. veterinary clinics of north america: equine practice. 33(2), 379–396. doi: https://doi.org/10.1016/j.cveq.2017.03.010 pérez-nogués, m., derham, a., marmion, j. & baker w.t. (2021). progression of shallow medial femoral condyle radiographic lucencies in thoroughbred repository radiographs and their influence on future racing careers. equine veterinary journal. 53(2), 287–293. doi: https://doi.org/10.1111/evj.13298 ravanetti, p., lechartier, a., hamon, m. & zucca, e. (2021). a composite absorbable implant used to treat subchondral bone cysts in 38 horses. equine veterinary journal. 54(1), 97–105. doi: https://doi.org/10.1111/evj.13428 ray, c.s., baxter, g.m., mcilwraith, c.w., trotter, g.w., powers, b.e., park, r.d. & steyn, p.f. (1996). development of subchondral cystic lesions after articular cartilage and subchondral bone damage in young horses. equine veterinary journal. 28(3), 225–232. doi: https://doi.org/10.1111/j.2042-3306.1996.tb03777.x rechenberg, b., guenther, h., mcilwraith, c.w., leutenegger, c., frisbie, d.d., akens, m.k. & auer, j.a. (2004). fibrous tissue of subchondral cystic lesions in horses produce local mediators and neutral metalloproteinases and cause bone resorption in vitro. veterinary surgery. 29(5), 420–429. doi: https://doi.org/10.1053/jvet.2000.7538 santschi, e.m., williams, j.m., morgan, j.w., johnson, c.r., bertone, a.l. & juzwiak, j.s. (2015). preliminary investigation of the treatment of equine medial femoral condylar subchondral cystic lesions with a transcondylar screw. veterinary surgery. 44(3), 281–288. doi: https://doi.org/10.1111/j.1532-950x.2014.12199.x santschi, e.m. (2021). treatment options and long-term outcomes of horses with subchondral lucencies of the medial femoral condyle. equine veterinary education. 33(7), 386–388. doi: https://doi.org/10.1111/eve.13338 santschi, e.m., whitman, j.l., prichard, m.a., lopes, m.a.f., pigott, j.h., brokken, m.t., jenson, p.w., johnson, c.r., morrow, c., brusie, r.w., juzwiak, j.s. & morehead, j.p. (2020). subchondral lucencies of the proximal tibia in 17 horses. veterinary surgery. 49(4), 778–786. doi: https://doi.org/10.1111/vsu.13387 schneider, r., jenson, p. & moore, r. (1997). evaluation of cartilage lesions on the medial femoral condyle as a cause of lameness in horses: 11 cases (1988–1994). journal of the american veterinary medical association. 210(11), 1649–1652. smith, m.a., walmsley, j.p., phillips, t.j., pinchbeck, g.l., booth, t.m., greet, t.r.c., richardson, d.w., ross, m.w., schramme, m.c., singer, e.r., smith, r.k. & clegg, p.d. (2005). effect of age at presentation on outcome following arthroscopic debridement of subchondral cystic lesions of the medial femoral condyle: 85 horses (1993–2003). equine veterinary journal. 37(2), 175–180. doi: https://doi.org/10.2746/0425164054223741 stewart, b. & reid, c. (1982). osseous cystlike lesions of the medial femoral condyle in the horse. journal of the american veterinary medical association. 180(3), 254–257. textor, j.a., nixon, a.j., lumsden, j. & ducharme, n.g. (2001). subchondral cystic lesions of the proximal extremity of the tibia in horses: 12 cases (1983–2000). journal of the american veterinary medical association. 218(3), 408–413. doi: https://doi.org/10.2460/javma.2001.218.408 verschooten, f. & de moor, a. (1982). subchondral cystic and related lesions affecting the equine pedal bone and stifle. equine veterinary journal. 14(1), 47–54. doi: https://doi.org/10.1111/j.2042-3306.1982.tb02334.x wallis, t.w., goodrich, l.r., mcilwraith, c.w., frisbie, d.d., hendrickson, d.a., trotter, g.w., baxter, g.m. & kawcak, c.e. (2008). arthroscopic injection of corticosteroids into the fibrous tissue of subchondral cystic lesions of the medial femoral condyle in horses: a retrospective study of 52 cases (2001–2006). equine veterinary journal. 40(5), 461–467. doi: https://doi.org/10.2746/042516408x258843 walmsley, j.p., phillips, t.j. & townsend, h.g.g. (2003). meniscal tears in horses: an evaluation of clinical signs and arthroscopic treatment of 80 cases. equine veterinary journal. 35(4), 402–406. doi: https://doi.org/10.2746/042516403776014163 contribute to the evidence there are two main ways you can contribute to the evidence base while also enhancing your cpd: tell us your information need write a knowledge summary either way, you will be helping to add to the evidence base, and strengthen the decisions that veterinary professionals around the world make to give animals the best possible care. learn more here: https://veterinaryevidence.org/index.php/ve/guidelines-for-authors licence copyright (c) 2023 charlotte taylor & julia dubuc intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s and owners’ circumstances. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use.   veterinary evidence is an rcvs knowledge initiative. issn: 2396-9776 first floor, 10 queen street place, london ec4r 1be resources student awards staff login policies privacy policy accessing information policy cookie declaration terms of use copyright notices stay connected podcasts twitter facebook instagram linkedin back to top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443. comparing clinical outcomes of dogs suffering from degenerative lumbosacral stenosis upon surgical or nonsurgical treatment | veterinary evidence skip to main content knowledge summary keywords: dogs; degenerative lumbosacral stenosis; dorsal laminectomy; epidural steroid injection; cauda equina; disc degeneration; transarticular fusion; transarticular stabilisation; canine dlss; foraminotomy comparing clinical outcomes of dogs suffering from degenerative lumbosacral stenosis upon surgical or nonsurgical treatment kristy goh rui qi, student1* 1 university of sydney, regimental drive, camperdown nsw 2050, australia * corresponding author email: kgoh8029@uni.sydney.edu.au vol 8, issue 2 (2023) submitted 13 jan 2022; published: 08 jun 2023; next review: 16 mar 2025 doi: https://doi.org/10.18849/ve.v8i2.575 pico question in dogs suffering from degenerative lumbosacral stenosis (dlss), is surgical treatment more effective than nonsurgical therapy in reducing lumbosacral pain and neurological dysfunction in the long-term? clinical bottom line category of research treatment. number and type of study designs reviewed two papers were critically reviewed. they were prospective and retrospective studies. strength of evidence weak. outcomes reported besides the two studies, there are no other studies currently available that directly compare long-term clinical outcome of patients that have undergone nonsurgical and surgical treatment respectively. in the study comparing clinical outcome of nonsurgical treatment by epidural steroid injection (esi) and surgical treatment of degenerative lumbosacral stenosis, dogs were classified into clinical severity groups ranging from mild to moderate to severe. mild cases demonstrated degenerative lumbosacral stenosis (dlss) compatible clinical signs such as lumbosacral pain, reluctance to climb stairs / jump / raise up, lameness and muscle atrophy but no neurological deficits. moderate cases presented dlss compatible clinical signs in combination with neurological deficits such as reduced flexor withdrawal, proprioceptive deficits and nerve root signature. severe cases demonstrated dlss compatible clinical signs with more severe neurological deficits such as tail paresis and absent perineal reflex. clinical outcomes were considered complete if clinical signs had resolved at follow-up consultations, partial if there was substantial but incomplete improvement in clinical signs and failed if the dog did not improve or deteriorated further. improvements in patient condition were measured in terms of clinical outcome grading which is in relation to the initial clinical severity group assigned to each dog. improvement after single dose of esi was seen in 27/32 dogs, with 17/22 (after accounting for four dogs whose owners have refused further treatment, five dogs lost to follow-up after re-check as well as one dog whose owners have opted for repeated esi instillations) relapsing within 6 months. all 17 of these dogs that suffered a relapse after single esi subsequently underwent surgical treatment and demonstrated improvement in clinical signs, with a complete response seen in eight dogs and a partial response seen in nine dogs. in the study comparing clinical outcome of conservative treatment of exercise restriction with phenylbutazone administration and surgical treatment of degenerative lumbosacral stenosis, outcomes were classified as good in dogs that regained preoperative activity levels; acceptable in dogs with persistent abnormality or requiring continued medication though otherwise active, and poor in all other cases. out of 16 dogs treated surgically, 11 were treated by dorsal lumbosacral laminectomy and excision of the dorsal portion of the lumbosacral disc, while the other five had additional unilateral facetectomy to decompress the seventh lumbar nerve. out of the 11 dogs treated with dorsal lumbosacral laminectomy and excision of the dorsal portion of the lumbosacral disc, 6/11 (54.5%) of dogs were deemed to have a good outcome, while 3/11 (27.3%) of dogs were deemed to have an acceptable outcome. out of the five dogs treated with dorsal lumbosacral laminectomy and excision of the dorsal portion of the lumbosacral disc with additional unilateral facetectomy, 3/5 (60%) of dogs were deemed to have an acceptable outcome. the outcome of conservative treatment was deemed good in 8/16 (50%) of dogs in the conservative treatment group. conclusion there is evidence suggesting that both nonsurgical and surgical treatments can improve clinical outcomes and reduce lower back pain and neurological deficits. however, based on the current limited literature, it cannot be ascertained whether surgical treatments are more effective than nonsurgical treatments in improving long-term clinical outcomes and vice versa. in the study that tested the efficacy of epidural steroid injection, only a single dose of steroids was given in this study, making it a potential reason for the high rate of relapse following nonsurgical treatment. for surgical treatment of dlss, the type of surgical procedure chosen would also depend on the part of the lumbosacral region which fails and leads to compression. in conclusion, randomised controlled trials that compare different forms of nonsurgical treatment with surgical treatment for dogs with dlss caused by different underlying factors need to be conducted to properly address the pico question. how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. the evidence only two studies compared the outcome after nonsurgical and surgical treatment and was thus included in this knowledge summary. several studies have elaborated on the efficacy of surgical procedures such as dorsal laminectomies, however, a lack of controlled studies prohibits direct comparison between those that receive nonsurgical treatment and surgical treatment. among the studies which have surfaced through the literature search but do not address the pico question, were those which evaluated the success of solely surgical treatment of degenerative lumbosacral stenosis (dlss). most papers focused on cauda equina syndrome only or were review papers on dlss pathogenesis, diagnosis, and management, with little focus on the treatment aspect of dlss. the studies which directly answered the pico question were prospective and retrospective studies, which rank low in the evidence hierarchy. summary of the evidence gomes et al. (2020) population: dogs presented to the neurology service at a single referral hospital between february 2017 and may 2019, with clinical signs compatible with degenerative lumbosacral stenosis (dlss) were recruited. inclusion criteria: clinical confirmation of dlss through compatible clinical signs. magnetic resonance imaging (mri) evidence of intervertebral foraminal stenosis with identification of l7 nerve root enlargement and / or lumbosacral vertebral canal stenosi. exclusion criteria: dogs presenting with concomitant relevant orthopaedic, neoplastic, inflammatory, developmental conditions or evidence of l7-s1 intervertebral disc extrusion. dogs that were recruited were classified into clinical severity groups. mild cases demonstrated dlss compatible clinical signs such as lumbosacral pain, reluctance to climb stairs / jump / raise up, lameness and muscle atrophy but no neurological deficits. moderate cases presented dlss compatible clinical signs in combination with neurological deficits such as reduced flexor withdrawal, proprioceptive deficits and nerve root signature. severe cases demonstrated dlss compatible clinical signs with more severe neurological deficits such as tail paresis and absent perineal reflex. sample size: 41 dogs. intervention details: 41 dogs underwent an epidural steroid injection (esi) of methylprednisolone acetate (depo-medrone 40 mg/ml, pfizer) into the lumbosacral epidural space, following a protocol of 1 mg/kg with a minimal volume of 0.5 ml. nine dogs were lost to follow-up. surgical decompression was performed in 17 out of the remaining 32 dogs following a minimum period of 2 weeks following esi, when unsuccessful or after relapse of clinical signs. study design: prospective study. outcome studied: clinical outcome as assessed by a board-certified neurologist on follow-up consultations. outcomes were based on the extent of resolution of presenting clinical signs, which include the following categories: complete: clinical signs resolved. partial: if there was substantial but incomplete improvement of clinical signs. failed: dog did not improve or deteriorated further. owner inferred outcome based on pain, mobility and quality of life scores obtained through questionnaires. main findings (relevant to pico question): improvement after esi was seen in 27/32 dogs, with 14 dogs showing partial response and 13 dogs showing complete response. all five dogs which had no clinical response to esi had subsequent decompressive surgery. out of 14 dogs with partial response, nine relapsed, with seven having surgical decompression. out of the 13 dogs with complete response to esi, eight relapsed, with five having subsequent surgical decompression. five dogs showed persistent improvement without relapse following esi. a total of 17 dogs underwent decompressive surgery, with surgery showing a trend towards reduced pain, increased mobility, and greater quality of life score in all dogs. complete response was seen in eight dogs and partial response in nine dogs. limitations: outcomes of dogs (complete, partial, failed) were determined by the neurologists, but information regarding the specific clinical signs displayed by each dog was not available. clinical outcome information relied on the expertise of the same people that performed the procedures, potentiating clinician bias. owner perceived outcome is inherently subjective, prone to caregiver placebo effect that may be impacted by the relative cost of esi versus surgical decompression. utilisation of a subjective numeric grading for owners perceived outcome was not based on a previously validated method.   ness (1994) population: dogs presented to the author between 1987 and 1992, which are diagnosed with degenerative lumbosacral stenosis (dlss). inclusion criteria: diagnosis of dlss based on history of low back pain for 3 weeks or longer, with or without a neurological deficit. history supported by evidence obtained from radiography and myelography. low back pain was detected by pressing over the dorsum at lumbosacral level or by applying lordosis test. exclusion criteria: dogs that presented with lumbosacral disorders which was not caused by degenerative lumbosacral stenosis. sample size: 30 dogs. intervention details: 16 dogs underwent conservative treatment, with a standard protocol of exercise restriction for 8–10 weeks and administration of phenylbutazone as required at a dose not exceeding 7.5 mg/kg twice daily for up to 6 weeks. 16 dogs (inclusive of four dogs originally under conservative treatment group which failed conservative treatment) underwent surgical treatment of dorsal laminectomy. excision of dorsal annulus and fenestration of the lumbosacral disc were performed. unilateral facetectomy was conducted to decompress the seventh lumbar nerve in five dogs which showed marked neurological signs with lateralisation. two dogs were withdrawn from the study as owners were not ready to begin treatment. study design: retrospective study. outcome studied: clinical outcome was assessed based on the alleviation of pain and the resolution of neurological defects. surgical treatment outcome was considered: good in dogs which regained preoperative activity levels (as assessed by owner). acceptable in dogs with a persistent abnormality or requiring continued medication though otherwise active. poor in all other cases. main findings (relevant to pico question): surgical treatment was successful in alleviating pain in 13/16 (81%) dogs, usually within 6 weeks of the operation. neurological defects responded more slowly to surgery, with time taken to best recovery varying from 8–30 weeks. out of 16 dogs treated surgically, 11 were treated by dorsal lumbosacral laminectomy and excision of the dorsal portion of the lumbosacral disc, while the other five had additional unilateral facetectomy to decompress the seventh lumbar nerve. out of these 11 dogs who were treated by dorsal lumbosacral laminectomy and excision of the dorsal portion of the lumbosacral disc, 6/11 (54.5%) of dogs were deemed to have a good outcome, while 3/11 (27.3%) of dogs were deemed to have an acceptable outcome, 1/11 (9.1%) of dogs were deemed to have poor outcome, while 1/11 (9.1%) of dogs were lost to follow-up. out of the five dogs who were treated by dorsal lumbosacral laminectomy and excision of the dorsal portion of the lumbosacral disc with additional unilateral facetectomy, 3/5 (60%) of dogs were deemed to have an acceptable outcome, 1/5 (20%) of dogs were deemed to have poor outcome, while 1/5 (20%) of dogs were lost to follow-up. conservative management was considered good in 8/16 (50%) dogs. limitations: there was no information provided on the initial clinical signs presented by each individual dog. no standardised method of assessing the post-surgical and post-conservative treatment outcome, leading to difficulties in comparison. no standardised review time, all dogs having different healing periods but no comparison of how the clinical status of the dogs at fixed periods after the treatment. owner perceived outcome is inherently subjective, prone to caregiver placebo effect.   appraisal, application and reflection canine degenerative lumbosacral stenosis (dlss) represents a syndrome in dogs that comprises of lumbosacral pain as well as neurological dysfunction in some cases. this syndrome is related to the degeneration and subsequent enlargement of the soft tissue structures of the lumbosacral junction as well as compression of the cauda equina (worth et al., 2019). it is a common disorder which is multifactorial in origin, with intervertebral disc degeneration (ivd) being a major contributor (meij & bergknut, 2010). in particular, intervertebral disc protrusion caused by fibroid metaplasia as well as the development of small separations in the lamellae of the annulus fibrosus has been identified as a contributing factor to dlss. the process of fibroid metaplasia refers to the increased collagen content and change in the notochordal cells to become more fibrocyte-like, coupled with the decreased integrity of the lamellae of the annulus fibrosus. this leads to extension of degenerative fibroid nuclear material into and between the fibres of the annulus. eventually, the surface of the annulus fibrosus gradually thickens and protrudes, displacing the dorsal longitudinal ligament and gradually compressing the nerve roots (fenn et al., 2020). possible causes of lumbosacral disease include cauda equina compression which can occur from lateral disc protrusion which compresses the sciatic nerve at the foramen level. other causes also include synovial cysts as well as dynamic compression in lumbosacral dorsi-flexion but otherwise minimal compression in neutral position. compression could be categorised as dynamic when instability and thus motion of the vertebral segments results in variation in severity of compression from moment to moment depending on the position of the vertebrae at a specific point in time (jeffery et al., 2013). the spinal nerves originating from the lumbosacral section of the vertebral column stretches to the hips, stifle, tarsus, urinary bladder as well as anal and urinary sphincters, in order from l4 to s3. neurological findings associated with degeneration at l4-s1 often presents as femoral pseudo-hyperreflexia, muscle atrophy and potentially decreased reflexes due to impingement of the femoral and sciatic nerves. the proposed pathogenesis for canine dlss involves disc degeneration resulting in ventral subluxation of the sacrum as well as thickening of the articular processes, which results in structural failure of the disc (meij & bergknut, 2010). in response to the proposed disease pathogenesis, current surgical treatments such as dorsal laminectomies are conducted to relieve pressure on the cauda equina and foraminotomies are performed with the aim of decompressing the sciatic nerve and releasing nerve roots which are entrapped. the type of surgery indicated would depend on the direction of protrusion, with dorsal laminectomies being indicated for dorsal ventral disc protrusion and foraminotomies being indicated for foraminal protrusions. presence of ventral subluxation of s1, which refers to the s1 disc being more ventrally displaced as compared to neighbouring vertebrae, as well as dynamic compression, often indicates the need for fixation and fusion stabilisation to reduce the abnormal mobility of the vertebrae which was identified as instability. it has been speculated that cell-mediated inflammatory responses occur upon disc damage, which results in ingrowth of blood vessels and nerves into the damaged disc, exacerbating lumbosacral pain. nonsurgical treatments for dlss work to mediate the inflammatory responses that occur during disc damage, often using nonsteroidal anti-inflammatory drugs (nsaids), a change in exercise pattern as well as reduction in body weight. in more recent times, lumbosacral epidural injections of corticosteroids have been reported to be effective in improving symptoms for dogs with dlss. only two studies out of the many focusing on treatment of dlss compared the efficacy of nonsurgical treatment compared to surgical treatment. in the first study, gomes et al. (2020) evaluated the efficacy of epidural steroid injection (esi) of methylprednisolone acetate. out of 32 dogs that received the esi, only five experienced persistent improvement without relapse, while 17 dogs ultimately underwent decompressive surgery. in this study, epidural steroid injection appears to only be successful in the long-term in a small number of dogs. in the second study, ness (1994) evaluated the clinical outcomes of 16 dogs being treated surgically against 16 dogs treated under conservative treatment. in this study, surgical treatment was successful in alleviating pain in 13/16 81.3% of dogs, while conservative treatment was considered good in 8/16 (50%) of dogs. while this study attempted to compare clinical outcomes of surgically and conservatively treated dogs with dlss, the outcome measures are not standardised, and it was not mentioned clearly what ‘good’ referred to in the dogs being conservatively treated. it is to be noted that the author conducted a facetectomy in five surgically treated cases, a technique which carries risks of exacerbating existing instabilities (bebchuk, 2017). with regards to papers published focusing on the clinical outcomes of dogs treated using surgical treatment only, hankin et al. (2012) evaluated dogs with dlss that had undergone transarticular facet screw stabilisation and dorsal laminectomy for long-term outcome through a retrospective study. follow-up radiographs of the surgical site showed evidence of bone healing and stabilisation of the distracted lumbosacral intervertebral disc (ivd) space in all 15 dogs available for long-term follow-up. 11/13 (84.6%) owner questionnaires returned also demonstrated that the dog had regained normal ability to run and jump without perceptible lameness, signaling that the surgical procedure was highly successful. gomes et al. (2018) evaluated the long-term outcome of dogs with dlss that have undergone lateral foraminotomy through a retrospective study and 33/34 (97.1%) of the cases showed a long-term complete resolution of clinical signs. golini et al. (2012) performed a retrospective study on dogs with dlss which had undergone dorsal laminectomy and transarticular fixation of the facet joints using screws instead of pins. clinical outcome improved in 13/17 (76.5%) dogs. as compared to a study conducted by hankin et al. (2012) which involved the same surgical procedure with a success rate of 23/26 (88.5%) in terms of improvement in clinical outcome, success rate appears to be lower at 13/17 (76.5%). despite the slight differences in success rates, transarticular facet screw stabilisation and dorsal laminectomy appears to be mostly effective in improving clinical outcome long-term in dogs with dlss. danielsson & sjöström (1999) monitored the long-term outcome of dogs with dlss that had undergone dorsal laminectomy and dorsal fenestration, with 122/131 (93.1%) of the dogs showing improvement clinically within the follow-up period. with regards to papers published focusing on the clinical outcomes of dogs treated using nonsurgical treatment only, de decker et al. (2014) evaluated the difference in clinical outcome for dogs treated nonsurgically through restricted exercise in combination with anti-inflammatory and analgesic drugs for dlss. it was found that 17/21 dogs on medical management had obvious improvement or resolution of clinical signs, which makes up 81%. based on this study, it appears that conservative treatment has reasonable success in resolving lower back pain and neurological deficits in the long-term. in a case report by mrkovaĉki et al. (2021), a dog diagnosed with dlss was injected with cultured autologous adipose tissue-derived mesenchymal stem cells (at-mscs) bilaterally at the level of l7-s1. clinical outcome 60 days post at-msc treatment was positive, with absence of pain upon l7-s1 region palpation and negative lordosis test. movement was also normal without stiffness of the hindlimbs, with preservation of all neurologic reflexes. however, due to the small sample size (n = 1), there is a need for further studies to be conducted on this treatment method to gather more meaningful data for widespread clinical use. in conclusion, while it appears that surgical treatment does resolve lumbosacral pain and neurological dysfunction in the long-term in a proportion of dogs with dlss, it is important to note that there is a serious lack of studies conducted on dogs diagnosed with dlss who have undergone nonsurgical treatment, although this is a very common form of treatment in dogs diagnosed with dlss today. it is generally understood that dogs with severe dlss tend to have higher rates of improvement with surgical treatment, though a standardised grading system for dlss according to clinical signs as well as pathogenesis would be helpful in streamlining dogs for further studies. investigations into how the underlying pathogenesis of dlss correlates with the success rate in surgical and / or nonsurgical treatment would greatly benefit from a dlss grading system. for surgical treatments, it is pertinent for the specific part of lumbosacral failure to be identified in dogs admitted to the sample population so that future evaluation of the efficacy of surgical treatments can be more targeted and allow for more informed decision-making in clinical practice. there should also be the establishment of a standardised pet owner questionnaire to be used across all dlss studies regarding the post-treatment condition of their dog. with these tools made available, more randomised control studies then need to be carried out. while considering the best type of treatment for long-term resolution of dlss, it is crucial to appreciate that lumbosacral disease waxes and wanes. in the case of severe uncontrollable pain, surgery is indicated with the purpose of controlling the pain using the shortest time possible, though it does sometimes resolve the signs of lumbosacral disease in the long-term. due to the current lack of reliable and strong evidence for the long-term outcome for dogs with dlss that had undergone surgical and nonsurgical treatment of dlss respectively, it cannot be confidently ascertained that surgical treatment is more effective than nonsurgical treatment in reducing lower back pain and neurological dysfunction in the long-term. methodology search strategy databases searched and dates covered: cab abstracts via web of science platform 1973–week 11 2023 medline via ovid 1946–mar 16 2023 search strategy: cab abstracts: (canine or dog or dogs or canines) and (dlss or degenerative lumbosacral stenosis or degenerative lumbosacral disease) and (surgical treatment or surgical decompression or dorsal laminectomy or foraminotomy) and (non-surgical treatment or medical treatment or conservative treatment or epidural steroid injection) and (lumbosacral pain or neurological dysfunction or neurological signs) medline via ovid: (canine or dog or dogs or canines) and (degenerative lumbosacral stenosis or dlss or degenerative lumbosacral disease) and (treatment or management) dates searches performed: 16 mar 2023   exclusion / inclusion criteria exclusion: papers inappropriate to the pico (non-related title and abstract; other species; papers unable to demonstrate long-term post-treatment outcome), papers not accessible. inclusion: papers identifying the long-term outcomes following surgical and medical / nonsurgical treatment of canine degenerative lumbosacral disease.   search outcome database number of results excluded – not in english language excluded – non-relevant to pico excluded – unable to access total relevant papers cab abstracts 7 0 4 1 2 medline 35 0 34 0 1 total relevant papers when duplicates removed 2   orcid kristy goh rui qi: https://orcid.org/0000-0003-3938-8543 conflict of interest the author declares no conflicts of interest. references bebchuk, t. (2017). lumbosacral decompression and foraminotomy. current techniques in canine and feline neurosurgery. 223–233. doi: https://doi.org/10.1002/9781118711545.ch26 danielsson, f. & sjöström, l. (1999). surgical treatment of degenerative lumbosacral stenosis in dogs. veterinary surgery. 28(2), 91–98. doi: https://doi.org/10.1053/jvet.1999.0091 de decker, s., wawrzenski, l. & volk, h. (2014). clinical signs and outcome of dogs treated medically for degenerative lumbosacral stenosis: 98 cases (2004–2012). journal of the american veterinary medical association. 245(4), 408–413. doi: https://doi.org/10.2460/javma.245.4.408 fenn, j., olby, n. & the canine spinal cord injury consortium (cansort-sci). (2020). classification of intervertebral disc disease. frontiers in veterinary science. 7, 579025. doi: https://doi.org/10.3389/fvets.2020.579025 golini, l., kircher, p.r., lewis, f.i. & steffen, f. (2012). transarticular fixation with cortical screws combined with dorsal laminectomy and partial discectomy as surgical treatment of degenerative lumbosacral stenosis in 17 dogs: clinical and computed tomography follow-up. veterinary surgery. 43(4), 405–413. doi: https://doi.org/10.1111/j.1532-950x.2014.12117.x gomes, s. a., lowrie, m. & targett, m. (2018). long-term outcome following lateral foraminotomy as treatment for canine degenerative lumbosacral stenosis. veterinary record. 183(11), 352–352. doi: https://doi.org/10.1136/vr.104741 gomes, s. a., lowrie, m. & targett, m. (2020). single dose epidural methylprednisolone as a treatment and predictor of outcome following subsequent decompressive surgery in degenerative lumbosacral stenosis with foraminal stenosis. the veterinary journal. 257, 105451–105451. doi: https://doi.org/10.1016/j.tvjl.2020.105451 hankin, e., jerram, r., walker, a., king, m. & warman, c. (2012). transarticular facet screw stabilization and dorsal laminectomy in 26 dogs with degenerative lumbosacral stenosis with instability. veterinary surgery. 41(5), 611–619. doi: https://doi.org/10.1111/j.1532-950x.2012.01002.x jeffery, n., levine, j., olby, n. & stein, v. (2013). intervertebral disk degeneration in dogs: consequences, diagnosis, treatment, and future directions. journal of veterinary internal medicine. 27(6), 1318–1333. doi: https://doi.org/10.1111/jvim.12183 meij, b.p. & bergknut, n. (2010). degenerative lumbosacral stenosis in dogs. the veterinary clinics of north america: small animal practice. 40(5), 983–1009. doi: https://doi.org/10.1016/j.cvsm.2010.05.006 mrkovaĉki, j., srzentić dražilov, s., spasovski, v., fazlagić, a., pavlović, s. & nikĉević, g. (2021). case report: successful therapy of spontaneously occurring canine degenerative lumbosacral stenosis using autologous adipose tissue-derived mesenchymal stem cells. frontiers in veterinary science. 8, 732073. doi: https://doi.org/10.3389/fvets.2021.732073 ness, m.g. (1994). degenerative lumbosacral stenosis in the dog: a review of 30 cases. journal of small animal practice. 35(4), 185–190. doi: https://doi.org/10.1111/j.1748-5827.1994.tb01683.x worth, a., meij, b. & jeffery, n. (2019). canine degenerative lumbosacral stenosis: prevalence, impact and management strategies. veterinary medicine (auckland). 10, 169–183. doi: https://doi.org/10.2147/vmrr.s180448 contribute to the evidence there are two main ways you can contribute to the evidence base while also enhancing your cpd: tell us your information need write a knowledge summary either way, you will be helping to add to the evidence base, and strengthen the decisions that veterinary professionals around the world make to give animals the best possible care. learn more here: https://veterinaryevidence.org/index.php/ve/guidelines-for-authors licence copyright (c) 2023 kristy goh rui qi intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use.   veterinary evidence is an rcvs knowledge initiative. issn: 2396-9776 first floor, 10 queen street place, london ec4r 1be resources student awards staff login policies privacy policy accessing information policy cookie declaration terms of use copyright notices stay connected podcasts twitter facebook instagram linkedin back to top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443. in dogs undergoing extrahepatic portosystemic shunt attenuation, does pretreatment with levetiracetam reduce postoperative seizure incidence? a knowledge summary by connor hawes bvetmed (hons) mrcvs 1* kali lazzerini dvm drmedvet msc dipecvn mrcvs 1 1bristol veterinary school, university of bristol, langford house, langford, bristol, bs40 5du *corresponding author (chawes2@rvc.ac.uk) vol 7, issue 3 (2022) published: 17 aug 2022 reviewed by: simon platt (dvm bvm&s mrcvs dacvim [neurology] decvn) and fabio stabile (dvm mrcvs phd dipecvn) next review date: 12 jan 2024 doi: 10.18849/ve.v7i3.581 pico question in dogs undergoing surgical attenuation of a congenital extrahepatic portosystemic shunt, does pretreatment with levetiracetam reduce the incidence of post attenuation seizures?   clinical bottom line category of research question treatment the number and type of study designs reviewed four papers were critically reviewed. all were retrospective cohort studies strength of evidence moderate outcomes reported in one paper levetiracetam was found to reduce the risk of post-attenuation seizures. in the remaining three papers no difference was found between the frequency of post-attenuation seizures and the use of levetiracetam conclusion that prophylactic levetiracetam is not indicated for the use of preventing post-attenuation seizures in dogs surgically treated for extrahepatic portosystemic shunts   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a 6 month old yorkshire terrier diagnosed with a single congenital portosystemic shunt has surgical attenuation with an ameroid constrictor following medical management with lactulose, amoxicillin and a hydrolysed diet. the dog develops post-attenuation seizures 24 hours after surgery, despite no prior history of seizures. would the administration of levetiracetam, an anti-epileptic drug, prior to attenuation reduce the risk of post-attenuation seizures? the evidence four retrospective cohort studies were found relevant to the pico (fryer et al., 2011; mullins et al., 2018; otomo et al., 2020; and strickland et al., 2018). all studies compared the frequency of post-attenuation seizures in patients treated with or without prophylactic levetiracetam. prior medical treatment, surgical technique, anaesthetic, frequency of preoperative neurological signs and levetiracetam protocols varied between and within studies, which all may have influenced seizure frequency.  fryer et al. (2011) was the only study to find a clinical benefit to prophylactic levetiracetam, the other three studies found no benefit (mullins et al., 2018; otomo et al., 2020; and strickland et al., 2018). the frequency of post-attenuation seizures were low in all studies. currently the evidence does not support the use of levetiracetam, although a prospective controlled study with standardised treatment protocol would be required. summary of the evidence otomo et al. (2020) population: dogs with single extrahepatic portosystemic shunts underwent gradual attenuation with a thin film band (tfb) or ameroid ring constrictor (arc) at two institutes between 2004–2017. criteria for exclusion: intrahepatic portosystemic shunt (ihpss), multiple shunts. sample size: 123 dogs. intervention details: 85 dogs were treated with a tfb. 64/85 (75%) received prophylactic levetiracetam. 38 dogs were treated with an arc. 15/38 (40%) received prophylactic levetiracetam. surgical technique was based on surgeon’s preference. no standardised preor postoperative treatment. no information on the decision to give levetiracetam was reported. study design: retrospective cohort. outcome studied: short term <30 days and long term >6 months outcome were studied.  cases were categorised as successful or unsuccessful. successful – no longer have clinical signs or require medication. unsuccessful – still on medication, have clinical signs or died. main findings (relevant to pico question): 10/123 (8%) dogs had postoperative seizures at <30 days, 9/10 (90%) of which died. levetiracetam was not shown to reduce the risk of seizures. 7/79 (9%) dogs treated with levetiracetam and 3/44 (7%) without levetiracetam had seizures p >0.99. there was no statistical difference in the number of dogs with postoperative seizures and the presence or absence of preoperative neurological signs p = 0.19, or surgical technique used p = 0.17. limitations: retrospective study. only two institutions. post-attenuation seizures were defined as occurring <30 days post operation and may include other causes of seizures. non-randomised treatment groups – dogs thought to be higher risk of seizures may have been treated with levetiracetam. no record of levetiracetam protocol. no grading of severity of preoperative neurological signs. non-standardised medical treatment or anaesthetic protocol. mullins et al. (2018) population: all dogs treated surgically, either with suture ligation, thin film banding (tfb), or an ameroid ring constrictor (arc)i for a single extrahepatic portosystemic shunt at 10 different institutes between 2005–2017. exclusions: intrahepatic portosystemic shunt (ihpss), multiple shunts, 24 hour postoperative death not related to seizures, previous anti-epileptic drugs. sample size: 940 dogs. intervention details: 523 control dogs received no anti-seizure prophylaxis. dogs were divided into two treatment groups lev1 and lev2. lev1 consisted of 188 dogs which received levetiracetam at a dose of ≥15 mg/kg every 8 hours for ≥24 hours preoperatively or a 60 mg/kg intravenous loading dose peri-operatively, with continuation postoperatively at a dose of ≥15 mg/kg every 8 hours. lev2 consisted of 229 dogs which received levetiracetam at a dose of <15 mg/kg every 8 hours, for <24 hours preoperatively, or continued at <15 mg/kg every 8 hours postoperatively. treatment groups were non-randomised and decided by the clinician. other treatments were not standardised. study design: retrospective cohort. outcome studied: focal or generalised seizures at less than or equal to 7 days postoperative, dogs which developed seizures at greater than 7 days were not classified as having post-attenuation seizures. main findings (relevant to pico question): 75/523 (8%) dogs had postoperative seizures, 35/523 (7%) control dogs, 21/188 (11%) lev1 dogs, 19/229 (8%) lev2 dogs. there was no statistical difference between the frequency of seizures and treatment group p = 0.14. there was no significant difference between signalment, treatment or previous seizure history and the presence of postoperative seizures. all postoperative seizure dogs were still on levetiracetam at the time of seizure. limitations: treatment groups were not randomised. retrospective study. no grading of severity of preoperative neurological signs. non-standardised medical treatment or anaesthetic protocol. strickland et al. (2018) population: all dogs that underwent surgical attenuation for a single intra or extrahepatic congenital portosystemic shunt at a single centre between 2000–2015. sample size: 253 dogs. intervention details: 148 dogs received partial attenuation, 105 complete attenuation. the decision to attenuate partially was based on perioperative portal pressure and visual assessment of the pancreas and intestinal tract. 12/148 (8%) dogs which received partial attenuation were with a cellophane band, and the remaining with suture ligation. 54 dogs received prophylactic levetiracetam at a dose of 20 mg/kg orally every 8 hours for a minimum of 24 hours preoperative and 5 days postoperative. prophylactic levetiracetam was started in patients from 2012 onwards. 238 dogs received preoperative medical treatment. study design: retrospective cohort. outcome studied: survival to discharge. presence of post-attenuation neurological signs (pans) up to discharge graded on severity from 1–3. changes to albumin osmolality, urea, glucose and electrolyte pre and postoperatively. main findings (relevant to pico question): 3/54 (6%) dogs receiving levetiracetam had seizures, 9/199 (5%) dogs not receiving levetiracetam had seizures. risk of postoperative seizures was not associated with prophylactic levetiracetam use p = 0.75. of the five dogs with seizures and did not survive to discharge, none received levetiracetam. limitations: non-randomised treatment groups. retrospective data. non-standardised treatment protocol. dogs only received levetiracetam after 2012 and other factors may have also changed at this time influencing seizure frequency. fryer et al. (2011) population: all dogs which received an ameroid ring constrictor (arc) for a single congenital extrahepatic portosystemic shunt at a single institution between 2003–2010. exclusion criteria: previous treatment with anti-epileptic drugs. sample size: 126 dogs. intervention details: all dogs received an arc. 42 dogs received prophylactic levetiracetam at a median dose of 60 mg/kg/day for a median duration of 6.5 days preoperative to 33 days postoperative. all dogs that received levetiracetam were recruited after 2007. 84 dogs received no anti-epileptic drugs. study design: retrospective cohort. outcome studied: presence, number, type, timing and treatment response of post-attenuation seizures as recorded on hospital documents for a minimum of 48 hours. main findings (relevant to pico question): four dogs (3%) developed post-attenuation seizures, none of which received prophylactic levetiracetam. there was no significant difference in the frequency of preoperative neurological signs or seizures between the levetiracetam treated and non-treated dogs. levetiracetam was found to significantly reduce the risk of seizures. risk <1, p = 0.0002. limitations: retrospective study. only a single institution. inconsistent dose and duration of levetiracetam. no dogs received levetiracetam prior to 2007, and other changes to the management of cases may have influenced seizure frequency. no grading of severity of preoperative neurological signs. low seizure frequency, low power to study. preoperative medical management is not described. appraisal, application and reflection following attenuation of a portosystemic shunt approximately 5–18% will experience post-attenuation seizures as a complication (gommeren et al., 2010; hardie et al., 1990; and tisdall et al., 2000). these seizures typically occur within 72 hours of attenuation, are refractory to treatment and are associated with a high mortality (gommeren et al., 2010). the pathophysiology of this condition is poorly understood and may be associated with a reduction in endogenous benzodiazepines, alongside postoperative metabolic events (hardie et al., 1990; and matushek et al., 1990), and may represent a number of aetiologies. reported risk factors for post-attenuation seizures include: increased age (hardie et al., 1990; matushek et al., 1990; strickland et al., 2018; and tisdall et al., 2000), porto-azygos shunts (tisdall et al., 2000), pre-existing signs of hepatic encephalopathy (strickland et al., 2018), and increase serum osmolality (strickland et al., 2018). because of the lack of predictive factors or effective treatment there is a growing interest in developing preventative measures for post-attenuation seizures. one such treatment is the anti-epileptic drug levetiracetam, used for the treatment of status epilepticus, focal and generalised seizures, as well as not being contraindicated in hepatic dysfunction (packer et al., 2015). fryer et al. (2011) was the first paper to explore the use of prophylactic levetiracetam, and the only study suggesting a benefit. no patients treated with levetiracetam had post-attenuation seizures, whereas 4/84 4.8% of patients not treated did. despite the promising results the further three papers reviewed showed no benefit to levetiracetam (mullins et al., 2018; otomo et al., 2020; and strickland et al., 2018). mullins et al. (2018) and strickland et al. (2018) also had substantially larger samples sizes and seizure frequencies compared to fryer et al. (2011). based on this it can be concluded that prophylactic levetiracetam does not reduce the risk of post-attenuation seizures. strickland et al. (2018) did suggest that the use of prophylactic levetiracetam did reduce the mortality associated with post-attenuation seizures, although frequency of seizures and number of patients on levetiracetam were low. the major limitation in all studies were other factors potentially contributing to post-attenuation seizures, and being able to determine if the seizures were secondary to other factors. no study was consistent in the use of anaesthetic protocol, surgical technique, and use of preoperative medication, all of which may contribute to seizure frequency. the use of levetiracetam was also not consistent, with varied protocols, which may alter its efficacy. lastly the presence of preoperative neurological signs and seizures varied largely between studies ranging from 64/123 (52%) (otomo et al., 2020), 85/125 (68%) (fryer et al., 2011), 61/75 (81%) (mullins et al., 2018), and 253/253 (100%) (strickland et al., 2018). strickland et al. (2018) was the only study to try and grade preoperative neurological signs, although did not appear to consider grade in their analysis. the presence of preoperative hepatic encephalopathy is considered a risk factor for post-attenuation seizures (strickland et al., 2018), and severity of preoperative neurological signs may be an important source of bias not considered in all of these studies. in conclusion the evidence does not support the use of prophylactic levetiracetam in reducing post-attenuation seizures, levetiracetam may be useful in reducing mortality associated with this condition although further studies would be required to conclude this. methodology section search strategy databases searched and dates covered: cab abstracts on the ovid interface, 1973–2022 week 01 pubmed on the ncbi interface. 1920–january 2022 search strategy: cab abstracts: (dog or dogs or canine or canines).mp. or exp dogs/  (congenital or primary).mp.  (portosystemic or portasystemic or porto-systemic or portasystemic or shunt* or pss or cpss or cehpss or extrahepatic or extra-hepatic).mp.  (levetiracetam or antiseizure or antiepileptic or anticonvulsant or anti-seizure or anti-epileptic or anti-convulsant).mp.  1 and 2 and 3 and 4 pubmed: #1 dog or canine  #2 congenital or primary  #3 portosystemic or portasystemic or porto-systemic or porta-systemic or shunt or pss or cpss or cehpss or extrahepatic or extra-hepatic  #4 levetiracetam or antiseizure or antiepileptic or anticonvulsant or anti-seizure or anti-epileptic or anti-convulsant  #5 #1 and #2 and #3 and #4 dates searches performed: 12 jan 2022 exclusion / inclusion criteria exclusion: not related to pico. review paper. book chapter. foreign language. inclusion: research papers including the use of levetiracetam in the prevention of post-attenuation seizures even if not the primary aim. search outcome database number of results excluded – not related to pico total relevant papers cab abstracts 7 3 4 pubmed 10 6 4 total relevant papers when duplicates removed 4 conflict of interest the authors declare no conflicts of interest. references fryer, k.j., levine, j.m., peycke, l.e., thompson, j.a. & cohen, n.d. (2011). incidence of postoperative seizures with and without levetiracetam pretreatment in dogs undergoing portosystemic shunt attenuation. journal of veterinary internal medicine. 25(6), 1379–1384. doi: https://doi.org/10.1111/j.1939-1676.2011.00819.x gommeren, k., claeys, s., de rooster, h., hamaide, a. & daminet, s. (2010). outcome from status epilepticus after portosystemic shunt attenuation in 3 dogs treated with propofol and phenobarbital. journal of veterinary emergency and critical care. 20(3), 346–351. doi: https://doi.org/10.1111/j.1476-4431.2010.00537.x hardie, e.m., kornegay, j.n. & cullen, j.m. (1990). status epilepticus after ligation of portosystemic shunts. veterinary surgery. 19(6), 412–417. doi: https://doi.org/10.1111/j.1532-950x.1990.tb01224.x matushek, k.j., bjorling, d. & mathews, k. (1990). generalized motor seizures after portosystemic shunt ligation in dogs: five cases (1981–1988). journal of the american veterinary medical association. 196(12), 2014–2017. mullins, r.a., sanchez villamil, c., de rooster, h., kummeling, a., white, r.n., thieman mankin, k.m., tivers, m.s., yool, d.a., anderson, d.m., pratschke, k.m., gordo, i., brissot, h., singh, a., olive, m., billet, j.p., selmic, l.e. & kirby, b.m. (2018). effect of prophylactic treatment with levetiracetam on the incidence of postattenuation seizures in dogs undergoing surgical management of single congenital extrahepatic portosystemic shunts. veterinary surgery. 48(2), 164–172. doi: https://doi.org/10.1111/vsu.13141 otomo, a., singh, a., jeong, j., dobberstein, r., lundhild, a., peter, e., brisson, b., oblak, m. & milovancev, m. (2020). longâ€�term clinical outcomes of dogs with single congenital extrahepatic portosystemic shunts attenuated with thin film banding or ameroid ring constrictors. veterinary surgery. 49(3) 436–444. doi: https://doi.org/10.1111/vsu.13384 packer, r., nye, g., porter, s.e. & volk, h.a. (2015). assessment into the usage of levetiracetam in a canine epilepsy clinic. bmc veterinary research. 11(1), 25. doi: https://doi.org/10.1186/s12917-015-0340-x strickland, r., tivers, m.s., adamantos, s.e., harcourt-brown, t.r., fowkes, r.c. & lipscomb, v.j. (2018). incidence and risk factors for neurological signs after attenuation of single congenital portosystemic shunts in 253 dogs. veterinary surgery. 47(6), 745–755. doi: https://doi.org/10.1111/vsu.12925 tisdall, p.l.c., hunt, g.b., youmans, k.r. & malik, r. (2000). neurological dysfunction in dogs following attenuation of congenital extrahepatic portosystemic shunts. journal of small animal practice. 41(12), 539–546. doi: https://doi.org/10.1111/j.1748-5827.2000.tb03150.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. immune-mediated polyarthritis in dogs: are corticosteroids the best bet? | veterinary evidence skip to main content knowledge summary immune-mediated polyarthritis in dogs: are corticosteroids the best bet? hannah walker, msc bsc1* 1 royal (dick) school of veterinary studies, university of edinburgh, bush estate, midlothian. eh25 9rg * corresponding author email: hannah3walker@gmail.com vol 8, issue 1 (2023) submitted 21 jan 2021; published: 25 jan 2023; next review: 01 sep 2024 doi: https://doi.org/10.18849/ve.v8i1.584 pico question in dogs with type i immune-mediated polyarthritis (impa), is sole treatment with other immunosuppressive agents as effective as treatment with corticosteroids at reducing clinical signs? clinical bottom line category of research treatment. number and type of study designs reviewed one pragmatic open-label randomised controlled clinical trial. strength of evidence weak. outcomes reported in the single randomised controlled clinical trial reviewed, 7/10 (70%) of dogs in both treatment groups (prednisone or cyclosporine), were reported to have shown resolution of owner-reported symptoms, clinical symptoms and improved locomotor scores and cytologic signs of disease at the end of the 90 day trial period. of the remaining dogs, 2/3 cyclosporine treated dogs required change to prednisone, and 2/3 prednisone treated dogs required combination therapy to achieve clinical response. conclusion there is insufficient evidence to support the use of alternative immunosuppressive agents in place of corticosteroids for the treatment of impa type i. further controlled clinical trials are needed before a change to clinical practice can be considered. how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario a dog presents to the clinic with severe bilateral front limb lameness, widespread joint pain and inflammation, pyrexia, inappetence and lethargy. clinical indications suggest the dog is likely experiencing idiopathic immune-mediated polyarthritis (impa type i). this speculation is confirmed through blood tests, x-rays, arthrocentesis, and cytological results. the patient has a history of iatrogenic cushing’s syndrome as a result of previous corticosteroid treatment. to avoid a recurrence of iatrogenic cushing’s, you wonder if any alternative immunosuppressive agents could provide as effective treatment for impa type i as prednisone. the evidence one relevant paper was found, describing a randomised controlled clinical trial comparing an alternative immunosuppressant to a corticosteroid for the treatment of impa type i. rhoades et al. (2016) compared the use of prednisone and cyclosporine in a population of 20 dogs with impa type i presenting to a californian veterinary hospital. the study had restricted selection criteria, pathologist blinding, randomisation of treatment allocation and multiple objective and subjective outcome measures. concurrent medication use was a potential confound. although rhoades et al. (2016) produced moderate evidence for an alternative immunosuppressant providing comparable treatment success to a corticosteroid, the power of this evidence was relatively weak and 2/10 (20%) of the cyclosporine group were ultimately switched to prednisone to achieve treatment success. therefore, additional randomised controlled clinical trials with larger sample sizes are required to validate immunosuppressants as an alternative to corticosteroids in clinical practice. summary of the evidence rhoades et al. (2016) population: dogs with type i (primary / idiopathic) immune-mediated polyarthritis. diagnosis of primary (type i) immune-mediated polyarthritis with no evidence of secondary causes. 10 males (nine neutered and one entire) and 10 spayed females. 12 dogs over 15 kg and eight dogs under 15 kg. five mixed breed dogs and 15 various pedigrees. ages of dogs were not reported. sample size: 20 client owned dogs. intervention details: prednisone group n=10. cyclosporine group n=10. dogs were randomly allocated into two groups: prednisone (starting at 1 mg/kg orally every 12 hours, tapered by 25% every 2–3 weeks). cyclosporine (5 mg/kg orally every 12 hours). allocation was determined by drawing cards from a hat: simple (unrestricted) randomisation is usually only recommended for studies with large sample sizes due to risk of covariates leading to allocation bias. however, no significant difference in any of the variables measured was found between the two groups (p = 0.54–1.0) at the beginning of the study period, suggesting that this form of randomisation may have been sufficient. clinical pathologists recording cytologic data were blinded to treatment group. clinicians and owners could not be blinded due to the different administration, tapering and monitoring protocols for each medication. authors attempted to reduce bias by ensuring only one clinician and owner provided reports for each dog. study design: pragmatic open-label randomised controlled clinical trial. outcome studied: data was collected at day 0 (pre-treatment), 14, 45, and 90. physical examination, survey data collection and cytologic analysis of multiple peripheral joint arthrocentesis samples were performed. an owner questionnaire provided data on: adverse effects: polydipsia, polyuria, panting, polyphagia, vomiting and diarrhoea (4-point likert scale). perceived comfort, gait and degrees of physical activity, lameness and lethargy (5-point likert scale). perceived quality of life (5-point likert scale). an overall mobility score was obtained by combining scores of owner-perceived comfort or gait and lameness. clinician assessment provided data on: variables including body weight, rectal temperature, hydration level, gait or lameness (5-point likert scale). signs of pain, grating, and swelling on 8 peripheral joints (carpi, tarsi, stifles, and elbows) (5-point likert scale). an overall locomotion score was calculated by combining gait and joint effusion scores and signs of joint pain. clinical pathologist assessment provided data on: total and differential cell counts from synovial fluid smears obtained through multiple arthrocentesis, including the carpi and tarsi, scored using a standard scoring system described by berg et al. (2009). in cases of impa, the carpus, stifle, and hock are the most commonly implicated joints and it is recommended that the carpi and tarsi are sampled as a minimum (jacques et al., 2002; and stull et al., 2008). bilateral paired joint sampling is suggested to increase diagnostic accuracy (stull et al., 2008). mean inflammation score and mean neutrophilic inflammation score across all joints (5-point likert scale). maximum neutrophilic inflammation score, obtained from the joint in the set with the highest neutrophilic inflammation (5-point likert scale). treatment was recorded as a failure if the dog had to be changed to a different medication due to either: lack of clinical improvement by day 14. lack of cytologic improvement by day 45. intolerable adverse effects. main findings (relevant to pico question): 7/10 (70%) of dogs in the prednisone-treated group were reported to have achieved successful treatment. of the three prednisone-treated dogs that did not achieve treatment success: two dogs showed lack of clinical improvement by day 14. one dog was switched to a combination therapy (prednisone and cyclosporine), though never achieved cytologic improvement. the other dog died (cause unknown).   one dog showed lack of cytologic improvement by day 45 and was successfully treated with a combination therapy (prednisone and azathioprine). by day 90, adverse effects was reported for nine dogs on prednisone treatment, including the two switched to combination therapy, but outcome data were only collected for the seven dogs on prednisone alone. 7/10 (70%) of dogs in the cyclosporine-treated group were also reported to have achieved successful treatment. of the three cyclosporine-treated dogs that did not achieve treatment success: one dog developed diarrhoea by day 5 of treatment and was switched to prednisone. prednisone treatment was successful. one dog showed lack of clinical improvement by day 14 and was switched to prednisone. prednisone treatment was successful. one dog showed lack of cytologic improvement by day 45. owner declined alternative immunosuppressant treatment, as clinical symptoms had been successfully resolved. cyclosporine was consequently tapered, but it is unclear whether this tapering occurred during or after the trial period. one dog developed an infection on day 75 and cyclosporine treatment was discontinued, having achieved an acceptable clinical response. this dog was still considered a treatment success. for both treatment groups, 7 of 10 dogs were reported to have shown a significant decrease from baseline in mean joint neutrophilic inflammation score by day 90. authors reported no significant difference in the change from baseline in mean inflammation score between the two treatment groups (p-value not stated). authors reported no significant difference in mean and maximum joint neutrophilic inflammation scores on day 14 (p = ≥ 0.81), day 45 (p = ≥ 0.49) and day 90 (p = ≥ 0.85). statistical significance was accepted when p = < 0.05. the authors used the wilcoxon-mann-whitney test to compare distributions of clinical, owner-perceived and cytological scores relative to baseline between groups at different time points. although the authors combined non-parametric tests with parametric by calculating standard deviation, non-parametric tests are often recommended for the analysis of scores obtained in medical trials due to their higher efficiency. limitations: very small sample size limits power of statistical results and validity of conclusions. the authors did not calculate minimum sample sizes required to achieve sufficient power. randomisation was conducted through the drawing of cards from a hat. this is a simple randomisation technique that does not account for confounding variables. the use of concurrent analgesics in the cyclosporine treatment group but not the prednisone group may have affected owner-reported and clinical results in the cyclosporine group. additionally, other medications such as antacids and antiemetics were not controlled or reported and this may have affected measures of adverse effects in both groups. researchers evaluating cytological improvement were blinded to the treatment, but clinicians and owners could not be blinded. this may have introduced data bias from clinician-reported and owner-reported signs and side-effects. there were limited correlations between owner-perceived mobility, clinician-assessed locomotion, and cytologic scores. this suggests that clinicians, owners, and pathologists were perceiving and reporting each dog’s improvement differently. a concurrent reliability study would clarify this lack of agreement. joint radiography was not performed on all patients. although radiographs are not always considered mandatory in the diagnosis of impa, radiographs allow for the exclusion of differential diagnoses (such as erosive immune-mediated polyarthritis, rheumatoid arthritis, polyarthritis-polymyositis syndrome and systemic lupus erythematosus) (bennett, 1987). therefore, it is plausible that differential conditions were actually the primary diagnosis for some individuals. standard deviation bars in the data concerning owner-perceived mobility do not overlap by day 90, suggesting a significant difference in owner-scored mobility between prednisone and cyclosporine-treated dogs at the end of the study period, with cyclosporine dogs showing potentially significantly worse mobility scores. however, this difference was not reported in the text. the authors omitted some information from the figures, including numbers of dogs from which the data was obtained. when numbers of dogs are reported graphically, this does not always correlate with information provided with the text. these gaps in data are not explained. the authors did not obtain longitudinal data, so were not able to assess rates of relapse between the two groups. as relapse is common in immune-mediated polyarthritis (bennett, 1987; clements et al., 2004) information on relapse rates would have been helpful. the study design does not conform to consort 2010 guidelines for an rct (schulz et al., 2010). the lack of methodological rigour in the study limits the power of conclusions drawn.   appraisal, application and reflection canine immune-mediated polyarthritis (impa) is a little understood condition (stull et al., 2008). symptoms include significant pain, lethargy, lameness, localised joint swelling, and pyrexia (itoh et al., 2010; jacques et al., 2002; and johnson & mackin, 2012). currently, corticosteroids are the primary treatment for type i impa (kohn, 2007; innes, 2012; and itoh et al., 2010). alternative immunosuppressants may also be used, often in combination with corticosteroids (colopy et al., 2010) or following corticosteroid treatment failure (bennett, 1987; itoh et al., 2010; and kohn, 2007). limited information exists on the efficacy of alternative immunosuppressants as standalone treatments. corticosteroid treatment can cause significant adverse effects (colopy et al., 2010; miller, 1992; perry, 2015; and whitley & day, 2011) and risks (viviano, 2013). since nsaids are contraindicated for use with corticosteroids (boston et al., 2003; and kohn, 2007), dogs undergoing treatment for immune-mediated polyarthritis have limited options for concurrent anti-inflammatory pain relief. exploration of alternative immunosuppressive therapies is warranted. single case studies (eom et al., 2015; and wilson-wamboldt, 2011) and case series with insufficient data (clements et al., 2004; colopy et al., 2010; itoh et al., 2010; and kohn et al., 2005) were excluded from this study due to low generalisability and power of conclusions. one clinically applicable primary research paper with reported promising results (rhoades et al., 2016) was identified from the literature search, comparing cyclosporine to prednisone treatment in canine impa type i patients. rhoades et al. (2016) reported successful treatment for 70% (7/10) of dogs in both cyclosporine and prednisone groups. of the three reported treatment failures in the cyclosporine group, two dogs were switched to prednisone (due to adverse effects or lack of improvement) and achieved resolution of symptoms. consequently, at the end of the study period, nine dogs from both groups had been successfully treated with prednisone alone. additionally, of the two dogs in the prednisone group switched to combination therapy, only the dog given prednisone and azathioprine achieved full symptom resolution, whilst the dog on prednisone and cyclosporine had persistent cytologic abnormalities. although owner-reported and clinical signs of impa are informative (colopy et al., 2010), dogs with impa may not show obvious discomfort or lameness (bennett, 1987; and jacques et al., 2002), therefore cytological results are thought to be the most reliable indicators of disease severity and improvement (johnson & mackin, 2012; kohn, 2007; and perry, 2015). therefore, although 70% of both treatment groups achieved treatment success, prednisone appeared to be more successful than cyclosporine overall. there were discrepancies in data collection that were not clearly explained in the text. adverse effects data for cyclosporine dogs was reported for only five of the sample dogs by day 90. the loss of two of the remaining cyclosporine-treated dogs by day 90 means their contribution to adverse effects data was not evaluated by the end of the trial period. this emission is not explained in the text, but it is possible that two additional dogs were censored from adverse data collection due to the addition of concurrent medications for opportunistic infections. as the adverse effects data is the only table that includes sample size, it is unclear whether cytological and clinical data were collected from these dogs at day 90. adverse effects data for the prednisone-treated dogs also introduced confusion, with adverse effects data being collected from nine dogs by the end of the study period, suggesting the two dogs switched from cyclosporine to prednisone treatment contributed to adverse effects data for the prednisone treatment group. this lack of clarity introduces uncertainty about reported conclusions. simple randomisation was used by rhoades et al. (2016) by drawing cards from a hat. selection bias is reduced through this process, but balanced distribution of population attributes or confounding variables cannot be achieved. with small samples, the risk of group differences being influenced by confounding variables is high. rhoades et al. (2016) reported no statistical differences between groups in any of the variables measured, though it is unclear whether regression analyses were performed to ensure similarity. additionally, the loss of dogs from both treatment groups over the trial period potentially created between-group differences not initially present. nevertheless, since canine demographical variables have not been found to affect risk of immune-mediated arthritis (clements et al., 2004; colopy et al., 2010; jacques et al., 2002; johnson & mackin, 2012; kohn, 2007; and stull et al., 2008) it may be that the study’s selection criteria sufficiently reduced the risk of confounding variables affecting results. blinding is important in controlled clinical trials to reduce the risk of conscious and unconscious bias. the follow-up regimes required for prednisone (gradual taper) versus cyclosporine (no taper, blood tests for trough concentration calculation) means rhoades et al. (2016) were unable to blind clinicians or owners to treatment. the known and observable side effects of corticosteroids also impact the study’s ability to prevent awareness of treatment condition. the pathologists analysing fluid samples were blinded, reducing influence of bias in their cytologic results. however, few of the subjective owner-reported and clinician-reported variables correlated with objective pathologist-obtained variables across the duration of study, which suggests a problem with either the validity of the subjective ratings or the objective results. rhoades et al. (2016) did not control the use of concurrent medications. other medications could have influenced adverse effect data throughout. in addition, cyclosporine-treated dogs were prescribed pain relief for the first 7 days of treatment, whilst prednisone-treated dogs were not. this regime choice was unexplained but may have been designed to balance pain relief across treatments. unlike cyclosporine, prednisone does have anti-inflammatory properties. however, this early provision of pain relief may not have impacted the post-treatment data collection, which started 7 days after cessation of analgesics. in conclusion, rhoades et al. (2016) provided some support for the efficacy of cyclosporine, in comparison to prednisone, as a treatment of type i impa in some dogs. the study sample size and design concerns limit the strength of the findings. the reported treatment response of the dogs in the study population suggests that prednisone was somewhat more effective than cyclosporine, since some cyclosporine-treated dogs were later successfully treated with prednisone. more robust comparative studies are needed to support the efficacy of alternative immunosuppressive agents. this study does provide weak evidence that other immunosuppressants may provide effective treatment if corticosteroids are contraindicated, (eg. for unacceptable adverse effects) (colopy et al., 2010; itoh et al., 2010; kohn, 2007; mackin et al., 2016; viviano, 2013; and whitley & day, 2011). currently, there is not enough evidence from controlled clinical trials to warrant change to clinical practice. methodology search strategy databases searched and dates covered: cab abstracts on ovid platform (1973–2021 week 50) web of science – core collection (results from 1983–2022) scopus (results from 1979–2022) search strategy: cab abstracts (keywords): [polyarth* and (immun* or inflammat* or immune-mediated) and (nonerosive or idiopathic or "type i" or impa) and (dog* or canid* or canine* or “canis familiaris”) and (treat* or corticosteroid* or immunosuppress* or immunomodulat* or azathioprine or prednis* or leflunomide or cyclosporine or levamisol or methotrexate or mycophenolate or cyclophosphamide or cytoxic or steroid* or medicat*)] web of science (topics): ts=[(polyarth* and (immun* or inflammat* or immune-mediated or nonerosive or idiopathic or "type i" or impa)) and (dog* or canid* or canine* or “canis familiaris”) and (treat* or corticosteroid* or immunosuppress* or immunomodulat* or azathioprine or prednis* or leflunomide or cyclosporine or levamisol or methotrexate or mycophenolate or cyclophosphamide or cytoxic or steroid* or medicat*)] scopus (title, abstract, keywords): ([ title-abs-key ( polyarth* )  and  title-abs-key ( immun*  or  inflammat*  or  immune-mediated  or  noncorrosive  or  idiopathic  or  "type i"  or  impa )  and  title-abs-key ( treat*  or  medicat*  or  immunosuppress*  or  immunomodulat*  or  medicat* )  and  title-abs-key ( azathioprine  or  leflunomide  or  cyclosporine  or  levamisole  or  methotrexate  or  mycophenolate  or  cyclophosphamide  or  cytoxic )  and  title-abs-key ( corticosteroid*  or  prednis*  or  steroid* )  and  title-abs-key ( dog*  or  canid*  or  canine* or  “canis familiaris”)  ( doctype ,  "ar" )] dates searches performed: 01 sep 2022   exclusion / inclusion criteria exclusion: other types of impa (non-idiopathic), studies with no control or comparative group, non english-language, popular press, single case studies. inclusion: any comparative systematic review / meta-analysis / randomised controlled clinical trial / cohort study that includes both corticosteroid (control) and alternative immunosuppressant (intervention) treatment.   search outcome database number of results excluded – lack of relevance to clinical question excluded – non-english language excluded – not meeting criteria for controlled clinical trial excluded – restricted access excluded – duplicate paper total relevant papers cab abstracts 40 34 0 4 0 1 1 web of science 75 67 0 6 0 1 1 scopus 32 24 3 4 0 0 1 total relevant papers when duplicates removed 1   orcid hannah walker: https://orcid.org/0000-0003-0941-9847 conflict of interest the author declares no conflicts of interest. references archer, t.m., boothe, d.m., langston, v.c., fellman, c.l., lunsford, k.v. & mackin, a.j. 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(2011). type i idiopathic non-erosive immune-mediated polyarthritis in a mixed-breed dog. the canadian veterinary journal. 52(2), 192–196. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help 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230886. registered as a company limited by guarantee in england and wales no. 598443. evaluation of iliopsoas strain with findings from diagnostic musculoskeletal ultrasound in agility performance canines – 73 cases robert e. cullen dvm1 debra a. canapp dvm, dacvsmr, ccrt1* brittany j. carr dvm1 david l. dycus dvm, ms, dacvssa, ccrp1 victor ibrahim md2 sherman o. canapp, jr dvm, ms, dacvssa, dacvsmr, ccrt 1 1veterinary orthopedic and sports medicine group, 10975 guilford rd, annapolis junction, md 20701 2regenerative orthopedics and sports medicine, 600 pennsylvania ave se, washington, dc 20003 *corresponding author (dcanapp@vosm.com) vol 2, issue 2 (2017) published: 13 jun 2017 reviewed by: wanda gordon-evans (dvm, phd, dacvs) and gillian monsell (ma, vetmb, phd, mrcvs) doi: 10.18849/ve.v2i2.93 section index:    abstract | introduction | methods | results | discussion | conflict of interest | references | supplementary files abstract objective: iliopsoas injury and strain is a commonly diagnosed disease process, especially amongst working and sporting canines. there has been very little published literature regarding iliopsoas injuries and there is no information regarding the ultrasound evaluation of abnormal iliopsoas muscles. this manuscript is intended to describe the ultrasound findings in 73 canine agility athletes who had physical examination findings consistent with iliopsoas discomfort. the population was chosen given the high incidence of these animals for the development of iliopsoas injury; likely due to repetitive stress. methods: medical records of 73 agility performance canines that underwent musculoskeletal ultrasound evaluation of bilateral iliopsoas muscle groups were retrospectively reviewed. data included signalment, previous radiographic findings, and ultrasound findings. a 3-tier grading scheme for acute strains was used while the practitioner also evaluated for evidence of chronic injury and bursitis. results: the majority of pathologies were localised to the tendon of insertion, with the majority being low grade i-ii strains (80.8%). tendon fibre disruption (71.2%) and indistinct hypoechoic lesions (91.8%) were the most common of acute changes noted. hyperechoic chronic changes were noted in 84.9 percent of cases. acute and chronic changes were commonly seen together (62.8%). conclusion: diagnostic musculoskeletal ultrasound was used to identify lesions of the iliopsoas tendon consistent with acute and chronic injury, as well as identifying the region of pathology. the majority of agility performance dogs had low grade acute strains based on the tiered system, with mixed acute and chronic lesions being noted frequently. application: diagnostic musculoskeletal ultrasound provides a non-invasive diagnostic modality for patients suspected of having an iliopsoas strain. introduction muscle strains are a commonly assessed injury amongst working and sporting animals.2,5,20 a previous survey with agility dogs found that thirty-two percent of the population had some degree of orthopaedic lameness during training, and that fifty-three percent of those evaluated by a veterinarian were due to muscle or tendon injury.5 the muscle is prone to acute strain from excessive stretch while engaged in eccentric contraction, wherein the external forces being driven across the muscle overload the contractile force of the muscle itself.3,4,23,28-29 the fibres of the muscle may then become disrupted and lose continuity, with additional disruption of the vascular supply leading to interstitial haemorrhage and swelling.28 thirty-two percent of hind limb muscle strains in dogs involve the iliopsoas muscle group.6  acute and chronic injury to the iliopsoas muscle groups has been a topic of interest in recent years with an increasing attention to diagnosis and treatment of this condition. clinical presentation with iliopsoas discomfort can include gait abnormalities and lameness with decreased coxofemoral extension. the lameness may be similar to patients with cranial cruciate ligament injury or hip dysplasia. when evaluating a patient with iliopsoas discomfort, a shortened stride with decreased hip extension is characteristic but not distinctive for iliopsoas in particular.2-3,20,22 upon palpation there may be pain, spasm, and discomfort of the iliopsoas. furthermore, many patients will be hesitant to allow coxofemoral extension with abduction and internal rotation as this specifically places stretch on the muscle and tendon in question. an acute injury to the muscle or tendon has been characterised in 3 grades based on appearance during advanced imaging. early human 3-tiered gradation structures have involved those based on clinical presentation33, but which have correlated well with later systems based on musculoskeletal ultrasound findings34,35, upon which we based our findings. grade i strains have intact architecture and muscle function but with focal oedema or haemorrhage with less than 5%of the muscle involved. such strains are generally the result of repeated muscle contractions resulting in mild muscle cell damage at the sarcomere. these injuries are rarely noted or diagnosed asides from athletic or performance animals, and generally resolve with appropriate rest in <1 week. grade ii strains have increased muscle involvement, mild fibre disruption, increased oedema or haemorrhage, and reduced strength of the musculotendinous unit. grade iii strains involve significant fascial tearing, muscle fibre disruption, and significant oedema or haemorrhage formation.2,33-35 (table 1) table 1: grading scheme for acute musculotendinous strain injury it is important to distinguish tendon strain and injury from muscle belly damage. the tendon unit primarily acts as a structure to transmit contractile force of the muscle. as such, they are often not rigid structures but have various degrees of elasticity and compliance. the general theorem of tendinous strain involves microtrauma and chronic overuse leading to a mechanical breakdown of the tendon. the lack of collagen support predisposes the structure to significant macroinjury. gradation of tendon strains follows the same criteria and categories as that involving muscle trauma, differing only in the component of elastic recoil deformation. 8-9 the bursa is a tissue envelope surrounding the tendon of insertion as it approaches to and attaches to the lesser trochanter. this fluid-filled membrane allows for decreased friction between the tendon and bone. bursitis, inflammation of the tissue membrane with resultant swelling and fluid collection, has been noted with other tendinous injuries. the bursa is collapsed in healthy patients, but can become enlarged and fluid distended in cases of acute or chronic injury.17-18,23-24 acute and chronic bursitis inflammation can often be characterised, with acute injury showing as an anechoic fluid pocket and chronic injuries often having a thickened membrane and hyperechoic changes or debris within the space.31,32 descriptions of imaging modalities for iliopsoas pathologies have been reported.11,14-17,19,23-26 radiographs are unlikely to show evidence for iliopsoas strain, although they may detect mineralisation of the tendinous attachments, or enthesiophytosis, which has been seen with some instances of fibrotic myopathy and other chronic injuries.11 computer tomography (ct) evaluation for acute iliopsoas strain has been previously described and found to be accurate for assessing intramuscular oedema and inflammation.14 magnetic resonance imaging (mri) has also been described for the assessment of iliopsoas injury in human and canine patients.15 however, these advanced imaging modalities are expensive to undertake, and require general anaesthesia. due to expense and anaesthesia, it is also difficult to coordinate recheck evaluations to assess the injury following treatments. diagnostic musculoskeletal ultrasound evaluation has become a valuable and practical tool in assessing the iliopsoas and surrounding musculature. it is used frequently in human medicine for diagnostic evaluation of iliopsoas injuries, as well as for therapeutic injections.19, 23-24 while sedation is required for veterinary evaluation, full anaesthesia is not needed to perform an evaluation, which makes it of benefit over ct and mri. it is also less expensive, making it a more viable option for both initial diagnostics and recheck examinations. ultrasound evaluation of normal iliopsoas muscles was first reported in 2008 by cannon and puchalski where it was found that assessment of the whole iliopsoas muscle group could be performed using 8-5mhz curvilinear and 12-5mhz linear transducers with similar findings in cadaver specimens and live dogs.16 additional ultrasound studies have been performed to identify the femoral nerve passage through the iliopsoas musculature.25-26 however, there have been few notations in literature regarding abnormalities of this muscle group using musculoskeletal ultrasound evaluation and no cataloguing of injury variety or severity. the goal of this paper is to report the diagnostic musculoskeletal ultrasound findings of iliopsoas muscle strains in seventy-three canine athletes who had physical examination findings consistent with iliopsoas discomfort. the population was chosen given the high incidence of these animals for the development of iliopsoas injury. methods case selection case records from january 2010 through july 2015 were analysed for agility dogs that underwent musculoskeletal ultrasound for iliopsoas discomfort assessed on physical examination (veterinary orthopedic sports medicine group, annapolis junction, maryland, usa). an assessment of iliopsoas injury on physical examination was found with dynamic evaluation, which involved placing the hip in extension and abduction and simultaneously internally rotating the stifle to evaluate for discomfort. all patients also experienced discomfort with direct palpation over the point of tendon insertion located cranial and deep to the pectineus muscle, at which point rigidity +/spasm was appreciated. all cases in this paper were recommended to have musculoskeletal ultrasound performed in order to identify lesions and facilitate a recommended treatment protocol. documentation of, and treatment for, co-morbidities (cruciate injury, hip dysplasia, lumbar discomfort, etc.) was not taken into account as this paper was intended to document musculoskeletal ultrasound findings for patients with physical examination findings consistent with an iliopsoas injury as either primary disease or secondary. evaluation of the iliopsoas using ultrasound during ultrasound, sedation was always performed to allow for a thorough evaluation of the structures. this was both due to discomfort from pressure from the transducer over inflamed muscle tendons and fibres, but also to facilitate dorsal recumbency and relaxation to obtain the best views. patients were sedated with dexmedetomidine 0.03mg/kg and butorphanol 0.2mg/kg iv or im prior to evaluation. ultrasound was performed using a hitachi-aloka noblus system with an 18mhz probe. all examinations were performed by a single experienced practitioner (dc). when approaching musculoskeletal ultrasound of the iliopsoas groups, the anatomy was loosely grouped into three regions: insertion, muscle belly, and origin, and the assessments are made in that order. acute injury would result in swelling, oedema, inflammation, and possibly haemorrhage. such changes would be evident on ultrasound based on enlargement of muscle fibres (swelling, inflammation) and a distinctly demarcated hypoechoic region (oedema, haemorrhage). such demarcated hypoechoic lesions were classified as “core lesions”. identification and characterisation of acute muscle and tendon injuries were done so using a grade i-iii scheme. a grade of i-ii or ii-iii was given to those cases with components of injury reserved for two different grade classes. for example, a case with signs of mild bruising and very mild fascial tearing may be given a grade of i-ii. (table 1) the musculoekeltal ultrasound evaluation was started with the probe placed cranial to the pectineus and parallel to the femur. this view allows for a general approach to the location to assess the anatomy. however, it results in obliquity of the tendon fibres, with variation on characterisation based on the patient. a more standardised view involves a caudal longitudinal evaluation of the insertion. (figure 1a) a more detailed image of the lesser trochanter and bursa is made from this angle. a transverse view across the femur from the caudal aspect is also of importance when evaluating the insertion tendon. (figure 1b) the tendon is seen as a short, linear, hyperechoic structure attaching to a small shadowing protrusion of the medial femur (the lesser trochanter). evaluation was made for fibre tears, bursitis, core lesions, or evidence of chronic fibrosis. following the muscle group, the myotendinous junction (mtj) was evaluated with the probe facing slightly cranial. (figure 1c) the mtj is seen as a fan-shaped structure that is generally hypoechoic with obliquely oriented hyperechoic strands. figure 1: evaluation of a normal iliopsoas tendon. (1a) longitudinal and (1b) cross-sectional views of the tendon of insertion onto the lesser trochanter. (1c) a longitudinal view of the tendon of insertion. (1d) a longitudinal view of the iliopsoas muscle belly. (1e) a longitudinal view of the margining of the psoas major (above) and iliacus (below) muscles. the muscle belly is found ventral to the lumbar vertebral bodies four through seven. normal muscle tissue is noted to have a generalised homogenous hypoechoic parenchyma with linear lines of hyperechoic muscle fibres obliquely oriented. differentiation of the iliacus muscle from the psoas major muscle is visualised over the ischium (figure 1d). the iliacus can then sometimes be traced back to its origin on the ilium (figure 1e). the femoral nerve can be found between the major psoas and iliacus muscle bellies. the psoas major origin is identified by tracing the muscle belly proximally to the transverse processes of the third lumbar veterbrae and observing the hypoechoic attachments with linear hyperechoic fibres oriented obliquely. the l3 origin can often be appreciated in smaller dogs (less than 50 pounds). the origin was often obscured in larger animals with large amounts of muscle or fat, and may also be obscured by gas shadowing from the colon. results signalment seventy-three dogs underwent diagnostic musculoskeletal ultrasound for suspected iliopsoas injury assessed on physical examination from january 2010 through july 2015. physical examinations on all canines evaluated included hind limb lameness (unilateral or bilateral), with discomfort on extension and internal rotation of the noted hind limb, and with rigidity +/spasm and discomfort on direct palpation of the iliopsoas muscle belly or tendon. mean age at the time of initial examination was 5.1 years (median 5.0 years, range 2 to 10 years). 54.8 percent were female (32 spayed, 8 intact), and 45.2 percent were male (20 neutered, 13 intact). excluding mixed breed canines, twenty-two breeds were evaluated. the most common breeds were border collies (27.4%), australian shepherds (11%), shetland shepherds (6.8%), and welsh corgis (5.5%). mean body weight was 44.15 pounds (20.07kg) with a median body weight of 42.4 pounds (19.27kg) and a range of 10 to 86.7 pounds (4.55-39.4kg). non-ultrasonic imaging of 73 cases, 59 had pelvis radiographs performed. of these, tendinous calcification (enthesiophytosis), an indication of severe chronic muscle tendon inflammation, was noted in four patients. mild remodeling changes to the lesser trochanter were noted in an additional five cases. (figure 2) five cases were also noted to have coxofemoral degenerative changes consistent with dysplasia or osteoarthritis. figure 2: ventro-dorsal pelvic radiographs. top image shows bilateral mineralisation in the areas of the iliopsoas tendon insertions at the lesser trochanter. bottom image shows unilateral (left) osseous changes to the lesser trochanter with mineralisation in the area of the iliopsoas tendon insertion. dysplastic changes to the right coxofemoral joint are also apparent. for our case population, there were eight mri reports available of the lumbosacral from board-certified radiologists to assess for vertebral and pelvic pathology (phillip gyroscan 1.5 tesla unit). five of these reports reported normal iliopsoas on mri with no apparent abnormalities. based on interpretation of ultrasound evaluation, three of these five cases had chronic changes, one had mild bursitis, and three had mild grade i-ii strains of the tendon. two of the eight mri reports made no mention of the iliopsoas muscle group. both of these cases had chronic changes noted on ultrasound, and one was found to have a significant grade ii-iii muscle strain. one mri report of the eight made mention of hyperintense streaks of the body and insertion unilaterally, which was noted as a mild grade i strain on ultrasound evaluation. no ct evaluations of the pelvis were made for this case series. musculoskeletal ultrasound figures 3-6 show gradations of hypoechoic lesions and fascial tearing using in the tiered grading system for muscular or tendinous injuries. a distinctly demarcated “core” lesion is noted in figure 3. figure 3: longitudinal view of a right iliopsoas tendon of insertion. note the hypoechoic changes of the fibrefibres consistent with a “coreâ€� lesion (circled). lying overtop the iliopsoas tendon is the adductor muscle (white arrow) figure 4: longitudinal (left image) and cross-sectional (right image) views of a grade i right iliopsoas tendon injury. note the mild hypoechoic changes but overall intact fibre pattern. figure 5: oblique cross-sectional view of a grade ii left iliopsoas tendon injury. note the hypoechoic changes and swelling with disruption of fascial lines (circled). figure 6: longitudinal view of a grade iii left iliopsoas tendon injury. note the hypoechoic changes and swelling with complete disruption of fascial lines (circled). this image shows a grade iii lesion not obtained from the case series presented in this paper, but is meant to illustrate the injury appearance. hypoechoic changes of the tendon of insertion were noted in 91.8 percent of cases (21 unilateral, 46 bilateral). various degrees of insertion tendon fibre disruption were seen in 71.2 percent of cases (25 unilateral, 27 bilateral). distinct hypoechoic core lesions were noted in 11 percent of cases (7 unilateral, 1 bilateral). lesions of the musculotendinous junction were noted in 4.1 percent of cases (2 core lesions, 1 case with fibre disruption). hypoechoic changes to the muscle belly were noted in 6.8 percent of cases (2 unilateral, 3 bilateral). no changes to the origins of the iliopsoas muscles were noted. (table 2) table 2: lesions noted on diagnostic ultrasound frequently noted were various hyperechoic abnormalities within the muscle belly or tendon of insertion that did not align with typical hyperechoic fibres of the iliopsoas muscular unit. enthesiophytes and remodeling changes of the lesser trochanter were also distinctly noted as hyperechoic and shadowing.1,2,16,27. (figure 7) figure 7: longitudinal views of the iliopsoas tendon of insertion of the left (labeled) and the normal right iliopsoas tendons of insertion. note the hyperechoic changes of the fibres of the left tendon as well as irregularities of the lesser trochanter (white arrow). hyperechoic fibres of the insertion tendon in 78.1 percent of cases (15 unilateral, 42 bilateral) and hyperechoic periosteal changes to the lesser trochanter in 27.4 percent of cases (15 unilateral, 5 bilateral). it is important to note that in only 5.5 percent of cases were lesser trochanter changes noted on radiographs. in one case, hyperechoic changes at the origin of the major psoas muscle bilaterally were noted. (table 2) it was not uncommon to see a mixture of lesions (hypoechoic +/fibre disruption and hyperechoic). for our case selection, 66.2 percent of cases with ultrasound findings of hypoechoic lesions +/fibre disruption were also found with hyperechoic lesions, as well. in one patient, inflammation of the femoral nerve, which supplies and runs between the major psoas and ilacus muscles, was noted during evaluation of the iliacus and psoas major muscle bellies. (figure 8) figure 8: a view of the iliacus and psoas major muscle bellies converging with an appreciation of the femoral nerve running between (circled). note the thickened appearance of the nerve consistent with femoral neuritis and enlargement, an uncommon sequelae of iliopsoas inflammation. the bursa was also examined during the musculoskeletal ultrasound evaluation. eleven cases (15.1 percent) had evidence of inflammation and fluid dilation within the bursa. of these, three (27.3 percent) showed to have mildly hyperechoic fluid (all unilateral). the remaining eight cases (72.7 percent) showed anechoic fluid distension (4 unilateral, 4 bilateral). (figure 9) figure 9: two longitudinal views of the left (labeled) and right iliopsoas tendons of insertion and bursas. note the distended anechoic bursa on the right (white arrow) compared to the left. when evaluating the findings from our case selection, musculoskeletal ultrasound found 6.8 percent (2 unilateral, 3 bilateral) with only hyperechoic changes. when using our tiered gradation system for hypoechoic and fibre disruption lesions, the results returned with 43.8 percent (19 unilateral, 13 bilateral) with grade i strain, 17.8 percent (9 unilateral, 4 bilateral) with grade i-ii strain, 19.2 percent (11 unilateral, 3 bilateral) with grade ii strain, and 11 percent (5 unilateral, 3 bilateral) with grade ii-iii strain. imaging showing complete grade iii strain was not found in our case selection. these final numbers are based on the most severe lesions seen on ultrasound, whether bilateral and unilateral, and do not account for lesser changes seen on the contralateral iliopsoas for those assessed with a unilateral condition. (table 3) table 3: tendon strain grade tabulation discussion diagnostic musculoskeletal ultrasound is utilised frequently in human orthopaedic and sports medicine as a means to identify injury, differentiate acute and chronic injury, and facilitate treatment protocols. this tool is frequently used in our facility to the same ends. to our knowledge, this is the first paper documenting lesions in a case series of the iliopsoas muscle using musculoskeletal ultrasound. we have used ultrasound assessment to identify lesions consistent with acute and chronic iliopsoas strains, with distinct characteristics associated with each grade of pathology that can be assessed. full assessment of the iliopsoas muscle with ultrasound takes time and practice to perform, but is often instrumental for the diagnostic process in nebulous hind limb lameness. the findings of hypoechoic lesions of the belly or tendon of a muscle are being interpreted as acute injury, and the result of oedema or haemorrhage within the muscle unit. fibre disruption was also noted with presumed acute injuries and was utilised in the tiered grading system along with severity of hypoechoic lesions in determining grade of the injury. while fibre disruption may be noted in chronic injuries, it was more typically noted as hyperechoic scar tissue or fibrosis, presumably from a previous acute strain. iliopsoas discomfort can present to clinicians as acute injury or the result of a chronic strain. chronic iliopsoas pain is often seen with, and presumed the result of long-term compensation for, a chronic primary hip, stifle, or lumbar spine pathology. the joint is protected by limiting its range of motion in abduction and rotation. such restriction puts additional burden on the hip stabilisers to maintain gait, resulting in chronic fatigue, decreasing muscle fibre elasticity, and can predispose the muscle group to cycles of local inflammation and strain.2,10,23,28-30 in the event of mild grade i strains, there is typically preservation of connective sheaths and sarcolemal cells that allows for complete regeneration of the fibres with proper activity restrictions. however, if extensive disruption and haemorrhage occur, or if acute injuries are not rested appropriately, a cycle of contracture and fibroplasia can be the result. fibroplasia from scar tissue formation provides stability but may prevent proper spread of myofibrils, inhibiting proper healing.2,10,29 scar tissue will inhibit normal muscular contraction and relaxation, resulting in chronic mechanical lameness from fibrotic contracture. 10, 29-30 in these injuries, chronic damage would be prone to repeated acute re-injury, which would explain the large number of cases with mixed (acute and chronic) changes noted on ultrasound. the accumulation of scar tissue from chronic injury can lead to an irreversible fibrotic myopathy, which has been described as necessitating a tenomyectomy procedure to alleviate clinical signs.7,11-13,29 given the proximity of the femoral nerve to the iliopsoas group, a further uncommon but reported sequelae is femoral nerve dysfunction resulting from iliacus compartment syndrome. this would present as pain, decreased patellar and withdrawal reflexes, and possibly decreased superficial medial limb sensation.2,6-7,12,29 femoral neuritis and enlargement was noted in one patient from our case population. given the lack of case numbers with this finding, it is difficult to make any further comment on this finding, but it worth consideration during evaluation of the iliopsoas muscle group as potential sequelae. bursitis was noted in eleven patients in this case series, with three and eight of the cases showing changes consistent with chronic and acute bursae inflammation, respectively. those three cases with mildly hyperechoic changes also demonstrated chronic changes of the iliopsoas tendon, and all eight cases showing anechoic fluid dilation also demonstrated acute injury to the iliopsoas tendon. the majority of lesions noted on ultrasound in our case population, both acute and chronic, were localised to the tendon of insertion. the tendon unit primarily acts as a structure to transmit contractile force of the muscle. as such, they are often not rigid structures but have various degrees of elasticity and compliance. the recoil action of certain tendons once loads are released in the form of passive energy can be important in preserving energy during locomotion. various loads held for various times or repetitions will alter this elasticity.8-9 in vitro testing of tendinous structures at increasing loads have found tendons to continuously elongate with aligned fibres until eventual end-point failure and breakage with increasing deformation and decreased elastic recoil potential over time due to a breakdown of collagen fibre crosslinking.9 the general theorem of tendinous strain involves microtrauma and chronic overuse leading to a mechanical breakdown of the tendon. the lack of collagen support predisposes the structure to significant macroinjury. gradation of tendon strains follows the same criteria and categories as that involving muscle trauma, differing only in the component of elastic recoil deformation. 8-9 the mri report findings demonstrated consistently inferior evaluation of the iliopsoas muscle group compared to diagnostic musculoskeletal ultrasound findings. mri failed to identify mild strains and chronic injury, as well as one instance of a grade ii-iii strain. it should be noted that the majority of these cases were undergoing mri to evaluate for lumbosacral pathology, rather than an evaluation of the iliopsoas, and so while the iliopsoas was within the field of view and was commented upon in several reports, the ideal parameters for evaluating the iliopsoas were not used for these studies and so comparison between the different imaging modalities is not possible for our case selection. further studies comparing the two modalities are warranted. an important limitation of this presentation is case selection. the ultrasound and physical examination findings show a fairly high percentage of moderate to high-grade iliopsoas sprains (grades ii or higher). also, no grade iii lesions were present in this case series. even so, in the authors’ experience, this is not an accurate assessment of the general population of iliopsoas strains. most of the cases assessed with ultrasound in this case series were presenting with significant acute or prolonged chronic discomfort, and often after a long history of activity restriction, anti-inflammatory and muscle relaxant medications, and various modalities of rehabilitation therapy prior to ultrasound evaluation. however, in the authors’ experience, the majority of iliopsoas strains presenting for evaluation with discomfort on iliopsoas palpation (of both athletic and companion animals) are mild grade i injuries which likely improve with rehabilitation therapy and medical management. in addition, our case selection consisted entirely of agility performance animals with excellent body condition and highly athletic lifestyles that is unlikely to be the norm for most companion animals. it is also important to note that the majority of cases presenting with iliopsoas discomfort often do so after a long history of nebulous hind limb lameness, with only rarely a distinct traumatic event initiating a diagnostic work-up. as such, the findings of acute vs chronic musculoskeletal changes on ultrasound must be interpreted with the understanding that these injuries are often cyclical, with repeated bouts of acute injury re-presenting with a slow accumulation of hyperechoic chronic changes. as such, while a clear timeline from time of first injury until presentation would be ideal, it is not always possible. another important limitation in this case series would be the lack of histologic testing to correlate with musculoskeletal ultrasound findings. so while distinct and differing changes to the muscle unit were noted, the assessment of these being acute or chronic (or mixed) injuries was done so by clinician interpretation based on experience and previous studies. the involvement of comorbidities is an important one to consider with evaluation of muscle strain injuries, especially of the iliopsoas muscle group. primary muscle injury as a result of rapid turns and twists inherent in a sporting dog’s lifestyle would be more likely than the typical routine of a companion animal. however, in the authors’ experience, ongoing muscle fatigue and microtrauma secondary to compensation from an underlying orthopaedic injury (stifle, hip, or lumbar) is an important consideration. this paper was intended to document lesions from musculoskeletal ultrasound evaluation following identification of iliopsoas discomfort on physical examination in canine agility athletes, and so an accounting of previous or subsequent comorbidities was beyond the intention or scope of this paper. however, further study in the correlation of treatment protocols following iliopsoas strain identification with repeat musculoskeletal ultrasound and lameness outcomes, while taking into account potential underlying or concurrent morbidities, is warranted. there has been no previous in-depth evaluation or description of diagnostic musculoskeletal ultrasound findings of iliopsoas muscle strains. this paper describes the most common lesions and findings associated with strains. appreciation of the severity of lesions can potentially be correlated with the degree of lameness but also play a role when deciding treatment strategies. further study on the utility of ultrasound assessment, especially in regard to monitoring of lesions through various treatment protocols and recovery process, is warranted. ultrasound re-evaluations can potentially be key component in assessing for structural integrity of the iliopsoas muscle and tendon during the treatment process. conflict of interest funding: no outside funding or grants were used for this research paper. competing interests: there are no competing financial interests or conflicts of interests involved with the production of this research paper. references breur, g.j. blevins, w.e. 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(2002) ultrasound of muscles. european radiology, 12 (1), pp. 35–43. http://dx.doi.org/10.1007/s00330-001-1164-6 intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. the evidence behind the diagnostic investigation of canine idiopathic epilepsy a knowledge summary by marios charalambous dvm gpcert(neuro) rsci mrsb mrcvs 1 * david brodbelt ma vetmb phd dva dipecvaa mrcvs 2 holger volk dvm phd dipecvn fhea mrcvs 2 1university college london 2royal veterinary college *corresponding author (marios.charalambous.15@ucl.ac.uk) vol 1, issue 1 (2016) published: 9 feb 2016 next review date: 23 nov 2017 doi: 10.18849/ve.v1i1.8 clinical bottom line there remains an overall lack of clarity for the practical criteria for the diagnosis of canine idiopathic epilepsy. signalment and an interictal neurological examination are vital for the diagnosis of idiopathic epilepsy. despite the current insufficient evidence, the emergence of new diagnostic methods, such as cerebrospinal fluid and/or serum biomarkers, advanced functional neuroimaging techniques and electroencephalography, is likely to change the diagnostic approach in canine epilepsy in the near future. question in dogs, are biomarker and advanced imaging methods superior to signalment and an interictal neurological examination for the diagnosis of epilepsy? clinical scenario a 5 years old 17 kg german shepherd intact male dog manifested generalized tonic-clonic seizures one year ago. in the last two months the dog manifested five episodes. the dog is normal between the episodes, idiopathic epilepsy is suspected. you wonder what the best diagnostic investigation to confirm the presumed idiopathic epilepsy would be. summary of the evidence ghormie (2015) population: dogs with idiopathic (tier ii) and structural epilepsy. sample size: 99 dogs, n=99 intervention details: dogs ≥ 5 years of age with a diagnosis of idiopathic or structural epilepsy were retrieved from medical files. classification of dogs based on age was performed. the prevalence of idiopathic and structural epilepsy and the proportion of subjects with secondary epilepsy due to neoplasia and other disorder was assessed. the sensitivity and specificity of abnormal neurological signs in cases with structural epilepsy were also evaluated study design: retrospective case series outcome studied: objective: to classify the origin of epilepsy and assess the neurological defects during clinical examination as a predictor of structural epilepsy in dogs ≥ 5 years of age main findings (relevant to pico question): it was shown that lack of deficits on neurologic examination does not exclude the possibility of intracranial lesions. neurologic deficits found during clinical examination had 74 % sensitivity and 62 % specificity to predict structural epilepsy. limitations: retrospective case series. van meervenne (2015) population: dogs with idiopathic epilepsy (tier i confidence level). sample size: 45 dogs (intact females only), n=45 intervention details: medical records of intact female dogs diagnosed with epilepsy. the stage of the estrous cycle as reported either by the owner or the veterinarian at the time of the first seizure was noted. unclear diagnostic procedures for idiopathic epilepsy. study design: retrospective case series. outcome studied: objective: to evaluate whether there is an association between onset of seizures and the estrous cycle in intact bitches with idiopathic epilepsy and whether a pattern to the onset of seizures could be recognized. main findings (relevant to pico question): the findings suggest an association between estrus and onset of seizures in intact bitches with presumptive idiopathic epilepsy. two hormonally based patterns could be recognized: one during heat and one during a specific time point at the end of diestrus. this could be explained by the proconvulsive effects of estrogen or loss of protective effect against seizures of progesterone, respectively. limitations: retrospective case series.tier i confidence level for diagnosing idiopathic epilepsy for some cases. armasu (2014) population: dogs with idiopathic (tier ii) and structural epilepsy. sample size: 258 dogs, n=258 intervention details: data including age, sex, neuter status, time until diagnosis, age of seizure onset in years, type of seizure, seizure symmetry, seizure severity, interictal neurological deficits, mri changes and side effects associated with antiepileptic drugs were extracted from medical files study design: retrospective case series. outcome studied: objective:  to assess the influence of the aforementioned factors, such as age, sex, interictal neuro exam, seizure type etc. on the likelihood of structural or functional brain disease, via a thorough history taking process and interictal neurological examination. main findings (relevant to pico question): this study demonstrated that breed and age alone should not be used to distinguish between idiopathic epilepsy and symmetrical or asymmetrical structural brain lesions. it was found that 89% of dogs with idiopathic epilepsy had an age of seizure onset <6 years and 84% of these had a normal neurological examination. limitations: retrospective case series study. however, multinomial statistics were used which were good in filtering out the non-significant. bartels (2014) population: dogs with srma, muo, ivdd, idiopathic epilepsy (tier i) and healthy dogs. sample size: 141 dogs, n=141 intervention details: 3 investigation groups, 1 control group. 1 group with healthy dogs investigation group 1: srma dogs n=51 (25 received no medication and the remaining received steroids) investigation group 2: muo dogs n=27 (16 received no medication and the remaining received steroids) investigation group 3: ivvd dogs n=36 (16 received no medication and the remaining received steroids) control group: idiopathic epilepsy dogs  n=21 healthy dogs: the dogs in this group compared only to idiopathic epilepsy group n=6 study design: open-labeled, non-randomised,controlledexperimental animal study. outcome studied: objective:  chemokines such as mip-3β/ccl19 are important factors in the mechanism of cell migration and pathogenesis of central nervous system (cns) inflammatory reactions. the hypothesis of this study is that ccl19, also known as mip-3β, is involved in the pathogenesis of inflammatory and non-inflammatory cns diseases of dogs. main findings (relevant to pico question): ccl19 csf concentrations were markedly elevated in patients affected with the neuroinflammatory diseases steroid-responsive meningitis arteritis (srma) and meningoencephalitis of unknown etiology (muo)(compared to idiopathic epilepsy group) and showed a strong correlation with the csf cell count. the comparison between ie and healthy animals showed significant difference in ccl19 concentrations which suggeststhat inflammatory processes might be involved in ie pathogenesis. limitations: non-blinded and non-randomised. tier i confidence level for diagnosing idiopathic epilepsy for some cases.since only a small number of neurologically normal dogs were available for evaluation, further studies with a larger cohort of dogs focusing on idiopathic epilepsy in comparison to healthy dogs are indicated before definite recommendations. fredsø (2014) population: dogs with idiopathic (tier i or insufficient level of confidence) and structural epilepsy sample size: 102 dogs, n=102 intervention details: one hundred and two client owned dogs; 78 dogs with idiopathic epilepsy and 24 dogs with structural epilepsy. a retrospective hospital based study with follow-up. dogs diagnosed with epilepsy between 2002 and 2008 were enrolled in the study. owners were interviewed by telephone using a structured questionnaire addressing epilepsy status, treatment, death/alive, and cause of death study design: retrospective case series, questionnaire. outcome studied: objective: to investigate risk factors for survival and duration of survival in a population of dogs with idiopathic or structural epilepsy. main findings (relevant to pico question): neutered male dogs with idiopathic epilepsy had a significant shorter survival (median: 38.5 months) compared to intact male dogs (median: 71 months). limitations: retrospective case series. tier i or insufficient or confidence level for diagnosing idiopathic epilepsy. hasegawa (2014) population: dogs with idiopathic (insufficient level of confidence) and structural epilepsy and healthy dogs sample size: n/a intervention details: 2 investigation group, 1 control group. investigation group 1:  idiopathic epileptic dogs investigation group 2:  structural epileptic dogs control group:  healthy dogs gas chromatography-mass spectrometry (gc-ms)-based metabolic profiling of csf and multivariate data analysis were performed. study design: open-labeled, non-randomised, controlled experimental animal study. outcome studied: objective: to explore canine epilepsy diagnostic biomarkers in the cerebrospinal fluid (csf). main findings (relevant to pico question): profiles for dogs with idiopathic epilepsy differed significantly from those of healthy controls and subjects with structural epilepsy. among 60 identified metabolites, the levels of 20 differed significantly among the three groups. glutamic acid was significantly increased in idiopathic epilepsy, and some metabolites including ascorbic acid were changed in both forms of epilepsy. these findings show that metabolic profiles of csf differ between idiopathic and symptomatic epilepsy and that metabolites including glutamic acid and ascorbic acid in csf may be useful for diagnosis of canine epilepsy. limitations: only abstract was retrieved. non-blinded and non-randomised.insufficient confidence level for diagnosing idiopathic epilepsy for some cases. merbl (2014) population: dogs with idiopathic epilepsy (tier i level of confidence) and healthy dogs. sample size: unclear number of dogs with seizures. number of healthy dogs was 12. intervention details: 1 investigation group, 1 control group. treatment group: dogs with seizures. unclear number. control group: healthy dogs  n=12 study design: blinded, randomized, controlled experimental animal study. outcome studied: objective: to investigate whether dogs with seizures have higher cerebrospinal interleukin-6 (il-6) and tumor necrosis factor-î± (tnf-î±) concentrations compared to dogs with no seizures. main findings (relevant to pico question): higher tnf-α and il-6 concentration in the csf of dogs with naturally occurring seizures were detected limitations: unclear number of dogs with seizures. tier i confidence level for diagnosing idiopathic epilepsy for some cases. r viitmaa (2014) population: dogs with idiopathic epilepsy (tier iii). sample size: 17 dogs, n=17 intervention details: 1 investigation group, 1 control group.  invetigation group:  dogs with idiopathic epilepsy  n=11  control group:  healthy dogs  n=6 study design: blinded, non-randomised controlled experimental animal study. outcome studied: objective: in human epileptic patients, changes in cerebral glucose utilization can be detected 2-deoxy-2-[18f] fluoro-d-glucose positron emission tomography (fdg-pet). the purpose of this prospective study was to determine whether epileptic dogs might show similar findings. electroencephalography (eeg) was also performed. main findings (relevant to pico question): findings were significantly associated with epileptic dogs compared to healthy ones by the use of both methods. both diagnostic tests were consensual and specific (100%) for occipital findings, but eeg had a lower sensitivity for detecting lateralized foci than fdg-pet. findings supported the use of fdg-pet as a diagnostic test for dogs with suspected idiopathic epilepsy. limitations: non-randomised low number of dogs.breed specific changes found might not be applicable for other breeds.the test was not evaluated in dogs with generalized seizures. creevy (2013) population: dogs with idiopathic epilepsy (tier ii) sample size: 17 dogs, n=17 intervention details: 2 investigation groups, 1 control group. investigation group 1:  idiopathic epileptic dogs with no abnormal mri findings  n=8  investigation group 2:  idiopathic epileptic dogs with hyperintense areas in the limbic system detected by means of t2w mri   n=4 control group:  healthy dogs  n=5 study design: open-labelled, non-randomised, controlled experimentalanimal study outcome studied: objective: to investigate differences in cerebrospinal fluid (csf) concentrations of excitatory and inhibitory neurotransmitters in dogs with idiopathic epilepsy with and without t2-weighted (t2w) mri hyperintense areas in the limbic system. main findings (relevant to pico question): no significant difference was evident between glutamate concentrations in csf of dogs with idiopathic epilepsy and with and without hyperintense areas detected by means of t2w mri, but glutamate, though, concentrations typically were higher in csf of dogs with idiopathic epilepsy and mri hyperintense areas. concentrations of gaba in csf were higher in dogs idiopathic epilepsy with mri hyperintense areas than in dogs with idiopathic epilepsy and normal mri and in latter dogs than in healthy dogs. limitations: non-blinded and non-randomised. low study population. gesell (2013) population: dogs with idiopathic epilepsy (tier ii). sample size: 56 dogs, n=56 intervention details: 1 investigation group, 1 control group.  invetigation group:  dogs with idiopathic epilepsy  n=40 control group:  healthy dogs n=16 study design: retrospective case series outcome studied: objective: the hypothesis was that cerebrospinal fluid (csf) concentrations of the endocannabinoids anandamide (aea) and 2-arachidonoyl glycerol (2ag) are altered in epileptic dogs. concentrations of aea and total ag (sum of 2ag and 1ag) were measured in dogs with idiopathic epilepsy and healthy control dogs using liquid chromatography combined with tandem mass spectrometry. main findings (relevant to pico question): an elevation of csf aea concentrations was found in dogs with idiopathic epilepsy compared to control group. the highest aea concentrations were found in dogs with severe seizures and a long disease history. it was suggested that the activation of the aea may serve as a counter-mechanism in order to regulate the seizure-threshold in epilepsy and that can alter or be altered by seizure activity; so further, prospective studies are warranted to investigate this mechanism limitations: retrospective case series viitmaa (2013) population: dogs with idiopathic epilepsy (insufficient level of confidence). sample size: 2069 dogs, n=2069 intervention details: from 2003 to 2004, questionnaires (n=5,960) were sent to all owners of 1to 10-year-old finnish spitz dogs (fsds) in finland. phone interviews were performed 1 to 2 years later. study design: prospective epidemiological study-questionnaires outcome studied: objective: to determine the phenotype, inheritance characteristics, and risk factors for idiopathic epilepsy in fsds. main findings (relevant to pico question): estimated prevalence of idiopathic epilepsy was 5.36% (111/2,069 of fsds that were still alive). males were predisposed to ie. the median age of onset was 3 years (range, 0.6 to 10 years). the median seizure frequency was 2 seizures/year (range, 0.5 to 48 seizures/year), the majority (85%) of the seizures had a focal onset, and 54% were characterized as generalized secondary. limitations: non-blinded, non-randomised and uncontrolled. insufficient confidence level for diagnosing idiopathic epilepsy for some cases. potential subjective assessment mainly by owners and secondary by investigators. akos (2012) population: dogs with idiopathic (tier ii) and structural epilepsy. sample size: 40 dogs, n=40 intervention details: dogs with structural and idiopathic epilepsy. propofol was used for chemical restraintin all dogs and electroencephalogram (eeg) was performed. study design: open-labeled, non-randomised, controlled experimental animal study outcome studied: objective: to identify interictal epileptiform discharges via eeg in a group of dogs with seizures of known aetiology and in dogs with idiopathic epilepsy. main findings (relevant to pico question): interictal eeg examinations of propofol-anaesthetised dogs suffering fromidiopathic and structural epilepsy rarely show epileptic discharges. this, the diagnostic value of such eegs in the work-up for epilepsy seems to be low as epileptic discharges were unlikely to be detected. limitations: non-blinded and non-randomised brauer (2012) population: dogs with idiopathic (tier iii) and structural epilepsy sample size: 89 dogs, n=89 intervention details: 2 investigation comparison groups investigation group 1 dogs with idiopathic epilepsy n=61 investigation group 2:  dogs with structural epilepsy n=28 electroencephalograms were recorded using five subdermal eeg electrodes (f3, f4, cz, o1 and o2). all 89 eegs were analysed visually and 61 were also evaluated quantitatively with fast fourier transformation. study design: open-labeled, non-randomised, controlled experimental animal study outcome studied: objective: to investigate the diagnostic value of interictal short time electroencephalographic (eeg) recordings in epileptic dogs under general anaesthesia with propofol and the muscle relaxant rocuronium bromide in epileptic dogs. main findings (relevant to pico question): interictal paroxysmal epileptiform activity was found in 25% of idiopathic and in 29% of symptomatic epileptic dogs. despite the use of activation techniques, the results showed that short time eeg recordings in epileptic dogs can detect interictal epileptic activity in less than one third of all seizuring dogs. therefore, it was not a useful diagnostic method when used during the interictal periods of epileptic dogs limitations: non-blinded and non-randomised calvo (2012) population: dogs with idiopathic epilepsy sample size: 56 dogs, n=56 intervention details: 2 investigation groups, 1 control group. 1 group with health dogs investigation group 1:  dogs with idiopathic epilepsy that had seizures within 24 hours from blood or liquor collection seizures  n=17 investigation group 2: dogs with idiopathic epilepsy that had after 24 to 120 hours from blood or liquor collection seizures within 24 hours n=16 control group:  healthy dogs  n=23 study design: open-labeled, non-randomised, controlled experimental animal study outcome studied: objective: to evaluate c-reactive protein concentration in blood of patients with idiopathic epilepsy and verify if the protein can be considered a biomarker to help its diagnose. main findings (relevant to pico question): seizures associated with idiopathic epilepsy promote an acute phase response characterized by an increase of blood c reactive protein concentrations within 24 hours, and after this period c reactive protein concentrations declined due to the liberation of inflammatory mediators by the brain and muscle contractions. therefore bloodand c reactive protein concetrations can be used as a biomarker to differentiate idiopathic epilepsy from other seizures causes. limitations: non-blinded and non-randomised. the elisa technique for c reactive protein liquor analysis needs to be validated.insufficient confidence level for diagnosing idiopathic epilepsy for some cases. de la fuente (2012) population: dogs with various neurological disorders, included idiopathic epilepsy (tier i and insufficient level of confidence) sample size: 169 dogs, n=169 intervention details: dogs with neurological disorders included 11 with steroid-responsive meningitis-arteritis (srma), 37 with other inflammatory neurological diseases (inf), 38 with neoplasia affecting the central nervous system (neo), 28 with spinal compressive disorders (scc), 15 with idiopathic epilepsy, and 40 with noninflammatory neurological disorders (non-inf), 7 dogs with systemic inflammatory diseases without central nervous system involvement (sid), and 7 healthy (control group) beagles were included in the study study design: prospective observational study outcome studied: objective: to investigate fibrinolytic activity in the csf of dogs with neurological disorders by measuring cerebrospinal fluid (csf) d-dimer concentration. main findings (relevant to pico question): all dogs with idiopathic epilepsy as well as dogs with systematic non-neurological inflammatory diseases and controls had undetectable concentrations of d-dimers in the csf. limitations: non-blinded and non-randomised. tier i and insufficient confidence level for diagnosing idiopathic epilepsy for some cases. seppälä (2012) population: dogs with idiopathic epilepsy (tier iii) sample size: 307 dogs, n=307 intervention details: investigators collected 159 cases and 148 controls and confirmed the presence of idiopathic epilepsy throughepilepsy questionnaires and clinical examinations via advance imaging (mri) and electroencephalograms(eegs) study design: epidemiological studyquestionnaires outcome studied: objective: to study the clinical and genetic background of epilepsy in belgian shepherds main findings (relevant to pico question): genetic predispose of belgian shepherd dogs limitations: non-blinded and non-randomised weber (2012) population: dogs with various neurological disorders, included idiopathic epilepsy (insufficient level of confidence) sample size: 328 dogs, n=328 intervention details: the dogs were assigned to seven different groups: steroid-responsive meningitis-arteritis (srma) intervertebral disc disease (ivdd) neoplasia of the central nervous system (n) idiopathic epilepsy bacterial meningoencephalomyelitis (bm) meningoencephalomyelitis of unknown origin (mue) healthy dogs study design: retrospective case series study outcome studied: objective: to evaluate the glucose ratio (glucose level in the cerebrospinal fluid [csf]/blood glucose level) as a quickly available marker for detecting bacterialmeningoencephalomyelitis and compared to other diseases main findings (relevant to pico question): the median of the csf-glucose level (mmol/l) and the median of the glucose ratio in the srma group displayed the lowest values and differed significantly from the csf-glucose levels of dogs in the groups ivdd, n, idiopathic epilepsy and healthy dogs (csf-glucose level: p<0.01; glucose ratio: p<0.05). therefore, the csf-glucose level and glucose ratio was not useful for supporting the diagnoses idiopathic epilepsy according to the findings of this study limitations: retrospective case series. subjective assessment. insufficient confidence level for diagnosing idiopathic epilepsy for some cases browand-stainback (2011) population: dogs with idiopathic epilepsy (insufficient level of confidence) sample size: 211 dogs and cats, n=211 intervention details: epileptic seizures in 211 canine and feline patients diagnosed with idiopathic epilepsy were evaluated for temporal significance in relation to the lunar cycle. seizure counts were compared among each of the eight individual lunar phases, among each of eight exact lunar phase dates, and by percent of lunar illumination using generalized estimating equations. study design: retrospective case series outcome studied: objective: to investigate the potential connection between canine and feline epileptic seizures and the lunar cycle. main findings (relevant to pico question): no statistical significance was found in any of these comparisons excluding a relationship between the onset of epileptic seizures and the phases of the moon. limitations: only abstract was retrieved. retrospective case series. ekenstedt (2011) population: dogs with idiopathic epilepsy (insufficient level of confidence). sample size: 34 dogs, n=34 intervention details: candidate genes known to be involved in human epilepsy, along with selected additional genes in the same gene families that are involved in murine epilepsy or are expressed in neural tissue, were examined in populations of affected and unaffected dogs. microsatellite markers in close proximity to each candidate gene were genotyped and subjected to two-point linkage in vizslas, and association analysis in ess, gsmd and beagles. study design: experimental study/genetic analysis outcome studied: objective: to investigate if there are simple genetic bases for ie in some purebred dog breeds, specifically in vizslas, english springer spaniels (ess), greater swiss mountain dogs (gsmd), and beagles, and that the gene(s) responsible may, in some cases, be the same as those already discovered in humans main findings (relevant to pico question): most of these candidate genes were not significantly associated with idiopathic epilepsy in these four dog breeds, while a few genes remained inconclusive. other genes not included in this study may still be causing monogenic idiopathic epilepsy in these breeds or, like many cases of human idiopathic epilepsy, the disease in dogs may be likewise polygenic. limitations: only abstract was available. insufficient confidence level for diagnosing idiopathic epilepsy for some cases. goncalves (2010) population: dogs with idiopathic epilepsy (tier i-ii) sample size: 124 dogs, n=124 intervention details: 3 investigation groups in comparison dogs were divided into three groups depending on the time interval between their last seizure and the cerebrospinal fluid (csf) collection: up to two days (group 1) between three and seven days (group 2) and >seven days (group 3) the dogs were also divided into two groups based on whether or not cluster seizures occurred before csf collection. study design: open-labeled, non-randomised experimental animal study. outcome studied: objective: to determine the effect of seizures on csf composition of dogs with idiopathic epilepsy. main findings (relevant to pico question): a significant association was observed between the total nucleated cell count (tncc) and the time interval between the last seizure and the collection of the csf, the longer the time interval, the lower the tncc. there was no association observed between time interval and csf protein concentration; and no association was also found between the current of cluster seizures and either tncc csf or protein concentration. it was suggested that alterations in the csf tncc can be induced by seizures in dogs. limitations: non-blinded and non-randomized. tier i confidence level for diagnosing idiopathic epilepsy for some cases. wessmann (2010) population: dogs with various neurological conditions, included idiopathic epilepsy (tier i-ii). sample size: 359 dogs, n=359 intervention details: the frequency of surface epithelial cells in 359 canine csf samples was analyzed for 5 disease groups: central nervous system (cns) neoplasia cns compression cns inflammation idiopathic epilepsy miscellaneous diseases. groups were also combined intothose with and without expected meningeal involvement. study design: retrospective case series outcome studied: objective: to identify the frequency of surface epithelial cells in csf from dogs with neurologic disease was investigated along with thepotential association with age, specific type of cns disease, and csf totalnucleated cell count (tncc) and protein concentration. main findings (relevant to pico question): surface epithelial cells were found in idiopathic epilepsy in 8/124 (6.5%), significant associations between surface epithelial cell presence in csf and age, disease type, csf tncc, and csf protein concentration were not found. the presence of surface epithelial cells was not related to aspecific disease group or csf changes in the studied population. thus, the presence of surface epithelial cells should be interpreted carefully, as it could represent an incidental finding in csf specimens. limitations: retrospective case series. tier i confidence level for diagnosing idiopathic epilepsy for some cases fujiwara (2008) population: dogs with various neurological disorders, including idiopathic epilepsy (insufficient level of confidence). sample size: 310 dogs, n=310 intervention details: blood serum samples were randomly collected from 310 dogs. the dogs were divided into three groups: nme cases (group 1), non-nme cns disease cases (group 2) and non-cns disease cases (group 3). twenty-six (26) serum samples from clinically healthy dogs were also included for comparison (control group). study design: open-labeled, randomised controlled experimental animal study outcome studied: objective: to determine whether serum autoantibodies against glial fibrillary acidic protein (gfap) can be used for diagnosing canine necrotizing meningoencephalitis (nme) and secondarily, other diseases. main findings (relevant to pico question): dogs with chari malformation and idiopathic epilepsy, prostate cancer, insulinoma, malignant lymphoma, pituitary-dependent hyperadrenocorticism, myasthenia gravis and polyarthritis also exhibited high values. thus, serum gfap autoantibodies might be non-specific and not of use for diagnosing nme or any of the diseases mentioned (including idiopathic epilepsy). limitations: non-blinded. insufficient confidence level for diagnosing idiopathic epilepsy. kloene (2008) population: dogs with idiopathic epilepsy (tier i) sample size: 365 dogs, n=365 intervention details: questionnaires and metabolic screening tests were used. dogs were also included in a large pedigree, which was subdivided into ten smaller subsets study design: prospective study: epidimiological-pedigree analysis. outcome studied: objective: to identify a genetic basis for the condition in border terrier dogs. main findings (relevant to pico question): about 70% of the affected dogs showed generalised seizures, and in about 45% of the cases the seizures had a tonic character. about 80% of the animals did not lose consciousness during the seizures. the median age of the border terriers included in the study was 3.73 years and the median age at seizure onset was 3.15 years. the inspection of the pedigrees showed that the majority of affected border terriers were descended from unaffected parents. matings among two unaffected animals or affected and unaffected animals resulted always in affected and unaffected offspring. limitations: tier i confidence level for diagnosing idiopathic epilepsy. risk of subjective assessment. pákozdy (2008) population: dogs with idiopathic (tier ii level of confidence) and structural epilepsy sample size: 240 dogs, n=240 intervention details: data search was performed. seizure aetiologies were classified as idiopathic epilepsy (n = 115) and structural epilepsy (n = 125). study design: retrospective case seriesr outcome studied: objective: to examine the underlying aetiology and to compareidiopathic epilepsy with symptomatic epilepsy concerningsignalment, history, ictal pattern, clinical and neurological findings main findings (relevant to pico question): status epilepticus, cluster seizures, partial seizures, vocalisation during seizure and impaired neurological status were more readily seen with symptomatic epilepsy. if the first seizure occurred between one and five years of age or the seizures occurred during resting condition, the diagnosis was more likely idiopathic epilepsy than structural epilepsy. no correlation of seizures with oestrus, full moon and stress or excitement could be found.golden retrievers and beagles were the most common reported pure breeds suffering from idiopathic epilepsy. limitations: retrospective case series smith (2008) population: dogs with seizures and idiopathic epilepsy (tier ii level of confidence) sample size: 76 dogs, n=76 intervention details: in this study the prevalence of clinically significant magnetic resonance imaging (mri) abnormalities was determinedin two groups of interictally normal dogs, those younger than 6 years and those older than 6 years of age study design: open-labeled, non-randomised controlled clinical study outcome studied: objective: to determine the prevalence of positive mr findingsin dogs with no evidence of forebrain dysfunction on interictal neurological examination and to determine whether it isaffected by patient age main findings (relevant to pico question): a low likelihood of revealing an underlying lesion by mri, in seizuring dogs limitations: non-blinded and non-randomised jokinen (2007) population: dogs with seizures and idiopathic epilepsy (tier ii). sample size: 25 dogs, n=25 intervention details: puppies (lagotto romagnolo) dogs presented on the hospital for examination and investigation of their simple or complex focal seizures. clinical and diagnostic evaluations of affected dogs were conducted, including electromyography, electroencephalography, blood test, advance imaging and other testing study design: uncontrolled experimental animal study-prospective case series study outcome studied: objective: to identify idiopathic juvenile epilepsies with benign outcomes in lagotto romagnolo dogs main findings (relevant to pico question): seizures in puppies began at 5 to 9 weeks of age and usually resolved spontaneously by 8 to 13 weeks. those with the most severe seizures also had signs of neurologic disease between these seizures, including generalized ataxia and hypermetria there were no abnormalities in routine laboratory screenings of blood, urine, and cerebrospinal fluid. electromyography, brainstem auditory-evoked potentials, and magnetic resonance imaging revealed no specific and consistent abnormalities. pedigree analysis suggests an autosomal recessive mode of inheritance. for the cases that had simple or complex focal seizures and cerebellar lesions, it represents a newly recognized epileptic syndrome in dogs. limitations: non-blinded, uncontrolled study licht (2007) population: dogs with idiopathic epilepsy (tier i level of confidence). sample size: 90 dogs, n=90 intervention details: 1 investigation group, 1 control group investigation group:  30 dogs with probable idiopathic epilepsy control group:  60 dogs without any history of seizures researchers contacted owners to determine whether dogs had ever had any seizures and, if so, the nature of any such seizures and any potential underlying causes.  to determine the mode of inheritance, segregation analyses were designed to allow the family to be analyzed as a whole, as opposed to as nuclear families. competing models of inheritance were compared statistically for their ability to explain the data. study design: prospective case series study. outcome studied: objective: to determine clinical characteristics and mode of inheritance of seizures in a family of standard poodles. main findings (relevant to pico question): results suggested that in this family of standard poodles, idiopathic epilepsy was inherited as a simple recessive autosomal trait with complete or almost complete penetrance. seizures often had focal, as opposed to generalized, onsets, and it was not uncommon for seizures to begin after 5 years of age. in addition, 28 (93%) had focal onset seizures with or without secondary generalization. median age of onset was 3.7 years limitations: tier i confidence level for diagnosing idiopathic epilepsy. part of the assessment of the study was subjective casal (2006) population: dogs with idiopathic epilepsy (insufficient level of confidence) sample size: 796 dogs, n=796 intervention details: clinical data and pedigrees from closely related irish wolfhounds were collected retrospectively and analysed study design: retrospective case series study. pedigree analysis outcome studied: objective: the aim of this study was to identify inheritance characteristics in irish wolfhounds main findings (relevant to pico question): idiopathic epilepsy was diagnosed, by exclusion of other causes for seizures, in 146 (18.3%) of 796 irish wolfhounds. the first seizure occurred by the age of 3 years in 73% of all dogs. males were more commonly affected than females (61.6% versus 38.4%), with males having a later average age of seizure onset. it was assumed that the complex pattern of inheritance observed is autosomal recessive, with incomplete penetrance and male dogs at increased risk limitations: retrospective case series insufficient confidence level for diagnosing idiopathic epilepsy pákozdy (2006) population: dogs with seizures in general and idiopathic epilepsy (tier ii level of confidence). sample size: 13 dogs, n=13 intervention details: all boxers with seizures within the last 7 years were included in this retrospective study study design: retrospective case series study outcome studied: objective: the aim of this study was to evaluate the aetiology of seizures in boxers of our patient-index and to compare it with literature data main findings (relevant to pico question): only 2 boxers were diagnosed with idiopathic epilepsy. the use of bloodtests and mri is recommended, independently of age, history and physical-neurologic examination indicating idiopathic epilepsy. limitations: retrospective case series. low study population viitmaa (2006) population: dogs with seizures sample size: 14 dogs, n=14 intervention details: 1 investigation group, 1 control group investigation group:  finnish spitz dogs with focal seizures  n=11 control group:  healthy dogs.  n=3 study design: open-labelled, non-randomized controlled experimentalanimal study outcome studied: objective: to investigate the magnetic resonance imaging findings in finnish spitz dogs with focal epilepsy main findings (relevant to pico question): general clinical and neurological examinations, blood examination, urinalysis, cerebrospinal fluid examination, electroencephalography (eeg), and magnetic resonance imaging (mri) of the brain were performed on all dogs. on eeg examination, focal epileptic activity was found in 7 of 11 dogs (64%), and generalized epileptic activity was observed in 4 of 11 dogs (36%). mri (performed with 1.5 t equipment) detected changes in 1 epileptic dog. finnish spitz dogs with focal seizures suffered from idiopathic epilepsy and had non-detectable findings on mri or pathology limitations: non-blinded and non-randomized low study population patterson (2005) population: dogs with idiopathic epilepsy (tier i-ii) sample size: 119 dogs, n=119 intervention details: forty-five dogs with idiopathic epilepsy and 74 siblings and their respective parents were included in the analysis study design: prospective case series study outcome studied: objective: to determine clinical characteristics and mode of inheritance of idiopathic epilepsy in english springer spaniels main findings (relevant to pico question): median age at the onset of seizures was 3 years; however, 9 (20%) dogs were between 5 and 6 years old at the time of the onset of seizures. twenty-one dogs (47%) had generalized seizures, and 24 (53%) had focal onset seizures. in english springer spaniels, idiopathic epilepsy segregated in a manner that is consistent with partially penetrant autosomal recessive inheritance (ie, a single major locus with modifying genes) or polygenic inheritance limitations: tier i confidence level for diagnosing idiopathic epilepsy in many cases ellenberger (2004) population: dogs with idiopathic epilepsy (insufficient level of confidence). sample size: 149 dogs, n=149 intervention details: thirty-five labrador retrievers with genetic epilepsy,94 non-labrador retrievers with idiopathic epilepsy, and 20 control dogs collection of csf was performed >72 h after the occurrence of seizures. cerebrospinal fluid concentrations of gamma -aminobutyric acid (gaba), glutamate (glu), aspartate (asp), serine, and glycine were determined by using high performance liquid chromatography with electrochemical detection. study design: open-labelled, non-randomized, controlled experimental animal study outcome studied: objective: to determine concentrations of excitatory and inhibitory amino acids in csf of a large number of dogs with idiopathic epilepsy and to evaluate changes in csf amino acid concentration with regard to drug treatment and sex main findings (relevant to pico question): csf concentrations of gaba and glu were significantly lower in labrador retrievers with genetic epilepsythan in control-group dogs or in non-labrador retrievers with idiopathic epilepsy. csf concentrations of glu and asp were significantly lower when all dogs with epilepsy were compared with control-group dogs limitations: non-blinded and non-randomized. insufficient confidence level for diagnosing idiopathic epilepsy rusbridge (2004) population: dogs with secondary syringomyelia and seizures sample size: 120 dogs, n=120 intervention details: a worldwide family tree of more than 5,500 ckcss spanning a maximum of 24 generations wasestablished by obtaining pedigree information from 120 dogs diagnosed with secondary syringomyelia secondary to occipital bone hypoplasia study design: retrospective case series-pedigree analysis outcome studied: objective: to identify the inheritance character of occipital bone hypoplasia (chiari type i malformation) in cavalier king charles spaniels main findings (relevant to pico question): idiopathic epilepsy is more frequent in lines originating from whole-color dogs. selection for coat color is believed to have influenced the development of both occipital hypoplasia with secondary sm and ie limitations: not identified but retrospective case series-pedigree analysis study lobert (2003) population: dogs with various neurological disorders, including idiopathic epilepsy (insufficient level of confidence). sample size: 130 dogs, n=130 intervention details: 2 investigation groups, 1 control group. investigation group 1:  dogs with different diseases of the central nervous system  n=104 investigation group 2:  dogs with exercise induced weakness n=6 control group:  neurologically healthy dogs  n=20 study design: open-labeled, non-randomised, controlled experimental animal study outcome studied: objective: to determine reference values for pyruvate, lactate and the pyruvate/lactate ratio in the blood and cerebrospinal fluid main findings (relevant to pico question): neurologically healthy dogs and patients with idiopathic epilepsy displayed nearly the same values. the highest lactate concentrations were measured in dogs with disc protrusion and inflammatory cns diseases limitations: non-blinded and non-randomized. insufficient confidence level for diagnosing idiopathic epilepsy. oberbauer (2003) population: dogs with idiopathic epilepsy (insufficient level of confidence) sample size: intervention details: genomic dna from families of affected tervuren and sheepdogs was screened with 100widely dispersed, polymorphic canine microsatellite markers study design: unclear outcome studied: objective: to investigate the genetics of epilepsy in the belgian tervuren and sheepdog. main findings (relevant to pico question): although not significant (lod scores <3.0), three genomic regions haveshown nominal linkage between markers and the epileptic phenotype limitations: only abstract was retrieved. insufficient confidence level for diagnosing idiopathic epilepsy. patterson (2003) population: dogs with idiopathic epilepsy (tier i-ii) sample size: 11 dogs, n=11 intervention details: medical record, seizure survey, and telephone interview information was obtained for 29 vizslas with idiopathic epilepsy (ie), 74 unaffected siblings, and 41 parents to determine the common clinical characteristics and most likely mode of inheritance study design: retrospective case series. questionnaire. survey outcome studied: objective: to identify clinical characteristics and inheritance of idiopathic epilepsy in vizslas main findings (relevant to pico question): idiopathic epilepsy in vizslas appears to be primarily a partial onset seizure disorder that may be inherited as an autosomal recessive trait limitations: overall high risk of bias related to the study design. tier i confidence level for diagnosing idiopathic epilepsy in some cases. morita (2002) population: dogs with idiopathic epilepsy (tier ii). sample size: 11 dogs, n=11 intervention details: epileptic focus by electroencephalography (eeg) was assessed by using an international 10-20 electrode system in 11 shetland sheep dogs affected with familial idiopathic epilepsy. also, evaluation of the amino acids in the cerebrospinal fluid (csf) and a pathologic examination of the brains of 8 dogs that died from status epilepticus were performed study design: open-labeled, non-randomised, uncontrolled experimental animal study outcome studied: objective: to investigate the clinicopathologic findings of familial frontal lobe epilepsy in shetland sheepdogs main findings (relevant to pico question): the eeg analyses indicated spike and sharp wave complexes, which were considered to be paroxysmal discharges. an increased value for glutamate or aspartate was found in the csf of some epileptic dogs. histologically, acute neuronal necrosis and astrocytosis were distributed predominantly limitations: non-blinded, non-randomised and uncontrolled study low study population kathmann (1999) population: dogs with idiopathic epilepsy (insufficient confidence level sample size: 50 dogs, n=50 intervention details: pedigree analysis was carried out on an open, non-preselected population of 4005 dogs. five different subpopulations with 50 epileptic dogs from 13 generations were included study design: pedigree analysis outcome studied: objective: to investigate clinical and genetic icharacteristics of idiopathic epilepsy in the bernesemountain dog main findings (relevant to pico question): idiopathic epilepsy has a polygenic, recessive mode of inheritance in the bernese mountain dog. a clear predisposition for males was also noted. the majority (62 per cent) of the epileptic dogs had had their first seizures at between one and three years of age limitations: only abstract was retrieved. insufficient confidence level for diagnosing idiopathic epilepsy lengweiler (1999) population: dogs with idiopathic epilepsy (insufficient level of confidence). sample size: 25 dogs, n=25 intervention details: questionnaire survey of the owners of 25 golden retrievers in switzerland [date not given], in which data were obtained on signs, clinical history, feeding and housing study design: questionnaire. survey outcome studied: subjective: to investigate clinical, epidemiological and treatment aspects of idiopathic epilepsy in 25 golden retrievers main findings (relevant to pico question): in half the dogs seizures first occurred between 1 and 3 years of age and were mostly generalized. at the beginning of long-term therapy with phenobarbital success was observed in two-thirds of dogs; after 4 years symptoms worsened considerably in half the dogs.  dogs responded well to therapy if treated as early as possible. no better success rate in castrated dogs. limitations: risk of subjective assessment. insufficient confidence level for diagnosing idiopathic epilepsy holliday (1998) population: dogs with idiopathic epilepsy (tier ii). sample size: unclear intervention details: inter-ictal electroencephalograms (eegs) were performed in sedated epileptic dogs study design: open-labeled, non-randomised, uncontrolled experimental animal study outcome studied: objective: to investigate interictal paroxysmal discharges in the eeg of epileptic dogs main findings (relevant to pico question): using appropriate methods, focal paroxysmal discharges can be detected and the hemisphere of origin and rostrocaudal location of their sources identified. paroxysmal discharges that are presumably generalized can be recorded from dogs withsignalments suggesting inherited/"idiopathic" epilepsy limitations: only abstract was retrieved. non-blinded and uncontrolled study. compared to similar studies, sedation instead of general anesthesia was used in the dogs of this study that might have affected the eeg findings jaggy (1998a) population: dogs with idiopathic epilepsy (insufficient confidence level). sample size: 792 dogs, n=792 intervention details: seven hundred and ninety-two pedigreecertificates from a population of healthy and epileptic dogs from 11 generations were evaluated. forty-four different families (giving a total of 55 epileptic dogs) were included and analysed study design: pedigree analysis outcome studied: subjective: to investigate genetic aspects of idiopathic epilepsy in labrador retrievers. main findings (relevant to pico question): results of pedigree analysis and from use of the binomial test support the hypothesis of a polygenic, recessive mode of inheritance in labrador retrievers. limitations: insufficient confidence level for diagnosing idiopathic epilepsy jaggy (1998b) population: dogs with idiopathic epilepsy (tier ii) sample size: 37 dogs, n=37 intervention details: interictal electroencephalographic recordings of 37 anaesthetised dogs were statistically analysed study design: retrospective case series study outcome studied: subjective: to investigate the clinical andelectroencephalographic findings in dogs. main findings (relevant to pico question): despite anaesthesia, electroencephalographic features were consistent and unique in dogs with idiopathic epilepsy. in this study males were predisposed to idiopathic epilepsy limitations: retrospective case series podell (1997) population: dogs with idiopathic epilepsy (insufficient confidence level). sample size: 29 dogs, n=29 intervention details: 2 investigation groups, 1 control group. investigation group 1:  drug-naive dogs with an initial generalized seizure  n=13 investigation group 2:  drug-naive dogs with an initial partial seizure  n=6 control group  clinically normal dogs  n=10 the csf glutamate (glu) and gamma-aminobutyric acid (gaba) concentrations were estimated by use of hplc with electrochemical detection. study design: open-labeled, non-randomised, controlled, experimental trial outcome studied: objectives: to investigate changes in csf concentrations of inhibitory and excitatory neurotransmitters in dogs with confirmed idiopathic epilepsy, and to evaluate them with regard to the clinical characteristics of the samplepopulation and of the seizures main findings (relevant to pico question): altered gaba and glu values in csf might be indicative of a state ofchronic overexcitation in the brain of dogs with idiopathic epilepsy limitations: non-randomised, non-blinded. insufficient confidence level for diagnosing idiopathic epilepsy. hall (1996) population: dogs with idiopathic epilepsy(insufficient level of confidence) and healthy animals sample size: unclear intervention details: pedigrees of 15 litters which included animals diagnosed as epileptic ('fitters') were compared with those of 34 contemporary, normal animals study design: prospective case series outcome studied: objective: to investigate a genetic counselling programme for keeshonds main findings (relevant to pico question): the predisposition of keeshonds (dutch barge dogs) to idiopathic epilepsy appears to be determined by a single autosomal recessive gene limitations: only abstract was retrieved insufficient confidence level for diagnosing idiopathic epilepsy srenk (1996) population: dogs with idiopathic epilepsy (tier ii), exercise induced weakness and healthy dogs sample size: 15 dogs, n=15 intervention details: electroencephalograms (eegs) were performed. constant and similar values of amplitude and frequency were found under medetomidine/propofol anaesthesia. 2 investigation groups, 1 control group. investigation group 1: dogs with idiopathic epilepsy  n=5 investigation group 2:  dogs with exercise induced weakness  n=6 control group:  neurologically healthy dogs  n=20 study design: open-labeled, non-randomised, controlled experimental animal study outcome studied: objective: to investigate interictal electroencephalographic findings in a family of golden retrievers with idiopathic epilepsy main findings (relevant to pico question): despite deep anaesthesia, the eeg abnormalities were consistent and extremely important for the confirmation of idiopathic epilepsy in the dog. eeg combined with pedigree analysis may be very helpful in risk assessment of ie in the dog limitations: non-blinded and non-randomised. low study population. only one breed was included. podell (1995) population: dogs with seizures sample size: 50 dogs, n=50 intervention details: fifty dogs were classified on the basis of antemortem and postmortem test results and history study design: retrospective case series study outcome studied: objective: to investigate the seizure classification in dogs from a nonreferral-based population main findings (relevant to pico question): a diagnosis of idiopathic epilepsy was more probable when the dog was between 1 and 5 years of age at the first seizure, when the dog was a large breed (>15 kg), when the seizure occurred between 8 am and midnight, or when the interval between the first and second seizure was long (>4 weeks). limitations: retrospective case series. koutinas (1994) population: dogs with idiopathic epilepsy (tier i level of confidence). sample size: 14 dogs, n=14 intervention details: study design: retrospective case series outcome studied: objective: to investigate the clinical and clinicopathological findings as well as response to treatment in epileptic dogs main findings (relevant to pico question): between seizures, neurological and funduscopic examinations were normal, and no important biochemical, haematological or cerebrospinal fluid abnormalities were observed. of 8 dogs treated with phenobarbital, seizures were controlled completely in 6 and partially in 2 limitations: retrospective case series. low study population. tier i level of confidence for diagnosing idiopathic epilepsy. srenk (1994) population: dogs with idiopathic epilepsy (insufficient level of confidence). sample size: 336 dogs, n=336 intervention details: analysis of the pedigrees of 336 swiss-bred golden retrievers over five generations study design: retrospective case series study outcome studied: objective: to investigate the genetic background for idiopathic epilepsy in golden retrievers main findings (relevant to pico question): males were particularly at risk. there was evidence of an autosomal multifactorial recessive mode of inheritance limitations: retrospective case series. insufficient confidence level for diagnosing idiopathic epilepsy the level of confidence for diagnosing idiopathic epilepsy (tier i-iii) used in this knowledge summary was based on the international veterinary epilepsy task force (ivetf) consensus statement on the diagnosis of idiopathic epilepsy (de risio, l. et al. 2015). any paper that included dogs with idiopathic epilepsy for which diagnostic investigations were below this tier level of evidence or unclear was considered to provide insufficient level of confidence for diagnosing idiopathic epilepsy. tier i was listed in the limitations of the papers as this could indicate that a few dogs might have suffered from structured epilepsy and as a result have not responded adequately or at all to the treatment. in addition, the terminology used was based on the ivetf consensus statement on the definition, classification and terminology of seizures in companion animals (berendt, m. et al. 2015). appraisal, application and reflection idiopathic epilepsy is a diagnosis of exclusion. the studies included in this summary supportthe fact that a thorough investigation of history and dog’s signalment are vital “starting points” for excluding other potential underlying causes of seizures. in all the studies the vast majority of dogs with confirmed or, at least, presumptive idiopathic epilepsy had an age onset less than 6-7 years. armaåÿu et al. (2014) found that 89% of dogs with idiopathic epilepsy had an age of seizure onset <6 years. similarly, smith et al. (2008) reported that only 2.2% of dogs <6 years old with unremarkable inter-ictal neurological examination had significant lesion (identifiable on mri), compared to 26.7% of dogs >6 years old.pákozdy et al. (2008) provided a more limited scale for the age of seizures onset (<5 years). podell et al. (1995) reported that the diagnosis of idiopathic epilepsy was more probable when the dog experienced the first seizure(s) between 1 and 5 years of age and was a large breed (>15 kg). viitmaa et al. (2013), kloene et al. (2008), casal et al. (2006) and patterson et al. (2005) found that the median age of seizure onset in their study population was 3 years. de risio et al. (2015) combined and analyzed the data from pákozdy et al. (2008) and armaåÿu et al. (2014) and found that there was a significant association between age of onset and cause of epilepsy for dogs under 6 years of age at epileptic seizure onset (chi-squared = 5.136, n = 431, p = 0.023) when the cut-off was set at 6 months. dogs aged between 6 months and 6 years were significantly more likely to be affected by idiopathic than structural epilepsy in comparison to the dogs aged beyond this range. various breeds have been considered to be prone to idiopathic epilepsy. multiple genes and recessive modes of inheritance have been investigated. seppälä et al. (2012), ekenstedt, k. et al. (2011), kloene, j. et al. (2008), pákozdy et al. (2008), licht et al. (2007), casal, m. et al. (2006), patterson et al. (2005), patterson et al. (2003), kathmann et al. (1999), jaggy et al. (1998a) and hall et al. (1996) reported various breeds. also, the consensus statement by hülsmeyer et al. (2015), reviewed all the current evidence available for breeds that have been identified as being predisposed to idiopathic epilepsy with a proven or suspected genetic background. specifically, breeds include german shepherds, australian shepherds, belgian shepherds, bernese mountain dogs, beagles, border collies, border terriers, cavalier king charles spaniels, dachshunds, dalmatians, english springer spaniels, finnish spitz, golden retrievers, hungarian vizslas, lagotto romagnolo, labrador retrievers, irish wolfhounds, italian spinone, petit basset griffon vendeen, shetland sheepdogs, standard poodles and keeshonds. jokinen et al. (2007) reported juvenile epilepsy in lagotto romagnolo with mainly focal seizures and seizure onset of5 to 9 weeks. rusbridge et al. (2004) reported that idiopathic epilepsy in cavalier king charles spaniels is more frequent in lines originating from whole-colour dogs. the latter characteristic was also considered to influence the development of occipital hypoplasia. distribution of epilepsy has been considered to be affected by gender. most reports suggest males have an increased likelihood to develop seizures compared to females. viitmaa et al. (2013), jaggy and bernadini (2008), pákozdy et al. (2008) and casal et al. (2006) found that males were predisposed to idiopathic epilepsy. fredsø, n. et al. (2014) reported that neutered male dogs with idiopathic epilepsy had a significant shorter survival (median: 38.5 months) compared to intact male dogs (median: 71 months). van meervenne et al. (2014) also reported and that there was an over-representation of male dogs with idiopathic epilepsy but no conclusions could be drawn as far as the effect of sterilisation status in seizures is concerned. in a retrospective case series study by van meervenne et al. (2014), it was suggested an association between oestrus and seizures onset in intact female dogs with presumptive idiopathic epilepsy. however, pákozdy et al. (2008) found no correlation of seizures with oestrus as well as stress or excitement. in addition, the relation between lunar cycle and seizures has been investigated by browand-stainback et al. (2011) and pákozdy et al. (2008) who showed no relationship between the two. apart from the signalment and history, the cornerstone for diagnosing idiopathic epilepsy is a normal inter-ictal neurological examination. prior to the neurological examination, though, a general clinical examination should be performed to detect possible signs that could be related to or even be confused with seizures. in all the studies the dogs with confirmed or presumptive idiopathic epilepsy had normal inter-ictal neurological status (only a few dogs had neurological signs but these were considered as postictal). indeed, armasu et al. (2007) reported that there are further risk factors, besides signalment, that increase or decrease the risk of intracranial pathology or provide one with a diagnosis of idiopathic epilepsy. precisely, the seizure severity (e.g. cluster seizures) and abnormal neurological examination findings (which was considered one of the most important) were highly associated withstructural epilepsy. the same authors reported that 84% of dogs with idiopathic epilepsy had a normal neurological examination. smith et al. (2008) and pákozdy et al. (2008) also supported that unremarkable inter-ictal neurological findings in combination with the age of seizure onset are important factors for diagnosing idiopathic epilepsy. specifically, pákozdy et al. (2008) reported that status epilepticus, cluster seizures, partial seizures, vocalisation during seizure and impaired neurological status were more readily seen with structural epilepsy. ghormie et al. (2015) found that in 99 dogs ≥ 5 years of age at seizure onset, an abnormal neurologic examination had 74 % sensitivity and 62 % specificity to predict structural epilepsy. armaåÿu et al. (2014) found that dogs with neurological abnormalities interictally were 16.5 and 12.5 times more likely to have an asymmetrical structural cerebral lesion and a symmetrical structural cerebral lesion, respectively, rather than idiopathic epilepsy. magnetic resonance imaging (mri) of the brain, clinicopathological tests, i.e. haematological, biochemistry profile and urinalysis as well as cerebrospinal fluid (csf) analysis can be considered an important part in the diagnostic investigation of idiopathic epilepsy. de risio et al. (2015) suggested that clinicians should perform brain mri and csf analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset <6 months or >6 years, inter-ictal neurological abnormalities as a result of intracranial lesion, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of ie and in refractory cases. the findings from these results are expected to be unremarkable and non-indicative of any known underlying cause of seizures. in the plasma and csf, in particular, various studies have been performed to reveal potential biomarkers that would help to identify epilepsy in dogs, either in earlier or later stages of the disease. bartels et al. (2014) showed that chemokines (e.g. ccl19) were increased in dogs with idiopathic epileptic compared to healthy individuals; but compared to dogs with other neuro-inflammatory diseases, chemokines were markedly decreased. hasegawa et al. (2014) showed that metabolites including glutamic acid and ascorbic acid in csf might be useful for the diagnosis of canine epilepsy. merbl et al. (2014) found higher csf concetrations of tumour necrosis factor-α (tnf-α) and interleukin-6 (il-6) in dogs with naturally occurring seizures compared to a control group of healthy dogs. wessmann et al. (2010) found epithelial cells in 6.5% of dogs of the study population affected by idiopathic epilepsy, although it was considered as a non-specific incidental finding. goncalves et al. (2010) reported that seizures could initially result in a mild increase oftotal nucleated cell count; thus, this fact should be considered when taking csf straight after a seizure (false positive elevation). podell, m. et al. (1997) reported that altered gamma-aminobutyric acid and glutamate values in csf might be indicative of a state of chronic overexcitation in the brain of dogs with idiopathic epilepsy. similarly, ellenberger et al. (2004), reported that csf concentrations of gamma-aminobutyric acid and glutamate were significantly lower in labrador retrievers with genetic epilepsy compared to control group dogs or in non-labrador retrievers with idiopathic epilepsy; the same study showed that csf concentration of aspartate was significantly lower in all the epileptic dogs. creevy et al. (2013) and gesell et al. (2013) found that glutamate and endocannabinoids anandamide (aea) concentrations, respectively, were higher in csf of dogs with idiopathic epilepsy compared to a control group of healthy dogs. calvo (2012) measured the c-reactive protein in the blood of dogs with idiopathic epilepsy and, contrary to dogs suffering from other causes of seizures as well as healthy dogs, detected increased concentrations within 24 hours but a decline after that period. further csf and/or plasma indicators that were investigated failed to contribute towards the diagnosis of idiopathic epilepsy. specifically, weber et al. (2012), fuente et al. (2012), fujiwara et al. (2008) and lobert, v. et al. (2003) showed that csf glucose level/glucose ratio, d-dimers, glial fibrillary acidic protein autoantibodies and pyruvate/lactate levels respectively were not useful for supporting the diagnoses of idiopathic epilepsy. in all, based on these results, researchers succeeded or failed to establish certain plasma and/or csf biomarkers associated with seizures in epileptic dogs. however, there is still research that could be performed in the future, either for the above or new biomarkers for epilepsy. electroencephalogram (eeg) is regularly used as one of the diagnostic procedures in humans and its utility in dogs has been assessed in a few studies. jaggy et al. (1998b) and srenk et al. (1996) reported that, despite anaesthesia, interictal eeg features were consistent and unique in dogs with idiopathic epilepsy. holliday and williams (1998) reported that interictal eeg might be useful diagnostic technique in dogs with idiopathic epilepsy. viitmaa et al. (2014)supported the use of fluoro-d-glucose positron emission tomography (fdg-pet) and to less extend, eeg in epileptic dogs as diagnostic tool.however, akos et al. (2012) revealed that interictal eeg rarely showed epileptic discharges and therefore the diagnostic value of the eeg in the diagnosis of epilepsy appeared to be low. brauer et al. (2012) found that interictal eeg was not a useful diagnostic method because it could detect epileptic activity in less than one third of all seizuring dogs (including symptomatic epilepsy) of the study population. all in all, there are quite a few challenges of using eeg routinely in animals and further work need to be performed. in conclusion, diagnosis should be based on history, signalment (age of onset (>6months and <6years), breed, sex), normal interictal neurological examination, seizure type, unremarkable complete blood count, biochemistry profile and urinalysis in the first instance. this can be supported by excluding structural lesions with advanced brain imaging techniques (i.e. mri) and an unremarkable csf analysis and cytology. eeg for identification of the characteristic patterns of epileptic seizures is highly recommended as a confirmation of the diagnosis.based on the recent consensus statement by de risio et al. (2015), all these diagnostic features and tests were categorized based on their value in criteria for the diagnosis of idiopathic epilepsy are described in a three-tier system.precisely, tier i is based on signalment, history, general and neurological examination as well as minimum data base blood tests and urinalysis. tier ii is based on tier i, plus unremarkable fasting plus post-prandial bile acids as well as brain mri and csf analysis. tier iii is based on tier i and ii, plus identification of electroencephalographic abnormalities characteristic for seizure disorders. implications for the future: advance diagnostic procedures, such as mri and eeg willbecome more widely available in order to improve the quality of diagnosis of canine epilepsy. recently, the consensus statements by rusbridge et al. (2015) and matiasek et al. (2015) recommended specific mri and diagnostic pathology protocol, respectively, for investigating idiopathic epilepsy. lastly, further studies with a high quality design (i.e. blinded randomised controlled studies), low overall risk of bias and greater number of dogs investigating established or new diagnostic methods (e.g. csf or serum biomarkers) for idiopathic epilepsy are needed because the current evidence in veterinary medicine is relatively weak. limitation of the summary: the main limitation of this summary is that we could not obtain full access to a few papers included in the summary of evidence. these included: hasegawa, t. et al. (2014), browand-stainback, l. et al. (2011), ekenstedt, k. et al. (2011), oberbauer, a. et al. (2003), kathmann, i. et al. (1999), holliday, t. and williams, d. (1998) and hall, s. et al. (1996) methodology section search strategy databases searched and dates covered: pubmed and cab abstracts 1973 to 2015 combined search on ovid platform search terms: (dog or dogs or puppy or puppies or canis or canine) and (idiopath*) and (epilep* or seizur* or convuls*) and (diagnos* or identif* or assess* or test* or exam* or history or compaint* or symptom* or risk* or aetiolog* or etiolog*) dates searches performed: 23 november 2015 exclusion / inclusion criteria exclusion: summary updates, non-systematic reviews* inclusion: studies evaluating or reporting the diagnosis of canine idiopathic epilepsy. *there was a non-systematic review van meervenne, et al. (2014) that was included because it made important conclusions and valuable up-to-date points for our summary. this paper was not included in the table but in the text. the same applies for the ivetf consensus statements by berendt et al. (2015), de risio et al. (2015), hã¼lsmeyer et al. (2015), matiasek et al. (2015) and rusbridge et al. (2015) search outcome database number of results excluded – study design excluded – did not answer pico question excluded – duplicates total relevant papers ncbi pubmed and cab abstracts 260 28 22 162 48 total relevant papers when duplicates removed 48   references armaåÿu, m., et al (2014) an exploratory study using a statistical approach as a platform for clinical reasoning in canine epilepsy the veterinary journal, 202(2), pp.292–296 http://dx.doi.org/10.1016/j.tvjl.2014.08.008 akos, p. et al (2012) electroencephalographic examination of epileptic dogs under propofol restraint. acta veterinaria hungarica, 60(3), pp. 309-324 http://dx.doi.org/10.1556/avet.2012.026 bartels, j. et al. (2014). mip-3beta/ccl19 is associated with the intrathecal invasion of mononuclear cells in neuroinflammatory and non-neuroinflammatory cns diseases in dogs. bmc veterinary research, 10:157  http://dx.doi.org/10.1186/1746-6148-10-157 berendt, m., et al. 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(1999) clinical, epidemiological and therapeutic aspects of idiopathic epilepsy in 25 golden retrievers: results of a long-term study. schweizer archiv fur tierheilkunde, 141(5), pp.231-238 licht, b. g., et al (2007) clinical characteristics and mode of inheritance of familial focal seizures in standard poodles. journal of the american veterinary medical association, 231(10), pp. 1520-1528 http://dx.doi.org/10.2460/javma.231.10.1520 lobert, v., mischke, r. and tipold, a. (2003) lactate and pyruvate levels in blood and cerebrospinal fluid. kleintierpraxis, 48(12), pp. 735-743 matiasek, k. et al. (2015) international veterinary epilepsy task force recommendations for systematic sampling and processing of brains from epileptic dogs and cats. bmc veterinary research, 11:216 http://dx.doi.org/10.1186/s12917-015-0467-9 merbl, y.,et al  (2014) tumor necrosis factor-α and interleukin-6 concentrations in cerebrospinal fluid of dogs after seizures. journal of veterinary internal medicine 28(6), pp.1775-1781 http://dx.doi.org/10.1111/jvim.12462 morita, t., et al (2002) cliniconeuropathologic findings of familial frontal lobe epilepsy in shetland sheepdogs. canadian journal of veterinary research, 66(1), pp. 35-41 oberbauer, a.m., et al (2003) the genetics of epilepsy in the belgian tervuren and sheepdog. journal of heredity, 94(1), pp.57-63 http://dx.doi.org/10.1093/jhered/esg010 pákozdy, a., et al (2006) seizures in boxer a retrospective study (1999-2005). wiener tierarztliche monatsschrift, 93, pp.270-276 pákozdy, a., et al. 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(1995) seizure classification in dogs from a nonreferral-based population. journal of the american veterinary medical association 206(11), pp.1721-1728 rusbridge, c., and knowler, s.p. (2004) inheritance of occipital bone hypoplasia (chiari type i malformation) in cavalier king charles spaniels. journal of veterinary internal medicine 18(5), pp.673-678 http://dx.doi.org/10.1111/j.1939-1676.2004.tb02605.x rusbridge, c., et al. (2015) international veterinary epilepsy task force recommendations for a veterinary epilepsy-specific mri protocol. bmc veterinary research, 11:194 http://dx.doi.org/10.1186/s12917-015-0466-x seppälä, e.h., et al (2012) identification of a novel idiopathic epilepsy locus in belgian shepherd dogs. plos one, 7(3): e33549 http://dx.doi.org/10.1371/journal.pone.0033549 smith, p.m., talbot, c.e. and jeffery, n.d. (2008) findings on low-field cranial mr images in epileptic dogs that lack interictal neurological deficits. the veterinary journal, 176(3), pp. 320-325 http://dx.doi.org/10.1016/j.tvjl.2007.03.003 srenk, p., et al. (1994) genetic background for idiopathic epilepsy in golden retrievers. tierarztliche praxis, 22(6), pp.574-578 srenk, p. and jaggy, a. (1996) interictal electroencephalographic findings in a family of golden retrievers with idiopathic epilepsy. journal of small animal practice 37(7), pp.317-321 http://dx.doi.org/10.1111/j.1748-5827.1996.tb02398.x van meervenne, s.a e. et al. (2015) association between estrus and onset of seizures in dogs with idiopathic epilepsy. journal of veterinary internal medicine 29(1) pp 251-263 http://dx.doi.org/10.1111/jvim.12505 van meervenne, s. a. e. et al (2014) the influence of sex hormones on seizures in dogs and humans. the veterinary journal, 201(1), pp.15–20 http://dx.doi.org/10.1016/j.tvjl.2014.05.008 viitmaa, r., et al . (2006) magnetic resonance imaging findings in finnish spitz dogs with focal epilepsy. journal of veterinary internal medicine 20(2), pp. 305-310 http://dx.doi.org/10.1111/j.1939-1676.2006.tb02861.x viitmaa, r., et al  (2013). phenotype, inheritance characteristics, and risk factors for idiopathic epilepsy in finnish spitz dogs. journal of the american veterinary medical association, 243(7), 1001-1009 http://dx.doi.org/10.2460/javma.243.7.1001 viitmaa, r., et al (2014) cerebral glucose utilization measured with high resolution positron emission tomography in epileptic finnish spitz dogs and healthy dogs. veterinary radiology & ultrasound, 55(4), pp.453-461 http://dx.doi.org/10.1111/vru.12147 weber, j., maiolini, a. and tipold, a. (2012) evaluation of decreased glucose levels in the cerebrospinal fluid of dogs. tierarztliche praxis kleintiere, 40(5) p325-332 wessmann, a., et al  (2010) significance of surface epithelial cells in canine cerebrospinal fluid and relationship to central nervous system disease. veterinary clinical pathology, 39(3), pp.358-364 http://dx.doi.org/10.1111/j.1939-165x.2010.00248.x intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. are dogs fed a kibble-based diet more likely to experience an episode of gastric dilatation volvulus than dogs fed an alternative diet? a knowledge summary by louise anne buckley phd, rvn 1* 1harper adams university, newport, shropshire, tf10 8nb *corresponding author (lbuckley@harper-adams.ac.uk) vol 2, issue 2 (2017) published: 19 apr 2017 reviewed by: nicola ackerman (bsc(hons), rvn, certsan, certvnecc, vts(nutr), a1 v1 mbvna) and sue badger (med, cert ed, rvn) next review date: 19 apr 2019 doi: 10.18849/ve.v2i2.63 clinical bottom line most of the studies that attempt to either partially or fully address the pico contain limitations that mean that they should either be rejected as unable to address the pico or viewed with caution due to potential bias in the population studied. of the two studies that remain, the findings conflict. one study found dogs fed a diet containing small particles only (<5mm, mainly dry kibble fed dogs) at greater risk of gdv than those fed a diet containing large particles (>30mm, at least partly non-kibble based). the other study found no significant effect of kibble on gdv risk once other potential risk factors were controlled for in the analysis. consequently, there is insufficient quality evidence to support the claim that feeding a kibble diet is associated with an increased risk of gdv. however, it is worth noting that no studies found that dogs fed a diet that contained no kibble (dry or moistened) were at increased risk of gdv, and the addition of either table scraps, canned food or non-kibble supplements to the dog’s diet reduced the risk in some studies but more research is needed to unpack the implications of this for feeding a kibble diet. question are dogs fed a kibble-based diet more likely to experience an episode of gastric dilatation volvulus than dogs fed an alternative diet? clinical scenario a client attends the veterinary clinic with a breed of dog considered to be at a high risk of gastric-dilatation volvulus (gdv). during the consultation, the dog’s dietary needs are being discussed. the client says that they have been on an internet discussion forum and other owners have warned them that feeding a dried, kibble-based diet will put their dog at an increased risk of having an episode of gdv. the client asks you, the veterinary practitioner, what the evidence is for this claim. the evidence the literature searches uncovered six papers (glickman et al., 1997; elwood, 1998; theyse et al., 1998; raghavan et al., 2004; pipan et al. 2012; uhrikova et al., 2015) that either partially or fully addressed the pico question. these papers do not neatly address the pico as the dogs studied either all/almost all were fed a kibble only diet or kibble as the primary diet (glickman et al., 1997; ragavan et al., 2004) or fed different diet types in combination (theyse et al, 1998; uhrikova et al., 2015) and/or assessed diet in terms of the maximum size of the food particles (theyse et al, 1998; uhrikova et al., 2015) that comprised the diet fed so the summaries of the experimental details should be examined for further understanding. of these papers, one paper found feeding a kibble diet increased gdv risk (pipan et al., 2012) but failed to match dogs for size between groups so the findings may have been biased if large breed dogs are more likely to be fed kibble-based diets. one paper (uhrikova et al., 2015) found no effect of feeding a kibble only diet, but dogs fed a diet containing some kibble were more likely to experience a gdv than dogs fed a diet with no kibble. however, in this study the median weight of the dogs in the control group was significantly different to those in the two gdv groups (groups based on gdv – survival: 1. survived, 2. died) making this study susceptible to the same criticism leveled at pipan et al. (2012). however, the direction of effect is not reported (i.e. it is not clear whether the dogs in the control group were lighter or heavier than one or both of the gdv groups). raghavan et al. (1997) claimed there was no effect of feeding a kibble diet but all, bar two, dogs (n = 318) in their study were being primarily fed a dry, kibble-based diet so there was no alternative diet control group to compare to and thus the effect of feeding kibble not amenable to meaningful statistical analysis. in elwood (1998), the main statistical analysis demonstrated no effect of kibble on gdv risk, but the initial analysis did identify kibble as a potential risk factor. however, feeding a diet that contained no kibble reduced the risk of gdv (uhrikova et al., 2015), as did feeding table scraps (but not canned commercial food) as part of the diet (glickman et al., 1997) or adding fish or egg supplements to the diet (pipan et al., 2012). several studies (glickman et al., 1997; elwood, 1998; raghavan et al., 2004; uhrikova et al., 2015) reported collecting data on dry and moistened kibble diets, but only one paper (glickman et al., 1997) reported their findings specifically in relation to dry kibble versus moistened kibble. they found that moistening the dry kibble diet before feeding did not affect risk of gdv compared with feeding dry kibble only. both of the papers (theyse et al., 1998; uhrikova et al., 2015) that focused on particle size present within the diet found that feeding a diet with small particles of food only (< 5mm; theyse et al., 1998) or medium particles of food as a maximum (5-30mm, but not small particles less than < 5mm; uhrikova et al., 2015) increased risk of gdv compared with dogs fed a diet containing some large particles of food (> 30mm). in these studies, any diet containing particles greater than > 30mm contained none-kibble components (either partially or exclusively). in the theyse et al. (1998) study, 83% (19/23 dogs) in the < 5mm category were fed a kibble only diet. no studies identified feeding a diet that did not contain kibble as a risk factor for gdv. summary of the evidence pipan (2012) population: privately owned dogs (any breed or mix, both sexes, neutered and entire) across a wide geographic area. the survey was potentially available to english speaking dog owners with access to the internet in any country worldwide. sample size: 2551 surveys included in the analysis: control group (dogs without a gdv): 1437 respondents gastric dilatation-volvulus group (gdv): 1114 respondents intervention details: online survey based study, with ad hoc convenience sampling of dog owners. the questionnaire was divided into three sections: demographic information (year of birth, breed, sex, neuter status, and purpose of the dog; country and postcode of respondent). whether the dog had ever had a gdv that required surgical intervention. this latter question was used to divide dogs into the control group and the gdv group. however, the authors then also included within the gdv group dogs that did not have surgery, or died / were euthanised without surgery but were considered to have a gdv (whether confirmed or presumed). gdv group: a series of 44 questions divided into 4 categories were asked that covered: dog specific factors management factors environmental factors personality factors control group: the same questions were asked of the control group dog owners as were asked of the gdv group, with the exception that they were not asked any questions about the gdv episode (as the dogs had not experienced a gdv). they were asked one additional question (had the dog had a prophylactic gastroplexy?). these changes reduced the total number of questions asked to 32. study design: cross-sectional study outcome studied: the outcome measure was a gdv episode that required surgical intervention in the dog’s history. the study looked for factors that were associated with an increased incidence of gdv in the population studied. of relevance to this pico, the authors’ asked owners: what type of diet the dog was fed? (dry kibble, canned food, raw commercial, cooked homemade, raw homemade) whether the dog’s diet was supplemented with any of the following? (eggs, cod liver oil, fish, cooked chicken, raw chicken, cottage cheese, yoghurt*) *plus others not clearly relevant to changing the diet texture or moisture content. main findings (relevant to pico question): the primary relevant finding was that feeding a kibble diet significantly increased the risk of gdv (odds ratio: 1.7, 95% confidence interval: 1.21 – 2.39, p = 0.002). adding the following supplements to the dog’s diet significantly reduced the risk of gdv: fish dietary supplements (odds ratio: 0.51, 95% confidence interval: 0.37 – 0.70, p < 0.001) egg dietary supplements (odds ratio: 0.57, 95% confidence interval: 0.44 – 0.73, p < 0.001) feeding table scraps had no effect on gdv risk. the authors mention this finding in the discussion and there is no statistical output reported. limitations: the incidents of gdv were retrospective so owners may have already altered their dog’s diet (either type or by the addition of supplements), on the basis of veterinary recommendation or lay research. the authors do not outline whether owners were asked to complete the form based on the dog’s diet at the time (or preceding) the gdv, or, the present time, or not given a time frame to use. the study recruited dogs of any size, breed, and age. there was no attempt to match control and gdv cases across other dimensions that may have been relevant (e.g. breed, size, and/or age) in the study design or analysis and this may have affected the results. for example, are owners of large or giant breed dogs more likely to feed a dry kibble diet than owners of small and medium sized dogs (e.g. for reasons of economy)? and, if so, is any significant effect of kibble real or an artefact of the fact that large and giant breed dogs are more likely to have a gdv than small breed dogs? this would potentially skew the data in the direction reported by the authors. this failure to match control and gdv cases across other potentially relevant dimensions is one of the biggest drawbacks of this study and it would have been more useful if the study authors had restricted the study only to at risk breeds and / or dogs over a certain size (large / giant breeds) when answering this research question. the authors do not report investigating interactions between diet type and supplements in terms of increased or decreased risk. e.g. did adding fish to the diet of kibble fed dogs reduce the risk of gdv, but have no effect on the risk of gdv of canned fed dogs? etc. this limits the ability of the reviewer to interpret the supplement findings in relation to the pico or develop hypotheses to explain the study’s primary diet type finding. theyse (1998) population: great danes. sample size: 109 dogs: 38 dogs that had presented at the authors’ vet clinic with a gdv 71 dogs owned by members of a great dane breed society intervention details: clinic records were retrospectively searched for cases of acute gdv in great danes presented to the clinic over a 14 year period (january 1981 – december 1994). no information is provided on the fate (survived or died) of the dogs that attended the clinic. control dogs were obtained by contacting a great dane breed society. owners of both groups of great danes were asked to complete a questionnaire that asked owners about their feeding and exercise regime. demographic information was also recorded (age, sex, neuter status; and, for gdv dogs only, type of food eaten before the gdv episode). of particular relevance to this pico, owners were asked about their dogs’ diet and asked to provide a sample of the diet fed to their dog. study design: a cross sectional study (based on the rcvs knowledge knowledge summary guide); the authors’ describe it as a case-control study. outcome studied: the outcome of interest was whether the dogs had had an episode of gdv. the authors were then interested in identifying risk factors that were associated with a gdv outcome. of relevance to this pico, the authors’ asked about the dog’s diet and requested to provide a sample of the diet they fed their dog. all owners in the study complied (n=109). because the diet fed was often a combination of commercial brand(s) and/or home – prepared food and meat, the authors altered the risk factor/variable studied to maximum food particle size within the sample ration provided. an ordinal scale was used: <5mm (kibble or kibble and ground home-prepared food) 5-30mm (dry dog food and/or canned dog food and/or small, cut up pieces of home-prepared food). the dry dog food was a mix of meat chunks, flakes and grains. > 30mm (commercial dog food and/or home-prepared food, plus large chunks of meat). the commercial dog food was either kibble, dry, or canned dog food. main findings (relevant to pico question): dogs fed a diet that contained some particles that were greater than 30mm were 75% less likely to have a gdv episode than dogs fed a diet in which the maximum particle size was <5mm (odds ratio: 0.25, p = 0.017). a significant difference in risk of gdv was not observed between dogs in the <5mm category and dogs in the 5-30mm category. no further output is provided here. eighty three percent (19/23) dogs in the <5mm category were fed a dry kibble diet only. limitations: the authors retrospectively searched clinic records for gdv cases in great danes between 1981 and 1994 and owners of affected dogs were contacted to complete a questionnaire that retrospectively assessed feeding and exercise regime and to provide a diet sample. thus, owners were often being asked to recall information about their dog’s exercise and diet regime many years (up to circa 13 years if they conducted their retrospective search in 1994/5) after the gdv episode and/or likely death of their dog. factual recall is likely to be poor under these circumstances and this will have implications for accuracy of both diet type recall and sample provision. whereas, control group owners were probably being asked about an existing, current dog that they own (not enough information is provided to say this for certain). alternatively, dietary and exercise regime modifications may have been implemented post-acute gdv episode (in the dogs that survived) and these reported by the owner as their regime. this would prevent accurate measurement of risk factors associated with gdv development. there is not enough detail provided by the authors to allow this possibility to be evaluated. there is not enough information provided regarding the way that the owners fed their dogs the diet type. for example, does dry kibble diet refer to the type of food or the way in which the dry kibble diet was fed (e.g. was it fed ‘dry’ or fed ‘soaked’?). if the kibble diet was fed soaked by the owners, did the researchers soak the kibble before measuring the particle size? was this information extracted from owners? glickman (1997) population: owned dogs within the usa. sample size: 202 dogs (101 matched case-control pairings). intervention details: several veterinary practices were contacted to complete a clinical data sheet for dogs that were presented at the clinic, diagnosed with gdv, and whose owners were willing to be contacted by researchers. vets were asked to also identify a similar dog (matched for age and breed if pure breed, or age and weight if cross bred). researchers provided their own case control dog through the university veterinary hospital if vets were unable to. all owners (gdv, and case-matched control) were interviewed by phone. data on the following areas were collected: the owner of the animal environmental factors clinical history physical activities dietary factors personality and temperament two types of questions were asked: those designed to evaluate the dog in the 8 hours preceding the gdv episode (gdv dogs) or telephone interview (casedogs) those designed to evaluate the dog’s behavior, diet, etc more generally over the preceding year. of particular importance to this pico was diet and nutrition. the authors do not set out within the methodology what type of data they collected in respect of this. from the results section, it is possible to identify that the owners were asked about: diet type (dry, canned) use of dietary supplements whether the dry food was moistened study design: a cross sectional study (based on the rcvs knowledge knowledge summary guide); the authors’ describe it as a case-control study. outcome studied: the outcome variable was an episode of gdv. the authors looked for risk factors associated with this. of relevance to this pico, the potential risk factor evaluated included: diet type (canned, dry) of possible relevance to this pico, the following additional potential risk factors were evaluated: use of dietary supplements whether the dry diet was moistened or not feeding of table scraps main findings (relevant to pico question): almost all of the dogs, irrespective of gdv development, were fed a dry diet on a regular basis so the authors concluded that it was not possible to evaluate dry diet as a risk factor. feeding canned dog food did not significantly affect risk of gdv (odds ratio: 0.72, 95% confidence interval: 0.32 – 1.42, p = 0.34)*. feeding table scraps significantly decreased the risk of gdv (odds ratio: 0.41, 95% confidence interval: 0.17 – 0.96, p = 0.04)*. moistening the dry dog food did not affect risk of developing a gdv (p >0.25, no other values reported). very few dogs in either group were fed supplements, so the authors concluded that it was not possible to evaluate supplement use as a risk factor. *please note: in the original identification of potential risk or protective factors to include in the multivariate final analysis, the authors used the following p value thresholds to determine potentially significant factors: p < 0.25: for the preliminary univariate analysis. p < 0.20: for the intermediary multivariate analysis. these are very generous thresholds that increase the risk of a type 1 error (a false positive). while the authors are using this threshold as an intermediary step to determine factors for inclusion in the final statistical models, readers of the paper who are not familiar with statistics may over-interpret tables 1 (pg. 199) and 2 (pg. 200) of this paper, including drawing the inference that feeding canned food significantly decreased the risk of a gdv. limitations: it is not clear whether the gdv group included dogs that were deceased as a consequence of the first gdv episode. it is possible that referring veterinarians would not approach owners of dogs that died or, alternatively, that owners whose dogs died were more or less willing to be interviewed. this may have introduced bias into the data set if survival rate from a gdv is associated with diet type fed. elwood (1998) population: irish setter dogs (both sexes, neutered and entire) owned by members of uk irish setter breed clubs. sample size: 669 dogs: 75 dogs that had had an episode of gastric dilatation and/or volvulus 594 control dogs intervention details: a questionnaire was sent to members of uk irish setter breed clubs, and requested to complete one form per irish setter that they had owned in the last ten years. demographic information included age, sex, neuter status and whether the dog had ever had an episode of bloat/gdv. owners were requested to complete the answer by providing data for the dog that applied at the time of the first gdv episode (gdv dogs) or current data (control dogs). a range of questions were asked about potential risk factors. these included a range of dietary, environment, temperament and exercise-related factors. of specific relevance to this pico, the owners were asked what diet they fed their dog. study design: cross-sectional study. outcome studied: the outcome variable was whether an episode of gdv occurred. the study then asked about a range of variables, in order to identify risk factors that were associated with a gdv episode. of specific relevance to this pico, the owners were asked what they fed their dog: dry (unsoaked) dry (soaked) meat and biscuits proprietary tinned food (alone) proprietary tinned food (with biscuit) other (the owner was asked to provide details) main findings (relevant to pico question): dogs fed a dry diet was no more likely to have an episode of gdv than dogs fed other types of diet (odds ratio: 1.97, 95% confidence interval: 0.7 – 5.56, p > 0.05). nb. the initial univariate statistical analysis found that dogs that were fed a dry diet were significantly more likely to experience a gdv than dogs not fed a dry diet (odds ratio: 2.13, 95% confidence interval: 1.01 – 4.5; p < 0.05). however, once incorporated into a multivariate analysis that included, where possible, the other risk factors previously identified, the adjusted risk factor was no longer significant. it is not clear which other risk factors were definitively included in this multivariate analysis. limitations: the authors requested owners complete a questionnaire form for every irish setter dog that they had owned in the previous ten years. this poses a number of related issues for the data: the dogs may not still be alive. thus, it is not clear how the owners of the dogs not affected (the control dogs) could complete the questionnaire as per the instructions as the dogs may have been dead at the time of completion. do the owners then complete the form based on the management, exercise, feeding, etc routines of the dog shortly before it died, or when it was younger/fitter/healthier? if the owners all elect for the form (as the closest point to ‘current’) this could introduce significant biases into the data set. up to ten years ago, is a long time to expect owners to accurately reflect back and recall their dogs feeding, exercise, housing regime, and so on. as the gdv group owners were asked to recall this information from the time the dog had its first episode of gdv, the length of time the owners were required to reflect back could be even longer. the questionnaire is not sensitive to variations in feeding regime. for example, the diet type fed may vary from day to day, or over a longer time frame. thus, any risk factor identified may be arbitrary and true risk factors may not be identified. raghavan (2004) population: dogs (male, female, neutered and entire) from eleven different large and giant dog breeds (akita, bloodhound, collie, great dane, irish setter, irish wolfhound, newfoundland, rottweiler, saint bernard, standard poodle, and weimaraner), that were located within the usa. dogs were required not to have a medical history that included an episode of gdv. sample size: 318 dogs: 106 dogs that developed a gdv 212 dogs that did not develop a gdv (the control group) intervention details: this study used dogs drawn from a larger study (glickman, et al., 2000). the methodology for this study was as follows: the study began in june 1994 and ended in february 1999. therefore, the maximum possible period that a dog could be studied for was 58 months. dogs were recruited through breed clubs and dog shows. at the start of the study, owners were asked about the presence of gdv in the medical history of the dog or any of its first-degree relatives. the dog was physically assessed for body condition and temperament, and conformational measurements taken. within thirty days of recruitment, owners were provided with a detailed questionnaire to complete that provided data on the dog’s gdv history (if positive, the dog was excluded), breeding, medical history, reproductive status, personality and temperament, and dietary factors. owners were instructed to notify the researchers if any of the following outcomes occurred: the dog developed a gdv (if so, the researcher confirmed this with the veterinarian who treated the dog) the dog died of another cause the ownership of the dog was transferred to another person owners were contacted in 1997, 1998, and 1999 to find out if, over the duration of the study, their dog had developed a gdv and, if so, whether the dog died or survived. 1991 dogs were registered at the initial state (dog show). of these, 77 were excluded due to a previous history of gdv. the remaining dogs (n = 1914) were enrolled on the study, of these, at least one follow up was obtained for 1843 dogs and the detailed questionnaire was completed for 1660. of the latter group, 23 were excluded for being less than six months old at the start. this left 1637 dogs o be included in the analysis of this study. at the end of that prospective study, there was sufficient information on diet and ‘vital status’ (not defined by authors, presumed to be gdv development and other demographic information matched for in the current study), for 1634 dogs (of the 1637) to be potentially included in this study. of these, all dogs that developed a gdv (n=106) were included. dogs that developed a gdv during the prospective study were divided into six groups based upon the calendar year in which they developed a gdv (1994 – 1999*). the control group (n=212) was then randomly selected  to ensure that for each year, for each gdv dog there were two control dogs that had been alive the year that the gdv dog developed a gdv but who never themselves developed a gdv. *nb. the original study (glickman et al. 2000) states 1994 – 1999 (which would be six calendar years). the current study refers to “follow – up ended in december 2000” (pg. 193) and six consecutive calendar years of 1994 – 2000. however, it then directs the reader back to the detailed study methodology described in the glickman et al. 2000 study for further details. this study does not refer to follow up data in 2000 and, indeed the study was published in january 2000. thus, it is assumed that the current authors mean 1994 – 1999. study design: case-control study. outcome studied: the outcome measure was whether the dog developed an episode of gdv during the course of the study and whether it survived this episode. the study then looked for factors that were associated with an increased risk of developing gdv in the population studied. of direct relevance to this pico, the authors’ asked the owners about: the diet type fed to the dog (dry, canned, semi-moist, unprocessed, home-prepared [raw versus cooked], table scraps, treats) of potential relevance to this pico, the authors’ also asked: whether food was moistened before feeding main findings (relevant to pico question): there was no significant effect on diet type on risk of gdv. all of the dogs that developed a gdv (n=106) and all, bar two, of the control dogs (n=210) were fed a dry diet as their primary diet type. the median (range) percentage of metabolisable energy derived from the dry component of the diet was similar between controls (97.1, 0 – 100) and gdv cases (96.1, 59.5 – 100) (p = 0.99). primary was defined as the dog obtained > 50% of its metabolisable energy from this food type. there was no effect of moistening the kibble on gdv risk (p >0.25). limitations: failure of the authors to report the findings of some of the data referred to in the methods section limits the ability to interpret some of the findings or draw conclusions. the authors collect data on diet type fed at the start of the study (within 30 days of recruiting dogs). no further attempts were made to collect further data on this at regular intervals. thus, unless diet type fed is static and does not change over time, this reduces the ability of the study to detect real effects or meaningfully explain the effects observed. all the dogs in the study (bar two) were fed dry food as the primary diet type. therefore, it is not clear how the study could evaluate kibble as a risk factor as there were inadequate numbers of dogs in each group (i.e. none in the gdv group and two in the no gdv control group) fed an alternative diet type. uhrikova (2015) population: dogs* owned by people who could read either czech or slovak language. the survey was distributed within the czech republic through various websites aimed at dog owners, some veterinary clinics and dog shows, and by emailing owners through kennel and large breed kennel club websites. however, survey distribution was not restricted to the czech republic, so respondents came from a wider geographic area, though predominantly czech (90.7% of respondents).  *the control dogs were dogs older than 5 years, and weighing > 30kg and/or taller than 50cm, and had not had a gastroplexy performed. it is not clear whether the same restrictions applied to the two gdv groups (see below).  however, it should be noted that, in the results section, the study population overview indicates that this weight restriction must have been lifted as the minimum weight in the control, gdv – survivor, and gdv – died groups was 17kg, 20kg, and 17kg respectively (see limitations). sample size: 785 usable responses: control group: 536 dogs survived gdv group: 127 dogs died from the gdv group: 122 dogs intervention details: the survey was comprised two parts: part a was accessible by all three groups of respondents; part b was accessible only by owners of dogs who had had an episode of gdv (regardless of survival). part a: demographic information included breed, age, sex, and weight was requested. a range of questions were asked about potential risk factors. these included a range of dietary, elimination and exercise related factors. family history of gdv was also asked. of specific relevance to this pico, owners were asked whether they mainly fed: kibbles kibbles with liquid (water, soup, or other) kibbles with meal (cooked or canned) meal (cooked or canned) barf (bones and raw food) other for the purpose of analysis, the diets fed were merged into the following categories: dry kibbles meals with kibbles other than dry (presumably liquid added) or other kinds of kibbles (not defined) and / or with the additional of either canned or cooked food no kibbles in food of potential relevance to this pico, the authors also asked about the size of the particles of food fed as the diet: < 5mm (small) 5mm – 30mm (medium) > 30mm (large) part b: information was requested about the gdv episode. of specific background relevance to this pico (i.e. was the dog actually fed the usual diet immediately prior to a gdv developing?), in part b, owners were asked about the last type of meal fed before the dog developed a gdv. 785 usable responses: control group: 536 dogs survived gdv group: 127 dogs died from the gdv group: 122 dogs study design: a cross sectional study. outcome studied: the outcome variable was a) episode of gdv (yes/no?), and, b) of dogs that developed a gdv, survived or died? the study then looked for risk factors that were associated with these outcomes. of specific relevance to this pico, the authors looked at different diet types normally fed as potential risk factors for gdv development. they also examined the type of diet last fed before the dog developed a gdv. of potential relevance, they also asked owners about the size of the particles of food that comprised the dog’s diet. in the analysis, in calculation of the odds ratios, the relative risk associated with feeding a diet with small or large particles was compared to that of dogs fed a diet in which the maximum size fed was medium sized particles. main findings (relevant to pico question): part a of the questionnaire: dogs fed a dry kibble diet only were no more likely to have a gdv episode than dogs fed other diet types/combinations (odds ratio: 1.111, 95% confidence interval: 0.802 – 1.539, p = 0.527) dogs fed diets that did not contain any kind of kibble were significantly less likely to have a gdv than dogs fed a diet containing kibbles (dry kibbles, kibbles and canned food, or kibbles and cooked food) (odds ratio: 0.486, 95% confidence interval: 0.283 – 0.834, p = 0.009). dogs fed large (> 3 cm) particles of food were significantly less likely to have a gdv episode than dogs fed small (< 0.5cm) or medium (0.5 – 3cm) particles of food. compared to medium particle fed dogs, large particle dogs were 0.344 times as likely to have a gdv (95% confidence interval: 0.224 – 0.529, p < 0.0001). there was no significant difference in gdv risk between dogs fed small and medium particles of dog food.  although the authors do not formally analyse the small versus large categories, it should be noted that the 95% confidence interval for the small and large particle categories overlap and so a significant difference was not observed between these two categories: maximum particle size < 0.5cm: odds ratio: 0.865, 95% confidence interval: 0.425 – 1.761 maximum particle size > 3.0cm: odds ratio: 0.344, 95% confidence interval: 0.224 – 0.529 part b of the questionnaire: 77% of dogs that had a gdv were fed their usual diet type as their last meal before the episode occurred. no further information relevant to the pico is supplied. limitations: the authors do not specifically outline whether owners were directed to record the biggest particles in the food before or after soaking the kibble. although the questionnaire design allowed the authors to compare dry kibble that had been moistened before feeding versus other non-kibble based diets, before analysis the authors merged diet categories into: dry kibble only meals with kibbles other than dry kibbles, moistened kibbles, kibbles plus other food type, etc. no kibbles as the non-dry kibbles category covered both moistened kibble only diets and kibbles with any other diet type as well, this limits any inferences that could be drawn versus the risk of dry kibble versus moistened kibble in this diet. the authors report that the control group was designed to be restricted to > 30kg, the results section indicates that all groups contained dogs weighing less than this. furthermore, the authors report that there were highly significant (p < 0.001) differences in the median weight between the control group and the gdv groups, but they fail to state the direction of the effect. however, the authors chose to report their data using means and the range (minimum – maximum values). the failure to report this data using the median and inter-quartile range (it is assumed that, as a non-parametric test was used, this data was skewed), means that it is impossible to evaluate how these groups differed. appraisal, application and reflection six studies were identified that purported to address the pico either partially or fully. the findings of these studies were mixed and of variable quality. however, no studies found that feeding kibble as a protective factor reduced the risk of an episode of gdv. teasing out the different potential aspects to this pico (e.g. dried kibble per se versus other diets; dry kibble versus moistened kibble, or diet fed immediately prior to gdv versus the usual diet fed) was difficult or impossible to evaluate due to limitations or differences in the study design. in some cases, diet type was described in terms of maximum particle size present in the diet, rather than diet type. these studies and information have been included for the following reasons: the author is unaware of any kibble diets that have kibbles that are bigger than 30mm; the authors report that any diet containing the largest particles contained non-kibble components (thereby fulfilling the inclusion criterion); the authors report other information that makes clear that some of these diet sizes were kibble based.  two studies should be removed from consideration before drawing any inference about the risk of gdv posed by feeding a dried kibble diet (moistened and/or fed dry) per se. the first of these, glickman et al. (1997), intended to evaluate kibble as a risk factor, but found that almost all owners reported feeding their dog (irrespective of whether the dog was in the gdv or control group) mainly a kibble diet. the authors rightly note that, consequently, it was not possible to evaluate a dried kibble diet per se as a risk factor for gdv as there is no comparator (for example, of non-kibble fed dogs, what proportion develop a gdv compared to dogs fed a kibble diet?). it should be noted though that this study did identify the addition of table scraps to a dog’s diet was a protective factor: dogs fed partially on table scraps had a significantly reduced risk of gdv of 59%. the study design does not allow the reader to tease apart the owner feeding regimes further so it is difficult to evaluate the impact of this finding in relation to the pico. however, this aspect of the study does not suffer from a lack of comparator so this finding should be taken forward to the final evaluation. although ragahavan et al. (2004) report that there was no significant effect of feeding kibble on risk of gdv, this study suffers from the same limitation as the glickman et al. (1997) study as all, bar two, of the dogs included were primarily fed on a kibble-based diet. the authors do extend their analysis by exploring the proportion of metabolisable energy derived from the kibble component of the diet (to account for mixed diet type feeding) to demonstrate that the proportions do not vary between groups, but this does not remove the limitation described here. of the remaining four studies, the pipan et al. (2012) study reports an impressive sample size (gdv group: n=1114; control group: n=1437) and reports that feeding a kibble diet significantly increases the risk of gdv. however, the population that the authors elected to study was not restricted to large and giant breeds/sized dogs (i.e. those which are considered to be at high risk of gdv). as the authors do not report requesting information about the body weight of the dogs included in the survey, and there is no evidence to suggest this in the results section, it is not possible to evaluate whether the two groups of dogs varied significantly across this potentially important dimension. consequently, the study findings should be approached with caution as a potential source of relevant bias has been introduced into the methodology if large and giant breeds are more likely to be fed a kibble based diet than small and medium sized breeds. as a dried kibble diet tends to cost less than commercial diets containing a higher moisture content, and big dogs cost more to feed than small dogs, the supposition of bias is reasonable. however, this study does also identify fish and egg-based dietary supplements (but not table scraps) as a highly significant protective factor against risk of gdv in dogs. whether this finding is also a potential artefact of the sample population is not necessarily clear, as the exact nature and form of the supplements is not clear. are smaller dogs more or less likely to be given supplements? uhrikova et al. (2015) also identified a dried kibble diet as part or all of the diet (but not dry, no liquid added before feeding, kibble only versus other diet combinations) as a risk factor for gdv compared to feeding a diet that contained no kibbles at all, however their study potentially suffers from the same criticism as the pipan et al. (2012) study. although uhrikova et al. (2015) appear to be alert to the bodyweight issue (their target control group definition attempted to restrict respondents to dogs weighing >30kg only), they were unsuccessful in achieving this. all groups of dogs included dogs lighter than 30kg, but a highly significant difference was observed in bodyweight between the control group and the two gdv groups (survived versus died). however, the authors fail to state the direction of effect and their choice of measure of variation (range) and central tendency (the mean is reported, despite using a non-parametric test to compare what was presumably skewed data) does not allow the reader to assess the impact of this difference. as a consequence, the findings of this study should also be viewed with caution in relation to the pico. uhrikova et al. (2015) also found that a diet with particles of food in which the maximum size was >3cm was a protective factor that reduced the risk of gdv compared with a diet containing diets in which the maximum particle size was 0.5 – 3cm, but significant differences between the smallest particle sized diets (<0.5cm) and the largest (>0.3cm) were not observed.   of the remaining studies, the elwood (1998) study most closely primarily addresses the pico. although a smaller sample size than some other studies (gdv dogs: n=75; control dogs: n=594), the methodology utilised by this study allowed the authors to examine the risk of feeding a kibble diet per se compared with other diet types, and the effect of the kibble diet being fed dry or moistened. the initial univariate analysis identified kibble as a potential risk factor; however, once other potential risk factors were built into the multivariate analysis, this potential risk factor was no longer significant. the primary issue with this study is that the authors requested that owners complete the form for any/all irish setter dogs that they had owned in the previous 10 years (regardless of whether they had had an episode of gdv or not). as owners of dogs that had had a gdv were instructed to answer the form by providing details of the dogs’ diet prior to the gdv episode, some owners may have had to recall back an even longer period of time. unless dogs are generally fed a relatively unvarying diet type over an extended period of time, this may reduce the value of owner recollection over such a long-time frame. the authors do not report data to allow the reader to evaluate whether the two groups differed across the dimension of ‘how long ago the dog was last owned/alive’ (or similar) to see if the demographics were similar between groups across this potential dimension. the remaining study (theyse et al., 1998) suffers from the same limitation in relation to the gdv group as they retrospectively searched records over a 13-year time span, for gdv cases (which may have died many years ago) and then contacted these owners to obtain, firstly, diet fed to the dog, and secondly, a sample of this diet. this was compared to a control group recruited through a breed society. this study identified feeding a diet with a maximum particle size of >30mm were significantly less likely to have a gdv than dogs fed a diet containing a maximum particle size less than <5mm (of which 19 of the 23 dogs in this category were fed a dry kibble diet only). if historical differences in trends in the type of diet fed were present (e.g. if dogs were more likely to be fed a raw diet in present time (at the time the study was conducted) than over the 13-year time frame studied, then this could have skewed the data in the direction described as the present-day dogs would have been primarily control group dogs. uhrikova et al. (2015) also found that feeding large particles of food had a protective effect against gdv and this study did not suffer the theyse et al. (1998) limitation described. however, the strength of the uhrikova et al. (2015) study in supporting the theyse et al. (1998) finding is weakened by the lack of transitive inference in their data, as no other size categories were significant (i.e. small > medium, and crucially small > large were not identified as relative risk factor relationships). in conclusion, most of the studies that form a part of this pico contained limitations that meant that they cannot specifically address the pico due to a lack of comparator (glickman et al., 1997; ragahavan et al., 2004), or viewed with considerable caution with regards to any significant effect of kibble feed due to issues with the population surveyed or reported (pipan et al., 2012; uhrikova et al, 2015). of the remaining two studies, the findings are not in agreement with one study (theyse et al. 1998) concluding that there was no effect of kibble, and one concluding that, relative to feeding diets with large particles, diets that were small particle sized (mainly dry kibble only feeders) were significantly more likely to experience a gdv. however, the long time frame over which owners were potentially asked to recall back (theyse et al., 1998; elwood, 1998), and the requesting of a diet sample for a dog that may have died up to 13 years ago (theyse et al, 1998) mean that these findings should not be accepted uncritically. however, the glickman et al. (1997) finding that table scraps significantly reduced the risk of gdv does provide some support for the alternative claim that feeding alternative diets may be a protective factor. however, there is a need for further research in this area, with adequate numbers of dogs being fed specific, identifiable, alternative diets (e.g. primarily raw, primarily home-made cooked, etc) in order for these hypotheses to be tested. the preponderance of dogs being fed primarily a kibble diet (based on the studies evaluated) may make this more problematic to investigate.  though as a consequence, the balance of unevaluated evidence supports the claim that kibble is a risk factor for gdv (and that non-kibble based diets or kibble plus non-kibble supplements or dietary additions may be a protective factor that reduces the risk of gdv), in practice, there is insufficient adequately controlled evidence to demonstrate this clearly. methodology section search strategy databases searched and dates covered: pubmed; science direct (all years, restricted to journals); web of science; cab abstracts. (1973-2016). search terms: (dogs or dog or canine or canines or canid or canis or bitch) and ("gastric dilatation" or "gastric dilation" or "gastric dilatation volvulus" or gdv or "gastric torsion" or "stomach volvulus") and (feed* or diet or diets or dietary or food or kibble dates searches performed: 29th march 2017 exclusion / inclusion criteria exclusion: pre-defined exclusion criteria: non-english language, popular press articles. inclusion: any comparative (control group utilised) study in which the effect of diet type* on development of a gastric dilatation (+/volvulus) was investigated. *diet type must refer to a dry or kibble based diet, plus at least one other type of diet in order for the study to be included. search outcome database number of results excluded – did not address the pico excluded – not english language excluded – conference abstract only excluded – duplication total relevant papers ncbi pubmed 35 30 0 0 0 5 thomson reuters web of science 35 28 1 0 5 1 cab direct 58 50 1 1 6 0 science direct 343 343 0 0 0 0 total relevant papers when duplicates removed 6 conflict of interest the author declares no conflicts of interest. references elwood, c. (1998) risk factors for gastric dilatation in irish setter dogs. journal of small animal practice, 39 (4), pp. 185 – 190. http://dx.doi.org/10.1111/j.1748-5827.1998.tb03627.x glickman, l. et al. (1997) multiple risk factors for the gastric dilatation – volvulus syndrome in dogs: a practitioner / owner case – control study. the journal of the american animal hospital association, 33 (3), pp. 197 – 206. http://dx.doi.org/10.5326/15473317-33-3-197 glickman, l. glickman, n. schellenberg, d. et al. (2000) incidence of and breed – related risk factors for gastric dilatation – volvulus in dogs. journal of the american veterinary medicine association, 216 (1), pp. 40 – 45. http://dx.doi.org/10.2460/javma.2000.216.40 pipan, m. brown, d. battaglia, c. et al. (2012) an internet – based survey of risk factors for surgical gastric dilatation – volvulus in dogs. journal of the american veterinary medicine association, 240 (12), pp. 1456 – 1462. http://dx.doi.org/10.2460/javma.240.12.1456 raghavan, n. glickman, n. mccabe, g. et al. (2004) diet – related risk factors for gastric dilatation – volvulus in dogs of high risk breeds. journal of the american animal hospital association, 40 (3), pp. 192 – 203. http://dx.doi.org/10.5326/0400192 theyse, l. van de brom, w. and van sluijs, f. (1998) small size of food particles and age as risk factors for gastric dilatation volvulus in great danes. veterinary record, 143 (2), pp. 48 – 50. http://dx.doi.org/10.1136/vr.143.2.48 uhrikova, i. machackova, l. rauserova – lexmaulova, l. et al. (2015) risk factors for gastric dilation and volvulus in central europe: an internet survey. veterinarni medicina, 60 (10), pp. 758 – 587. intellectual property rights knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. an exploratory study investigating the non-clinical benefits of evidence-based veterinary medicine elizabeth l. jackson bag (hons), mba, phd, sfhea1* sarah hauser bsc (hons), mpa, mpp1 1the royal veterinary college, hawkshead lane, north mymms, hatfield, hertfordshire, al9 7ta, united kingdom *corresponding author (eljackson@rvc.ac.uk) vol 2, issue 2 (2017) published: 30 may 2017 reviewed by: dr sebastian arlt and virginia fajt (dvm, phd, dacvcp) doi: 10.18849/ve.v2i2.93 section index:    abstract | introduction | methods | results | discussion | footnotes | conflict of interest | references | supplementary files abstract objective: as little prior research exists about the non-clinical benefits of evidence-based veterinary medicine (ebvm), this exploratory study was conducted to identify non-clinical benefits of ebvm to veterinary practices, as well as highlighting the barriers to further implementation, and ways to overcome them. background: a pico-based literature review (hauser and jackson, 2016) was conducted to establish current knowledge about the non-clinical benefits of ebvm. it found that while there are some papers suggesting a link between the practice of ebvm and better non-clinical benefits such as client satisfaction and client retention, a single study, focusing on the non-clinical benefits of ebvm, had yet to be conducted. evidentiary value: this exploratory study provides a solid basis for the further development of a confirmatory study of the themes identified in the interviews. the impact on practice from our findings is significant as it details the key areas where the use of ebvm can yield commercial benefits from the perspective of a group of ebvm experts via interview. it is entirely possible that international veterinary environments which mirror that of the uk will find this research beneficial. methods: due to the paucity of data about the non-clinical benefits of ebvm, an exploratory, qualitative approach was taken to this research in order to build a platform for further confirmatory, quantitative investigation (zikmund, 2003). in february and march 2016 interviews with 16 rcvs knowledge group chairs[1] were conducted. the interview guide contained broad, open-ended questions to explore existing tacit knowledge about the non-commercial benefits of ebvm. the interviews were audio recorded and transcribed verbatim and subsequently analysed using nvivo 11 software. results: this qualitative enquiry showed that the key areas where the use of ebvm can yield non-clinical benefits are through increased client satisfaction and retention, improved reputation and confidence of the veterinarian,  as well as employee engagement. in order to yield these benefits the two main barriers, time and resources, need to be overcome. conclusion: the themes highlighted in this paper provide a solid, real world base for further, quantitative study of the non-clinical benefits of practising ebvm.   application: the results of this research are applicable to practicing veterinarians, nurses and other practice staff. it is clear that practising ebvm not only leads to better clinical outcomes, but can also result in commercial benefits, such as better client retention and employee engagement [1] chairs of rvcs knowledge groups are recognised leaders in the field of ebvm and hold these invited positions within the uk’s royal college of veterinary surgeons. introduction little research exists on the non-clinical benefits of ebvm. while the clinical benefits have been fairly well documented, the business aspect of evidence-based veterinary medicine has not. in a situation such as this, zikmund (2003) suggests an exploratory approach to help inform a more rigorous, conclusive study when there is a need for generating new ideas. exploratory research is often qualitative in nature and thus does not attempt to provide conclusive answers to research questions. rather, it allows researchers to gain access to cultural norms and attitudes that are often too complex for confirmatory, quantitative enquiry. as such, sample size is often very small in comparison to quantitative studies because qualitative research focuses on the depth of understanding cultural knowledge, rather than how many or what kinds of people hold the knowledge. mccracken (1988, p. 17) summarises this methodological paradigm perfectly: “…qualitative research does not survey the terrain, it mines it. it is, in other words, much more intensive than extensive in its objectives”. a pico-based literature review (hauser and jackson, 2016) was conducted to establish current knowledge about the non-clinical benefits of ebvm and it concluded that while there are some papers suggesting a link between the practice of ebvm and better non-clinical benefits such as client satisfaction and client retention, a single study, focusing on the non-clinical benefits of ebvm, had yet to be produced. with the limited knowledge generated from this activity, this study was designed to gain further understanding of the non-clinical benefits of ebvm. as recommended by yin (2014), an interview guide containing broad, open-ended questions was developed to explore four key themes that emerged from the sparse existing knowledge: the definition of ebvm, the benefits of ebvm, the barriers to the adoption of ebvm and ideas for exploring the broader adoption of ebvm. this study forms the first phase of a two-part, mixed-method research project that will establish the non-clinical benefits of ebvm. this first phase is a qualitative enquiry essential for determining the under-studied area of the non-clinical benefits of evidence-based medicine. zikmund (2003) emphasises that this first, exploratory phase of a mixed-method project is particularly important when addressing under-studied areas of research as the discovery of new ideas is paramount in developing a well-informed confirmatory study. the secondary aim of this research was to use the results of the interviews to create a survey that will empirically test the tacit knowledge documented in this paper. as such it was important that the interview participants were experienced supporters of ebvm and were able to share their intimate knowledge about this way of practicing veterinary medicine. with this in mind, the interview participants were recruited from the list of chairs of the rcvs knowledge groups. chairs of rvcs knowledge groups are recognised leaders in the field of ebvm and hold these invited positions within the uk’s royal college of veterinary surgeons. bogner, littig and menz (2009) discuss the virtues of conducting expert interviews in exploratory research. these authors suggest that efficiencies in time and knowledge are gained when qualitative data are collected from experts as they share a common background and relevance of the topic with the researcher so no time is lost with superfluous background explanations. methods as one of the aims of this research was to use the results of the interviews to create a survey for the second part of this study, it was important that the interview participants were champions of ebvm and were able to share their success stories about this way of practicing veterinary medicine. with this in mind, the interview participants were recruited from the list of chairs of the rcvs knowledge groups. the interview participants were approached via e-mail which explained the purpose of the project and the ethics of the data collection process (i.e. participation in the research is entirely voluntary, despite the interviews being audio recorded all data would be anonymised and anyone was free to withdraw from the research at any time without fear of retribution). two pilot interviews were conducted prior to the formal data collection and yielded no requirements for the data collection instrument or the research setting to substantively change. interviews were conducted in person and via skype in february and march, 2016. the interviews were audio recorded and transcribed verbatim and subsequently analysed using nvivo 11 software. interviewees were asked about their views on financial, commercial and business impacts of ebvm on the individual business. while financial benefits only include monetary aspects such as profit and loss of a practice, business and commercial benefits include a wider spectrum of benefits such as client satisfaction, employee engagement and reputation. these benefits can have a major impact on the success of a business despite being difficult to measure. wider economic benefits, that include potential impacts on other industries, such as increased revenue in the meat processing industry due to better veterinary practice, were outside the scope of this study. the interview guide (available as a supplementary file), the information sheet about the project and the consent form to be signed by research participants was scrutinised and approved by the royal veterinary college’s clinical research ethical review board (approval #2015 1457). results with ethical approval from the royal veterinary college’s clinical research ethical review board (urn 2015 1457), a total of 16 interviews were conducted with people who are dedicated to the practice of veterinary medicine through the principles of ebvm. participants were self-selecting as their primary reason for contributing to this research was their dedication, enthusiasm and experience of practicing ebvm.  table 1 provides a summary profile of the research participants in terms of their main area of veterinary focus, age, gender, year graduated and whether or not they are a registered veterinarian. a seventieth ebvm knowledge chair was approached by declined to participate in the data collection because he considered that the research questions were being asked too prematurely for the current state of ebvm in uk veterinary practice. table 1: an overview of interview participant characteristics almost all participants were veterinarians, however, the interviews also included a veterinary technician and an animal nutritionist. interviewees have a great range of focus and experience in veterinary medicine. seven participants had some link to academia, while other participants worked in private practice, corporate practice, a government agency, or an ngo. while participants were purposefully not selected to be representative of the industry, it was ensured that the interviews were conducted with representatives from different fields of work, including: small animal, farm animal, equine, lab animal and mixed practices (which included exotics). the following is a thematic analysis of the interview data. many qualitative researchers follow the classic advice of glaser and strauss (1967) and take a grounded theory approach by allowing themes to naturally emerge from the data. due to the specific nature of this research, we have been guided by the advice of miles and huberman (1994) who advocate using a ‘start list’ for generating themes. the ‘start list’ for this research was based on the research questions which were, of course, developed from existing literature  (discussed in the introduction to this paper).  as such, the ‘start list’ was a loose list of themes that were grounded in the research questions. the ethos and presentation of qualitative research is often criticised as being unsystematic, impressionistic, sloppy and unsophisticated (glaser and strauss, 1967). similarly, creswell (2009) discusses the erroneous sentiment of ‘generalisability’ of qualitative research. he goes to some lengths to explain that the virtue of qualitative research lies in the multidimensional description and development of themes in the specific context of the research setting and how particularity, rather than generalisability is the hallmark of qualitative research. for presenting the results of the thematic analysis, we look to the advice of mccracken (1988) who discusses the method of inquiry associated with long interviews. he talks about the rich and useful knowledge that can be gained from the researcher providing sample quotes to capture the ideas and concerns of participants. the overall aim of this reporting method is for the abundant data to speak to the reader and provide a guided tour of the participants’ thoughts and opinions on each theme.   defining ebvm in order to properly set the scene of ebvm for the research participants, it was necessary to first determine their understanding of the concept so participants were asked to define ebvm. participants generally concurred that ebvm is “practicing medicine in a way that is supported by published evidence” (participant 11) and is an effort for practitioners to separate themselves from practicing veterinary medicine on the way they were taught as opposed to making clinical decisions based on high-quality published data and published evidence. support for these conclusions comes from the following participants: “clinical practice that is based on current research and experience of, the pooled experience of many clinicians, that has been validated to be a good way of doing things…” (participant 5) “…plying my craft or my trade in making my treatment decisions based upon the evidence that i have in front of me. all of the evidence, just not my personal opinion.” (participant 7) while most participants were clear about the definition of ebvm, some participants extended the definition to include ensuring that the quality of evidence was sufficient to make good clinical decisions: “it's just how you evaluate and choose your evidence…/…to actually structure and to formalise, to establish protocols for how you evaluate the information in front of you.” (participant 2) “…different scales of evidence, which might be, we've got very few meta-analyses in veterinary practice, but it might be published literature in your discipline or related disciplines.” (participant 10).   non-clinical benefits of ebvm discussing the non-clinical benefits of ebvm initially proved difficult for participants as their immediate response was that the adoption of ebvm results in clinical success: it leads to an improved standard of care. deeper questioning lead to further discussion about client satisfaction, client retention, improved reputation, confidence and a feel-good factor amongst practitioners. the best evidence about the commercial benefits for ebvm that emerged from the data was from participant 15 who said: “it's demonstrated that you know we're seeing increased sales of those things through the use of evidence based medicine”. participants largely agreed that practising ebvm will give a veterinary practice competitive advantage: “but what you can't get from anywhere else, are science and ethics. and if veterinary medicine can say, okay we're going to be scientific and practice evidence and we're going to be ethical, we then stand out.” (participant 9) “you can sustain a competitive advantage compared to your rivals because you’re staying in touch and you know what works best, if it doesn’t work best you remove it from your practice and replace it with something else that you have the evidence…/…when you are using evidence-based it gives you value, it’s valued by the customer, it’s rare because they don’t use the same stuff you use, and at the same time it’s inimitable which means it cannot be copied by [competitors] because they are not using the same approach as you are using.” (participant 1).   i. client satisfaction an improvement in client satisfaction was clear from a number of perspectives: saving the client money “it can save your client money because if you’re not trying different things to see what works and you’re using what has been shown to work there’s potentially a knock on financial benefit there, unless it’s something expensive.” (participant 11); the perception of value held by the client “i would say input-output-outcome. this is the outcome that is valued by the customers, by clients, and evidence-based research studies is valued better by clients because they see it’s working and it works in any circumstances.” (participant 1); trust “i think the trust building aspect of it is really, really important.” (participant 9) and “people choose a vet because they get on with them, because a relationship is formed, because the trust, the bond formed between them and the practice.” (participant 2); client appreciation “i think people generally appreciate that because it shows that you're being thorough” (participant 10), “based on the evidence and as soon as [the client is] invested and they are part of the treatment choice, ultimately everybody gets happier.” (participant 7) and “that client not only [is] receptive to the veterinarian looking into their animals specifically in disease, but really appreciate, you know, it is, it's extra work, it's extra time, it's a more personal touch.” (participant 13), over-coming the unknown “the best thing that i did and [clients] are so much more grateful, people respond so much better when you tell them i don't know, you know i don't know, i'm going to look it up, or we don't know, these are the options and this is why these are the options.” (participant 12) and “potentially more damaging to kind of trust with relationships with clients, and to be honest, people don't believe you that you've got all the answers all the time without having to go and look it up and that sort of thing.” (participant 10).   ii. client retention while the ideas of client satisfaction and client retention are closely linked in the data, there was sufficient discussion to separate these as disparate concepts: client satisfaction being a short-term yet positive outcome from the provision of good clinical practice while client retention is focused on the longer-term positive externality of a trusting relationship being developed between client and veterinarian whereby the veterinarian is more than a valued service provider. the veterinarian takes on a more sophisticated relationship than an expert for hire and assumes the role of the client’s trusted partner in providing long-term veterinary care: “you know from a very basic level, the longer your patient is away then the healthier they are, the more bonded your clients become and the more likely they are to come back and spend money with you. so you know from that perspective, there's a longevity to the relationship that you can form with the patients and the clients, so if you can keep animals healthy and provide them with the best possible care.” (participant 15) “i think that the main benefits are number one from a client standpoint is, it engenders a lot of trust, and if they understand where you're coming from, and they don't, they don't feel like they're being targeted and they feel like you're working in their best interests and the horse's best interests, i really do think that builds a strong loyal client base…/…well how about practising evidence based medicine to try to do the right thing? that's when people will continue to come back to you. that's what i think.” (participant 9).   iii. reputation another closely-related issue to client satisfaction and retention is reputation. this emerged as a key theme from the data, which presented itself in a number of different ways: approach to veterinary medicine “but the first opinion people coming through the door, why do they choose us over the other four practices in town? because they like what they've heard about the reputation, they like the way we work, not especially what we do.” (participant 2) trusted clinical practice “i know that [my vet] is evidence based, i know she reads the literature, i know she talks to her peers, i know she practices well.” (participant 12) reliable procedures “and now everything’s questioned so i think from a business point of view to support your integrity you have to be able to do some form of clinical governance” (participant 4) intangible value “i'm not sure quite how i would actually physically measure that. i guess there's maybe some value in having a reputation for doing things well” (participant 11).   iv. confidence  discussions on the increased standard of care attributed to ebvm developed into insights into client satisfaction, client retention and reputation but most unexpectedly a lot of evidence emerged about how vets’ confidence was developed from the application of ebvm and how it was a valuable opportunity to stimulate engaging, challenging discussions with colleagues. in terms of the non-clinical benefits of ebvm discussed for this research, the confidence that ebvm builds amongst vets and the satisfaction they gain from practicing good medicine was by far the most discussed theme within the data. satisfaction was a key word often used: “i think, in terms of job satisfaction, you get a lot more out of it because you don’t feel like you’ve gone to work and winged it…you feel like you’re …doing clinical research, you feel like you’re contributing to the wider port of knowledge. you feel like you’re actually you’re doing something to help improve the profession you work in so it’s got a personal satisfaction element to it as well…/… and the process i think makes everyone a lot happier because, if you like, there’s stuff to support what they’re doing.” (participant 11); “i think it gives me individual satisfaction that you're hopefully doing a good job and you are providing the 'best', in inverted commas, service you can do under the circumstances.” (participant 16). employee engagement emerged as another key theme-based on the ideas that ebvm creates debate and develops an intellectual challenge for veterinary professionals who are motivated by constantly being challenged: “by getting people together and sharing the ideas and being collaborative about it, then you know then we've been able to drive enthusiasm amongst ourselves and the barriers can fall away really, once you do that.” (participant 15).; “when you do evidence based medicine you become more invested in what you're doing and when you become more invested in what you're doing, you become more passionate about what you're doing. so in an intangible way, i see evidence based medicine, just being a huge asset in terms of confidence and, ownership or passion in the field…/…i mean from my own personal perspective, it has certainly invigorated my passion for the field.” (participant 13); “and another perk is to share the experience. if you do evidence-based [sic] you can share the experience and you can get the best experience in this regard.” (participant 8). clinical decision making and the confidence that comes with good decision making were key issues raised; as was the issue of minimising waste generated by bad decision making: “i think it gives more confidence in clinical decision making, which everybody wants, right?” (participant 13); “[you] have more confidence in what you’re doing…you’ve not got that internal doubt or panic of is what i’m doing the right thing to do because you always have that no matter how many times you do something.” (participant 11); “it's personal, more than anything else. i can actually go to bed with a hand on my heart and say, i applied the best evidence as far as i am aware, because … the evidence that i have today, right now, means i can hand on heart, go to sleep and tell them i did the best possible job.” (participant 7). the ability to deal with clients, particularly, difficult questions from clients emerged as an issue that built confidence: “…ebvm may form part of your defence” (participant 2); “the client, they think they’re so much better informed so they can access doctor google, so i think you’ve got to be able to justify what you’re doing in a constructive way, in a proven” (participant 4); “i think when challenged about the reasons why we do things, then we are able to support the reason why we do things with evidence” (participant 15).   3. barriers to the wider adoption of ebvm the two major barriers that were cited to the wider adoption of ebvm were time and resources. “i think the two big barriers are time, and access to evidence.” (participant 16) while participants recognised the long-term benefits of ebvm (e.g. developing staff knowledge and their confidence, knowing that clients are being provided with the best care for their animal(s)), there was much discussion around the idea that ebvm is a long-game that is resource-intensive and time-consuming in the short term. time was discussed in terms of the time required to investigate the evidence based for individual cases: “ the ability to understand and interpret research findings.” (participant 12); “i think time is the big issue in practice, because you're just so busy all the time, to sit down and actually look at journals, it's really difficult.” (participant 6). discussing the evidence with colleagues was discussed in a positive light for sharing information and engaging with like-minded people but it did also involve taking time away from clinical practice: “i think the time is probably the next biggest barrier. people are overstretched and overworked and feel that it's just yet another thing that they have to do.” (participant 15). there was an overwhelming response from participants that there is a paucity of publicly-available resources for truly adopting ebvm in practice. upon digging deeper into this theme, there is evidence to suggest that access to literature may not actually be the true problem. the problem may actually lie in vets’ readiness and willingness to access the literature in that actually sourcing literature to make clinical decisions is not at the top of their minds: “i think the biggest barrier is probably access to evidence” (participant 11) “…one of the problems is in veterinary medicine we don't have the huge number of resources that have been developed to support physicians.” (participant 3) “possibly access to the materials as well, because i know that we tell the students here and i tell colleagues, you can go to the rcvs library and you can get access, and if you're a member of bscvu you can get access, but i think there's still a bit of a barrier that a lot of people don't know, that they can actually access all these articles really easily.” (participant 6). “the industry culture is the enemy of innovation and it’s the enemy of evidence-based research and studies” this evidence from participant 1 summarises another theme that emerged from the data about the barriers to adopting ebvm. to start with, some participants discussed their perceptions of the profession’s current reliance on ‘eminence rather than evidence’: “most of veterinary medicine that i see has no evidence base, and is detrimental to animal welfare, doesn't work, and that is very difficult, so i think there's a huge barrier” (participant 12) “i think there's a lot of pride that goes with veterinary medicine with practising medicine…/…anecdotal evidence is extremely powerful, so having a case that you treated one particular way and it seemed to work, you know it's extremely powerful and it can be very difficult to overcome that, if it's not evidence based practice.” (participant 15) “[ebvm] never occurred to me as a new grad, i just believed everything.” (participant 6). there also appears to be a problem with the quality of evidence available to practitioners in terms of depth of coverage, validity of information and quality of information: “the evidence base in veterinary medicine is so weak and patchy, that it's very, very difficult to practice anything approaching what doctor greenhalgh or cochrane would recognise as evidence based medicine.” (participant 14) “a little knowledge is dangerous” (participant 11) “but certainly in the veterinary field there is a huge lack of evidence, and a lot of what is written is clinically irrelevant or only marginally relevant so the quality of the stuff that's out there is always going to be a challenge.” (participant 14). an issue associated with industry culture is the lack of awareness by clients, their lack of demand for ebvm and some owners’ demand for ‘quick-fix, low-cost solutions’: “so you have to educate clients, number one. about the true cost of healthcare.” (participant 7) “i think for most owners and most practitioners, both side of the patient on the veterinary client patient transaction, i think it's more important for them to have something to do, than it is to do something that's effective.” (participant 9) “…the challenge is getting the public to come with us really.” (participant 15). the final issue that emerged from the data about barriers to the adoption of ebvm is the attitudes of educational institutions. the foremost issue here related to veterinary schools’ lack of attention to ebvm but the issue of teaching and assessing these skills was also raised: “so eminence based medicine is the biggest barrier to evidence based medicine. and that's deeply, deeply rooted in the vet schools.” (participant 14) “i think it's a cultural educational issue, first and foremost, but assuming we have the attitude to practice ebvm, then it comes down to time and access.” (participant 13) “and then the next big barrier i guess is the skills gap. it's you know not feeling that you have the skills necessary to appraise evidence and to, you know to formulate the right sort of questions and to put together, you know the, the information needed in a format that's, you know that's acceptable.” (participant 15).   4. increasing the adoption of ebvm the two most prominent issues to emerge from the data about increasing the adoption of ebvm are that 1) ebvm needs management support: journal clubs, forums, training opportunities, cpd, time for reading, all members of the vet team need to be included, senior vets as role models, vet techs/nurses need to be involved in ebvm (not just vets) and 2) ebvm needs investment: funded research projects, support services, journal access. in terms of management support for ebvm, the interview data showed support for the heightened level of employee engagement that came about from vets and vet nurses who are given the time and intellectual freedom  to practice ebvm rather than being trapped under a heavy case load. further evidence is provided by these quotes: “i think businesses would definitely benefit if they were to allow, you know, you could just like one afternoon a week or every month or something tell people to go and spend time reading or looking up things. i think that would be a really good move because i think they would see a definite improvement in terms of staff performance and turnover.../…i think management generally need to be more accepting of ebvm, of what it can do for their business in terms of improved client satisfaction, improved turnover, improved handling of client complaints and things like that.” (participant 11) “…we kind of embark on the journey together…/… it's been a pleasure to work through the challenges together really.” (participant 15) “i think that [good medicine, good science and good ethics] go hand in hand, and i think that the important thing, i think that ebvm can be a cornerstone of that, and should be a cornerstone of that, but i just think that, like i said change has to come top, from top down.” (participant 9) i'm a huge proponent for the role of veterinary nurse, veterinary technician in this process and i think ebvm can only be accomplished as a team.” (participant 13) as for increased investment in ebvm, the following data showed demand for opportunities to teach practitioners about considering and understanding high-quality evidence, how to discuss high-quality evidence with important stakeholders and that using ebvm is easier over time as it becomes habit: “i think more cpd events on how to perform ebvm would be quite useful. i think the knowledge[ebvm learning] the learning resource that they’ve published is really good and i think they just need to work and make sure as many vets know about that as possible because it is a really good open source of information on how to ebvm.” (participant 11) “the development of the rcvs knowledge and the introduction of the grants for, for supporting ebvm, were probably a turning point for us as a business and i guess my activity, with regards to ebvm has increased significant learning since then.” (participant 15). participants 3 and 12, respectively, commented on the need for open-access publications: “so this is where we get into open publication, the whole concept of open access science, and i think that's another barrier, or another way to break down the barriers would be to have more open access.” and “i think scientific publishing is going to have to change. it's going to, i mean it's changing already right with open access, and you know more and more is open access, more and more is free” which is linked to comments made by participant 2: “it's there, but you know you want to bring people together, and i think that's probably the key thing, is that if we find to make bridging university, like academia and practice gap, people will start seeing more relevant meaning to it…/…the way barriers can be overcome fundamentally is communication and not protectionism.”; “i think that there needs to be some acknowledgment, there might need to be some financial support or expertise support that go into groups and practices and help them do that. i think it’s unrealistic to expect practitioners to do that.” (participant 4) participant 5 provided some constructive comments to improve the adoption of ebvm: “spread it out a bit, i mean having two major conferences a year at the moment. you should perhaps take it smaller, you've probably done a bit of this i think, perhaps going out to local veterinary societies, but maybe even contact larger practices in an area where they've perhaps got, you know we've got a room downstairs, our waiting room we use as a meeting room sometimes for the vets from other practices…./…somebody from nottingham or from the university, committee of ebvm should come and perhaps, talk about it a bit more, so that everybody knows about it, the nurses and everybody as well.”. participant 4 provided another interesting idea: “well i tell you what the college needs to do, they need to buy into the fact that you can do a residency in practice, because this would fit a residency so well. that’s what they need to do. it doesn’t need to be hospital-based or university-based. it can be in practice.” discussion this research yielded themes that are of considerable importance to the veterinary professions at present and that practicing ebvm may derive greater benefits than superior clinical outcomes. mccracken (2013) suggested that financial and operational efficiencies are outcomes of evidence based medicine (ebm) in the human world but these did not emerge as themes from the data. more in-keeping with the logic of caldwell (2001) who advocates the convergence of ebm healthcare systems objectives, we found that practicing ebvm is not restricted to strong clinical practice but is also related to greater client satisfaction in the short term, and to long-term client retention. however, it was also highlighted that often clients are not aware of ebvm or prefer a ‘quick fix’ solution. another closely-related issue to client satisfaction and retention is reputation. this emerged as a key theme from the data, which presented itself in a number of different ways including the way a better reputation is gained by a different approach to veterinary medicine and performing reliable procedures. these themes essentially link to professionalism and professional identity. one of the key constructs of professionalism is the professional’s ability to communicate. previous studies have discussed the importance of communicating with clients to develop sustainable business practice (backynsky et al., 2013) and managing client expectations (mossop et al., 2015). the present research adds to this body of knowledge by providing ebvm as another tool for enhancing client satisfaction and enabling client retention.   by far the most discussed theme that emerged from the data, was how ebvm influences vets’ confidence and the satisfaction they gain from practicing good medicine. the practice of ebvm was seen as a valuable opportunity to stimulate engaging, challenging discussions with colleagues. similarly, employee engagement emerged as another important theme based on the ideas that ebvm creates debate and develops an intellectual challenge for veterinary professionals. this is a particularly important finding of the research due to the current climate of the uk veterinary professions. the royal college of veterinary surgeons and the british veterinary association have collaborated in the vet futures initiative (http://www.vetfutures.org.uk/). research findings of this initiative have outlined several key ambitions and recommendations for the profession, two of which are: 1) “confident, resilient, healthy and well-supported [professionals]” and 2) “a broad range of diverse and rewarding career paths” (vet futures, 2015, p. 4). the present research demonstrates that practicing of ebvm could be one of the avenues the profession could pursue in its efforts to ensure its people are well-supported and work in interesting, developing careers. similarly, vn futures (2016) discusses some of the causal factors of stress in the veterinary professions and cites “professional isolation” as one of the reasons why people in the veterinary professions are so stressed. once again, the social and developmental aspects of practicing ebvm that emerged from the present research could offer an important opportunity for relieving this pressure point. a theme to recently emerge from the veterinary professionalism literature is professional identity. the development of professional identity starts with the understanding of professionalism and under-lying foundations of professionalism are the ability to balance multiple responsibilities and manage professional challenges (armitage-chan, maddison & may, 2015). balancing multiple responsibilities involves engaging with different parties both internal and external to the veterinary environment who, managing professional challenges, relates to controlling work/life balance and responses to difficult or emotional clients. evidence from the present research suggests that vets’ ability to deal with the increasing expectations of clients, achieving goals through team performance, and gaining confidence from practicing good veterinary medicine could be yet another benefit of ebvm to the audience interested in professional identity formation. one of the main limitations of this study was that there were a number of important general issues that also emerged about the non-clinical benefits of ebvm that did not suitably fit into the results of the thematic analysis of interview data. one of the rcvs knowledge chairs who was invited to participate in this research declined because he considered that it was far too early to attempt to quantify the non-clinical benefits of ebvm; similarly, one participant could not see a direct link between practising ebvm and a direct business advantage. a further limitation was that the increased standard of care was the most intuitive response participants gave when discussing ebvm, and it was at times challenging to move the discussion to the non-clinical benefits. however, through further questioning far more detailed themes emerged about clients, practice reputation and staff confidence. we take a pragmatic philosophical stand point to this research and acknowledge that this exploration of expert opinions of ebvm is not where this enquiry terminates. this qualitative phase of the research has allowed for the rich and in-depth exploration of key stakeholder perceptions on which we can now use as a platform for confirmation and explanation of the non-clinical benefits of ebvm in a survey of the professions; that is, empirically testing the theories that were grounded in our research questions. this pragmatic, pluralist approach is best described as mixed-method research (johnson & onwuegbuzie, 2004) which rejects howe’s (1988) incompatibility thesis that the quantitative and qualitative methodologies can never be combined. in summary, this study forms the first phase of a two-part, mixed-method research to establish the non-clinical benefits of ebvm. from the findings of this explorative study a survey will be created that will empirically test the knowledge documented in this paper. conflict of interest acknowledgments: we would like to thank rcvs knowledge for its generous support of this project, our co-investigator: graham milligan mrcvs and all the interview and survey participants funding: rcvs knowledge grants. competing interests: there are no areas of conflicting interest associated with this work. references armitage-chan, e. maddison, j. & may, s. a. (2016) what is the veterinary professional identity? preliminary findings from web-based continuing professional development in veterinary professionalism. veterinary record, 178 (13), p. 318. http://dx.doi.org/10.1136/vr.103471 bachynsky, e. a. et al. (2013) a survey of the opinions of recent veterinary graduates and employers regarding early career business skills. veterinary record, 172 (23), p. 604. http://dx.doi.org/10.1136/vr.101376 bogner, a. littig, b. & menz, w. (2009) introduction: expert interviews – an introduction to a new methodological debate in interviewing experts, palgrave macmillan: uk. caldwell, c. (2001) the business case for evidence-based medicine. international journal of medical marketing, 2 (1), pp. 54-72. http://dx.doi.org/10.1057/palgrave.jmm.5040055 creswell j.w. (2009) research design: qualitative, quantitative and mixed methods approaches. 3rd sage publications: california, usa. glaser b.g. & strauss a.l. (1967) the discovery of grounded research: strategies for qualitative research. aldine de gruyter: new york, usa. hauser, s. & jackson e.l. (2016) non-clinical benefits of evidence-based veterinary medicine.veterinary evidence, [s.l.], 1(3), aug. 2016. issn 2396-9776. available at: <https://veterinaryevidence.org/index.php/ve/article/view/34> [accessed: 27 march2017]. henry, c. & jackson, e.l. (2015) ‘women’s entrepreneurship and the future of the veterinary profession’, e-organisations and people, 22 (3), pp. 34-42. howe, k. r. (1988) against the quantitative-qualitative incompatibility thesis or dogmas die hard. educational researcher, 17 (8), pp. 10-16. http://dx.doi.org/10.3102/0013189x017008010 johnson, r. b. & onwuegbuzie, a. j. (2004) mixed methods research: a research paradigm whose time has come. educational researcher, 33 (7), pp. 14-26. http://dx.doi.org/10.3102/0013189x033007014 mccracken, b. (2013) building a business case for evidence-based medicine, clinicalkey, elsevier. mccracken, g. (1988) the long interview, qualitative research methods series 13, sage publications: california, usa. miles m.b. & huberman m. (1994) qualitative data analysis: a sourcebook of new methods, sage publications: california, usa. mossop, l. et al. (2015) communication skills training: what the vet schools are doing. veterinary record, 176 (5), pp. 114-117. http://dx.doi.org/10.1136/vr.h425 vet futures (2015) taking charge of our future: a vision for the veterinary profession for 2030, available at: http://www.vetfutures.org.uk/resource/vet-futures-report/ [accessed: 27 march2017]. vnfutures (2016) vnfutures – taking charge of our future together. available at: http://www.vetfutures.org.uk/resource/vn-futures-report-and-action-plan/ [accessed: 27 march2017]. r.k. (2014) case study research design and methods. 5th ed. sage: thousand oaks, usa. zikmund, w.g. (2003) business research methods. 7th thomson south-western: ohio, usa. supplementary files, images & tables all the supplementary files are available here. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. in cats and dogs does laparoscopic ovariectomy offer advantages over open ovariectomy for postoperative recovery? a knowledge summary by cherry phypers bsc, msc 1* 1university of bristol, senate house, tyndall ave, bristol bs8 1th *corresponding author (cherry.phypers.2014@my.bristol.ac.uk) vol 2, issue 2 (2017) published: 22 jun 2017 reviewed by: gillian monsell (ma, vetmb, phd, mrcvs) and kit sturgess (ma, vetmb, phd, certvr, dsam, certvc, mrcvs) next review date: 22 jun 2019 doi: 10.18849/ve.v2i2.59 clinical bottom line available research suggests ovariectomy by laparoscopy leads to a more positive recovery following surgery, due to reduced pain and smaller reductions in activity levels postoperatively when compared to open ovariectomy. in practices where laparoscopic equipment and expertise are available, offering laparoscopic ovariectomy for routine spays of cats and dogs may be advantageous to patients. question in cats and dogs does laparoscopic ovariectomy offer advantages over open ovariectomy for postoperative recovery? the evidence there are a number of major constraints in evaluating the evidence from these studies to draw a clear conclusion to the original question, including the variety of recovery outcomes measured, the subjective nature of interpreting animals behaviours for pain scoring, lack of blinded pain assessors in four of the five studies, as well as varying different methods and scales used to assess pain. the lack of a blinded trial to evaluate the different techniques is ultimately the major constraint to drawing a definitive clinical bottom line and is required to validate this conclusion from the current evidence available. summary of the evidence coisman (2013) population: domestic, female cats from animal rescue centres sample size: n=24 intervention details: intervention groups 1-portal laparoscopy using extracorporeal suture (l-ecs) method (n=8) 1-portal laparoscopy using ligasure (l-ligasure) method (n=8) open ovariectomy (n=8) inclusion criteria intact, not pregnant females, assessed as normal on physical examination group characteristics mean age 16.5±6.8 months mean weight 3.02±0.35kg no significant difference for either age or weight between groups statistical analysis one-way anova using welch’s method to assess for unequal variance was used to test for differences in age, body weight and surgical time tukey-kramer test used for post-hoc analysis complications compared by pearson’s x2 contingency analysis repeated measures anova to test differences in pain scoring wilcoxon method for nonparametric comparisons between pairs study design: blinded, randomised controlled trial outcome studied: pre and postoperative pain scores (1,2,3,4 hrs following extubation) using visual analogue scale (vas), simple descriptive scale (sds) and von frey meter (vf) assessors blinded to surgical group surgical complications (scored 0-3 on occurrence) surgical duration (start of skin incision through to time of skin closure) main findings (relevant to pico question): surgical duration significantly longer in l-ecs group (71 minutes; p<0.001) than l-ligasure (25.5 minutes) and open (17 minutes) groups no difference between l-ligasure and and open groups surgical complications more frequent in l-ecs group than l-ligasure (p=0.049) and open groups (p=0.008) no difference was seen between l-ligasure and open groups postoperative pain scores (vas, sds and vf) significantly greater vas score in l-ecs vs. l-ligasure, p=0.011 at time point 4 hours following extubation no difference in vas score seen at any other time point between the three groups no differences seen in sds or vf pain score between the three groups limitations: pain scores were determined by two observers blinded to treatment this could have resulted in variation between pain scoring between individuals when using the vas and sds methods a standardised incision was made for all techniques (location and length) to allow the blinding of pain scorers this could have strongly impacted on pain scores since invasiveness and tissue damage has been shown to be associated with postoperative pain. this evidence is currently weak in the veterinary field but has been shown more strongly in human medicine laparoscopic technique was the less commonly used 1-portal method and the study did not include a 2-portal method comparison, which may not be so relevant for practices. no reporting of breeds and small sample sizes were used with no statistical analysis performed on whether these numbers were suitable. this makes it possible a type-ii statistical error may have occurred especially when considering surgical duration results showing no significance between l-ligasure and open groups no reporting of confidence intervals, so precision of effect is unknown culp (2009) population: small breed <10kg female dogs from animal welfare society sample size: n=20 intervention details: intervention groups 2-portal laparoscopic ovariectomy (n=10) open ovariectomy (n=10) inclusion criteria intact, females weighing <10 kg group characteristics age (years): open median, 2, range 0.5 3; laparoscopic median, 1, range 0.5 3, weight (kg): open median, 4.6, range 2 4.8; laparoscopic median, 5, range 2 10 presurgical activity: open median, 235,170; range 57,322-677,623, laparoscopic median, 256,166; range 71,928-542,956 statistical analysis mann whitney test to compare surgical times wilcoxon signed test to compare activity counts linear regression analyses to evaluate association of surgical procedure and activity counts change study design: randomised, controlled trial outcome studied: surgical duration (start of skin incision through to time of last suture) degree of haemorrhage (minor, moderate, severe) incision length activity levels preand postoperative (previously reported as an objective measure of pain in humans) main findings (relevant to pico question): degree of haemorrhage 6/10 dogs in the open group experienced minor bleeding compared to 3/10 dogs in the laparoscopic group surgical duration significantly shorter (p=0.005) in the open group (21 minutes) compared to the laparoscopic group (30 minutes) postoperative activity levels 25% decrease (non-significant) in dogs undergoing laparoscopic surgery in days 1 and 2 post-surgery compared to preoperative baseline activity levels (95% confidence intervals 11-38%) 62% (p=0.002) decrease for days 1 and 2 compared to preoperative baseline activity (confidence intervals 95%, range 48-76%) limitations: activity levels were measured in animal welfare centre runs not viewed by study investigators so the type of activities were unable to be reported, however baseline activity levels were shown to be comparable with pet dogs within the home over 24 hours the ligasure device used for haemostasis in the laparoscopic group was not used in the open surgical group adding a further variable between the two groups only individuals working within the welfare centre were blinded to surgical treatment and not the study investigators, which provides a source of bias into the study the use of accelerometry was at the time a relatively new technique (this has since been validated in veterinary medicine to monitor activity levels within osteoarthritis, belshaw et al., 2016, brown et al., 2010) gauthier (2015) population: domestic, female pet cats sample size: n=60 intervention details: intervention groups open flank ovariectomy (n=20) open ventral midline ovariectomy (n=20) 2-portal laparoscopic ovariectomy (n=20) inclusion criteria healthy classified as american society anesthesiologists category (asa) category asa 1 females suitable temperament based on a behavioural assessment (aggressive cats excluded) not administered analgesics within 48 hours of surgery group characteristics mean age (months): open flank, 10.2±1.3; open midline, 8.3±0.8; laparoscopic, 11.0±1.7 body weight (kg): open flank, 3.14±0.61; open midline 2.70±0.39, laparoscopic, 2.62±0.47 no significant difference between groups for age, laparoscopic group weight p<0.05 statistical analysis 1-way anova tukey test for post hoc analysis fisher exact test study design: randomised, controlled trial outcome studied: postoperative pain (1, 2, 4, 6, 12 hours following extubation) using 4a vet composite pain scale. this is a compound pain scale, which has been validated to assess postoperative pain in dogs and cats. five parameters are evaluated through behaviour and response to give an overall rating of pain between 0-18 (d holopherne-doran et al 2010, mahler and reece 2007). the assessors were not blinded to surgical group number of additional morphine boluses given postoperatively quality and duration of recovery surgical duration (first skin incision through to last suture) anaesthesia duration (induction through to endotracheal extubation) preand postoperative body temperature main findings (relevant to pico question): surgical duration significantly longer in the laparoscopic group (41±16 minutes, p=0.019; 36.8°c, p=0.033) compared to open flank (24±9 minutes) and open midline (35±9 minutes) postoperative body temperature significantly lower in the laparoscopic group (36.8°c, p=0.033) compared to open flank (37.7°c) and open midline (37.4°c) subjective quality and duration of recovery no differences were seen between the three groups pain scores significantly lower in animals following laparoscopic ovariectomy vs. open midline (p<0.001) and open flank techniques (p=0.016) in the laparoscopic group, no animals experienced severe pain following surgery at any time point, however following open midline surgery this was recorded in 5% of animals 2, 4 and 6 hours postoperatively and in 5-20% of animals following open flank surgery at varying time points weak pain was experienced by 50% of animals 1 hour following laparoscopic surgery and increased to 95% at 12 hours; the remainder having experienced moderate pain. following open midline surgery, weak pain was experienced in 50% of animals 1 and 12 hours postoperatively with the remainder having experienced moderate or severe pain postoperative morphine boluses significantly lower in animals undergoing laparoscopic ovariectomy (0.55±0.61) compared to open midline (2.30±2.39) and flank (3.25±3.18) techniques (p<0.001) limitations: the study investigators including pain scorer were not blinded to surgical method providing a large source of potential bias the number of observers evaluating pain score postoperatively was not reported, so it is unclear whether additional variation in pain scores may have been present all surgeries were performed with inexperienced vet students assisting the surgeon which could have impacted on surgical duration, especially in the laparoscopic surgeries due to unfamiliarity with the endoscope tool no reporting of confidence intervals, so precision of effect is unknown breeds were not reported, so it is unclear how this relates to in practice vasiljeviä‡ (2015) population: female dogs, medium to large breeds sample size: n=20 intervention details: intervention groups laparoscopic ovariectomy (n=10) open ovariectomy (n=10)  inclusion criteria healthy asa classified category asa 1females  group characteristics not reported  statistical analysis 1-way anova dependent t-test   study design: randomised, controlled trial outcome studied: intraoperative pain score using changes in heart rate, arterial blood pressure, respiratory rate and body temperature at certain time points during surgery postoperative pain score using multifactor pain scale (0-9) at 15, 30 minutes, and 1, 3, 6 hours following surgery evaluated by same observer, not blinded to surgical group main findings (relevant to pico question): intraoperative parameters of pain significant changes in parameters during all surgical time points when compared to baseline values in animals undergoing open ovariectomy (p<0.05) in animals undergoing laparoscopic ovariectomy no significant changes were recorded from baseline except within phase iii for respiratory rate and arterial blood pressure (p<0.05) pain scores animals within the laparoscopic ovariectomy group experienced either mild or moderate pain at 15 and 30 minutes post-surgery, and either no or mild pain at 1, 3 and 6 hours post-surgery a maximum of two animals experienced moderate pain, and no animals experienced severe pain animals undergoing open ovariectomy experienced either mild, moderate or severe pain at all time points following surgery, with two animals experiencing severe pain, up to seven animals experiencing moderate pain and a maximum of five animals experiencing mild pain. limitations: the study investigators including pain assessor were not blinded to surgical method providing a large source of potential bias in terms of pain scoring the study did not report the laparoscopic technique used or how many surgeons were involved in performing the surgeries, so we cannot know whether variation was controlled in these areas no reporting of confidence intervals, so precision of effect is unknown breed, mean ages of the groups were not reported, nor was the source of the animals so it is unclear whether groups were considered similar at the start of the trial freeman (2010) population: female dogs both research and shelter animals sample size: n=30 research animals (n=10) shelter animals (n=20) intervention details: intervention groups ovariectomy performed by natural orifice transluminal endoscopic surgery (notes) using a transgastric approach (n=9 or 10). this technique involved passing an endoscope through the mouth into the stomach and through an incision in the gastric wall into the abdominal cavity 2-portal laparoscopic ovariectomy (n=10) open ovariectomy (n=10) inclusion criteria healthy, females group characteristics mean body weight (kg): notes, 21.7±10.5; laparoscopic, 18.8±4.4; open, 20.4±3.8 no significant differences between groups statistical analysis repeated-measures analysis of variance for effects of surgical procedure, time and interaction between the two bonferroni-adjusted post-tests for each group to baseline if indicated by significant f test (ratio of two variances) spearman’s correlation coefficient for relationship between serum il-6 and cortisol study design: non-randomised controlled trial outcome studied: blood markers of systemic stress and surgical stress postoperative pain at 2, 4, 6, 12, 18, 24, 36, 48, 72 hours following surgery using a pain scale nociceptive threshold using cuff placed around abdominal cavity (used to interpret abdominal pain) using a previously documented method surgical duration rectal temperature main findings (relevant to pico question): surgical duration significantly longer (p<0.001) in the notes group compared to the laparoscopic and open groups little difference between mean surgical duration between laparoscopic (44 minutes, range 35-65) and open (35 minutes, range 25-65) groups, but no statistical analysis was performed on these data rectal temperature significantly lower (p<0.05) at time points 36 and 48 hours post-surgery in the notes group compared to the laparoscopic and open groups postoperative pain scores significantly lower in animals undergoing notes surgery compared to animals undergoing open ovariectomy at all time points (p<0.05) and animals undergoing 2-portal laparoscopic surgery at time points 0, 12, 24 and 36 hours (p<0.05) lower in animals undergoing laparoscopic ovariectomy when compared to the open ovariectomy group across most time points following surgery, however statistical comparisons were not reported postoperative nociceptive threshold significant lower in animals undergoing open surgery when compared to animals in the laparoscopic surgical group (at time points 6 and 12 hours, p<0.05) and the notes group (at time point 18 hours, p<0.05) limitations: no direct statistical comparison of pain scores, rectal temperature or surgical duration was reported for the laparoscopic ovariectomy and open surgery groups so differences can only be tentatively suggested no reporting of confidence intervals, so precision of effect is unknown two major sources of bias within the study result from no random assignment of animals to surgical groups and the subjective nature of pain scoring performed by two assessors unclear if pain assessors were blinded therefore means a large source of bias is possible no reporting of number of surgeons involved with surgeries across both groups so it cannot be determined if variation was controlled in this aspect type of pain scale used was not reported making it difficult to compare results to those of other studies as two populations of animals were used and mean ages of groups not reported, the groups may not have been similar at the start of the trial appraisal, application and reflection there are a number of major constraints in evaluating the evidence from these studies to accurately draw a conclusion to the original question, including the variety of recovery outcomes measured, the subjective nature of interpreting animals behaviours for pain scoring, lack of blinded pain assessors in four of the five studies, as well as varying different methods and scales used to assess pain. there is much variation in surgical duration of the laparoscopic procedures across the studies this is difficult to accurately evaluate due to the different laparoscopic techniques used. the experience of the surgeon must also be taken into consideration, as their experiences and confidence is expected to heavily impact on the success of the surgery. when compared to open techniques, surgical duration was longer for laparoscopic procedures across the majority of studies, however this was not always significant, and associations to recovery cannot be drawn. while results of studies measuring surgical complications (coisman et al.) and degree of haemorrhage (culp et al.) cannot be linked directly to recovery success, these results may offer advantages postoperatively. complications were significantly more frequent in only one of the laparoscopic groups in the study by coisman et al., and this is most likely to be attributable to the vessel sealing method used rather than surgical technique. culp et al. reported fewer dogs experienced haemorrhage during laparoscopic surgery, which is a positive aspect of this technique that is valuable to mention, but further studies are needed to validate this result and to assess impact on recovery. pain scales are not inclusive of all variables, so different factors relating to pain may be overlooked, depending on the pain scoring method used. the large variability in the recording of pain is a major limitation to how accurately results of these studies can be compared. this highlights the need for greater use of objective pain scoring methods and consistency of pain scoring tools in order to assess pain levels and drawing conclusions between different studies. four out of the five studies suggest laparoscopic techniques are associated with reduced postoperative pain and less reduced activity levels. however in these four studies, the investigators assessing pain were not blinded to treatment, which is a large source for bias that ultimately limits the conclusions that can be drawn. blinding to surgical treatment could have been possible using a large abdominal plaster or bandage to conceal the surgical incision length, and this highlights the need for a fully blinded study to be conducted to provide a stronger level of evidence. from the studies available, the two which offer the strongest level of evidence are culp et al., 2009 and gautier et al., 2015. both randomly assigned animals to surgical groups using computer generated or statistical methods, and sample sizes were appropriate for analysis. both studies reported characteristics of surgical groups and the number of surgeons carrying out surgeries, and used a consistent, standard anaesthetic protocol for all groups within each study as well as the commonly described 2-portal laparoscopic method. both studies reported significant and substantial beneficial treatment effects of laparoscopic surgery compared to open surgery. the only study which did not report postoperative recovery advantages following laparoscopic ovariectomy vs. open ovariectomy was coisman et al., 2013. this was also the only study using a standardised incision site and length for all techniques studied. while this meant observers could be blinded to the surgical intervention, this may have impacted on postoperative pain scores. some studies have shown associations between pain, surgical invasiveness and tissue damage, however the evidence is weak, so this can only be speculated but is a factor readers must take into consideration when interpreting results of this study. freeman et al., 2010 primarily investigated the notes technique (using a transgastric approach) vs. a 2-portal laparoscopic and open ovariectomy methods. while limited direct statistical comparisons were reported between laparoscopic and open surgeries, it is valuable to include these results, as pain scores were lower in animals undergoing laparoscopic techniques. these results are in line with other studies included in this summary, but they must be considered with more caution. while the evidence suggests laparoscopic techniques can lead to a better recovery, the lack of a blinded trial to evaluate the different techniques is ultimately a major constraint to drawing a definitive clinical bottom line and is required to validate this conclusion from the current evidence available. reduced pain and smaller reductions in activity levels have been attributed to the less invasive nature of laparoscopic techniques, due to the shorter surgical incisions, reduced tissue damage and less organ handling. reduced haemorrhage risk is a further advantage that may be beneficial to postoperative recovery, whereas surgical duration does not seem to be associated with recovery parameters. duration is highly variable between studies this is likely due to the laparoscopic method used and experience of the surgeon. further benefits of laparoscopic surgery also suggested include reduction in materials required, such as suturing material, anaesthetic volume and postoperative analgesia. finally, it is important to consider a number of factors when adopting laparoscopic ovariectomy including carbon dioxide insufflation risks associated with laparoscopic techniques, the cost of equipment and surgical training and whether these factors result in additional costs for clients. methodology section search strategy databases searched and dates covered: cab abstracts 1973 to 2016 week 22 medline 1950 to june 2016 web of science (citation search) search terms: cats/ cat or cats or “felis sylvestris catus” or “felis domesticus” or “domestic cats” or “domestic cat” or “felis catus” or “felis domestica” or “felis silvestris” or “felis silvestris catus” or “felis sylvestris” or “felis sylvestris catus”or “felis catus domestica” or feli* queens/ queen or queens 1 or 2 or 3 or 4 dogs/ bitches/ dog or dogs or bitch or bitches or “canis familiaris” or cani* 6 or 7 or 8 5 or 9 ovariectomy/ oophorectomy or ovariectomy or “open ovariectomy” or “conventional ovariectomy” or “traditional ovariectomy” or “open oophorectomy” or “conventional oophorectomy” or “ traditional oophorectomy” or ovariectomies or oophorectomy or oophorectomies or “female castration” or “female castrations” or “bilateral ovariectomy” or “bilateral ovariectomies” or “flank ovariectomy” or neuter or neutering or spay or spaying or spey or speying or desex or sterilise or sterilisation 11 or 12 laparoscopy/ laparoscopy or “laparoscopic ovariectomy” or “ovariectomy by laparoscopy” or “laparoscopic oophorectomy” or “oophorectomy by laparoscopy” or laparoscopies or peritoneoscopy or peritoneoscopies or celioscopy or celioscopies or “laparoscopic surgical procedure” or laparoscopic surgery” or laparoscopic surgeries or “laparoscopic surgical procedures” 14 or15 10 and 13 and 16 dates searches performed: july 2016 exclusion / inclusion criteria exclusion: studies were excluded if they did not investigate the two ovariectomy methods relevant to the clinical question. these included studies comparing open ovariohysterectomy vs laparoscopic ovariectomy or comparison of different laparoscopic ovariectomy techniques only. papers were also excluded if the study populations were those other than domestic dogs or cats, or, if parameters and outcomes were not linked to patient pain or recovery. inclusion: papers were included if the studies compared open ovariectomy and laparoscopic ovariectomy techniques. all laparoscopic methods (1-, 2and 3portal access and natural orifice transluminal endoscopic surgery (notes) techniques) were included, as were different laparoscopic instruments and vessel-sealing technologies and methods. only those studies measuring intraand postoperative parameters linked to recovery and pain outcomes in domestic dogs and cats were considered. the notes technique involves passing an endoscope through a natural orifice and then through an internal incision within an organ to reach the desired location in a body cavity. search outcome database number of results excluded – duplicates excluded – not english excluded – study design excluded – did not answer pico total relevant papers cab abstracts 127 0 5 1 117 4 medline 70 3 0 0 66 1 total relevant papers when duplicates removed 5 conflict of interest the author declares no conflict of interest. references belshaw, z. asher, l. and dean, r. s. (2016) systematic review of outcome measures reported in clinical canine osteoarthritis research. veterinary surgery, 45 (4), pp. 480-487 http://dx.doi.org/10.1111/vsu.12479 brown, d. c. boston, r. c. and farrar, j. t. (2010) use of an activity monitor to detect response to treatment in dogs with osteoarthritis. journal of the american veterinary medical association, 237 (1), pp. 66–70 http://dx.doi.org/10.2460/javma.237.1.66 coisman, j. et al (2013) comparison of surgical variables in cats undergoing single-incision laparoscopic ovariectomy using a ligasure or extracorporeal suture versus open ovariectomy. veterinary surgery, 43 (1), pp. 38-44. culp, w. t. n. mayhew, p. d. and brown, d. c. (2009) the effect of laparoscopic versus open ovariectomy on postsurgical activity in small dogs. veterinary surgery, 38 (7), pp. 811-817 http://dx.doi.org/10.1111/j.1532-950x.2009.00572.x freeman, l. j., rahmani, e. y., al-haddad, m., et al. 2010. comparison of pain and postoperative stress in dogs undergoing natural orifice transluminal endoscopic surgery, laparoscopic, and open oophorectomy. gastrointestinal endoscopy, 72(2):373-380 http://dx.doi.org/10.1016/j.gie.2010.01.066 gauthier, o. holopherne-doran, d. gendarme, t. et al ( 2015) assessment of postoperative pain in cats after ovariectomy by laparoscopy, median celiotomy, or flank laparotomy.  veterinary surgery, 44 (s1), pp. 23-30 http://dx.doi.org/10.1111/j.1532-950x.2014.12150.x holopherne-doran, d. et al. (2010) validation of the 4a-vet post-operative pain scale in dogs and cats. veterinary anaesthesia and analgesia, 37 (383)(abstr). mahler, s.p. and reece, j. l. m. (2007) electrical nerve stimulation to facilitate placement of an indwelling catheter for repeated brachial plexus block in a traumatized dog. veterinary anaesthesia and analgesia, 34 (5) pp. 365-370 (abstr) http://dx.doi.org/10.1111/j.1467-2995.2006.00335.x vasiljeviä‡, m. et al. (2015) comparative analysis of parameters of intraoperative and postoperative pain in bitches undergoing laparoscopic or conventional ovariectomy. acta veterinaria, 65 (4), pp. 488-495 http://dx.doi.org/10.1515/acve-2015-0041 intellectual property rights knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. don’t be afraid to ask the question: a simple guide for veterinary nurses to conducting evidence-based research in clinical practice sue badger med cert ed rvn1 andrea jeffery dipavn(surgical) rvn1* 1university of bristol, senate house, tyndall ave, bristol, bs8 1th *corresponding author (andrea.jeffery@bristol.ac.uk) vol 2, issue 1 (2017) published: 13 jan 2016 doi: 10.18849/ve.v2i1.91 the evolution of veterinary nursing over the past fifty years combined with the introduction of the rcvs register and code of conduct means that rvn's are now accountable for their actions and as a result must develop the ability to critically appraise, both their own practice and the protocols of the organisation in which they work, as part of clinical governance. it is therefore important that they develop the tools which enable them to confidently question all aspects of their clinical practice, but especially patient care and welfare, where necessary. this is a podcast of sue and andrea's talk at the veterinary evidence today conference, edinburgh november 1, 2016. find out more about sue and andrea. view presentation slides comments: the efficacy of trazodone in reducing stress related behaviours in hospitalised dogs or dogs confined postsurgery | veterinary evidence skip to main content knowledge summary keywords: dogs; stress; trazodone; postsurgical confinement; veterinary practice; anxiety; anxiolytic the efficacy of trazodone in reducing stress related behaviours in hospitalised dogs or dogs confined postsurgery lara dillon, bvetbio dvm1* 1 university of sydney, regimental drive, camperdown nsw 2050, australia * corresponding author email: lara.h.d.ld@gmail.com vol 8, issue 2 (2023) submitted 26 oct 2021; published: 26 may 2023; next review: 01 feb 2025 doi: https://doi.org/10.18849/ve.v8i2.550 pico question in hospitalised dogs or dogs confined postsurgery, does administration of trazodone reduce stress related behaviours compared to no treatment with trazodone? clinical bottom line category of research treatment. number and type of study designs reviewed three papers were critically reviewed. one was a prospective, randomised, blinded observational study, another was a randomised, placebo-controlled clinical trial, and the last was a non-randomised prospective, open-label clinical trial. strength of evidence weak. outcomes reported the administration of trazodone to hospitalised dogs reduced several observed stress related behaviours compared to a control group that was environmentally matched to the treatment group (gilbert-gregory et al., 2016). in dogs subjected to postsurgical confinement at home, trazodone administration was not more effective at reducing stress related behaviours compared with a placebo in one study (gruen et al., 2017); however, it was effective when observed in a non-placebo controlled clinical trial (gruen et al., 2014). further investigation with a larger sample size would assist in strengthening the evidence of an association between trazodone administration and a reduction in the behavioural signs of stress in dogs. conclusion the available evidence weakly supports the hypothesis that administration of trazodone is an effective treatment in reducing stress related behaviours in hospitalised dogs and dogs confined post-surgery, and further studies are required to confirm its efficacy. the quality of the evidence when hospitalised dogs was studied was moderate (gilbert-gregory et al., 2016), however in dogs studied that were confined postsurgery, the evidence is weaker (gruen et al., 2014; gruen et al., 2017). different trazodone doses were evaluated in the studies and so further studies focusing on dose effects are required to determine appropriate dose rates. further studies also need to be conducted to evaluate the appropriate length of time that trazodone should be given prior to a stressful event, as well as whether trazodone needs to be used in conjunction with other anxiolytic drugs to optimise efficacy. how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are a small animal veterinarian working in a private practice with a high surgical case-load. the recognition and reduction of iatrogenic stress has become a large focus in companion animal veterinary practice, especially with the increase in patients undergoing longer hospitalisation stays to receive postoperative care. trazodone, an anxiolytic, is increasingly used in dogs to reduce stress and stress related behaviours. however, there have been debates between colleagues about its efficacy. an example is a 5-month-old puppy that was hospitalised after a castration procedure. in recovery the puppy became quite stressed – vocalising and trying to dig out of its cage – and your colleague recommended giving trazodone. you decide to investigate the efficacy of trazodone in hospitalised patients and those confined postsurgery. the evidence three studies evaluated the efficacy of trazodone in reducing stress related behaviours in dogs undergoing hospitalisation, or postsurgery confinement. one prospective, randomised, blinded observational study compared the behaviour observed after trazodone administration with no trazodone administration in environmentally matched dogs that were hospitalised after surgery (gilbert-gregory et al., 2016). through the use of a blinded observer, randomisation, and matching the environment of the treatment and control dogs, the quality of evidence in this study is moderate. another randomised, placebo-controlled clinical trial compared the stress related behaviours of two groups of dogs who were confined after orthopaedic surgery, who were administered either trazodone, or a placebo (gruen et al., 2017). use of a placebo strengthens the evidence in this study, however utilising a small number of dogs for the whole study (n = 29) makes it weak. a third prospective, non-randomised, open-label clinical trial evaluated the behaviour, compared to baseline behaviours, of dogs administered trazodone after orthopaedic surgery and subjected to postsurgery confinement and rest (gruen et al., 2014). however, the strength of the evidence in this study is reduced due to a lack of comparison with a placebo or control group, and a small study size (n = 36), deeming the evidence weak. overall, the available evidence is weak. summary of the evidence gilbert-gregory et al. (2016) population: recruitment: client-owned dogs admitted to ohio state university veterinary medical center for a non-specified surgical procedure from june 22 to october 8, 2015. collection of history and a physical examination were performed prior to enrollment. criteria for eligibility and inclusion for treatment group: dogs prescribed trazodone hydrochloride at any point during hospitalisation. criteria for eligibility and inclusion for control group: dogs not administered trazodone during hospitalisation. selected on the basis of similar housing environment and proximity within the hospital to the treatment dogs to the control dogs for environmental variables that could be associated with stress. criteria for exclusion and rejection from both groups: if they had been administered oral or injectable medications that could alter mentation ≤ 2 hours before observation. sample size: 120 dogs. intervention details: group allocation: there were two groups: treatment group (received trazodone) (n = 59 dogs) and control group (did not receive anything) (n = 58 dogs). one dog in the control group was matched to a dog in the treatment group in a similar housing environment. the age, body weight, sex, ratio of mixed-breed to purebred dogs, hospital admission service, time interval between the two behavioural observations, and the number and proportion of dogs that were concurrently receiving mentation-altering medications (besides trazodone) were not significantly different between the treatment and control groups. procedure: trazodone was administered to dogs displaying signs of fear, anxiety or aggression (unless contra-indicated for the patient), and these dogs formed the treatment group. trazodone was administered at a starting dose of 3.5 mg/kg every 12 hours by a veterinary student or a veterinary assistant / technician hidden inside food. each dog was monitored to ensure that the medication was consumed. the medication was not administered to patients who were not being given food at the time; i.e., prior to surgery, or who were not being fed orally, such as through a feeding tube. some dogs who had been in surgery were concurrently administered tramadol hydrochloride at the discretion of the clinical veterinarian. treatment was continued throughout the hospitalisation period as needed based on stress related behaviour. adjustments to dosage were made at the discretion of the attending clinician as needed. study design: prospective, randomised, blinded controlled study. outcome studied: 17 signs and / or behaviours associated with fear, anxiety and aggression grouped into three behavioural summation categories that were observed at time 1 (≤ 45 minutes after trazodone administration) and at time 2 approximately 90 minutes after the first observation. these behaviours were: frenetic: lip licking, pacing, panting, spinning, trembling, whining, yawning, wet dog shake, pupil dilation, lifting a forelimb. fractious: growling, lunging, showing teeth, pupil dilation, lifting a forelimb. freeze: averting gaze, pinning back ears, whale eye sign, pupil dilation, lifting a forelimb. the number of observed stress related signs or behaviours were summed for each group, with each dog receiving a total stress related score and a behaviour summation score that was compared between time 1 and time 2. behavioural assessment: once paired dogs were selected, a blinded observer performed 60 second behavioural observations on each of the dogs, observing them for 30 seconds from a distance of 3 feet, and then for an additional 30 seconds directly in front of the door. the dogs were assessed one after another, and the order was maintained when the next observation occurred. the first observation was conducted ≤ 45 minutes after trazodone administration to the treatment dog. if the first observation was performed more than 45 minutes after administration of trazodone, the dog was removed from the study for undisclosed reasons. the second observation was conducted approximately 90 minutes after the first observation. observations were conducted utilising a checklist developed by the first author in conjunction with a board-certified veterinary behavioural specialist. main findings (relevant to pico question): 117 dogs from an original sample size of 120 dogs: one dog was removed from the treatment group as the first observation was performed more than 45 minutes after trazodone administration, and two dogs from the control group were removed as they were not present in the ward when the second round of observations were due to occur. treatment with trazodone resulted in a reduction in the observed signs of stress and stress related behaviours. this observation was made when a sign from time 1 was absent when observed during time 2. in the treatment group this included a 29% reduction in lip licking (p = 0.007), 34% reduction in panting (p < 0.001), 24% reduction in whining (p = 0.004), and 24% reduction in whale eye sign (p = 0.004). there was no significant reduction in the other observed signs. the control group did not show a reduction in stress related signs, besides a 24% reduction in whale eye sign (p = 0.031). median total stress related behaviour scores, and median summation scores for frenetic and freeze behaviours were lower at time 2 compared to time 1 for the treatment group (p ≤ 0.009), while they were not significantly lower for the control group. the fractious behaviours were not reduced between time 1 and time 2 for the treatment or control group. limitations: during the study, 54% (32/59) of the dogs that received trazodone were also administered one or more concomitant medications. most (18/32) received non-steroidal anti-inflammatories (nsaids) (carprofen, deracoxib, tepoxalin, firocoxib or meloxicam) or tramadol (14/32), however some (9/32) were also administered gastroprotectants (omeprazole, sucralfate, pantoprazole sodium, or famotidine), systemic antimicrobials (6/32) (metronidazole, cephalexin, amoxicillin-clavulanic acid, enrofloxacin, ampicillin sodium-sulbactam, marbofloxacin, or amikacin sulfate), opioids (6/32) (hydromorphone hydrochloride, butorphanol tartrate, fentanyl citrate, or methadone hydrochloride), a tranquilliser (5/32) (acepromazine maleate), an anti-epileptic with analgesia (4/32) (gabapentin), a corticosteroid (4/32) (prednisolone), antiemetics (4/32) (ondansetron hydrochloride, maropitant citrate, or metoclopramide hydrochloride), an antihistamine (3/32) (diphenhydramine hydrochloride), an appetite stimulant (1/32) (mirtazapine), a laxative (1/32) (lactulose), and an anthelmintic (1/32) (fenbendazole). any or all of these could have contributed to a reduction of stress related behaviour in the dogs. there is also the potential for drug interactions to occur, especially those that induce the cytochrome p450 system. there was potential for selection bias to have impacted which dogs were chosen for either treatment or control group based on their initial behaviour as this was not randomised and treatment dogs were chosen on the basis of their perceived level of stress in hospital. the environmentally matched dogs were not true controls as they may not have had the same levels of stress at baseline – this was not tested and accounted for as the dogs’ baseline behaviour was not observed. the behaviours were only analysed within groups and not between groups whereby the same behaviours were not observed by both the treatment and control group at time 1. there was a higher chance of type i errors (false positives for trazodone efficacy) when multiple comparisons were made between and within groups without adjusting the p value. whether the dog had undergone surgery or not, the time in recovery if surgery had occurred, or duration of the hospital stay overall was not taken into consideration when selecting the dogs for the control group, and was in fact significantly different (p = 0.015) between treatment and control groups. when comparing the time of assessment pre or post surgery, there were a higher proportion of dogs evaluated who had surgery pending in the treatment group than surgical patients who were recovering post surgery, compared to the control group where there was an equal number of dogs evaluated either pre or post surgery, potentially exacerbating the stress related behaviours in time 1, and the changes between when they were first evaluated compared to the second evaluation. there was a higher proportion of postoperative patients in the control group compared to the treatment group, therefore the changes between time 1 and time 2 may have been less obvious compared to the treatment group as other factors such as the anaesthetic, pain and duration of hospitalisation may all have contributed to stress related behaviours or lack thereof. when selecting the environmentally matched dogs, duration of hospitalisation was not considered. it is therefore possible that the lack of changes of behaviour between time 1 and time 2 may have been due to the dogs having already been in hospital for longer compared to the treatment dogs, and had already acclimatised to the environment.   gruen et al. (2017) population: recruitment: dogs that were admitted to the north carolina state veterinary hospital orthopedic surgery service. patients recruited were enrolled in the study if they met the criteria for eligibility and exclusion following physical examination and collection of patient history, including history of prescription of mentation-altering drugs. as an incentive for participation, enrolled participants were provided with free postoperative laboratory tests and $100 off the price of postoperative radiographs 8 weeks after surgery. criteria for eligibility and inclusion: owned, with attainment of informed owner consent. sample size: 33 dogs. intervention details: group allocation: control group (n = 15 dogs) administered placebo and treatment group (n = 14 dogs) administered trazodone. there were no differences between the distribution of sexes, mean age or mean weight between the treatment and placebo groups. the enrolled dogs were undergoing either stifle stabilisation (n = 23), fracture repair or external fixator placement (n = 5), or a total hip replacement (n = 1). there was no significant difference (fisher exact test, p = 1.00) between the groups in the distribution of types of surgery by location procedure: owners of enrolled dogs completed a presurgical questionnaire about the dogs’ baseline behaviour to determine; baseline activity level, degree of control of dog during leashed walks, tolerance of confinement. cases were assigned randomly to either control or treatment group. owners of enrolled dogs, veterinarians, technicians and members of staff were blinded to the treatment except when needed. after surgery owners were given standard postoperative instructions for confinement and reducing activity for 4 weeks. during this time period, owners were to administer: days 1–10, daily nonsteroidal anti-inflammatory; days 1–7, oral tramadol (4–6 mg/kg every 12 hours); and days 1–7, half dose of treatment (either trazodone at 3–5 mg/kg every 12 hours, or an equivalent tablet size and quantity of placebo given every 12 hours). when tramadol was discontinued after day 7, the dose of the treatment was increased to the assigned level (trazodone at 5–7 mg/kg every 12 hours or an equivalent tablet size and quantity of placebo given every 12 hours) and continued for 4 weeks. dosage was altered without releasing the blinding if any of the following occurred: the dose of treatment seemed too high for a dog (e.g., if the owner reported that the dog was excessively sleepy) and could be decreased. the owner reported lack of efficacy, and was given an increased dose. the owner reported lack of efficacy and wanted to withdraw – the assigned treatment would cease and known trazodone would be dispensed for the duration of the study. each week, owners were required to submit an emailed questionnaire about their dog’s behaviour, with a follow-up call if they did not return the questionnaire on time. questions included: tolerance of confinement and restriction of activity. control of the dog on leash walks. overall activity levels. confirmation of dosing schedule. reporting of any adverse events related to medication. owner satisfaction with the treatment (either placebo or trazodone). owners were called after 4 weeks, whereby they could elect to continue administration of treatment for up to 8 weeks postoperatively. the final dosage range received ranged from 5.6–21.6 mg/kg/day. 25 of the 29 dogs that were enrolled in the study completed it, with 3 in the trazodone group and 1 in the placebo group withdrawing. at the 4 week time point, most owners in both the trazodone (11/11 [100%]) and placebo (12/14 [85.7%]) groups elected to continue the assigned treatment at the assigned dose. study design: randomised placebo-controlled clinical trial. outcome studied: the behaviours studied related to the dog’s behaviour postsurgery with treatment administration, and were compared to baseline behaviours determined before surgery: greeting behaviour. calmness. willingness to be controlled on leash. pulling. tolerance of confinement at home. reported by owners, based on questionnaires. main findings (relevant to pico question): 29 dogs from an original sample size of 33 dogs: dogs were removed from the study when diagnosed with a clinical disease during the study (n = 1), the owner did not return the questionnaire or the owner removed the dog from the study due to lack of efficacy of treatment (n = 3). in baseline ratings, no significant differences were found between the trazodone and placebo groups for greeting behaviour (p = 0.21), calmness (p = 0.15), willingness to be controlled on leash (p = 0.86), pulling whilst on leash (p = 0.53), or tolerance of confinement at home (p = 0.68). when baseline and post-treatment ratings were compared, there were no significant differences found between the trazodone and placebo groups for greeting behaviour (p = 0.69), calmness (p = 0.39), ability to be controlled on leash (p = 0.69), pulling whilst on leash (p = 0.12), or tolerance of confinement at home (p = 0.68). the treatment was rated as moderately or extremely helpful in 8/11 (72.7%) owners of the trazodone group and 11/14 (78.6%) of owners of the placebo group for facilitating both calmness and manageability. there were no significant differences between groups in regard to the duration of the effect (p = 0.84), or the change in the effect over time (p = 0.62). therefore, when compared with a placebo, trazodone did not demonstrate an effect on calmness, manageability and stress reduction that was more effective than the placebo. limitations: systemic bias may have existed due to the existing use of trazodone at the clinic for postsurgical confinement, as veterinary surgeons at the clinic were already convinced about the efficacy of trazodone, and therefore were hesitant to enrol their own patients in the trial in case they received a placebo, contributing to a reduced number of study participants. case selection when enrolling participants may have been biased towards dogs that were inherently calm and more accepting of confinement to reduce the potential for complications postsurgery due to the preconceived efficacy of trazodone. there was no evidence or information provided about why particular parameters were chosen to assess behaviour, and the investigators did not justify their selection of behaviour markers of calmness, manageability and stress. owners’ evaluation is subjective and may not have been entirely accurate, with the potential for social desirability bias on the part of the owners have an effect. owners may not have properly followed prescribed medication and activity regime. placebo-by-proxy effect may have affected results, whereby the belief of the owners that their dog is receiving an anxiolytic medication could change the way that the owner interacts with the dog and could thereby lead to an actual change in the dog's behaviour due to the interaction. the outcome assessment tool used may not have been sensitive enough to capture the differences between the groups. sample size determined by a pilot study (gruen et al., 2014) was not large enough (dhand & khatkar, 2014) to capture the effects when utilised in a placebo controlled study.   gruen et al. (2014) population: recruitment: 36 client-owned dogs that underwent orthopaedic surgery at north carolina state university college of veterinary medicine veterinary health complex. criteria for eligibility and inclusion: in good health and weighed at least 5 kg (11 lb). owned, with attainment of informed owner consent. not receiving concomitant behavioral medications or monoamine oxidase inhibitors, such as amitraz products before the study commenced. castrated males and spayed females. owners agreed to administer medication as required, report adverse effects if they occur, and complete weekly online surveys describing features of their dog’s behaviour. sample size: 41 dogs: 25/41 (52.2%) were female, the mean age was 3.0 ± 2.46 years, and the mean weight was 32.0 ± 10.6 kg (70.4 ± 23.3 lb). study participants underwent a variety of orthopaedic surgeries, and were grouped into surgery type by hip joint (n = 11 dogs), stifle joint (n = 21 dogs), and other (n = 4 dogs). intervention details: all dogs were administered trazodone, with the initial dose being 5 mg/kg, po, q 12 h before moving to the standard dose of approximately 7 mg/kg, po, q 12 h. the standard dosage was determined by the authors in accordance with a small pilot study (gruen, 2012). after week 2, the owners of 25 dogs requested a higher dosage of trazodone, and these dogs became the high-dosage group (mean total daily [within 24 hr period] peak dosage was 21.19 ± 39 mg/kg, po). 11 dogs received the standard dosage (mean, 6.86 mg/kg, q 12 h). procedure: when enrolled, the owners completed a presurgical survey evaluating their dog’s behaviour. surveys asked owners to rate the following on a scale from 1–4 with lower scores indicating calmness and manageability: tolerance of confinement when left alone. tolerance of confinement when owner is home. tendency to pull on a leash during walks. willingness to be controlled by the owner. intensity of greeting behaviour to the owner and other familiar people. overall calmness. owners were sent questionnaire (via email) and asked to complete the same online survey evaluating their dog’s behaviour each week for 4 weeks. a fifth survey was completed 8–12 weeks after surgery at the patient’s final postoperative evaluation. for days 1–3 postsurgery, owners were instructed to administer trazodone at half the standard dose (approximately 3.5 mg/kg every 12 h) and tramadol for pain management (4–6 mg/kg every 8–12 h) – the researcher’s rationale for this was to establish initial blood concentrations of trazodone, reduce the possibility of receiving excess serotonin, and to develop tolerance to the fluctuating sedative effect of trazodone (the authors did not disclose why the dose was approximate, however it is assumed that it was due to the tablet size and dose of trazodone per tablet in milligrams). after 3 days, tramadol administration ceased, and trazodone dosage was increased to the standard dosage (approximately 7 mg/kg, every 12 h). during the study, if the standard dosage was considered insufficient by the owner, the dosage and administration schedule of trazodone were increased after consultation with a veterinary behaviourist (approx 7–10 mg/kg, every 8 h). total daily dose was calculated as the total amount of trazodone administered po during a 24 hour period. administration of trazodone continued for 4 weeks postoperation. study design: prospective non-randomised open-label clinical trial. outcome studied: the effect of trazodone on tolerance to confinement and calming by comparing baseline behaviours before surgery, and behaviour after surgery with trazodone administration: intensity of greeting behaviour to the owner and other familiar persons. overall calmness. willingness to be controlled by the owner. tendency to pull on a leash during walks. trazodone dosage. trazodone onset of action and duration. adverse events after trazodone administration. main findings (relevant to pico question): 36 dogs from an original sample size of 41 dogs: dogs were withdrawn from the trial when the owner was not compliant with online surveys and communication (n = 4), and / or it was determined that they were concurrently receiving mentation-altering medications (n = 1 dog). in the final survey 8–12 weeks after surgery (depending on the surgery) 32/36 (89%) of dogs improved in their calmness and tolerance to confinement either moderately or extremely. when compared with the presurgical surgery responses, the dogs significantly improved with respect to the intensity of greeting behaviour to the owner and to other familiar persons (p = 0.003) and in overall calmness (p = 0.032). the dogs did not improve with respect to willingness to be controlled by the owner (p = 0.492) and tendency to pull on a leash during walks (p = 0.097). no owners rated trazodone as not at all helpful with regard to facilitating confinement tolerance. in some final surveys, trazodone was reported as extremely helpful in dogs that initially resisted confinement, compared with those that initially accepted confinement (p = 0.011). an exact number of dogs that initially resisted confinement versus dogs that initially accepted confinement was not disclosed. approximately 90% (37/41) of owners reported that trazodone was moderately or extremely efficacious in positively effecting the dogs confinement and calmness. the mean standard dose (low dose group, n = 11) over 24 hours was 13.73 mg/kg and mean peak dosage over 24 hours (high dose group, n = 25) was 21.19 ± 6.39 mg/kg, po.  there was no significant difference between the two groups in regards to age (p = 0.568), weight (p = 0.770), or surgery type (p = 0.703). the median time for trazodone to cause an effect was 31–45 minutes after administration, with 37/41 (90%) of owners reporting effect between 16 and 90 minutes post administration. the median duration of action of trazodone was ≥ 4 hours. twenty dogs reported adverse events including: soft stool, loose stool or diarrhoea (1), constipation (1), increased thirst (1), signs of anxiety, restlessness, or agitation (2), aggression (1), moaning (1), drowsiness (2), somnolence (5), panting (2), teeth chattering (1), drooling (1), signs of paranoia (1), incontinence (1). two instances occurred where dogs accidentally received higher doses than prescribed: one received total dose of 600 mg (20 mg/kg) and was slightly sleepy; the other was given tramadol longer than prescribed concurrently with the standard trazodone dose and no adverse event was reported. limitations: any dog could receive other concomitant drugs including nsaids, buprenorphine, amantadine, or antimicrobials during the study period depending on the veterinary surgeons prescription, which may have impacted on their behaviour. three dogs received fluoxetine or acepromazine, however only one dog was withdrawn from the study for receiving a drug that may have altered its behaviour. two dogs received gabapentin for pain which may have influenced stress related behaviour due to its anxiolytic and / or analgesic properties (papich, 2016a). the study design did not include a control group. it was not stated whether there was a difference in behaviour after administration between the dogs who received a higher dose of trazodone versus a lower dose. positive effects may have also been due to the dog acclimatising to confinement. a change in behaviour may also have been due to behavioural correction by the owner. a placebo-by-proxy effect may have influenced the dog’s behaviour, whereby the owners may have acted differently around the dogs due to the knowledge of trazodone administration and effects of surgery and elicited a calm response in return. results depended on the owner’s accurate evaluation of the dog’s behaviour, and the compliance with confinement and calmness parameters. results depended on owners’ compliance in treatment administration.   appraisal, application and reflection behaviour as a measure of stress in all three papers, the primary outcome measured was the reduction in stress related behaviours (gilbert-gregory et al., 2016), and increased calmness and manageability (gruen et al., 2014; and gruen et al., 2017). gilbert-gregory et al. (2016) assessed this through creating a checklist comprised of 17 signs and behaviours that were associated with fear, anxiety and aggression. gruen et al. (2014) assessed intensity of greeting behaviour, overall calmness, willingness to be controlled and pulling on the leash, and gruen et al. (2017) similarly assessed stress related behaviour in five provocative situations (tolerance of confinement when left by themselves, tolerance of confinement when the owner was home, tendency to pull on the leash whilst on walks, willingness to be controlled by the owner such as through obeying familiar commands, and intensity of greeting behaviour towards the owner and other known persons), and one temperament measure (overall calmness). provided correct behaviours are observed and observers are well trained and accustomed to using these tools, assessing specific postures, mannerisms and activities related to stress can be an accurate measurement tool (beerda et al., 1997; beerda et al., 1998; and overall, 2013). however, it is important to consider that dogs who are not inherently stressed normally may not demonstrate a change in behaviour after trazodone administration, and a large sample size would be needed to accommodate for this. there is also the requirement to determine the difference between pain related behaviour and stress related behaviour, as the two often overlap and different pain management strategies and type of procedure can impact the amount of stress related to this, as well as individual pain tolerance thresholds. an animals’ behaviour when it is experiencing stress depends on numerous factors such as genetic predisposition, past experiences, and the current environment (lloyd, 2017). thus age, sex, health status, and any previous experiences they may have had during hospitalisation or confinement all of which may impact stress related behaviour and therefore may inflate or reduce the perceived effect of trazodone. the type of behaviour elicited by a dog when it is experiencing stress depends on the type of threat that it is perceiving, whether it is escapable or inescapable, as well as personal characteristics including individual variations in coping styles (lloyd, 2017; and steimer, 2022). gilbert-gregory et al. (2016) acknowledges the variety of behaviours displayed when a dog is experiencing stress, and draws from physiologic knowledge through the creation of the behavioural checklist utilised in the study, however gruen et al. (2014; and 2017) does not describe why the factors in their checklist were chosen, or how they reflect increased manageability and calmness, or a reduction in stress. this makes it more difficult to interpret the results, and compare the findings to other studies. canine specific stress related behaviours responses to stressful stimuli can vary between individual species, therefore it is important to analyse and interpret the behaviour of dogs through referring to species-specific behaviours and responses. studies such as those by beerda et al. (1997; and 1998) aimed to determine the behavioural, hormonal and physical responses elicited by stressful and provocative stimuli such as electric shock. the responses typically involved vocalisation, trembling, altered posture usually into a lowered position, averting their gaze and displaying the whites of the eyes in a distinctive ‘whale eye’ sign, along with quickened breathing, lifting a paw, yawning, circling, and generally becoming more agitated, escalating to urination and / or defecation in some instances (beerda et al, 1997; and beerda et al., 1998). these behaviours were accompanied by an increased heart rate, along with increased levels of salivary cortisol, indicative of a stress response (beerda et al., 1997). more subtle signs of stress and anxiety that have been described in dogs include darting eyes and scanning for potential dangers or means of escape, refusing treats or becoming inappetent in general, and appearing distracted by sniffing, sighing or stretching (overall, 2013). gilbert-gregory et al. (2016) developed the checklist utilised in their study with the assistance of a board-certified veterinary behaviourist. the 17 behaviours utilised in this checklist echo the responses observed in numerous studies (beerda et al., 1997; and beerda et al., 1998), strengthening the conclusion that these behaviours were indeed stress related. the first author also mentored the observer for 2 weeks before the commencement of the study on how to properly identify the behaviours through conducting preliminary investigations on all dogs housed at the hospital (n = 100), and comparing scores produced concurrently by both the first author and the observer (gilbert-gregory et al., 2016). this increased interobserver reliability, ensured that the observer was aware and skilled in recognising stress related signs and behaviours. gruen et al. (2014) developed the survey utilised in the study through evaluating the dog’s responses to situations that were deemed relevant to successful management after orthopaedic surgery, including greeting behaviour and the level of calmness and manageability that the dog demonstrated. however, the authors did not specify why these parameters were chosen to demonstrate tolerance of confinement. the study by gruen et al. (2017), utilised this assessment tool (gruen et al., 2014), however, the authors commented that non-specific behavioural changes due to trazodone administration may have been missed if the tool was not sensitive enough to be used in a placebo-controlled trial. one important consideration that may have been overlooked in these studies is the potential for the involvement of different emotions in these stress related responses. for example, a dog confined at home in a crate may appear stressed, not due to anxiety, but due to being unable to undertake normal behaviours that they are accustomed to such as having free roam of the house, eliciting high arousal, excitement or frustration. a dog confined in a hospital situation may be displaying stress related behaviours due to high energy that cannot be expelled due to confinement, or frustration due to separation from the owner. administration of other behaviour altering drugs as a confounding factor in the study by gilbert-gregory et al. (2016), 32/59 (54%) of the dogs enrolled in the trazodone group were also administered one or more than one concomitant medications that were prescribed by the attending clinicians. whilst no adverse reactions were reported through the use of more than one drug, these medications included opioids, tranquillisers and gabapentin which are known to alter mentation (papich, 2016a; papich, 2016b; and papich, 2016c) and may therefore impact stress related behaviours. the study did try and account for this as the study participants were excluded if they had been administered oral or injectable mentation altering medications within 2 hours of observation, however there was still the possibility that the results may have been confounded by any administration of these medications with trazodone during their hospitalisation. similarly, in gruen et al. (2014; and 2017), potential mentation-altering drugs were also administered to the patients undergoing observation. a dog that has been administered any of these drugs may display reduced stress related behaviours that are also commonly seen in dogs administered trazodone (papich, 2016a; papich, 2016b; papich, 2016c; and papich, 2016d), therefore if they were administered within the observation period of the study, they may have been altering the subjects’ behaviour, rather than the actual treatment. pain as a confounding factor pain presents in animals in a variety of ways, with specific and non-specific pain behaviours recognisable in dogs (gaynor & muir, 2009). some of these behaviours could be mistaken by an observer as demonstrating a reduction in anxiety. for example, a dog in pain may become hunched up and be reluctant to move as pain progresses and worsens, which could be mistaken for being relaxed, compared to a dog that is lunging and growling (steimer, 2022). similarly, pain may be mistaken for anxiety, whereby a dog in pain due to a limb injury may lift its paw and not weight bear on the limb, while an anxious dog may demonstrate a freeze behaviour through lifting a forelimb (overall, 2013; and gaynor & muir, 2009). a dog in pain may also experience stress and demonstrate stress related behaviours due to the pain itself. gilbert-gregory et al. (2016) reduced the effect of pain as a confounder through mentoring the observer for two weeks prior to the commencement of the study, as mentioned previously. this increased the likelihood that what the observer recorded were true and accurate assessments of behavioural signs of stress, rather than confusing them with signs of pain, assuming that the training was sufficient to determine the difference. certain behavioural observations were also removed from the list that may be confused with pain, such as hunching the hindquarters, reducing the effect of pain on the results (gilbert-gregory et al., 2016). the potential for pain to confound results was evident in the studies by gruen et al. (2014; and 2017), as the owners were responsible for observing their dogs and reporting their behaviours. it is not specified whether the owners received any training or mentorship regarding how they assessed their dogs. in gruen et al. (2014), all dogs concurrently received nsaids but they did not specify the course length or dose. therefore, dogs in this study may have appeared more calm and manageable, and less stressed due to increased pain felt as the pain relief medication was removed, or subsequently wore off. hospitalisation as a confounding factor whilst the effect of hospitalisation, and any environmental stressors such as fire alarms, building construction, and general foot traffic was reduced in the study by gilbert-gregory et al. (2016) through environmentally matching the treatment and control dogs, it is not specified whether the reason for hospitalisation was accounted for when choosing the study subjects. therefore, some procedures may have impacted more on stress levels compared to others through being more invasive, therefore causing more pain, having longer or shorter surgery time, or through the utilisation of different premedications and anaesthetic drugs which may have provided anxiolysis such as benzodiazepines (grimm et al., 2015). the physical effects of being anaesthetised may also have an effect on whether dogs exhibit signs of stress. dogs that are cold after anaesthesia may shake, and vice versa a dog that is warm and pyrexic due to an illness, or becoming too hot during surgery, may pant (grimm et al., 2015). it is not discussed how long after surgery dogs were evaluated in the gilbert-gregory et al. (2016) study, therefore what may have been perceived as stress induced behaviours, may have instead been due to the physical effects of anaesthesia or surgery. gilbert-gregory et al. (2016) reduced the confounding impact of hospitalisation through excluding particular behaviours from the final checklist that were difficult to distinguish as indicators of stress due to the physical limitations or discomfort caused by their various ailments, as mentioned previously. however, there was also a significant (p = 0.015) difference between the groups in regards to surgical status (gilbert-gregory et al., 2016), whereby more of the treatment group participants were awaiting surgery, compared to a more even split between patients who had undergone surgery and those that were waiting in the control group. patients awaiting surgery may have displayed more stress related behaviours compared to those that had already undergone an operation due to the effects previously discussed, which may have affected the results. in gruen et al. (2017), there was no significant difference between the trazodone and placebo groups in the distribution of surgery types by the surgical site (p = 1.0). as all dogs received trazodone in gruen et al. (2014), and were rated by comparing their behaviour before and after trazodone administration, hospitalisation and surgery type were less likely to be confounders. however, the type and duration of postsurgical confinement were not specified in either study (gruen et al., 2014; and gruen et al., 2017), therefore calmness and manageability may have been directly affected by the type and duration of confinement. subjective measurement and assessment whilst there are studies that evaluate specific behavioural indicators of stress in dogs (beerda et al., 1997; and beerda et al., 1998), appraisal of behaviour can differ between operators. as mentioned previously, gilbert-gregory et al. (2016) attempted to minimise the impact of interoperator variability through the first author mentoring the observer for a 2 week period prior to the commencement of the study. after this, a preliminary investigation occurred whereby the observer and first author scored all dogs in the study hospital for another 2 weeks in order to evaluate the reliability between the two investigators. the trained observer was blinded to the treatment given, and assessed all study participants (gilbert-gregory et al., 2016). in both studies, gruen et al. (2014; and 2017) reported a large amount of variability between the reported observations of stress and calmness in dogs as the owners of the subjects were the assessors. owner’s observations could have been made more reliable through filming the dogs and sending footage to a trained assessor, or providing the owners with detailed instructions as to how to observe and assess their dogs’ behaviour. blinding of assessors and administrators blinding is used in clinical trials to remove any bias that can be caused intentionally or unintentionally if participants or the research team are aware of who is receiving an active or placebo treatment (hadgu et al., 2012). in one of the studies, the observer was blinded as to which dog had received the trazodone treatment, and which dog had not received any treatment (gilbert-gregory et al., 2016), and in another the administrators and observers were blinded as to whether their dog received the trazodone treatment or the placebo (gruen et al., 2017). in the third study, however, all dogs received the trazodone treatment, and no blinding was used (gruen et al., 2014). gruen et al. (2017) discussed the placebo-by-proxy effect and how it may have affected the results through the owners acting differently towards their dogs no matter which treatment they received. this may also have affected the results of the study by gruen et al. (2014) whereby all dogs received treatment administered by their owners. the authors also highlight the effect that the belief system of the owners clearly had on their ratings of their dog’s behaviour, as three owners with dogs within the treatment group requested known trazodone as they believed that the unknown medication was not benefitting their dogs (gruen et al., 2017). after the switch, two of these owners then rated trazodone as moderately or extremely effective. one of these dogs had already received an increased dose of trazodone with no improvement, however, when known trazodone was prescribed it was administered at the initial target dosage which was lower than the dose the dog had been receiving before (gruen et al., 2017). once the owner was giving the dog what they knew to be trazodone, their ratings of treatment efficacy changed to positive. this could reflect a placebo effect. sample size when designing a research study, a sample size calculation should always be conducted to determine the number of participants needed to detect a clinically relevant treatment effect (hammond et al., 2014). if the sample size is too small, a true treatment effect may not be detected (type ii error). however, a large sample size may prove unethical (if unnecessary) and costly (hammond et al., 2014). gruen et al. (2017) describe their sample size as being based on a priori power calculation utilising the effect from gruen et al. (2014), whereby 15/17 dogs in the treatment group demonstrated a treatment effect that was deemed to be clinically significant. however, if utilising this expected proportion (88%) from this pilot study, the study by gruen et al. (2017) would require a sample size of 163 in order to estimate the expected proportion of dogs responding to trazodone with 5% absolute precision and a level of confidence of 95% (dhand & khatkar, 2014). the authors also did not provide the justification of their sample size (gruen et al., 2017). gilbert-gregory et al. (2016) and gruen et al. (2014), did not specify why certain sample sizes were chosen for the studies and did not report a sample size calculation. in both studies, if an expected proportion of 50% and 95% confidence level were chosen to account for an unknown expected effect of the use of trazodone, then a sample size of 385 in each study would be required to produce a reliable and valid result (dhand & khatkar, 2014). however, it would be extremely costly and logistically difficult to recruit that many participants and perform a study of this size. duration of time in a novel environment novelty and uncertainty can increase arousal and anxiety by activating the behavioural inhibition system, which inhibits normal behaviours and is one of the first behavioural signs of an anxious state in the dog (steimer, 2022). when a stimulus is no longer perceived as novel, the anxiety associated with uncertainty is reduced. this is echoed in animals when they acclimatise to their environment and the stressors associated with it. in gilbert-gregory et al. (2016), the duration of stay of the dogs was not taken into account when the environmentally matched dogs in the control group were chosen. when analysed, there was a significant (p = 0.01) difference in the mean duration of time in hospital between the treatment and control group dogs, whereby it was shorter for the treatment group (1.5 ± 0.8 days) compared to the control group (2.0 ± 2.0 days) (gilbert-gregory et al., 2016). therefore, the lack of significant decreases in behavioural signs of stress in the control group could reflect acclimatisation to their environment as they had been in the environment for a longer duration of time. however, it should be acknowledged that prolonged hospitalisation and time spent in a novel environment may cause increased levels of stress in some dogs. in gruen et al. (2014; and 2017), the impact of residing in a novel environment is next to null as the dogs were evaluated within their own homes, with the main difference from normal potentially being confined to a crate, pen, or particular area of the house compared to free reign throughout the home. again, it should be acknowledged that this may be a major stressor in some dogs, as well as the stress of imposed restrictions such as reduced exercise. health as a confounding factor illness and disease can significantly alter animal behaviour (frank, 2014). it therefore needs to be considered as a confounding factor when evaluating behaviour as a marker of stress. only gruen et al. (2014), specified that dogs must be in good health to be enrolled in the study. gilbert-gregory et al. (2016) and gruen et al. (2017), did not disclose nor specify the health status of the subjects enrolled in their studies, stating that general health checks were conducted, but not disclosing the outcomes of these examinations. as animals were admitted for surgery, they were not disease free. procedural confounding factors numerous differences in methodology need to be considered as confounders when evaluating the three studies. in gilbert-gregory et al. (2016), a trained veterinarian, veterinary technician or veterinary student administered the treatment to the subjects by hiding it within a treat, reducing confounding factors by maintaining consistency. in comparison, it is unknown how the owners of the subjects in gruen et al. (2014; 2017) administered the trazodone or placebo, and whether they had been informed of how to give medication appropriately without causing undue stress, and also ensure that the dog actually received the intended dose. this would have increased the possibility of procedural confounding factors having an effect on the results. other potential procedural confounding factors include the overall patient health and reason for hospitalisation; the measurement and assessment of the outcome; and the variables associated with the environment that the subjects resided in. when interpreting the results of the three studies, it is therefore important to consider and acknowledge these variations in methodology as potential confounders. it is also important to acknowledge the differences in the methodologies of the three studies examined and what is feasible in the assessment of behaviour in a hospital setting compared to in a home environment. statistical analysis all three papers used appropriate statistical analysis tools to assess the results (gilbert-gregory et al., 2016; gruen et al., 2014; and gruen et al., 2017). gilbert-gregory et al. (2016) performed a wilcoxon signed rank test to assess the data, which is appropriate for use in non-normally distributed data. the use of a fisher exact chi-squared test was also appropriate for analysing categorical data. however, drawing strong conclusions from the results and the provided p-values is overly optimistic, as the differences in p-values were very slight and almost insignificant when evaluating the total stress-related behaviours (p <0.001 for treatment group, and p = 0.078 for control group) (gilbert-gregory et al., 2016). gruen et al. (2017) did not use a transformation or test such as kappa to reduce bias caused by the owner as the assessor. they also used a wilcoxon test which was appropriate, however, the presentation and lack of disclosure of all p-values created confusion for the reader. overall, however, the statistical analysis is appropriate for the data available (gruen et al., 2017). gruen et al. (2014) recognised that the data was ordinal and used the cochran-mantel-haenszel test which was appropriate for the data. however, no information was provided as to the baseline scores that were used to compare to the final results, and so it is also confusing for the reader to determine the reliability of the results. application when evaluating the efficacy of trazodone in dogs who have undergone hospitalisation, it is important to acknowledge the limited available evidence on trazodone use in dogs, and the ongoing reliance on pharmacokinetic data from humans (jay et al., 2013). it has been reported (ciribassi & ballantyne, 2014) that trazodone is helpful as an anxiolytic for events such as veterinary visits, separation anxiety and thunderstorms, for example, however, the onset of activity is generally delayed by up to an hour, and the effects induced by the drug can be unpredictable (papich, 2016d). this is acknowledged by gilbert-gregory et al. (2016) through the assessor waiting at least 90 minutes before observing the study dogs to assess the effects of trazodone. trazodone itself has a wide half-life range (166 ± 47 minutes) and in reaching peak plasma concentration (445 ± 271 minutes), therefore, it is important to consider this when adjusting the dosage to account for variations between individuals (ciribassi & ballantyne, 2014). individual differences in baseline behaviour, personality characteristics, behavioural issues, confounding stimuli and use of concomitant medications all have the potential to influence the efficacy of trazodone use, and need to be considered when prescribing the drug as an anxiolytic for dogs experiencing stress induced by hospitalisation (jay et al., 2013; ciribassi & ballantyne, 2014; and gruen & sherman, 2008). safety and adverse effects trazodone hydrochloride has been administered to dogs orally without serious adverse effects reported (beerda et al., 1998). at higher doses sedation commonly occurs, however this effect may be desirable (beerda et al., 1998). adverse events reported after oral administration included vomiting, gagging, colitis, increased excitement, sedation, increased appetite, and behavioural disinhibition such as getting onto counters (gruen & sherman, 2008), and hypersalivation (jay et al., 2013). intravenous administration of trazodone is not recommended (beerda et al., 1998) as it appears to cause more serious adverse effects, with one study reporting that transient tachycardia and ataxia developed in all dogs involved in the study, and in another study 3/6 (50%) of the dogs briefly became aggressive (jay et al., 2013). caution should also be taken when administering trazodone concurrently with other drugs as it is highly metabolised by the cytochrome p450 enzymes, and these enzymes can be inhibited or induced if other drugs are administered alongside trazodone (jay et al., 2013). serotonin syndrome is also a possibility when using drugs that effect serotonin receptors, and although again the effects of this syndrome have not been observed or reported in dogs in trazodone studies, trazodone should be used with caution when concurrently administering drugs that act on the serotonergic system including selective serotonin reuptake inhibitors, tricyclic antidepressants, tramadol, and monoamine oxidase inhibitors (lloyd, 2017). overall, it is concluded that oral administration of trazodone hydrochloride within dosage limits (starting dose typically 2–5 mg/kg with maximum dose 19.5 mg/kg po daily or 300 mg/dose in highly anxious or aggressive patients) appears to be safe for use in dogs (lloyd, 2017; jay et al., 2013; and gruen & sherman, 2008). clinical application the reduction of stress in canine patients undergoing hospitalisation not only improves the emotional welfare of these patients, but also results in improved health implications and reduced iatrogenic harm associated with veterinary care (gilbert-gregory et al., 2016). incorporating an effective anxiolytic into a pre or postoperative protocol may assist veterinarians in reducing the effects of stress on their patients. the goal of utilising trazodone in hospitalised dogs and dogs undergoing postsurgical confinement is to minimise the stress associated with the often necessary and common practice of hospitalisation and / or confinement – whether before or after surgery, before a noninvasive procedure such as a nail clip, or to allow for an aggressive or nervous dog to be more thoroughly examined without exacerbating the risk to a veterinarian, veterinary nurse, or owner. other drugs such as acepromazine are not considered effective anxiolytics, and have even been shown to potentially increase anxiety and noise sensitivity depending on the dose used (gilbert-gregory et al., 2016; and overall, 2013). there is, therefore, a need in the veterinary practice for an agent that also provides anxiolytic benefits. it is also important for veterinarians to administer a drug that is proven to reduce the physical and emotional consequences of stress if an agent is prescribed for that reason, otherwise the welfare of the dog may be at risk even if the administering veterinarian is satisfied with the act itself of prescribing a drug that will supposedly reduce the patients’ stress i.e., due to the placebo effect. trazodone is widely used in many clinics and is considered an effective means of reducing anxiety in their patients. even in the analysed studies, the authors themselves were perceived to have a selection bias as they were expecting trazodone to be effective and produce positive outcomes in the study participants (gruen et al., 2014; and gruen et al., 2017). it is therefore important to consider the differences in the three studies evaluated when determining the effectiveness of trazodone in reducing signs of stress in hospitalised dogs and dogs confined postsurgery, as well as the rationale of trazodone use by veterinarians as determined by anecdotal and experiential evidence. reflection there is currently evidence of weak strength that demonstrates that trazodone reduces stress related behaviour in hospitalised dogs (gilbert-gregory et al., 2016), and weak evidence that it reduces stress related behaviour in dogs confined postsurgery (gruen et al., 2014; and gruen et al., 2017), however, it is difficult to compare trazodone to other anxiolytics due to the lack of studies into other medications and their efficacy in these contexts. gilbert-gregory et al. (2016) has the strongest evidence due to a better study design, however it also includes many confounding factors that weaken the evidence of trazodone efficacy such as the administration of concomitant medications, not utilising true controls, selection bias, and not accounting for the type of surgery and duration in hospital. gruen et al. (2014; and 2017) demonstrates weak evidence reflecting the small sample sizes used in the studies, and the inconsistency of assessment of behaviour. taken together the evidence of efficacy of trazodone in this context of postsurgical confinement is inadequate. given that all three studies are weakened by various limitations and confounding factors, further studies are required to provide conclusive evidence, utilising a larger sample size, standardised measurement and assessment tools strengthened by evidence surrounding dog behaviour such as the assessment tool utilised by gilbert-gregory et al. (2016) alongside a veterinary behaviourist, which was lacking in gruen et al. (2014; and 2017), the use of healthy patients in a novel hospital environment when assessing hospitalised patients which would not be feasible in all studies, and incorporating blinding of administrators and assessors using a placebo and randomisation. statistically, a sample size of 323 dogs would be required to detect a perfect change with 60–70% of dogs affected by the drug (dhand & khatkar, 2014). also, in an ideal world, it would be important to ensure that trazodone is the sole therapeutic agent administered to subjects during the study to eliminate the confounding effects of other drugs. however, this would prove difficult unless a research population was utilised. whilst there are practical constraints and financial limitations involved in acquiring strong evidence in this subject, the absence of evidence suggests that more research must be conducted in this field for appropriate and correct recommendations to be made about the use of trazodone within a veterinary clinic. methodology search strategy databases searched and dates covered: cab abstracts on ovid platform 1973 to 2023 week 4 pubmed 1920 – january 2023 search strategy: cab abstracts: (dog or dogs or canine or canines).mp. or exp dogs/ (trazodone or desyrel or oleptro).mp. (stress or stressed or stressful or anxiety or anxious or nervous or nervousness or distressed or distress or fear or fearful).mp. (hospital or hospitals or hospitalised or hospitalized or clinic or clinics or consult or consultation or surgery).mp. 1 and 2 and 3 and 4   pubmed: dog or canine trazodone or desyrel or oleptro stress or stressed or stressful or anxiety or anxious or nervous or nervousness or distressed or distress or fear or fearful hospital or hospitalised or hospitalized or clinic or consult or consultation or surgery 1 and 2 and 3 and 4 dates searches performed: 01 feb 2023   exclusion / inclusion criteria exclusion: not related to the pico parameters (non-dog patients; not evaluating the effects of administration of trazodone; not evaluating effect of administration of trazodone for a hospital setting or postsurgical confinement). case studies. systematic reviews. study summary / article. inclusion: dog subjects. evaluating effects of trazodone in a hospital setting (in hospital; confined after hospital).   search outcome database number of results excluded – case study excluded – non-canine excluded – not evaluating effects excluded – not evaluating in hospital setting or confinement excluded – article excluded – systematic review total relevant papers cab abstracts 14 4 0 1 3 3 1 2 pubmed 18 4 2 2 4 3 1 2 total relevant papers when duplicates removed 3   orcid lara dillon: https://orcid.org/0000-0001-5843-3421 conflict of interest the author declares no conflicts of interest. references beerda, b., schilder, m.b.h., van hooff, j.a.r.a.m. & de vries, h.w. 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(2002). the biology of fearand anxiety-related behaviors. dialogues in clinical neuroscience. 4(3), 231–249. doi: https://doi.org/10.31887/dcns.2002.4.3/tsteimer contribute to the evidence there are two main ways you can contribute to the evidence base while also enhancing your cpd: tell us your information need write a knowledge summary either way, you will be helping to add to the evidence base, and strengthen the decisions that veterinary professionals around the world make to give animals the best possible care. learn more here: https://veterinaryevidence.org/index.php/ve/guidelines-for-authors licence copyright (c) 2023 lara dillon intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use.   veterinary evidence is an rcvs knowledge initiative. issn: 2396-9776 first floor, 10 queen street place, london ec4r 1be resources student awards staff login policies privacy policy accessing information policy cookie declaration terms of use copyright notices stay connected podcasts twitter facebook instagram linkedin back to top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443. in dogs with atopic skin disease, is lokivetmab more effective than oclacitinib in reducing the score of a recognised scoring system? a knowledge summary by bonnie y. t. cheung ba [camb] msci [ucl] 1* 1department of veterinary medicine, university of cambridge, madingley road, cambridge cb3 0es *corresponding author (bytc2@cam.ac.uk) vol 7, issue 2 (2022) published: 22 jun 2022 reviewed by: paul bloom (dvm) and roberta perego (dmv phd) next review date: 07 dec 2023 doi: 10.18849/ve.v7i2.569 pico question in dogs with atopic skin disease, is lokivetmab more effective than oclacitinib in reducing the canine atopic dermatitis lesion index score (or some other recognised scoring system)?   clinical bottom line category of research question treatment the number and type of study designs reviewed one randomised controlled trial and one before and after study were critically appraised strength of evidence weak outcomes reported one randomised controlled trial studied the effects of lokivetmab and oclacitinib and found that both drugs were similar in reducing the canine atopic dermatitis lesion index (cadesi-03) score. an additional study was evaluated but had non-standardised data as it was a before-and-after study on use of lokivetmab. the paper noted that dogs’ response to oclacitinib can be used to predict how well these dogs respond to lokivetmab. this study also reported a reduction in pruritus visual analog scale (pvas) score between before and after lokivetmab administration conclusion in view of the strength of evidence and outcomes from the studies, there is insufficient quality of evidence to answer the pico question and so further comparative study is required   how to apply this evidence in practice the application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. knowledge summaries are a resource to help reinforce or inform decision making. they do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. clinical scenario you are a small animal veterinarian working in a private practice where one of your clients brings in a dog with a history of licking and itching parts of their body. upon clinical examination, you find the axillae, feet, face, and groin are severely pruritic with no secondary bacterial infection present. the clients note that the dog is already on a hypoallergenic diet, has flea and worming treatment up to date, and is currently on glucocorticoids which owner notices is not as effective as it was before in pruritic control. therefore, you wish to use immune-modulating drugs: oclacitinib or lokivetmab as they are relatively new to the market and have been approved for use in dogs with canine atopic dermatitis (cad). the client has no restrictions financially, but wants to get their beloved pet’s itching and pruritus under control. oclacitinib is administered orally and given initially twice a day for 2 weeks and then once a day whereas lokivetmab is given as a subcutaneous injection every 4 weeks. oclacitinib and lokivetmab target similar pathways known to reduce pruritus, e.g., il-31, so when choosing, which one is better? the evidence there were many studies investigating the efficacy of oclacitinib and lokivetmab individually in dogs diagnosed with canine atopic dermatitis (cad) (cosgrove et al., 2013; fleck et al., 2015; michels et al., 2016(a); michels et al., 2016(b); marsella & ahrens, 2018; szczepanik et al., 2019; and van brussel et al., 2021), but few compare the effects of both drugs in the same study. to investigate efficacy of drugs for cad, scoring systems have been useful to provide a comparable method of assessment. a common scoring system used is canine atopic dermatitis extent and severity index (cadesi), which is utilised by clinicians for its thorough assessment of cad patients. there are currently four iterations, the latest being cadesi-04 (olivry et al., 2014). each iteration assesses the patient using a different list of body areas to score severity of lesions (e.g., erythema, lichenification). overall scores between iterations cannot be compared. therefore, extrapolating scores from different studies that individually studied the efficacy of oclacitinib and lokivetmab cannot be used reliably for this knowledge summary. however, there are other scoring systems like pruritus visual analog scale (pvas), which is more accessible for owners to use when assessing cad (hill et al., 2007), or cosmetic assessment by owners from bensignor & videmont (2021) but this has not currently been validated. moreover, overall pvas scores from studies which have assessed either efficacy of oclacitinib or lokivetmab cannot be used for this knowledge summary as these are subjective to owners’ perception and bias. therefore, pvas scores from different studies cannot be used for direct comparison to assess whether lokivetmab is better than oclacitinib. for this knowledge summary, only cadesi and pvas scoring systems were used to compare the efficacy of oclacitinib and lokivetmab because these have been used more widely across studies and have been validated in assessing severity of cad (hill et al., 2007; olivry et al., 2007; and olivry et al., 2014). therefore, two studies were found to be relevant to the pico question, but there was only one controlled study directly comparing the effects between lokivetmab and oclacitinib using cadesi-03 and pvas (marsella et al., 2020). an additional study was evaluated because it included some comparison between lokivetmab and oclacitinib treatment using pvas, but this was a before-and-after study where oclacitinib was assessed before lokivetmab treatment (souza et al., 2018). summary of the evidence marsella et al. (2020) population: atopic beagle dogs: 8 years old. intact females (n = 9), intact males (n = 9) and neutered male (n = 1). maintained in a research facility (university of florida). sample size: 19 dogs. intervention details: all dogs were fed the same diet, housed where runs were cleaned daily and there were no toys that trap dust. all dogs were at a research facility sensitised to dermatophagoides farinae and were exposed to the allergen twice a week. dogs were housed in pairs, but it is unclear how they were allocated. a pair of dogs were allocated to receive either: oclacitinib – oral administration of 0.5 mg/kg twice daily for 2 weeks then once daily for 2 weeks. ciclosporin – oral administration of 5 mg/kg once a day for 28 days. lokivetmab – subcutaneous administration of 2 mg/kg on first day of allergen challenge. prednisone – oral administration of 5 mg/kg twice daily for 2 weeks, then 0.5 mg/kg once daily for 1 week and then 0.5 mg/kg once every 48 hours for 1 week. control – no treatment. allocation of dogs in each group was not mentioned. study design: randomised, controlled, blinded study. outcome studied: canine atopic dermatitis and extent severity index, third iteration (cadesi-03) scoring: subjective assessment by investigator who was unaware of treatment allocation. performed once on day 0, twice on the days of the allergen challenge (before exposure and 6 hours after), and 24 hours after each allergen challenge. allergen challenges were on days 2, 6, 9, 13, 16, 20, 23, and 27. behavioural observation research interactive software (boris) recording: subjective assessment performed by two people who were unaware of treatment allocation. this was used to score the duration(s) of pruritic behaviour (e.g., licking, biting and scratching). when the dog was biting or scratching, the observer pressed a key which indicated the start of behaviour and then pressed again to indicate the end. for licking behaviour, each lick was indicated by a key press. camera recordings were taken on day 0 and on days 2, 9, 16 and, 23, recordings were taken 4 hours after allergen exposure. pruritus visual analog scale (pvas): subjective assessment performed by the same evaluators that reviewed the boris recordings. scoring scale from 0 to 10 where 0 was described as ‘no itching is observed’ whereas 10 was described as ‘severe itching, manifested as interruption of eating, playing or resting, in order to itch’. transepidermal water loss (tewl): objective assessment performed on days 0, 14 and 28. measured as evaporation rate (g/m2/h) using a closed chamber device (vapometer®) at ambient temperature (20–26°c). three unclipped areas were evaluated (concave surface of pinnae, axilla and inguinal). hydration: objective assessment performed on days 0, 14 and 28. measured using a corneometer® where a probe is placed perpendicular to the skin for 10 seconds and expressed as micro-siemens (μs). for statistical analysis, the four weeks of study was divided into two periods (t1/acute phase = first 2 weeks, t2/chronic phase = final 2 weeks). statistical evaluation of data was performed using mixed-model restricted maximum-likelihood 5-group x 2-time analysis of variance (reml-anova) with a between-subjects factor of group (control, ciclosporin, lokivetmab, oclacitinib, prednisone) and within-subject factor of time (t1, t2). area under the curve (auc) was calculated for each dog (cadesi-03 scores, tewl and hydration for each site examined). additionally, kruskal-wallis test r was used to determine differences between groups whereas friedman’s test was used to investigate the effect of time. significance was set at p < 0.05. main findings (relevant to pico question): oclacitinib had a statistically significantly lower cadesi-03 score than controls during t1 (p = 0.015) whereas there was no statistical significance found for the lokivetmab-treated group. at day 28, dogs treated with lokivetmab and oclacitinib had mild to no erythema from pictures of a representative dog in each group. no statistical significance was detected for mean pvas as well as auc for the duration of scratching between t1 and t2 phase for either lokivetmab or oclacitinib treatment. on day 28, controls had a higher tewl than the lokivetmab-treated group (p = 0.031) in pinnae and axillary regions, but none reported for the oclacitinib-treated group. no changes in tewl were seen in oclacitiniband lokivetmab-treated groups for any of the assessed regions over time. auc for hydration over time were higher in lokivetmaband oclacitinib-treated groups (p = 0.014 and p = 0.04, respectively) which authors presume that dogs in these groups were more hydrated than control dogs. cadesi-03 and tewl show positive correlation (r = 0.21, p = 0.0043) which authors suggest is a positive effect for oclacitinib and lokivetmab treated groups as there is no further inflammation due to cad. limitations: even though authors mention the study being randomised, there is no detail in the methodology section about how this was carried out and how many dogs were assigned in total to each treatment or control group. small sample size: there was no information about the power of the study and why sample size of 19 dogs was chosen. and so, conclusions of no statistical significance will need to be interpreted with caution. limited body areas measured for tewl but this limitation has been acknowledged by the authors. subjective assessment by investigators using cadesi-03 and pvas but has been used consistently for assessing recordings as well as scoring the dogs in the study. cadesi-03 and pvas are both validated scales but cadesi-03 has undergone an amendment to become cadesi-04 which is simpler, quicker to administer and more selective for body sites where there is high sensitivity and specificity for cad diagnosis (olivry et al., 2014). there was very little presentation of data obtained in terms of boris recordings in the results section, especially since time of pruritic behaviour was included in statistical analysis. pruritic reactions were experimentally induced, hence are not representative of allergens which typically cause cad in a clinical context. souza et al. (2018) population: medical records at colorado state university veterinary teaching hospital from november 2015 to the end of october 2016. dogs were treated for allergic dermatitis and received lokivetmab. diagnosis of atopic dermatitis (ad) was made if pruritus was seasonal (considered showing signs of persistent allergic dermatitis for more than 1 year) or by exclusion if dog failed to have an adverse food reaction (afr) (positive response to an 8 week restrictive diet using either novel protein or hydrolysed diet). dogs were further diagnosed into three main groups: ad, afr and ad, allergic dermatitis of undetermined cause (aduc), based on case history and clinical signs as well as ruling out other pruritic diseases through appropriate diagnostic tests and / or therapeutic trials. medications for treatment of allergic dermatitis were either discontinued prior to lokivetmab injection or maintained at their current doses and frequencies of administration. sample size: 135 dogs. intervention details: age of dogs and dose of lokivetmab (mg/kg) at initial administration was recorded. frequency of dosing ranged between every 2–7 weeks. dogs included in study were treated with one or more lokivetmab injection. ad (n = 80; seasonal = 7 and non-seasonal = 73), afr and ad (n = 10) and aduc (n = 45). study design: retrospective, before and after study. outcome studied: subjective assessment by owners: owners documented severity of pruritus at each visit with a pruritus visual analog scale (pvas) score. pvas consists of a 10 cm line with descriptions at 2 cm intervals. all individuals were sequentially grouped based on severity of pruritus: very severe (>8–10) severe (>6–8) moderate (>4–6) mild (>2–4) very mild (>0–2) treatment success was empirically defined as ≥2 cm reduction in pvas score from baseline on the day of assessment. more than 50% reduction of pvas score compared to baseline on day of assessment day was also recorded. time to clinical improvement after initial lokivetmab administration: assessed by owners either within 24 hours, between 1 and 3 days or after 3 days. frequency of administration required to maintain control of pruritus was recorded (weeks). number of dogs initially classified as treatment success but failed to respond to subsequent lokivetmab injections was noted in addition to the number of injections prior to encountering this lack of response. previous therapy for cad: dose, frequency of administration and success (no response, partial response or total response) were recorded based on previous records or client’s report. dogs that had failed oclacitinib but responded to lokivetmab were recorded. previous responses to ciclosporin, corticosteroids and immunotherapy were recorded in categories: no response, partial response or total response. concurrent therapies: any dog receiving another treatment for allergic dermatitis / pruritus at time of initial lokivetmab administration was recorded (e.g. allergen-specific immunotherapy), including the duration prior to lokivetmab administration. concurrent illnesses: dogs that had concurrent allergic conditions and systemic and / or cutaneous diseases were noted, including their response to lokivetmab treatment. adverse events: documentation of adverse events associated with lokivetmab administration or any of the various therapies used concurrently with lokivetmab. statistical analysis: treatment success was defined as ≥2 cm reduction in pvas score. categorical data was expressed as frequencies, whereas continuous data was expressed as median and range. wilcoxon matched pairs signed-rank test was used to analyse pvas scores reported after drug administration compared to pretreatment scores. factors that were potentially associated with response included: type of allergic disease duration of clinical signs, age and size of dog, lokivetmab dosage, previous response to oclacitinib or other therapy (ciclosporin, corticosteroids, immunotherapy, dietary trial), concurrent therapy with a previous response and pruritus severity prior to lokivetmab. these factors were evaluated for association with two outcomes: dichotomous outcome of treatment success or failure, and magnitude of change, measured by difference in pvas score after and prior to treatment. univariate logistic regression, yielding odds ratio (or) and 95% confidence intervals (ci) and linear univariate regressions were used to associate continuous and categorical risk factors with outcome variables. pearson’s chi-squared test was used to evaluate dichotomous risk factors for treatment success or failure when cell counts were greater than 5 whereas two-tailed fisher’s exact test was used when cell counts were 5 or less. significance was set at p < 0.05. main findings (relevant to pico question): response to lokivetmab treatment: prior to lokivetmab administration, 135 dogs had a median pvas score of 6.5 (range 1–10), but after lokivetmab administration, 132 dogs had a median pvas score of 1.5 (range 0–8.5). this decrease in pvas score preand post-lokivetmab administration was found to be statistically significant (p <0.001). there was no outcome information for 3/135 dogs. improvement of pruritus in 116/132 (87.8%) of dogs following lokivetmab administration at 1.8–3.7 mg/kg. oclacitinib therapy as predictor of lokivetmab success: 66/135 dogs had received oclacitinib for pruritus control prior to lokivetmab and were treated for at least 3 weeks. 45/66 dogs had total response to oclacitinib when receiving it twice daily whereas the other 21 dogs had partial or no response to twice daily oclacitinib. 40/45 dogs that had total response to twice daily oclacitinib were partially responsive to once daily oclacitinib. 37/40 dogs were lokivetmab responders. 15/21 dogs that had partial or no response to twice daily oclacitinib were also lokivetmab responders. odds of lokivetmab treatment success on average was 7.4 times higher (95% ci = 1.3–40.9; p = 0.03) for dogs showing total response to twice daily oclacitinib (and partial response to once daily dosing) when compared to dogs with incomplete response to twice daily oclacitinib therapy. limitations: not a controlled study. non-standardised pvas between clinicians (i.e., not the same clinician assessing all the dogs in the study) hence this introduces a bias in giving scores. no supporting pruritus assessment (e.g., cadesi-04) performed by clinician. subjective assessment using pvas by owners as well as assessing time to improvement which could introduce bias to the data and placebo-effect. inclusion of other concurrent treatments and illnesses, e.g., glucocorticoids which could overestimate the effects of lokivetmab treatment. pvas assessment time-frame not standardised as it was performed with each visit to the hospital. frequency of lokivetmab injections were not the same for every dog included in the study which affects the data assessing efficacy of lokivetmab over a fixed period of time. unclear about meaning of no / partial / total response when assessing other therapies for pruritus. appraisal, application and reflection canine atopic dermatitis (cad) is one of the most common skin diseases in general practice which is diagnosed through the elimination of other pruritic skin disorders (e.g., flea allergic dermatitis, sarcoptic mange or cutaneous adverse food reaction) as well as history (seasonal or non-seasonal). cad is defined as ‘a genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features associated with immunoglobulin e (ige) antibodies most commonly directed against environmental allergens’ (halliwell, 2006). the disease is often non-specific in cause, but it is a lifelong condition which requires constant monitoring and pruritus control. typically, treatment for cad includes glucocorticoids (e.g., prednisolone), topical steroids and ciclosporin which are drugs that have sufficient evidence for efficacy (olivry et al., 2002). however, adverse effects can occur associated with long-term use of glucocorticoid treatment, or gastrointestinal signs (e.g., vomiting) in the case of ciclosporin (steffan et al., 2003). topical therapy tends to be reserved for short-term and / or localised therapy but commonly in cad, many dogs present with more than one region of pruritus and / or greater in severity. therefore, newer treatments are immune-modulating drugs such as oclacitinib and lokivetmab which selectively inhibits janus kinase-1 receptor and il-31, respectively. overall, there was relatively little evidence available directly comparing the effects of lokivetmab and oclacitinib in studies using an updated scoring system, e.g., cadesi-04, consistently. hence, extrapolating from other studies which individually assessed the efficacy of either oclacitinib or lokivetmab with a placebo cannot be used due to the different scoring systems utilised. for instance, cadesi-03 and cadesi-04 focus on different areas of the body to determine overall score and severity of pruritus and so the scores cannot be used to justify whether lokivetmab has more efficacy than oclacitinib (olivry et al., 2007; and olivry et al., 2014). additionally, scoring systems such as cadesi and pvas are subjective to the clinician or owner and so comparing the scores between studies cannot reliably determine whether lokivetmab has more efficacy than oclacitinib in treating cad. marsella et al. (2020) reported that lokivetmab is more effective for preventing flare ups given before an allergy challenge, but oclacitinib and lokivetmab overall had similar effects on transepidermal water loss (tewl) and hydration. despite the paper mentioning it was randomised, there were no details as to how this was carried out in the trial. therefore, the lack of randomisation and small sample size limits the value of the study which performing a sample size calculation before recruiting dogs for the study would have strengthened the data collected. additionally, authors reporting no statistical significances between mean pvas scores could be influenced by small number of dogs in study and so results should be interpreted with caution. in souza et al. (2018), it is a retrospective before-and-after study which collected data that was already recorded, but since it is neither a randomised nor controlled trial, there are many variable factors included in the study. for example, the inclusion of dogs with concurrent systemic and / or cutaneous illnesses as well as other concurrent treatments (e.g., corticosteroids) adds another limitation to the data because these could influence the outcomes detected and overestimate the effectiveness of lokivetmab. furthermore, the frequency of lokivetmab treatment varied from 2–7 weeks which authors argued that lokivetmab treatment was given as frequent as needed to keep pruritus under control. however, this does not truly assess the effectiveness of lokivetmab over a fixed period of time and so limits the strength of the data. moreover, many studies using lokivetmab typically administered every 4 weeks which is also recommended by cytopoint® dosage chart (ah430/17) (moyaert et al., 2017; and szczepanik et al., 2020). additionally, increasing lokivetmab frequency to more than every 4 weeks shows a decline in efficacy in terms of pvas scores (michels et al., 2016[a]). hence, in the souza et al. (2018) study, there are many confounding factors which have not been accounted for. since the pvas assessment in souza et al. (2018) were only performed by owners, there is certain bias to the data collected e.g., time to improvement after initial lokivetmab administration, as well as introducing a placebo-effect. the authors also suggest that previous response to oclacitinib is a good predictor for response to lokivetmab therapy – dogs that responded poorly to oclacitinib respond well to lokivetmab therapy. however, knowing that oclacitinib is a janus kinase-1 inhibitor whereas lokivetmab is a monoclonal antibody to il-31, it is understandable that blocking il-31 which is further upstream will inhibit other downstream pathways including the janus kinase-1 pathway. since cad is a multi-faceted disease, it is recommended that a combination of treatments should be used for optimal benefit (olivry et al., 2015). the evidence above is insufficient to say one drug is more effective than the other, but both treatments are certainly effective in the treatment for cad and potentially are safe to use together (gortel, 2018). since there are various scoring systems used in the assessment of cad, only pvas has been consistently used across the literature whereas cadesi has undergone several iterations and so is not as easily comparable for efficacy of oclacitinib and lokivetmab. therefore, comparing pvas scores between placebo-controlled trials for either oclacitinib or lokivetmab suggest both treatments result in similar outcomes (average score of 2–3 from treatment up to day 28 after administration) (cosgrove et al., 2013; michels et al., 2016[a]; szczepanik et al., 2020; and van brussel et al., 2021). this, however, is a very crude comparison and what is inferred cannot compare to randomised controlled trials (rct) directly observing and assessing the efficacy of oclacitinib and lokivetmab together. furthermore, there has not been any further updated guidelines from the international committee on allergic diseases of animals (icada) since 2015 which does not include recommendations for lokivetmab, but for oclacitinib, its short-term use is shown to be beneficial in treating cad (olivry et al., 2015). as a result, there is simply not enough evidence available to answer the pico question and further randomised controlled studies are required to demonstrate the efficacy of both lokivetmab to oclacitinib. methodology section search strategy databases searched and dates covered: cab abstracts on ovid platform (1973–week 48 2021) pubmed on the ncbi interface (1920–december 2021) search strategy: cab abstracts: (dog or dogs or canine or canines or bitch or bitches).mp. or exp dogs/ or exp canis/ or exp bitches/ (atopic and (skin or pruritus or pruritis or dermatitis)).mp. (lokivetmab or cytopoint or oclacitinib or apoquel).mp. 1 and 2 and 3 pubmed: dog or bitch or canine atopic and (skin or pruritus or pruritis or dermatitis) lokivetmab or cytopoint or oclacitinib or apoquel 1 and 2 and 3 dates searches performed: 7 dec 2021 exclusion / inclusion criteria exclusion: non-english language study, conference papers, case studies, review articles and articles that did not compare lokivetmab and oclacitinib in atopic dogs and so was not relevant to pico question. inclusion: peer-reviewed, controlled studies comparing the effects between lokivetmab and oclacitinib in dogs with atopic dermatitis using a recognised scoring system. search outcome database number of results excluded – non-english language publication excluded – not relevant to pico question excluded – case studies in english excluded – conference papers excluded – reviews in english total relevant papers cab abstracts 76 22 26 6 8 12 2 pubmed 39 0 32 1 0 4 2 total relevant papers when duplicates removed 2 conflict of interest the author declares no conflicts of interest. the author would like to thank dr kit sturgess for his guidance with this article and clare boulton for her assistance in obtaining papers. references bensignor, e. & videmont, e. 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(2016a). a blinded, randomized, placebo-controlled, dose determination trial of lokivetmab (zts-00103289), a caninized, anti-canine il-31 monoclonal antibody in client owned dogs with atopic dermatitis. veterinary dermatology. 27(6), 478–e129. doi: https://doi.org/10.1111/vde.12376 michels, g.m., walsh, k.f., kryda, k.a., mahabir, s.p., walters, r.r., hoevers, j.d. & martinon, o.m. (2016b). a blinded, randomized, placebo-controlled trial of the safety of lokivetmab (zts-00103289), a caninized anti-canine il-31 monoclonal antibody in client-owned dogs with atopic dermatitis. veterinary dermatology.27(6), 505–e136. doi: https://doi.org/10.1111/vde.12364 moyaert, h., van brussel, l., borowski, s., escalada, m., mahabir, s.p., walters, r.r. & stegemann, m.r. 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(2007). validation of cadesi-03, a severity scale for clinical trials enrolling dogs with atopic dermatitis. veterinary dermatology. 18(2), 78–86. doi: https://doi.org/10.1111/j.1365-3164.2007.00569.x olivry, t., saridomichelakis, m., nuttall, t., bensignor, e., griffin, c.e. & hill, p.b. (2014). validation of the canine atopic dermatitis extent and severity index (cadesi)-4, a simplified severity scale for assessing skin lesions of atopic dermatitis in dogs. veterinary dermatology. 25(2), 77–86. doi: https://doi.org/10.1111/vde.12107 olivry, t., deboer, d.j., favrot, c., jackson, h.a., mueller, r.s., nuttall, t. & prélaud, p. (2015). treatment of canine atopic dermatitis: 2015 updated guidelines from the international committee on allergic diseases of animals (icada). bmc veterinary research. 11(1), 1–15. doi: https://doi.org/10.1186/s12917-015-0514-6 souza, c.p., rosychuk, r.a.w., contreras, e.t., schissler, j.r. & simpson, a.c. (2018). a retrospective analysis of the use of lokivetmab in the management of allergic pruritus in a referral population of 135 dogs in the western usa. veterinary dermatology. 29(6), 489–e164. doi: https://doi.org/10.1111/vde.12682 steffan, j., alexander, d., brovedani, f. & fisch, r.d. (2003). comparison of cyclosporine a with methylprednisolone for treatment of canine atopic dermatitis: a parallel, blinded, randomized controlled trial. veterinary dermatology. 14(1), 11–22. doi: https://doi.org/10.1046/j.1365-3164.2003.00318.x szczepanik, m., wilkoå‚ek, p., goå‚yå„ski, m., sitkowski, w., taszkun, i. & toczek, w. (2019). the influence of treatment with lokivetmab on transepidermal water loss (tewl) in dogs with spontaneously occurring atopic dermatitis. veterinary dermatology. 30(4), 330–e93. doi: https://doi.org/10.1111/vde.12758 szczepanik, m.p., popiel, j., cekiera, a., pomorska-handwerker, d., karaå›-tä™cza, j., åšciskalska, m., oczkowska, k., taube, m., olender, v. & parys, p. (2020). evaluation of the clinical efficiency of lokivetmab in client privately owned atopic dogs – multicenter study. polish journal of veterinary sciences. 23(2), 191–195. doi: https://doi.org/10.24425/pjvs.2020.132765 zoetis. (2017). 'cytopoint® solution for injection for dogs'. ah430/17 datasheet, june 2017. [online] available from: https://www.zoetis.co.uk/products/dogs/cytopoint/img/cytopoint_dosing_chart.pdf [accessed 5 jan 2022]. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence to publish including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use. which antibacterial agent performs best for the treatment and clearance of chlamydophila felis infection in cats? a knowledge summary by david mills ma, vetmb, certavp(vc), mrcvs1* 1rspca putney animal hospital, 6 clarendon drive, london, sw15 1aa *corresponding author (dmills@rvc.ac.uk) vol 2, issue 1 (2017) published: 07 march 2017 reviewed by: eva spada (dvm, phd) and kit sturgess (ma vetmb phd certvr dsam certvc frcvs) next review date: 20 march 2019 doi: 10.18849/ve.v2i1.55 clinical bottom line based on the current evidence, oral doxycycline (10mg/kg po q24h or 5mg/kg po q12h) for at least 21 days represents the most efficacious treatment, both in terms of clinical improvement and permanent clearance of chlamydophila felis infection in cats. in chronic infections, or where the duration of disease is unknown, a longer treatment course of 28 days is indicated. there is limited evidence that co-amoxiclav (12.5-22.5mg/kg q12h po) may be used as an alternative, though a treatment period of at least 30 days is required. question in feline patients infected with chlamydophila felis (c felis), which antibacterial regime shows greatest efficacy in both improving clinical signs and permanent clearance of the organism? the evidence whilst the methodology of most of the available studies is reasonable, their usefulness is limited due to most being experimental trials, and all having low numbers of participants. the use of experimental animals with defined infection periods limits extrapolation to general practice where the chronicity of infection is unknown, especially in stray or shelter cats. feline chlamydophilosis has attracted a reasonable amount of research interest, and various antibacterial regimes have been trialled: doxycycline, co-amoxiclavpotentiated amoxicillin, enrofloxacin, pradofloxacin, azithromycin, roxithromycin, as well as topical fusidic acid and chlortetracycline. in the case of potentiated amoxicillinco-amoxiclav enrofloxacin and pradofloxacin, these trials were funded by manufacturers of veterinary-licensed versions of these compounds. nevertheless, from the studies available, systemic doxycycline has shown repeated and significant superiority to other antibiotics in both treating the disease and preventing recrudescence, if a course of sufficient length is administered. summary of the evidence sykes (1999) population: experimental colony cats aged 10-12 months weighing approximately 5kg. sample size: 8 cats (3 neutered males, 5 entire females). intervention details: all cats pre-infected with feline herpes virus 3 months pre-trial and asymptomatic. all cats infected with cultured c. psittaci via cornea and after 6 days split into one of three treatment groups: 4 cats treated with doxycycline 5mg/kg po q12h for 21 days. 4 cats left untreated. monitoring of response to treatment: pcr and culture from conjunctival swabs daily (objective). clinical signs of infection (non-blinded except for day 9 when an outside clinician blinded to treatment groups used). separate rooms for each group. all treated cats euthanised on day 41, all untreated on day 64, and tissue submitted for chlamydial dna pcr analysis. study design: non-randomised, non-blinded controlled trial. outcome studied: comparison of pcr versus culture in diagnosis. investigate whether shorter course of doxycycline for 28-42 days is sufficient to clear infection with c psittaci. investigate possible sites of persistent infections following conjunctival clearance. main findings (relevant to pico question): doxycycline-treated cats: rapid improvement in clinical signs, average duration of signs 9.3 days. pcr negative after 8 days on average. remained pcr/culture negative and disease free following treatment end until euthanasia on day 42. untreated cats showed signs for 30 days on average, pcr positive for 30.5 days on average. limitations: insufficient numbers to answer all three questions. very small study numbers (4 treated cats) which preclude the strong conclusion that 21 days of doxycycline is sufficient. short follow-up of 14 days post-treatment cessation. clinical signs reported in untreated groups correlate poorly with natural infections, with cats in the study developing a severe rhinitis. this suggests a particularly virulent experimental strain and the study does not detail whether the inoculum was a field or experimental isolate. limits extrapolation to field cases. use of experimental colony cats limits extrapolation to field or natural infection. this represented a mono-infection, compared to field infections, where multiple infections, infectious dose, strain variation, genetic diversity of the cats and nutritional plane could impact on severity of infection and response to treatment. only a single blinding event at day 9 with an outside clinician – rest of clinical sign logging was by unblinded investigators. questionable use of an untreated group – these cats lost weight, had reduced appetite and generally suffered for an extended period with the disease. the authors’ aims regarding treatment were to ascertain a shorter course of doxycycline so different treatment length groups could have been used. sparkes (1999) population: pathogen-free experimental colony cats aged 4-11 months. sample size: 24 (21 entire females, 3 neutered males). intervention details: inoculated with field strain of c. psittaci via cornea 7 days post-infection randomised into 4 treatment groups (6 cats in each): placebo (topical artificial tears) topical 1% chlortetracycline drops to both eyes q12h topical 1% fusidic acid drops to both eyes q12h doxycycline 10mg/kg po q24h & topical 1% fusidic acid drops to both eyes. all treated for 28 days. monitoring of response to treatment: culture from conjunctival swabs to generate chlamydial isolation scores (objective) clinical signs recorded at same time (subjective) separate rooms not available so randomly assigned to one of three rooms during trial. study design: randomised, non-blinded controlled trial. outcome studied: comparison of topical and systemic therapies for the treatment of experimental chlamydiosis. main findings (relevant to pico question): doxycycline/fusidic acid group: significantly fewer clinical signs (p<0.011) from day 1, maintained throughout with the exception of day 9. culture negative from day 4 post-treatment commencement and throughout the study thereafter (except 1 cat on day 18) significantly (p<0.05) lower median duration of shedding (3 days) than placebo and fusidic acid groups (28 days). chlortetracycline group: lower median shedding duration (8 days) than placebo and fusidic acid groups (28 days) higher median shedding than doxycycline/fusidic acid group (3 days) most cats in placebo and fusidic acid only groups were still shedding at the end of the study. fusidic acid had no treatment effect above placebo for chlamydophilosis. limitations: small numbers of cats in each treatment group. randomisation method for assigning treatment groups and room to be housed is not detailed. use of experimental colony cats limits extrapolation to field or natural infection. this represented a mono-infection, compared to field infections, where multiple infections, infectious dose, strain variation, genetic diversity of the cats and nutritional plane could impact on severity of infection and response to treatment. housing cats together from different treatment groups was a confounder that was not controlled for, and may have led to false positives from cross-contamination e.g. cat from doxycycline/fusidic acid group on day 18. use of clinical scoring is subject to subjective bias, especially as the treatment groups were not blinded to the investigators. culture of chlamydial organisms is less sensitive for detecting chlamydial organisms than pcr, but has the advantage of only identifying live bacteria. no long-term follow-up, so the persistence of freedom from infection in the doxycycline/fusidic acid and chlortetracycline groups could not be assessed. funded in part by producers of fusidic acid eye ointment at that time (leo laboratories) – theoretically fusidic acid (working on primarily gram-positive organisms) would have no effect on gram-negative chlamydial organisms. sturgess (2001) population: pathogen-free experimental colony cats aged 5 months. sample size: 24 (13 females, 11 males). intervention details: inoculated with a field strain of c. psittaci via the cornea. 7 days post-infection randomised into 3 treatment groups (8 cats in each group): placebo (gelatin capsule) doxycycline 10-15mg/kg po q24h co-amoxiclav 12.5-22.5mg/kg po at 0900 and 1700 all treated for 19 days. placebo group treated with co-amoxiclav for 30 days after trial end as a model of chronic infection. co-amoxiclav group were treated with further 30-day course co-amoxiclav after infection returned after 14-20 days. monitoring of response to treatment: culture from conjunctival swabs taken three times a week (objective) to generate a chlamydial isolation score. clinical scoring of disease (subjective but investigator blinded to treatment group) including weight and rectal temperatures (objective). trial formally concluded after 91 days and cats observed daily for 6 months after this. study design: randomised, single-blinded controlled trial. outcome studied: comparison of systemic co-amoxiclav with doxycycline and an untreated control group in the treatment and clearance of c psittaci infection in experimentally infected cats. main findings (relevant to pico question): doxycycline and co-amoxiclav groups versus placebo: isolation scores significantly lower by day 9 (p<0.01) fivefold decrease in clinical scores in first week (p<0.01) doxycycline group showed no recurrence after treatment end, demonstrating efficacy in clearing acute infections. co-amoxiclav showed efficacy in acute infections, but with high rate of recurrence (62.5%) between 14-20 days after treatment end. co-amoxiclav given for 30 days in chronic disease model cats (formerly placebo) and recurrent cats (following initial 19 days treatment) cleared infection with no recurrence. limitations: small number of participants per treatment group (8) make statistical tests less valid, especially with no confidence intervals stated. randomisation method for assigning treatment groups not detailed. use of experimental colony cats limits extrapolation to field or natural infection. this represented a mono-infection, compared to field infections, where multiple infections, infectious dose, strain variation, genetic diversity of the cats and nutritional plane could impact on severity of infection and response to treatment. culture is less sensitive than pcr for the detection of chlamydial organisms – the 5 cats from the co-amoxiclav treated group that showed recrudescence were likely still infected by the end of treatment, which was not detected by culture. clinical scoring is subject to subjective bias, though this was reduced by blinding the investigator to the treatment group. author conclusions describe co-amoxiclav as an effective treatment in acute and chronic stages of chlamydiosis, but with the proviso that a further 30 day treatment course may be required after treatment of acute phase. this would mean a 49 day treatment course versus 19 days for doxycycline. co-amoxiclav is a time-dependent antibiotic, so treating at 0900 and 1700 is likely suboptimal in maintaining mic values in conjunctivae for sufficient periods. no investigation into the effects of doxycycline in chronic chlamydophilosis. funded by pfizer animal health, manufacturers of a licensed co-amoxiclav preparation for cats. owen (2003) population: pathogen-free experimental colony cats aged 5-6 months. sample size: 9 (3 entire females, 6 neutered males). intervention details: inoculated with field strain of c felis via the cornea 4 days post-infection all cats were showing clinical signs and randomly assigned to one of 3 groups: 2 cats untreated. 2 cats doxycycline 10-15mg/kg po q24h. 5 cats azithromycin 10-15mg/kg po q24h for 3 days then twice weekly. treatment for 28 days. after initial treatment period the 2 untreated cats were given azithromycin 10-15mg/kg po q24 for 25 days as a model of chronic disease. at the end of the trial the 2 initially untreated cats and 5 azithromycin cats were given a 28-day course of doxycycline to eradicate infection. monitoring of response to treatment: culture from conjunctival swabs (objective). clinical scoring of disease (subjective, but investigator blinded to treatment group). cats housed in 2 rooms, with one cat from the untreated group and one from doxycycline group in each room and the rest from azithromycin group. monitored for 6 months post-trial for recurrence. study design: randomised, single-blinded controlled trial. outcome studied: determination of the efficacy of azithromycin compared to doxycycline-treated controls for the treatment of c felis infection in experimentally infected cats. main findings (relevant to pico question): doxycycline group: culture negative 7 days after starting treatment. rapid decrease in clinical scores from day 2. no recurrence after initial treatment course. cleared infection in chronically infected cats (5 azithromycin group cats and 2 untreated cats) at end of study with 28-day course. azithromycin group: culture negative 7 days after starting treatment. rapid drops in clinical scoring from day 2. infection cleared in only 1 out of 5 cats (20%). rest either remained positive or became positive again whilst still on treatment or after treatment end. azithromycin failed to clear chronic infection in the two untreated cats given azithromycin daily for 25 days. limitations: small numbers precluded statistical analysis. randomisation method for assigning treatment groups and housing not detailed. experimental colony cats, due to their husbandry, may possess a less robust immune system than free-living domesticated cats. housing treated and untreated cats together can lead to cross-contamination and affect culture results. culture is less sensitive than pcr for the detection of chlamydial organisms – it is likely the azithromycin cats that were negative on culture remained persistently infected. clinical scoring is subject to subjective bias, though this was reduced by blinding the investigator to the treatment group. dosage and dosing regime for azithromycin is poorly characterised in cats and the regime used in this study may have negatively affected the results dean (2005) population: pathogen-free experimental colony cats aged 5-6 months. sample size: 15 (13 entire females, 2 entire males). intervention details: inoculated with field strain of c. felis via the cornea. 7 days post-infection all cats were showing clinical signs and randomly assigned to one of three groups: 4 cats untreated 6 cats doxycycline 10mg/kg po q24h for 7 days 5 cats doxycycline 10mg/kg po q24h for 14 days if treatment was ineffective at eliminating infection (continued/ recurrence of clinical signs, or pcr-positive), rescue treatment 21-day course doxycycline 10mg/kg po q24h was initiated. monitoring of response to treatment: pcr copy numbers from conjunctival swabs (objective). clinical scoring of disease (subjective but investigator blinded to treatment group). cats were housed in rooms according to treatment group. monitored for 6 months post-trial for recurrence. study design: randomised, single-blinded controlled trial. outcome studied: assess efficacy of 7-day and 14-day doxycycline treatment courses on the treatment and elimination of c felis using real-time pcr to monitor course of infection and response to treatment. main findings (relevant to pico question): doxycycline treated groups: rapid decrease in pcr copy numbers and clinical scores within 2 days of treatment and apparent clinical cure by the end of treatment. all cats showed recurrence of disease after treatment end: 7-day cats within 4-7 days and 14-day cats within 14-21 days. all cats underwent 21-day rescue treatment: 8/11 cleared the infection. 3/11 required second rescue treatment of 28 days. one of these cats was from the 7-day doxycycline group and two of these cats were from the 14-day doxycycline group. all cats showed no recurrence in the following 6 months since last treatment. authors’ recommendation is a 28-day course of doxycycline at 10mg/kg po q24h required for elimination. limitations: small number of participants means statistical analysis could not be applied. use of an untreated group is questionable given previous studies. randomisation method for assigning treatment groups and housing is not detailed. experimental colony cats, due to their husbandry, may possess a less robust immune system than free-living domesticated cats. clinical scoring is subject to subjective bias, though this was reduced by blinding. pcr does not necessarily detect active infection as it can also pick up dead bacterial material. authors’ recommendation is not fully supported by the results. it is based on 3 cats failing to clear the infection following a 21-day rescue treatment, and clearing the infection following a 28-day treatment course. however, issues of resistance and a difference in the disease (acute versus chronic) may have played a role in the lack of elimination in 3 cats undergoing 21-day treatment reinfection from other cats, or fomites, rather than true recrudescence could be responsible for the recurrence of clinical disease – housing the cats separately would have avoided this possible confounder. this means that it cannot categorically be said that 7 or 14 day courses of treatment do not fully eliminate infection in some cats. gerhardt (2006) population: owned cats presented to university of munich teaching hospital suffering with conjunctivitis. all were negative for fiv/felv, had not been pre-treated with antibacterial agents, and were not showing clinical signs of central nervous system or renal disease. sample size: 25 cats. intervention details: randomly assigned to one of two treatment groups: 14 cats enrofloxacin 5mg/kg sq q24h for 3 days then 15mg enrofloxacin q24h po for 11 days 11 cats doxycycline 5mg/kg sq q12h for 3 days then 5mg/kg po q12h for 11 days all cats received bromhexine hydrochloride 0.5mg/kg po q8h and terbutaline 0.03mg/kg po q8h for 14 days all cats were examined on days 1, 5, 10 and 14. monitoring of response to treatment: ifa (immunofluorescence) detection of c felis by conjunctival swabs (objective). conjunctivitis scores (subjective). modified karnofsky quality of life scores (subjective). study design: randomised, non-blinded controlled trial. outcome studied: compare efficacy of enrofloxacin and doxycycline in the treatment of conjunctivitis and c felis infection in naturally infected cats, and investigate the pharmacokinetics of enrofloxacin. main findings (relevant to pico question): enrofloxacin group: generally more rapid improvement in conjunctivitis scores, though similar total improvement in groups by trial end. greater improvement in quality of life scores on average than doxycycline. both groups showed reduced shedding of c felis but none eliminated the organism during the trial limitations: small numbers make statistical analysis less useful. title references treatment of cats with c felis but the hypothesis is treatment of conjunctivitis and c felis infection. no details of cats’ sex, age or weight. no details on randomisation procedure. use of injectable doxycycline for 3 days before starting oral therapy is not common practice. no details as to whether cats were hospitalised during study or owners were involved in treatment – potential non-compliance. only treated for 14 days with no follow-up. only 15 cats were positive for c. felis – 9 in the enrofloxacin group and 6 in the doxycycline group. however all 25 cats including those not infected with c. felis were included in the results, and not censored. modified kanorfsky scoring for quality of life scores to track clinical improvement is not widely used or well established, and subject to operator bias – it was developed by one of the authors in a previous paper and is an adaption of a human cancer patient scoring system from 1948. no details regarding which clinician was involved in scoring. ifa is considered the least sensitive method of diagnosing c. felis, largely surpassed by culture or pcr. concurrent use of bromhexine hydrochloride and terbutaline may have affected clinical progression of disease the discussion does not reference all relevant preceding papers regarding doxycycline use in cats with c felis. the recommendation to treat for 21 days with enrofloxacin is not supported by the results. use of enrofloxacin as a first-line treatment in the treatment of c felis is not compliant with best antibiotic prescribing guidelines. cats should have been tested for other infectious agents e.g. fhv-1 and fcv as cofounding agents no details on funding or conflicts of interest. hartmann (2008) population: cats presented to university of munich teaching hospital showing signs of upper respiratory disease or conjunctivitis or both. all were >6months of age, negative for fiv/felv, had not been pre-treated with antibacterials in the last 6 weeks, were not showing clinical signs of liver or renal disease and were not pregnant or nursing. cats were either client-owned (10), farm cats (11) or shelter cats (18), and were of estimated ages (<1year: 13; 1-4 years: 16; 5-8 years: 8; 8-12 years: 2). duration of clinical signs was unknown for most cats. sample size: 39 cats (21 female, 13 neutered; 18 male, 12 neutered). intervention details: cats randomly assigned to one of two groups: 17 cats pradofloxacin 5mg/kg po q24h and placebo q12h 22 cats doxycycline 5mg/kg po q12h and placebo q24h. treatment for 42 days. monitoring of response to treatment: pcr for c felis, fhv and mycoplasma from conjunctival swabs pcr for fcv and mycoplasma spp. from pharyngeal swabs (objective). clinical scoring (subjective but investigators blinded to treatment group). modified kanorfsky quality of life score (subjective). study design: randomised, double-blinded controlled trial. outcome studied: investigate efficacy of pradofloxacin in the treatment of cats with clinical signs of upper respiratory tract disease and its ability to eliminate c felis and mycoplasma infection in these cats. main findings (relevant to pico question): doxycycline group: 13/22 infected with c felis. all pcr negative and asymptomatic by trial end. 2/13 still pcr-positive by day 28, cleared by day 42. pradofloxacin group: 10/17 infected with c felis. 4/10 (40%) pcr positive and showing clinical signs by trial end – 2 remained pcr positive throughout, 2 apparently cleared infection then recurred. ineffective at predictably clearing c felis infections. limitations: small numbers make statistical analysis less useful. no details on randomisation procedure. apart from the 2 cats in the pradofloxacin group that remained pcr positive throughout, no indication which cats were hospitalised or treated at home, so compliance or chances of reinfection could not be assessed. no long-term follow up (trial stopped at 42 days). rationale for 42 days’ treatment is a textbook reference. pcr is the most sensitive method of finding chlamydial dna but does not differentiate between live and dead organisms. clinical scoring subject to subjective bias. modified kanorfsky scoring for quality of life scores to track clinical improvement is not widely used or well established, and subject to operator bias. use of pradofloxacin as a first-line treatment in the treatment of c felis is not compliant with best antibacterial prescribing guidelines. the recommendation to use pradofloxacin in young cats and those with liver disease as an alternative to doxycyline is not supported by the results. the implied contraindication in young cats is predicated on tooth discolouration which is infrequent and of no obvious clinical significance. funded by bayer healthcare, who make a licensed pradofloxacin for cats and dogs. ploneczka-janeczko (2008) population: privately-owned cats, aged 3-10 years, which had undergone doxycycline therapy and developed vomiting or diarrhoea within the first 3 days of treatment. sample size: 14 cats (8 male, 6 female). intervention details: cats treated with roxithromycin 5mg/kg po q12h for 28 days then had a treatment-free period of 28 days. monitoring of response to treatment: pcr from conjunctival swabs (objective). clinical scoring and weekly change in clinical signs (same/increased/decreased). study design: case series. outcome studied: evaluate the clinical efficacy of systemic roxithromycin in treating tetracycline-intolerant cats with chronic conjunctivitis caused by c felis. main findings (relevant to pico question): all cats showed improvement in clinical scores with treatment. no cats cleared infection, and 9/14 showed increase in dna copy numbers by end of the study (day 56). limitations: case series with no controls. rare to see c felis in cats of these ages, normally a disease of cats <12 months old so the possibility of co-morbidities is high. cats were chronically infected – 8 cats had shown signs for >12months, 5 for 6-12 months and 1 for 3-6 months. pcr is the most sensitive method of finding chlamydial dna but does not differentiate between live and dead organisms. conjunctival samples only taken at beginning and end of trial, so difficult to ascertain if ever pcr-negative. clinical scoring subject to subjective bias and a change determined by increase/decrease/same lacks sensitivity. relied on owners for compliance. appraisal, application and reflection in all of the studies presented, systemic doxycycline therapy shows consistent efficacy against c felis both in bringing about rapid clinical improvement (however measured) within the first week of treatment, and, when given for a sufficient time period, has the most evidence for permanently eliminating infection. it is this latter aspect that makes it currently the most useful therapy versus other compounds studied (co-amoxiclav, pradofloxacin, enrofloxacin, azithromycin, roxithromycin), which, whilst bringing about clinical improvement appear insufficiently consistent at clearing infection. this is especially pertinent for shelter or stray cats, where c felis is commonplace, and infectious diseases require effective and reliable treatment to prevent spread within the facility. however, the question of how long a course of doxycycline needs to be is more difficult to answer from the studies available. the different course lengths can be summarised as follows: table 1:* = these cats had received either 7 or 14 day courses before the 21 day course. the 3/11 cats (27%) which recurred after 21 day treatment cleared infection with a subsequent 28-day course. the evidence available indicates that a 14-day course is insufficient, whilst a 21-day course may be sufficient in acute-stage infections which the experimental trials model. however, in field-infected cats, especially those in which the duration of infection is unknown, such as strays, a longer course may be indicated. in the study by dean et al (2005), all the cats required rescue treatment after 7 or 14-day courses of treatment, and could therefore be considered chronically infected – in these, a 28-day course was required to eliminate infection from all cats (though 73% or 8/11 cleared the infection with a 21-day course). in shelters without finances to test for organism clearance, a 28-day course may be considered more appropriate; equally, in owned cats with acute infection, a 21-day course is likely to suffice. however, without more trials with greater participant numbers involving naturally infected cats, firm conclusions cannot be drawn. by way of alternatives to doxycycline, co-amoxiclav has shown similar efficacy to doxycycline in improving clinical signs (sturgess et al 2001) and pradofloxacin and enrofloxacin have shown a mildly better rate of clinical improvement (gerhardt et al 2006; hartmann et al 2008). however, only co-amoxiclav has been shown to consistently (that is, in all cats) clear infection, though a 30-day course was required for chronically infected cats, and a 19-day course given to acutely-infected cats that showed a high rate (62.5%) of recurrence (sturgess et al 2001). whilst doxycycline should remain the first-line treatment, co-amoxiclav, if given for a sufficient length of time (30 days), is a reasonable alternative. one of the main weaknesses with the evidence presented here is the use of experimental cats, as their use limits extrapolation of results to field-infected free-living cats. field infections may occur with greater doses of infectious agent, of different pathogenecity, in the face of multiple infections with other agents or against a background of other disease processes, in cats with greater genetic variation and on a variable nutritional plane. therefore disease presentation, severity, and response to treatment may not match that seen in the field. for example, in stray or unowned animals, the chronicity of disease is unknown and response to treatment in these cases may be suboptimal, especially where secondary sequelae such as tear-duct scarring has occurred. cats commonly present with c felis in addition to other pathogens of the upper respiratory tract disease complex (hartmann et al 2010); secondary bacterial infection may complicate the clinical picture and delay resolution especially as tetracyclines appear to have only moderate efficacy against studied isolates (schulz et al 2006). however, doxycycline has well-documented anti-inflammatory effects (e.g. krakauer and buckley 2003) which may help with improvement of clinical signs associated with viral co-infections several side-effects of oral doxycycline have been described. in a retrospective study of 168 cats, 13% developed vomiting, 11% diarrhoea, and 6% decreased appetite, and 36-40% showed increases in alt or alp during therapy (schulz et al 2013). oesophagitis, oesophageal stricture and tooth discolouration, whilst described elsewhere, (e.g. mcgrotty and knottenbelt 2002; german et al 2005) were absent. gastrointestinal side effects may be attributable to the use of the doxycycline-hyclate salt which is acidic in solution, and is the compound present in the uk licensed veterinary agent (ronaxan; merial). administration with food, or providing food or water after administration may reduce potential gastrointestinal side effects, whilst others (liver enzyme increase, tooth discolouration) appear clinically insignificant and do not represent valid reasons for not using the drug. methodology section search strategy databases searched and dates covered: cab abstracts and pubmed from january 1973 to september 2016 search terms: (cat or cats or feline or kitten) and (chlamydia or chlamydophila or chlamydiosis or chlamydophilosis or psittaci) and (treat* or manag*) dates searches performed: 3rd august and 4th september 2016 exclusion / inclusion criteria inclusion and exclusion criteria were defined before searching and are detailed below. exclusion: review articles, single case reports, textbook chapters, conference proceedings. papers not available in english or not accessible. papers that described supportive treatment measures without concurrent antibiotic treatment assessment. papers that described c felis infection in animals other than felis catus. inclusion: papers published between 1973 and present that evaluated the efficacy of antibiotic compounds for the treatment of clinical (experimental or natural) c felis infection in cats. studies which had more than one aim, such as diagnostic modality investigation, were included. search outcome database number of results excluded – review articles, single case reports etc. excluded – not relevant to pico excluded – chlamydial studies in other species excluded – not available in english or not accessible total relevant papers cab direct 133 72 48 5 0 8 ncbi pubmed 54 8 17 21 0 7 total relevant papers when duplicates removed 8 conflict of interest the author declares no conflict of interest. references dean, r. et al. (2005) use of quantitative real-time pcr to monitor the response of chlamydophila felis infection to doxycycline treatment. journal of clinical microbiology, 43 (4), pp. 1858–1864. doi: http://dx.doi.org/10.1128/jcm.43.4.1858-1864.2005 gerhardt, n. et al. (2006) pharmacokinetics of enrofloxacin and its efficacy in comparison with doxycycline in the treatment of chlamydophila felis infection in cats with conjunctivitis. veterinary record, 159 (18), pp. 591–594. doi: http://dx.doi.org/10.1136/vr.159.18.591 german, a. et al. (2005) oesophageal strictures in cats associated with doxycycline therapy. journal of feline medicine and surgery, 7 (1), pp. 33–41. doi: http://dx.doi.org/10.1016/j.jfms.2004.04.001 hartmann, a. et al. (2010) detection of bacterial and viral organisms from the conjunctiva of cats with conjunctivitis and upper respiratory tract disease. journal of feline medicine and surgery, 12 (10), pp. 775–82. doi: http://dx.doi.org/10.1016/j.jfms.2010.06.001 hartmann, a. et al. (2008). efficacy of pradofloxacin in cats with feline upper respiratory tract disease due to chlamydophila felis or mycoplasma infections. journal of veterinary internal medicine, 22, 44–52. doi: http://dx.doi.org/10.1111/j.1939-1676.2007.0012.x krakauer, t., buckley, m. (2003). doxycycline is anti-inflammatory and inhibits staphylococcal exotoxin-induced cytokines and chemokines. antimicrobial agents and chemotherapy, 47 (11), pp. 3630–3. doi: http://dx.doi.org/10.1128/aac.47.11.3630-3633.2003 mcgrotty, y. and knottenbelt, c. (2002) oesophageal stricture in a cat due to oral administration of tetracyclines. the journal of small animal practice, 43 (5), pp. 221–3. http://dx.doi.org/10.1111/j.1748-5827.2002.tb00062.x owen, w. et al. (2003) efficacy of azithromycin for the treatment of feline chlamydophilosis. journal of feline medicine and surgery, 5(6), 305–11. doi: http://dx.doi.org/10.1016/s1098-612x(03)00072-x ploneczka-janeczko, k. et al. (2015) reduction of chlamydophila-felis-associated signs by roxithromycin treatment regimen in cats showing doxycycline intolerance. veterinarni medicina, 60 (11), pp. 654–661. doi: http://dx.doi.org/10.17221/8534-vetmed schulz, b. wolf, g. and hartmann, k. (2006) bacteriological and antibiotic sensitivity test results in 271 cats with respiratory tract infections. veterinary record, 158, pp. 269-270. doi: http://dx.doi.org/10.1136/vr.158.8.269 schulz, b. et al. (2013) side effects suspected to be related to doxycycline use in cats. veterinary record, 172, pp. 184–185. doi: http://dx.doi.org/10.1136/vr.101031 sparkes, a. et al. (1999) the clinical efficacy of topical and systemic therapy for the treatment of feline ocular chlamydiosis. journal of feline medicine and surgery, 1 (1), pp. 31–35. doi: http://dx.doi.org/10.1016/s1098-612x(99)90007-4 sturgess, c. (2001) controlled study of the efficacy of clavulanic acid-potentiated amoxycillin in the treatment of chlamydia psittaci in cats. veterinary record, 149, pp. 73–76. doi: http://dx.doi.org/10.1136/vr.149.3.73 sykes, j. (1999) comparison of the polymerase chain reaction and culture for the detection of feline chlamydia psittaci in untreated and doxycycline-treated experimentally infected cats. journal of veterinary internal medicine, 13, pp. 146–52. doi: http://dx.doi.org/10.1111/j.1939-1676.1999.tb02171 intellectual property rights knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. is the use of hypertonic saline effective in reducing intracranial pressure after traumatic brain injury in dogs? a knowledge summary by alexandra tischer drvetmed, vets now1* ava firth dvm, dacvecc1 1vets now support office, penguin house, castle riggs, dunfermline, fife, ky11 8sg *corresponding author (a.tischer@gmail.com) vol 2, issue 2 (2017) published: 15 may 2017 reviewed by: shailen jasani (ma, vetmb, mrcvs, dacvecc) and bruce smith (bvsc, ms, fanzcvs, dacvs) next review date: 15 may 2019 doi: 10.18849/ve.v2i2.94 clinical bottom line hypertonic saline appears to be effective in reducing intracranial pressure after traumatic brain injury in dogs in experimental studies. question in dogs with traumatic brain injury, does hypertonic saline, compared to lactated ringer’s solution, reduce intracranial pressure? clinical scenario a three year old 15kg male entire terrier cross is brought in after running into the road and colliding with a car. it is in hypovolaemic shock and after fluid resuscitation (25ml/kg lrs in 15 minutes) the only visible injuries found are epistaxis and a fractured jaw. however, the dog is stuporous and consciousness does not seem to improve with stabilising cardiovascular parameters. would treatment with hypertonic saline be beneficial for this dog? the evidence nearly all available evidence for this pico question comes from experimental studies. how much experimental and clinical traumatic brain injury differ is unclear. summary of the evidence abbreviations used cpp    cerebral perfusion pressure cvp    central venous pressure icp      intracranial pressure lrs     lactated ringer’s solution map    mean arterial pressure prough (1986) population: dogs sample size: 17 intervention details: after 30 minutes of experimentally induced haemorrhagic shock (map <50mmhg) dogs were resuscitated with hypertonic saline solution or lrs. study design: randomised, experimental study. outcome studied: systolic and diastolic blood pressure, cardiac output, map and icp. main findings (relevant to pico question): icp after resuscitation with hypertonic saline was lower than after lrs while restoring systolic blood pressure and cardiac output to the same level. limitations: experimental study no brain injury or increased icp to begin with small number of cases gunnar (1988) population: laboratory beagles sample size: 22 intervention details: hypovolaemic shock and closed head injury were simulated via bleeding of 40% of blood volume and epidurally inflated balloon in 17 dogs. this was maintained for 1h, after that resuscitation with the shed blood and either 3% hypertonic saline (6 dogs), 0.9% saline (5 dogs) or dextran-40 (6 dogs) was attempted. a solution of evans blue was also injected. after 2h of resuscitation the dogs were euthanised and their brains weighed and checked for evans blue staining under microscope. a control group of five dogs wasn’t bled or ballooned but normal saline and evans blue solution only. study design: experimental controlled study. outcome studied: continuous icp monitoring, blood brain barrier function assessed by degree of evans blue staining and cerebral oedema formation assessed by wet brain weights. main findings (relevant to pico question): 3% hypertonic saline caused lower intracranial pressure and less cerebral oedema than either 0.9% saline or dextran-40, but blood brain barrier integrity is not restored. limitations: experimental study no survivors to assess clinical outcome short term study of only 3h duration small number of cases gunnar (1989) population: laboratory beagles sample size: 18 intervention details: hypovolaemic shock and closed head injury were simulated via bleeding of 40% of blood volume and epidurally inflated balloon. this was maintained for 1h, after that resuscitation with the shed blood and either 3% hypertonic saline, 0.9% saline or dextran-40 was attempted, after this, normal saline was given at a rate to maintain cvp at 10mmhg. study design: experimental uncontrolled study. outcome studied: cerebral blood flow and icp were measured at baseline, at the end of the shock period, during resuscitation and after resuscitation. main findings (relevant to pico question): though the intracranial pressure was lower in the hypertonic saline group, cerebral blood flow did not vary. limitations: experimental study no assessment of clinical outcome short term study of only 3h duration small number of cases pinto (2006) population: crossbreed dogs sample size: 15 intervention details: 20 minutes after experimentally induced haemorrhagic shock via bleeding to map of 40mmhg and simulated traumatic brain injury via fluid percussion and epidural balloon, volume was replaced with 3% hypertonic saline (8ml/kg over 10 min) or lrs (16ml/kg over 10 ml) in five dogs each. 20 minutes later shed blood and more of the previous fluids were given to a haematocrit of 30% and a map of >70mm hg. a control group of five received no fluids at either point. after 60 minutes the epidural balloon was deflated in the treatment groups. study design: experimental, randomised, controlled study. outcome studied: map, cardiac index, icp, cpp, biochemistry and blood gases. main findings (relevant to pico question): 3% hypertonic saline results in lower icp than lrs even though cpp remains similar. hypertonic saline also causes higher serum sodium concentration and osmolarity than lrs. limitations: experimental study no clinical outcome described small number of cases sharma (2015) population: client-owned dogs with head trauma <5 days before hospital admission. sample size: 72 intervention details: no specific interventions, clinical records were analysed. study design: retrospective descriptive study, based on medical records. outcome studied: the prognostic value of clinical and laboratory variables, scoring systems and treatments (such as hypertonic saline) in dogs with head trauma was calculated. main findings (relevant to pico question): hypertonic saline administration was associated with lower likelihood of survival to discharge (8 survivors, 4 nonsurvivors). limitations: retrospective case study no control group multiple parameters observed, prognostic value of individual variables on their own hard to quantify small number of cases pinto (2015) population: crossbreed dogs sample size: 15 intervention details: 20 minutes after experimentally induced haemorrhagic shock via bleeding to map of 40mmhg and simulated traumatic brain injury via fluid percussion and epidural balloon, volume was replaced with 3% hypertonic saline (8ml/kg over 10 min) or lrs (16ml/kg over 10 min) in 5 dogs each. 20 minutes later shed blood and more of the previous fluids were given to a haematocrit of 30% and a map of >70mm hg. a control group of five dogs received no fluids at either point. after 1h the epidural balloon was deflated in the treatment groups. all dogs were euthanised after 3h and the brains removed, visually assessed and further analysed after tissue fixation. study design: experimental controlled study. outcome studied: map and icp were measured, changes in pupil state were assessed every 10 minutes, macroscopic and microscopic brain pathology and prostaglandoid production were assessed. main findings (relevant to pico question): icp was the lowest in the hypertonic saline cases during the initial 60 minutes. in brains that had received hypertonic saline, no cerebral oedema was identified macroscopically and ischaemic lesions were less evident. in cases with pupil changes, the pupils reversed to normal sooner in the hypertonic saline group. limitations: experimental study no survivors to assess clinical outcome short term study of only 3h duration macroscopic assessment for cerebral oedema only small number of cases appraisal, application and reflection the purpose of this knowledge summary was to look at the evidence for the use of hypertonic saline in reducing intracranial pressure in head trauma patients. the experimental studies available in dogs seem to indicate that hypertonic saline might have a good effect on increased intracranial pressure after traumatic brain injury while achieving desirable haemodynamic parameters. there are no controlled clinical studies that evaluate the use of hypertonic saline as an independent variable. in the descriptive study from sharma & holowaychuck (2015) the decision to use hypertonic saline was the clinician’s, and sometimes made after other treatment options had been unsuccessful. the choice to use hypertonic saline appears mostly to have been made in very severe cases, which may explain the negative predictive value of hypertonic saline use on survival until discharge. in conclusion, hypertonic saline appears to be effective in reducing intracranial pressure after traumatic brain injury in experimental studies. how effective its use might be in clinical settings cannot be answered. methodology section search strategy databases searched and dates covered: pubmed database, accessed via the ncbi website (1910-2015) and the cab abstracts database (1973-2015) search terms: (dog or dogs or canine or puppy or puppies or canis) and (((brain and (trauma or injur*)) or (head and (trauma or injur*))) and (hypertonic and (saline or sodium)) dates searches performed: 18th july 2016 exclusion / inclusion criteria exclusion: articles not available in english or german, single case reports, book chapters and conference proceedings, articles which were not relevant to the question. inclusion: articles available in english or german, which were relevant to the question. search outcome database number of results excluded – language excluded – not relevant to question total relevant papers cab abstracts 2 0 1 1 ncbi pubmed 15 0 9 6 total relevant papers when duplicates removed 6 conflict of interest the authors declare no conflicts of interest. references gunnar, w. et al. (1988) head injury and hemorrhagic shock: studies of the blood brain barrier and intracranial pressure after resuscitation with normal saline solution, 3% saline solution, and dextran-40. surgery, 103 (4), pp. 398–407. gunnar, w. kane, j. & barrett, j. (1989) cerebral blood flow following hypertonic saline resuscitation in an experimental model of hemorrhagic shock and head injury. brazilian journal of medical and biological research = revista brasileira de pesquisas medicas e biologicas / sociedade brasileira de biofisica ... [et al.], 22 (2), pp. 287–289. pinto, f.c.g. et al. (2015) effect of volume replacement during combined experimental hemorrhagic shock and traumatic brain injury in prostanoids, brain pathology and pupil status. arquivos de neuro-psiquiatria, 73 (6), pp. 499–505. http://dx.doi.org/10.1590/0004-282x20150039 pinto, f.c.g. et al. (2006) volume replacement with lactated ringer's or 3% hypertonic saline solution during combined experimental hemorrhagic shock and traumatic brain injury. the journal of trauma, 60(4), pp. 758–63– discussion 763–4. 10.1097/01.ta.0000214581.89316.73 prough, d.s. johnson, j.c. & poole, g.v.j. (1986) effects on intracranial pressure of resuscitation from hemorrhagic shock with hypertonic saline versus lactated ringer's solution. journal of trauma and acute care surgery, 26 (1), p. 97. sharma, d. & holowaychuk, m.k. (2015) retrospective evaluation of prognostic indicators in dogs with head trauma: 72 cases (january-march 2011). journal of veterinary emergency and critical care, 25 (5), pp. 631–639. 10.1111/vec.12328 intellectual property rights knowledge summaries are a peer-reviewed article type which aims to answer a clinical question based on the best available current evidence. it does not override the responsibility of the practitioner. informed decisions should be made by considering such factors as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. knowledge summaries are a resource to help inform and any opinions expressed within the knowledge summaries are the author's own and do not necessarily reflect the view of the rcvs knowledge. authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. the evidence behind the treatment of canine idiopathic epilepsy a knowledge summary by marios charalambous dvm gpcert(neuro) rscimrsb mrcvs 1 * david brodbelt ma vetmb phd dva dipecvaa mrcvs 2 holger volk dvm phd dipecvn fhea mrcvs 2 1university college london 2royal veterinary college *corresponding author (marios.charalambous.15@ucl.ac.uk) vol 1, issue 1 (2016) published: 10 feb 2016 next review date: 23 nov 2017 doi: 10.18849/ve.v1i1.9 clinical bottom line oral phenobarbital and imepitoin in particular, followed by potassium bromide and levetiracetam are likely to be effective for the treatment of canine idiopathic epilepsy. there is strong evidence supporting the use of oral phenobarbital and imepitoin as ‘first line’ medications. however, there remains a lack of evidence for targeted treatment for the various individual epileptic phenotypes and quite limited evidence on direct comparisons of the efficacy between various anti-epileptic drugs. question in dogs with epilepsy, what is the best treatment to reduce seizures. clinical scenario a 5 years old 17 kg german shepherd intact male dog manifested generalized tonic-clonic seizures one year ago. in the last two months the dog manifested five episodes. the dog is normal between the episodes; idiopathic epilepsy is suspected. you wonder what the best treatment in a dog with presumed idiopathic epilepsy would be. summary of the evidence law (2015) population: dogs with idiopathic epilepsy (tier ii). sample size: 21 dogs n=21 intervention details: dogs were fed either ketogenic medium-chaintag diet (mctd) or placebo diet for 3 months followed by a subsequent respective switch of diet for a further 3 months. seizure frequency, clinical and laboratory data were collected and evaluated for twenty-one dogs completing the study. study design: blinded randomized placebo-controlled cross-over trial. outcome studied: objective: to compare the mctd with a standardized placebo diet in chronically antiepileptic drug-treated dogs with idiopathic epilepsy. main findings (relevant to pico question): the data showed antiepileptic properties associated with ketogenic diets and provided evidence for the efficacy of the mctd used in this study as a therapeutic option for epilepsy treatment. seizure frequency was significantly lower when dogs were fed the mctd (2·31/month, 0–9·89/month) in comparison with the placebo diet (2·67/month, 0·33–22·92/month, p=0·020); three dogs achieved seizure freedom, seven additional dogs had ≥50 % reduction in seizure frequency, five had an overall <50 % reduction in seizures (38·87 %, 35·68–43·27 %) and six showed no response.there were no significant changes in serum concentrations of glucose (p=0·903), phenobarbital (p=0·422), potassium bromide (p=0·404) and weight (p=0·300) between diet groups. limitations: small number of dogs; however, calculations showed that it should be adequate for this study. risk of incomplete outcome data due to ten dogs withdrawals; however reasons are thoroughly explained by the authors and in this case they might not have changed the final outcome.  also, these ten dogs were not included in the total number of 21 dogs initially recruited and finally completed the data. the study had financial support by a food company, although it is stated that the company was not involved with the study design and data analysis. packer (2015a) population: dogs with idiopathic epilepsy (tier ii). sample size: 52 dogs n=52 intervention details: 2 treatment groups, no control group treatment group 1:  drug: levetiracetam maintenance (as an adjunct to other aeds) dose: 19.5 mg/kg po tid treatment period:>3 months n=29  treatment group 2:  drug:levetiracetam pulse (as an adjunct to other aeds) dose:22.2 mg/kg po tid treatment period:> 3 months n=23  pulse group protocol: an initial dose of ~60 mg/kg after a seizure occurred or pre-ictal signs were recognised by the owner, followed by ~20 mg/kg every 8 h until seizures did not occur for 48 h.  five dogs in group 1 did not respond adequately to levetiracetam and zonisamide (n=3) or gabapentin (n=2) was added after 168 days. one dog did not respond to levetiracetam in the group 2 and topiramate was added after 92 days. study design: retrospective case series. outcome studied: objective: evaluation of the antiepileptic action of levetiracetam based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for levetiracetam. the treatment resulted in 69% of dogs having > 50% reduction in seizure frequency whilst 15% of all the dogs were completely free from seizures. seizure frequency reduced significantly in the whole population. levetiracetam pulse might be a treatment for cluster seizures. limitations: retrospective case series but mainly good follow up time 1.1 years (median). rundfeldt (2015) population: dogs with idiopathic epilepsy. (tier i-ii). sample size: 120 dogs n=120 intervention details: 2 treatment groups (including the control group)  blinded part: treatment group 1:  drug: imepitoin dose: 30 mg/kg po bid treatment period: 3 months n=66 treatment (control) group 2:  drug: imepitoin dose: 1 mg/kg po bid treatment period: 3 months n=61   open-labelled follow-up: only 1 treatment group:  drug: imepitoin dose: 30 mg/kg po bid treatment period: 3 months n=100 study design: blinded, randomised, controlled clinical trial (first phase) with an open-labelled follow-up (second phase). outcome studied: objective: to support the antiepileptic activity and safety of imepitoin in dogs with idiopathic epilepsy. main findings (relevant to pico question): administration of imepitoin twice daily at a dose of 30 mg/kg results in significant and persistent antiepileptic effects in patients with newly diagnosed epilepsy suffering from generalized tonic-clonic seizures compared to ‘pseudoplacebo’ control group (1 mg/kg bid) of the same drug. the safety profile of imepitoin was good, and mostly cns related ars were transient and predominantly observed in the first weeks of treatment. limitations: short follow up time for first phase of study (12 weeks). open-labeled phase was an additional 12 weeks. a few cases had tier i confidence level for the diagnosis of idiopathic epilepsy. tipold (2015) population: dogs with idiopathic epilepsy (tier i). sample size: after exclusion: 152 n=152  before exclusion: 195 n= 195 intervention details: 1 treatment group, 1 control group.  treatment group:  drug: imepitoin dose: 10-30 mg/kgpo bid treatment period: 5 months n= 64 (after exclusion), n= 93 (before exclusion)  control group:  drug: phenobarbital dose: 2-6 mg/kgpo bid treatment period: 5 months n= 88 (after exclusion), n= 102 (before exclusion) study design: blinded, randomised, controlled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of imepitoin and phenobarbital based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): the majority of the dogs were managed successfully with imepitoin. the same study confirmed non-inferiority of imepitoin to phenobarbital. limitations: statistical analysis was conducted before unblinding only on the per-protocol population and not on the intent-to-treat population. tier i confidence level for the diagnosis of idiopathic epilepsy. charalambous (2014) population: dogs with idiopathic epilepsy. sample size: 1153 dogs n= 1153 intervention details: studies were grouped based on the antiepileptic drugs they evaluated and their overall quality of evidence. details of drug’s doses, treatment period, preand posttreatment seizure frequency, 95% confidence interval of the successfully (≥50% reduction in seizure frequency) study population were provided. study design: systematic review. outcome studied: objective: individual studies were evaluated based on the quality of evidence (study design, study group sizes, diagnostic procedures for enrolling dogs with idiopathic epilepsy and overall risk of bias) and the outcome measures reported (in particular the proportion of dogs with ≥50%reduction in seizure frequency). main findings (relevant to pico question): overall risk of bias was moderate/high to high in 85% of the studies included. the diagnostic investigation procedures were poorly defined or unclear. in 50% of the studies. small population of dogs (<20) included in 77% of the studies.  oral phenobarbital and imepitoin in particular, as well as potassium bromide and levetiracetam are likely to be effective for the treatment of ie. limitations: the review was an in depth and objective assessment of the drugs’ efficacy and studies’ quality of evidence. therefore, the limitations occurred in this review, derived from the studies included and evaluated in this review.  precisely, the overall low quality of evidence, the variations in baseline characteristics of the dogs involved, the significant differences between study designs and several potential sources of bias that were identified preclude definitive recommendations.  the main limitation of this review is that it did not have free full access to unpublished data (e.g. emea report). fredsø (2014) population: dogs with idiopathic epilepsy (tier i or insufficient level of confidence) and structural epilepsy. sample size: 102 dogs n=102 intervention details: one hundred and two client owned dogs; 78 dogs with idiopathic epilepsy and 24 dogs with epilepsy associated with a known intracranial cause.  a retrospective hospital based study with follow-up. dogs diagnosed with epilepsy between 2002 and 2008 were enrolled in the study. owners were interviewed by telephone using a structured questionnaire addressing epilepsy status, treatment, death/alive, and cause of death. study design: retrospective case series. questionnaire. outcome studied: objective: to investigate risk factors for survival and duration of survival in a population of dogs with idiopathic epilepsy or epilepsy associated with a known intracranial cause. main findings (relevant to pico question): in dogs where monotherapy was not sufficient, the need for treatment with two aed's is not linked to a poor prognosis. limitations: retrospective case series – questionnaire. insufficient or tier i confidence level for diagnosing idiopathic epilepsy. packer (2014) population: dogs with idiopathic epilepsy (tier ii). sample size: 344 dogs n=344 intervention details: data from dogs was retrospectively collected from electronic patient records. clinical data was originally gained via standardised owner questionnaires for epilepsy patients at their first appointment, and longitudinal follow up data was gained via telephone interview with the dogs’ owners. study design: retrospective case series. outcome studied: objective: to identify clinical risk factors associated with antiepileptic drug responsiveness in canine epilepsy. main findings (relevant to pico question): the presence of cluster seizures and thus seizure density is a more influential risk factor on the likelihood of achieving remission in canine epilepsy than seizure frequency or the total number of seizures prior to treatment. limitations: retrospective case series study.  however, thorough statistics were used which were good in filtering out the non-significant. kiviranta (2013) population: dogs with idiopathic epilepsy (tier i). sample size: 10 dogs n=10 intervention details: 1 treatment group, no control group.  treatment group:  drug: topiramate as an adjunct to phenobarbital and/or potassium bromide and/or levetiracetam dose: 5 mg/kg po bid for 2 months, then 10 mg/kg po bid for 2 months and then 10 mg/kg po tid for 2 months; doses of other aeds were not available but reported to be within normal reference values treatment period: 6-15 months n= 10 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of topiramate based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for topiramate adjunctive therapy. approximately half of the study population had ≥50% reduction in seizure frequency. limitations: non-blinded, non-randomised and uncontrolled trial. low study population. precise doses of concurrent aeds were not reported. tier i confidence level for the diagnosis of idiopathic epilepsy. srivastava (2013) population: dogs with idiopathic epilepsy (insufficient level of confidence). sample size: 6 dogs n=6 intervention details: 1 treatment group, no control group.  treatment group:  drug: potassium bromide as an adjunct to phenobarbital dose: potassium bromide: 30 mg/kg po sid; phenobarbital: 4.25 mg/kg po bid treatment period: 6 months n=6 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of potassium bromide based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for potassium bromide adjunctive therapy in all dogs. limitations: only abstract was retrieved. low study population. insufficient confidence level for the diagnosis of idiopathic epilepsy. precise reduction in seizure frequency could not be detected only based on the abstract. non-blinded, non-randomized, uncontrolled trial. boothe (2012) population: dogs with idiopathic epilepsy (tier i). sample size: 43 dogs n= 43 intervention details: 2 comparison treatment groups  treatment group 1:  drug: phenobarbital dose: mean 4.11, range 3.9-4.9 mg/kg po bid treatment period: approximately 6 months n= 20  treatment group 2:  drug: potassium bromide dose: mean 30.6, range 26-35 mg/kg po bid treatment period: approximately 6 months n= 23 study design: blinded, randomised, controlled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of phenobarbital in comparison to potassium bromide based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for phenobarbital and potassium bromide monotherapy. the majority of the study population had ≥50% reduction in seizure frequency in both groups. the percentage of successfully treated cases was higher in phenobarbital group. phenobarbital treated dogs had less side effects than potassium bromide dogs. limitations: tier i confidence level for diagnosing idiopathic epilepsy. chung (2012) population: dogs with idiopathic epilepsy (tier ii). sample size: 10 dogs n=10 intervention details: 1 treatment group, no control group.  treatment group:  drug: zonisamide dose: median 9.5, mean 8.65, range 2.5-12 mg/kg po bid treatment period: 5 median 12, mean 11.2 months n= 10 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of zonisamide based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for zonisamide monotherapy. approximately half of the study population had ≥50% reduction in seizure frequency. limitations: non-blinded, non-randomised and uncontrolled trial. low study population. research support but unclear if it was financial. kis (2012) population: dogs with idiopathic epilepsy (tier i). sample size: 70 dogs n=70 intervention details: 1 investigation group, no control group.  treatment group:  drug: phenobarbital dose: mean 2.15, range 0.65-10.44 mg/kg po bid treatment period: na study design: retrospective case series study. outcome studied: objective: to determine the concentration of phenobarbital in dogs with idiopathic epilepsy in croatia. main findings (relevant to pico question): in the investigated population 25 patients (36%) had measured concentration of phenobarbital under the lower therapeutic limit with adequate control of seizures.  only in 16% phenobarbital was ineffective in eradication of seizures.  phenobarbital is reasonable first-choice antiepileptic drug for treatment of canine idiopathic epilepsy in croatia. limitations: conference abstract. retrospective case series (high risk of bias). tier i confidence level for diagnosing idiopathic epilepsy. matthews (2012) population: dogs with idiopathic epilepsy (insufficient level of confidence). sample size: 15 dogs n= 15 intervention details: 1 treatment group, 1 control group.  treatment group: fatty acid placebo group: olive oil  twelve weeks of treatment with fatty acid supplementation, followed by a 12-week placebo period of olive oil supplementation. study design: blinded, placebo-controlled, clinical trial. outcome studied: objective: evaluation of the effect of fatty acid supplementation based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): fatty acid supplementation did not reduce seizure frequency or severity in dogs with idiopathic epilepsy. limitations: low study population. non-randomised. short study duration.  insufficient confidence level for diagnosing idiopathic epilepsy. muñana (2012) population: dogs with idiopathic epilepsy (tier i level of confidence). sample size: 34 dogs n= 34 intervention details: 1 treatment group, 1 control group.  treatment group:  drug: levetiracetam as an adjunct to phenobarbital and/or potassium bromide and/or levetiracetam and/or gabapentin dose: levetircetam: median 20.6, range 17-23.1 mg/kg po tid; phenobarbital: median 8.7, range2.9-17.2 mg/kg po bid; potassium bromide: median 39.1; range 13.6-133.3 mg/kg po sid treatment period: 9 months (during the 5th month no antiepileptic was administered) n= 22  control group:  drug:placebo medication dose:na treatment period: 9 months (during the 5th month no antiepileptic was administered) n= 12 study design: blinded, randomised, placebo-controlled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of levetiracetam based mainly on the seizure frequency change during specific treatment period and compared to the placebo group. main findings (relevant to pico question): favourable results for levetiracetam adjunctive therapy. the majority of the study population had ≥50% reduction in seizure frequency. the latter was reduced significantly compared to baseline but no difference was detected when compared to the placebo group (dogs in both the placebo and levetiracetam group were on maintenance therapy with phenobarbital and/or potassium bromide and/or gabapentin). limitations: potential risk of comparing to retrospective baseline. the study had financial support but unclear if it influenced the results. tier i confidence level for diagnosing idiopathic epilepsy. jambroszyk (2011) population: dogs with idiopathic epilepsy (tier i-ii). sample size: 6 dogs n=6 intervention details: 1 treatment group, no control group.  treatment group:  drug: verapamil as an adjunct to phenobarbital dose: verapamil: 1-1.5 mg/kg po bid; phenobarbital: 4 mg/kg po sid treatment period: 4 months n= 6 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of verapamil based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): failure of the maximum tolerated dose to improve seizure control. limitations: non-blinded, non-randomised and uncontrolled trial.  low study population. tier i confidence level for diagnosing idiopathic epilepsy for some cases. gaskill (2010) population: dogs with idiopathic epilepsy (insufficient level of confidence). sample size: 62 dogs n=62 intervention details: 2 comparison treatment groups. phenobarbital (n=30) and potassium bromide (n=32) were compared as monotherapies for 12 months. details of doses are not given. study design: open-labeled, randomised, controlled trial. outcome studied: objective: to compare phenobarbital to potassium bromide monotherapy. main findings (relevant to pico question): phenobarbital was more effective and better tolerated than potassium bromide monotherapy. limitations: conference paper. nonblinded and non-randomised. insufficient confidence level for diagnosing idiopathic epilepsy. dewey (2009) population: dogs with idiopathic epilepsy (tier i-ii). sample size: 9 dogs n=9 intervention details: 1 treatment group, no control group.  treatment group:  drug: pregabalin as an adjunct to phenobarbital and potassium bromide dose: pregabalin: 2 mg/kg po tid (dose was increased up to until 3-4 mg/kg po tid); doses of other aeds were not available but reported to be within normal reference values treatment period: 3 months n= 9 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of pregabalin based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for pregabalin adjunctive therapy. the majority of the study population had ≥50% reduction in seizure frequency. limitations: non-blinded, non-randomised and uncontrolled trial low study population. short follow up 3 months study duration.  precise doses of concurrent aeds were not reported. tier i confidence level for diagnosing idiopathic epilepsy for some cases. scorza (2009) population: dog with idiopathic epilepsy(insufficient level of confidence). sample size: 1 dog n=1 intervention details: 1 case. supplement the dog’s diet with moderate amounts of fish oil (oral omega-3 polyunsaturated fatty acids, 2 g/day). phenobarbital (2.5 mg/kg, twice a day orally) study design: case report. outcome studied: subjective: to evaluate the effectiveness of daily intake of a moderate amount of fish oil in a case of canineepilepsy. main findings (relevant to pico question): the frequency of the epileptic seizures markedly fell after 50 days of combination therapy with phenobarbital and omega-3 fatty acid. during the subsequent 18-month period, seizure frequency fell to one per 3 months, a reduction of about 85%. limitations: case report (high risk of bias). insufficient confidence level for diagnosing idiopathic epilepsy. insufficient details on the type of fish oil used or specific concentrations. volk (2009) population: dogs with idiopathic epilepsy (tier ii level of confidence). sample size: 22 dogs n=22 intervention details: 1 treatment group, no control group.  treatment group:  drug: levetiracetam as an adjunct to phenobarbital and potassium bromide dose: levetircetam: 10 mg/kg for 2 months, 20 mg/kg for further 2 months, 10-20 mg/kg for further 2 months and then 10-20 mg/kg long-term po tid; doses of other aeds were not available but reported to be within normal reference values treatment period: 2-6 months or more n=14   this study included also a retrospective case series part:  drug: levetiracetam as an adjunct to phenobarbital and potassium bromide dose: levetircetam: median 22.15, mean 21.7, range 10-32.8 mg/kg po tid; doses of other aeds were not available but reported to be within normal reference values treatment period: approximately 2-3 months n=8 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of levetiracetam based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for levetiracetam adjunctive therapy. the majority of the study population had ≥50% reduction in seizure frequency in both, clinical trial and case series part. limitations: non-blinded, non-randomised and uncontrolled trial. the study had financial support but unclear if it influenced the results. part of the study was retrospective. precise doses of concurrent aeds were not reported; but phenobarbital and potassium bromide serum levels were reported. musteata (2007) population: dogs with idiopathic epilepsy (insufficient level of confidence). sample size: 11 dogs n=11 intervention details: 1 treatment group, no control group.  treatment group:  drug: gabapentin as an adjunct to phenobarbital dose: gabapentin: mean 40 mg/kg po bid;initial doses of other aeds were not available based on the abstract only treatment period: unclear n=11 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of gabapentin based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for gabapentin as adjunctive therapy. significant reduction in frequency of epileptic attacks (67.29+or-9.03%) in the majority of the dogs (7 patients) (63.63%) allowing a progressive reduction in the pb doses to 5 mg/kg po bid. limitations: non-blinded, non-randomised, uncontrolled trial. only abstract was retrieved. low study population. insufficient confidence level for diagnosing idiopathic epilepsy. varshney (2007) population: dogs with idiopathic epilepsy seizures (insufficient level of confidence) and head tremors. sample size: 10 dogs n=10 intervention details: 1 treatment group, no control group.  treatment group:  belladona was administerd for approximately 8 months in all the dogs and cocculus for approximately 3 months in 4 dogs of the group. no other drug was used. study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of belladonna and cocculus based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): seizure-free status was achived during the treatment period, but 20% of the dogs had again seizures 15-25 days after belladona stopped. then, it was restarted for 2-3 months until seizures were ceased. limitations: non-blinded, non-randomised and uncontrolled trial. controversial results. unclear/insufficient confidence level for diagnosing idiopathic epilepsy. von klopmann (2007) population: dogs with idiopathic epilepsy (tier i-ii level of confidence). sample size: 11 dogs n=11 intervention details: 1 treatment group, no control group.  treatment group:  drug: zonisamide as an adjunct to phenobarbital and/or potassium bromide dose: zonisamide: mean 8.9 mg/kg, range 5-11 mg/kg po bid; doses of other aeds were not available but reported to be within normal reference values. treatment period: range 4-17 months n=11 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of zonisamide based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for zonisamide adjunctive therapy. the majority of the study population had ≥50% reduction in seizure frequency. limitations: non-blinded, non-randomised and uncontrolled trial. low study population. precise doses of concurrent aeds were not reported. tier i confidence level for diagnosing idiopathic epilepsy for some cases. platt (2006) population: dogs with idiopathic epilepsy (tier i level of confidence). sample size: 11 dogs n=11 intervention details: 1 treatment group, no control group.  treatment group:  drug: gabapentin as an adjunct to phenobarbital and potassium bromide dose: gabapentin: mean 10.9 mg/kg, 9.3-13.6 mg/kg po tid; doses of other aeds were not available but reported to be within normal reference values treatment period: 3 months n=11 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of gabapentin based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for gabapentin adjunctive therapy. approximately half of the study population had ≥50% reduction in seizure frequency. limitations: non-blinded, non-randomised and uncontrolled trial. low study population. less than 6 months study duration. precise doses of concurrent aeds were not reported. tier i confidence level for diagnosing idiopathic epilepsy. rieck (2006) & löscher (2004) (two papers reporting similar outcomes) population: dogs with idiopathic epilepsy (tier i-ii level of confidence). sample size: 143 dogs n=143 intervention details: 5 treatment groups, no control group  treatment group 1:  drug: imepitoinmonotherapy dose: 5 mg/kg for 1 week and then increased to 10-30 mg/kg po bid treatment period: mean 7.7 ± 0.7 months n=12  treatment group 2:  drug: imepitoin as an adjunct to phenobarbital or primidone dose: imepitoin: 7.7 ± 0.7 mg/kg po bid; phenobarbital: 6-23 mg/kg po sid; primidone: 25-53 mg/kg po sid treatment period: mean 5.6 ± 0.7months n=17 treatment group 3:  drug: phenobarbital monotherapy dose: mean 6 mg/kg, range 4–13 mg/kg po sid treatment period: 5.9 +/-0.4 months n=44  treatment group 4:  drug: primidone monotherapy dose: mean 51 mg/kg, range 24–70 mg/kg po sid treatment period:mean 6.0 ± 0.6 months n=26  treatment group 5:  drug: potassium bromide as an adjunct to phenobarbital and/or primidone dose: potassium bromide: 40-60 mg/kg po sid; phenobarbital: 6–17 mg/kg po sid; primidone: 50-70 mg/kg po sid treatment period: mean7.3 ± 0.6 months n=44 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of imepitoin, phenobarbital and primidonemonotherapy as well as potassium bromide adjunctive treatment based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): only less than the half of the study population had ≥50% reduction in seizure frequency with imepitoin monotherapy, imepitoin adjunctive therapy and potassium bromide adjunctive therapy. the majority of the study population had ≥50% reduction in seizure frequency with phenobarbital and primidone monotherapy. limitations: non-blinded, non-randomised and uncontrolled trial. part of the study was retrospective. tier i confidence level for diagnosing idiopathic epilepsy for some cases. govendir (2005) population: dogs with idiopathic epilepsy (tier i level of confidence). sample size: 17 dogs n=17 intervention details: 1 treatment group, no control group.  treatment group:  drug: gabapentin as an adjunct to phenobarbital and/or potassium bromide dose: gabapentin: mean 35 mg/kg, range 32-40 mg/kg po sid; phenobarbital: median 8 mg/kg, range 6-12 mg/kg po sid; potassium bromide: median 24 mg/kg; range 14-30 mg/kg po sid treatment period: 4 months n=17 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of gabapentin based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for gabapentin adjunctive therapy. approximately more than the half of the study population had ≥50% reduction in seizure frequency. limitations: non-blinded, non-randomised and uncontrolled trial. a few cases were treated by the referring vets. the study had financial support. tier i confidence level for diagnosing idiopathic epilepsy for some cases. patterson (2005) population: dogs with idiopathic epilepsy (insufficient level of confidence). sample size: 12 dogs n=12 intervention details: 1 treatment group, 1 control group.  treatment group:  ketogenic food treatment period: 6 months n=6  control group:  controlled food treatment period: 6 months n=6 study design: blinded, randomised, placebo-controlled clinical trial. outcome studied: objective: evaluation of the ketogenic food effectiveness in the seizure control based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): only 33% of the study population had ≥50% reduction in seizure frequency. no difference between two groups. limitations: conference abstract. doses/quantity of food or aeds are not mentioned. low study population. needed 22 dogs per group based on power calculation; thus, insufficient power in this study. insufficient confidence level for diagnosing idiopathic epilepsy. dewey (2004) population: dogs with idiopathic epilepsy (tier i-ii level of confidence). sample size: 12 dogs n=12 intervention details: 1 treatment group, no control group.  treatment group:  drug: zonisamide as an adjunct to phenobarbital and/or potassium bromide dose: zonisamide: mean 8.9 mg/kg, range 5-11mg/kg po bid; doses of other aeds were not available but reduced or eliminated in 9/12 dogs treatment period: mean 8, median 9, range 2 -18 months n=17 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of zonisamide based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for zonismide adjunctive therapy. approximately half of the study population had ≥50% reduction in seizure frequency. limitations: non-blinded, non-randomised and uncontrolled trial. low study population. short follow-up period. tier i confidence level for diagnosing idiopathic epilepsy for some cases. steinberg (2004) population: dogs with idiopathic epilepsy (insufficient level of confidence). sample size: 15 dogs n=15 intervention details: 1 treatment group, no control group.  treatment group:  drug: levetiracetam as an adjunct to phenobarbital and potassium bromide dose: levetiracetam: range 7.1-23.8 mg/kg po tid; doses of other aeds were not available but reported to be within normal reference values treatment period: median 38, range 13.8-95.5 months n=15 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of levetiracetam based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for levetiracetam adjunctive therapy. all the dogs of the study population had ≥50% reduction in seizure frequency. limitations: low study population. insufficient confidence level for diagnosing idiopathic epilepsy. non-blinded, non-randomised and uncontrolled trial. conference abstract. muñana (2002) population: dogs with idiopathic epilepsy (tier ii confidence level). sample size: 10 dogs n=10 intervention details: 1 treatment group, 1 control group.  treatment group:  vagal nerve stimulation adjunctive to phenobarbital and/or potassium bromide and/or felbamate  control group:  no device  method: 13 weeks of treatment followed (after 4 weeks wash-out) by 13 weeks of control (inactive device) study design: double blinded crossover controlled clinical trial outcome studied: objective: to investigate the antiepileptic efficacy of vagal nerve stimulation. main findings (relevant to pico question): mean decrease in seizure frequency between the 2 groups was 5.1% and not significant. limitations: low study population. assessment bias in favor of the device introduced by owners’ assessment could be a possibility. ruehlmann (2001) population: dogs with idiopathic epilepsy (tier i-ii level of confidence). sample size: 6 dogs n=6 intervention details: 1 treatment group, no control group.  treatment group:  drug: felbamate as an adjunct to phenobarbital dose: felbamate: median 63 mg/kg (initial dose) and 77 mg/kg (final dose) po bid; phenobarbital: 3.75 mg/kg pobid (stopped 2 months after felbamate started) treatment period: median 9 months n=6 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of felbamate adjunctive therapy based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for felbamate adjunctive therapy. all the dogs of the study population had ≥50% reduction in seizure frequency. limitations: non-blinded, non-randomised and uncontrolled trial. low study population. part of the study was retrospective. no clarification of statistical analysis. tier i confidence level for diagnosing idiopathic epilepsy for some cases. trepanier (1998) population: dogs with idiopathic epilepsy (insufficient level of confidence). sample size: 122 dogs n=122 intervention details: 1 treatment group, no control group.  treatment group:  drug: potassium bromide as an adjunct to phenobarbital or primidone dose: doses were not available but adjusted according to the therapeutic serum levels and clinical response treatment period: mean 14.2 +/4.7 months n=6 study design: retrospective case series study. outcome studied: objective: evaluation of the antiepileptic action of potassium bromide as adjunctive therapy based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for potassium bromide adjunctive therapy. the majority of the study population had ≥50% reduction in seizure frequency. limitations: retrospective nature of study. insufficient confidence level for diagnosing idiopathic epilepsy. heynold (1997) population: dogs with idiopathic epilepsy (tier i-ii level of confidence). sample size: 37 dogs n=37 intervention details: 1 treatment group, no control group.  treatment group:  drug: phenobarbital dose: mean 2.5 mg/kg po bid treatment period: mean 50.4, range 8-18months n=37 study design: retrospective case series study. outcome studied: objective: evaluation of the antiepileptic action of phenobarbital based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for phenobarbital monotherapy the majority of the study population had ≥50% reduction in seizure frequency. limitations: retrospective nature of study. less than 6 months study duration. the study had financial support but unclear if it influenced the results. tier i confidence level for diagnosing idiopathic epilepsy for some cases. o'brien (1997) population: dogs with idiopathic epilepsy (insufficient level of confidence). sample size: 10 dogs n=10 intervention details: 1 treatment group, no control group.  treatment group:  drug: nimodipine as an adjunct to phenobarbital or primidone. dose: nimodipine: 2.5 mg/kg po bid; doses of phenobarbital or primidone were ot available gradually tapered during a minimum of 4 weeks) treatment period: 6 months n=10 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of nimodipine as adjunctive therapy based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): nimodipine was not successful in controlling seizures in dogs. limitations: non-blinded, non-randomised and uncontrolled trial. insufficient confidence level for diagnosing idiopathic epilepsy. podell (1993) population: dogs with idiopathic epilepsy (tier i-ii level of confidence) sample size: 37 dogs n=37 intervention details: 1 treatment group, no control group.  treatment group:  drug: potassium bromide as an adjunct to phenobarbital dose: potassium bromide: mean 20.75 mg/kg, range 13-40 mg/kg po bid; phenobarbital: not available treatment period: mean 15, range 4-33 months n=37 study design: retrospective case series study. outcome studied: objective: evaluation of the antiepileptic action of potassium bromide as adjunctive therapy based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for potassium bromide adjunctive therapy. the majority of the study population had ≥50% reduction in seizure frequency. limitations: retrospective case series. tier i confidence level for diagnosing idiopathic epilepsy for some cases. schwartz-porsche (1991) population: dogs with idiopathic epilepsy (tier ii level of confidence). sample size: 19 dogs n=19 intervention details: 1 treatment group, no control group.  treatment group: drug: potassium bromide as an adjunct to phenobarbital or primidone dose: potassium bromide: range 17-58 mg/kg po sid; doses of other aeds were not available but reported to be within normal reference values or kept in the maximum therapeutic doses treatment period: mean 21, range, 7-61 months n=19 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of potassium bromide as adjunctive therapy based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for potassium bromide adjunctive therapy. more than half of the study population had ≥50% reduction in seizure frequency. limitations: non-blinded, non-randomised and uncontrolled trial. pearce (1990) population: dogs with idiopathic epilepsy (tier i-ii). sample size: 10 dogs n=10 intervention details: 1 treatment group, no control group.  treatment group:  drug: potassium bromide as an adjunct to phenobarbital dose: potassium bromide: 22 po sid (dose increases occurred);phenobarbital: median 3.3 mg/kg, mean 3.8 mg/kg po bid (dose was reduced by a mean of 50% in 7/10 dogs during the pbrtreatment) treatment period: median 7, mean 7.8 months n=10 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of potassium bromide as adjunctive therapy based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for potassium bromide adjunctive therapy. the majority of the study population had ≥50% reduction in seizure frequency. limitations: non-blinded, non-randomised and uncontrolled trial. low study population. tier i confidence level for diagnosing idiopathic epilepsy for some cases. morton (1988) population: dogs with idiopathic epilepsy (insufficient level of confidence). sample size: 19 dogs n=19 intervention details: 2 treatment groups  treatment group 1:  drug: phenobarbital dose: median 180 mg/kg, mean 283 mg/kg, range 60-90 mg/kg po sid treatment period: unclear n= 7  treatment group 2:  drug: primidone dose: median 50 mg/kg, mean 48 mg/kg, range 18-94 mg/kg po sid treatment period: unclear n= 12 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of primidone and phenobarbital monotherapy based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for primidone and phenobarbital monotherapy the majority of the study population had ≥50% reduction in seizure frequency in primidone group. approximately half of the study population had ≥50% reduction in seizure frequency in phenobarbital group. limitations: non-blinded, non-randomised and uncontrolled trial. a few cases were treated by the referring vets. the study had financial support but unclear if it influenced the results. insufficient confidence level for diagnosing idiopathic epilepsy. schwartz-porsche (1985) population: dogs with idiopathic epilepsy (insufficient level of confidence). sample size: 35 dogs n=35 intervention details: 2 treatment groups  treatment group 1:  drug: phenobarbital dose: mean 15 mg/kg, range 7.3-32 mg/kg po sid treatment period: unclear n= 15  treatment group 2:  drug: primidone dose: range 17-107 mg/kg po sid treatment period: mean 14, range 6.0-35months n= 20 study design: open-labeled, randomized, controlled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of primidone and phenobarbital monotherapy based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for phenobarbital and primidone monotherapy. the majority of the study population had ≥50% reduction in seizure frequency. limitations: non-blinded. the study had research support but unclear if it influenced the results. no clarification of statistical analysis. insufficient confidence level for diagnosing idiopathic epilepsy. cunningham (1983) population: dogs with idiopathic epilepsy (tier ii level of confidence). sample size: 15 dogs n=15 intervention details: 1 treatment group, no control group.  treatment group:  drug: primidone dose: unclear treatment period: 9 months n=15 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of primidone based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for primidone monotherapy. the majority of the study population had ≥50% reduction in seizure frequency. limitations: conference abstract. non-blinded, non-randomised and uncontrolled trial. low study population. schwartz-porsche (1982) population: dogs with idiopathic epilepsy (tier ii level of confidence). sample size: 30 dogs n=30 intervention details: 1 treatment group, no control group.  treatment group:  drug: primidone dose: 13-100 mg/kg po sid treatment period: approximately 6 months n=15 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of primidone based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): favourable results for primidone monotherapy. the majority of the study population had ≥50% reduction in seizure frequency. limitations: non-blinded, non-randomised and uncontrolled trial. nafe (1981) population: dogs with idiopathic epilepsy (tier i-ii level of confidence). sample size: 57 dogs n=57 intervention details: 4 treatment groups  treatment group 1: drug: sodium valproate as an adjunct to phenobarbital and phenytoin dose: sodium valproate: range 25-40 mg/kg po sid; the doses of other drugs were not reported treatment period: mean 4.9, range 1-8 months n=11  treatment group 2: drug: sodium valproate as an adjunct to primidone dose: sodium valproate: range 30-45 mg/kg po sid; the doses of other drugs were not reported treatment period: mean 4.9, range 1-8 months n=6  treatment group 3: drug: sodium valproate as an adjunct to phenobarbital dose: sodium valproate: range 30-110 mg/kg po sid; the doses of other drugs were not reported treatment period: mean 4.9, range 1-8 months n=21  treatment group 4: drug: sodium valproate dose: range 25-105 mg/kg po sid; the doses of other drugs were not reported treatment period: mean 4.9, range 1-8 months n=16 study design: uncontrolled clinical trial. outcome studied: objective: evaluation of the antiepileptic action of sodium valproate as adjunctive therapy or monotherapy based mainly on the seizure frequency change during specific treatment period. main findings (relevant to pico question): the majority of the study population did not have ≥50% reduction in seizure frequency in groups 1,2 and 4. in group 3, approximately half of the study population had ≥50% reduction in seizure frequency. limitations: non-blinded, non-randomised and uncontrolled trial. less than 6 months study duration. no seizure-free dogs. tier i confidence level for diagnosing idiopathic epilepsy for some cases. * the level of confidence for diagnosing idiopathic epilepsy (tier i-iii) used in this knowledge summary was based on the international veterinary epilepsy task force (ivetf) consensus statement on the diagnosis of idiopathic epilepsy (de risio, l. et al. 2015). any paper that included dogs with idiopathic epilepsy for which diagnostic investigations were below this tier level of evidence or unclear was considered to provide insufficient level of confidence for diagnosing idiopathic epilepsy. tier i was listed in the limitations of the papers as this could indicate that a few dogs might have suffered from structured epilepsy and as a result have not responded adequately or at all to the treatment. appraisal, application and reflection various antiepileptic drugs (aeds) are used for the management of canine idiopathic epilepsy. charalambous et al. (2014) performed a systematic review and suggested that the evidence-base in therapy of canine epilepsy is still unsatisfactory for some aeds. only four blinded randomized clinical trials (brcts) were reported which were considered to offer the highest quality of evidence amongst all the studies evaluated.the most recent one was performed by rundfeldt et al. (2015) who compared imepitoin high (30 mg/kg bid) to low (1 mg/kg bid) doses and concluded that doses of 30 mg/kg bid are effective in managing seizures in dogs with idiopathic epilepsy. apart from these brcts, the majority of the evidence derived from non-blinded, non-randomised, uncontrolled clinical trials and case series. the studies included in this summary and the systematic review charalambous et al. (2014) suggested that oral phenobarbital and imepitoin in particular, as well as potassium bromide and levetiracetam are likely to be effective for the treatment of idiopathic epilepsy. precisely, a good level of evidence supported the efficacy of oral phenobarbital and imepitoin as monotherapy aeds, fair and insufficient level of evidence supported the efficacy of potassium bromide as monotherapy and adjunct aed respectively and fair level of evidence supported the efficacy of levetiracetam as adjunct aed. levetiracetam can be also used effectively as pulse therapy against cluster seizures according to a recent report by packer, nye et al. (2015). for the remaining aeds (i.e. zonisamide, primidone, gabapentin, pregabalin, sodium valproate, felbamate, topiramate) favorable results were reported regarding their efficacy, but there was insufficient evidence to support their use mainly due to lack of brcts.  although individual assumptions for aeds’ efficacy could be made based on the studies’ results and the level of evidence provided, direct comparisons of efficacy between aeds were limited due to lack of controlled studies. precisely, based on the controlled studies, direct aed comparisons include:  phenobarbital vs imepitoin tipold et al. (2014) showed that monotherapy with imepitoin in dogs with newly diagnosed epilepsy was almostsimilarly effective and potentially more tolerated than phenobarbital. the same result was reported within other studies investigated in the systematic review by charalambous et al. (2014).  phenobarbital vs potassium bromide bootheet al. (2012) and gaskill and kimber (2010) found that phenobarbital was more effective and better tolerated than potassium bromide monotherapy.  phenobarbital vs primidone schwartz-porsche et al. (1985) reported that the difference between the efficacy of phenobarbital and primidone was not significant, but primidone caused signs of liver toxicity in 70% of the dogs in the group.  primidone vs imepitoin in a us field study, as reported in the emea (2012) report, imepitoin failed to demonstrate higher efficacy compared to primidone. however, this study was considered only as supportive information because the control group therapy (primidone) is not approved in europe.  finally, muñana et al. (2012) compared levetiracetam to placebo and found that seizure frequency was reduced significantly compared to baseline but no difference was detected when compared to the placebo group. direct comparisons between other aeds could not be performed based on the current published evidence. generally, aed monotherapy or adjunctive therapy with multiple drugs can be chosen accordingto the clinically successful control of seizures (i.e. usually >50% or, ideally, 100% reduction in seizure frequency) and side effects. fredsø et al. (2014) reported that in dogs where monotherapy was not sufficient, the need for treatment with two aeds has not been linked to a reduced survival. packer et al. (2015) demonstrated that 37.5% of dogs that received a third-line aed after treatment failure with two aeds were responsive to this drug (achieving > 50% reduction in seizure frequency). the same study found that only dogs that responded to the first aed became seizure-free. lastly, packer et al. (2014) found that the presence of cluster seizures and thus seizure density is a more influential risk factor on the likelihood of achieving remission in canine epilepsy than seizure frequency or the total number of seizures prior to treatment.  alternative therapies have been also investigated for treating canine epilepsy (including diet trials, nerve stimulation, homeopathic agents), but the results were not very encouraging based on these. munana et al. (2002) tried vagal nerve stimulation but the mean decrease in seizure frequency was approximately 34.4%. varshney (2007) administered belladona and cocculus, which appeared to prevent further seizures, but in a few dogs these restarted once the agents were stopped. patterson et al. (2005) tried ketogenic food to control seizures but included only 6 dogs (considerably less than the number that was initially estimated by power calculations). the results from the last two studies were considered controversial. matthews et al. (2012) compared fatty acid supplementation to placebo but no differences in median seizure frequency or severity were detected between the two groups.scorza et al. (2009) reported that the administration of fish oil at 2 g/d to a 2 year old female great dane successfully decreased the frequency of epileptic seizures. however, details on the type of fish oil used or specific concentrations were not reported. in a recent blinded randomised placebo-controlled cross-over trial, law et al. (2015) compared a ketogenic medium-chain tag diet (mctd) with a standardised placebo diet in chronically antiepileptic drug-treated dogs with idiopathic epilepsy and showed that ketogenic diets can have antiepileptic properties translated as reduction in seizure activities.  jambroszyk et al. (2011) investigated verapamil as an adjunct to phenobarbital but even the maximum tolerated dose failed to improve seizure control in dogs. o'brien et al. (1997) investigated nimodipine as an adjunct to phenobarbital or primidone but the results of the study did not support its use.  at this point it is worth mentioning that the international veterinary epilepsy task force (ivetf) recently published a consensus statement (bhatti et al. 2015) for treatment suggestions based mainly on current published evidence as provided and analyzed in this knowledge summary and in the systematic review by charalambous et al. (2014) and it was additionally supported and adjusted by expert's opinions.  implications for the future: generally, several potential sources of bias and limitations were identified in the studies. many of the studies included dogs with poor or unclear diagnostic investigations for idiopathic epilepsy and smallstudy population and, consequently, definite recommendations are precluded. therefore, further brcts are needed mainly for the aeds, such as zonisamide, for which there are no high quality studies to support their favorable efficacy. lastly, further and stronger evidence is vital for imepitoin as a new licensed drug in europe before definite recommendation on its efficacy and tolerability are drawn.  limitation of the summary: the main limitation of this summary is that we could not obtain full access to a few papers included in the summary of evidence. these included: srivastava m. et al. (2013), kis, i. et al. (2012), musteata, m. et al. (2007), patterson. e. et al. (2005), steinberg, m. (2004), cunningham, g. et al. (1983) methodology section search strategy databases searched and dates covered: pubmed and cab abstracts 1973 to 2015 combined search on ovid platform search terms: (dog or dogs or puppy or puppies or canis or canine) and (idiopath*) and (epilep* or seizur* or convuls*) and (treat* or manag* or guideline* or guidance or principle* or recommend*) dates searches performed: 23/11/15   exclusion: summary updates, non-systematic reviews* inclusion: studies evaluating or reporting the treatment, management and diagnosis of canine idiopathic epilepsy  *there was one non-systematic review, packer et al. (2014) that was included because it made important conclusions and valuable up-to-date points for our summary. the same paper was not included in the table though but in the text. the same applies for the ivetf consensus statements by bhatti et al. (2015) and de risio et al. (2015). search outcome         total number of papers retrieved from pubmed and cab abstracts number of duplicates excluded number excluded due to study design number excluded as did not satisfy inclusion criteria total relevant papers 165 96 11 15 43   references bhatti, s. f., et al. (2015) international veterinary epilepsy task force consensus proposal: medical treatment of canine epilepsy in europe. bmc veterinary research, 11:176 http://dx.doi.org/10.1186/s12917-015-0464-z boothe, d. m., dewey, c. and carpenter, d.m. (2012) comparison of phenobarbital with bromide as a first-choice antiepileptic drug for treatment of epilepsy in dogs. journal of the american veterinary medical association, 240 (9), pp. 1073-1083 http://dx.doi.org/10.2460/javma.240.9.1073 charalambous, m., brodbelt, d., & volk, h. a. (2014). treatment in canine epilepsy–a systematic review. bmc veterinary research, 10:257 http://dx.doi.org/10.1186/s12917-014-0257-9 chung, j. y., et al. (2012) zonisamide monotherapy for idiopathic epilepsy in dogs. new zealand veterinary journal, 60 (6), pp. 357-359 http://dx.doi.org/10.1080/00480169.2012.680855 cunningham, j. g., haidukewych, d., jensen, h. a. (1983) therapeutic serum concentrations of primidone and its metabolites, phenobarbital and phenylethylmalonamide in epileptic dogs. journal of the american veterinary medical association, 182(10), pp. 1091-1094 de risio, l., et al. (2015) international veterinary epilepsy task force consensus proposal: diagnostic approach to epilepsy in dogs. bmc veterinary research, 11:148. http://dx.doi.org/10.1186/s12917-015-0462-1 dewey, c. w., et al. (2009) pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with suspected idiopathic epilepsy. journal of the american veterinary medical association, 235 (12), pp. 1442-1449 http://dx.doi.org/10.2460/javma.235.12.1442 dewey c.w. et al. (2004) zonisamide therapy for refractory idiopathic epilepsy in dogs. journal of the american animal hospital association, 40 (4), pp. 285-291 http://dx.doi.org/10.5326/0400285 european medicines agency (2012) cvmp assessment report for pexion (emea/v/c/002543/0000). london: emea fredsø, n. et al. (2014) risk factors for survival in a university hospital population of dogs with epilepsy. journal of veterinary internal medicine 28 (6), pp. 1782-1788 http://dx.doi.org/10.1111/jvim.12443 gaskill, c.l. and kimber, w.j. (2010) comparison of phenobarbital and potassium bromide monotherapies in the treatment of canine epilepsy. journal of veterinary internal medicine, 24 (3), pp. 696 govendir, m., perkins, m. and malik, r. (2005) improving seizure control in dogs with refractory epilepsy using gabapentin as an adjunctive agent. australian veterinary journal, 83 (10) pp. 602-608 http://dx.doi.org/10.1111/j.1751-0813.2005.tb13269.x heynold, y. et al. 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(2005) results of a ketogenic food trial for dogs with idiopathic epilepsy. journal of veterinary internal medicine,19 (3) p. 421 http://dx.doi.org/10.1111/j.1939-1676.2005.tb00640.x pearce, l.k. (1990) potassium bromide as an adjunct to phenobarbital for the management of uncontrolled seizures in dogs. progress in veterinary neurology, 1, pp. 95-101 platt, s.r. et al. (2006) treatment with gabapentin of 11 dogs with refractory idiopathic epilepsy. veterinary record, 159(26), pp. 881-884 http://dx.doi.org/0.1136/vr.159.26.881 podell, m. and fenner, w.r. (1993) bromide therapy in refractory canine idiopathic epilepsy. journal of veterinary internal medicine, 7 (5), pp. 318-327 http://dx.doi.org/10.1111/j.1939-1676.1993.tb01025.x rieck, s., rundfeldt, c. and tipold, a. (2006) anticonvulsant activity and tolerance of elb138 in dogs with epilepsy: a clinical pilot study. veterinary journal, 172 (1), pp. 86-95 http://dx.doi.org/10.1016/j.tvjl.2005.04.003 ruehlmann, d., podell, m., march, p. (2001) treatment of partial seizures and seizure-like activity with felbamate in six dogs.  journal of small animal practice, 42 (8), pp. 403-408 http://dx.doi.org/10.1111/j.1748-5827.2001.tb02490.x rundfeldt, c., tipold, a. and löscher, w. (2015) efficacy, safety, and tolerability of imepitoin in dogs with newly diagnosed epilepsy in a randomized controlled clinical study with long-term follow up. bmc veterinary research, 11: 228 http://dx.doi.org/10.1186/s12917-015-0548-9 schwartz-porsche, d.j.u. (1991) wirksamkeit von bromid bei den therapieresistenten epilepsien des hundes. tierarztliche praxis, 19 (4), pp. 395-401 schwartz-porsche, d., loscher, w. and frey, h.h. 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(2004) levetiracetam therapy for long-term idiopathic epileptic dogs. acvim abstracts. journal of veterinary internal medicine. 18 (3), p 410 tipold, a. et al. (2015) clinical efficacy and safety of imepitoin in comparison with phenobarbital for the control of idiopathic epilepsy in dogs. journal of veterinary pharmacology and therapeutics 38 (2) pp. 160-168  http://dx.doi.org/10.1111/jvp.12151 trepanier, l.a. et al. (1998) therapeutic serum drug concentrations in epileptic dogs treated with potassium bromide alone or in combination with other anticonvulsants: 122 cases (1992-1996). journal of the american veterinary medical association, 213 (10), pp. 1449-1453 varshney, j. p. (2007) clinical management of idiopathic epilepsy in dogs with homeopathic< i> belladonna 200c: a case series. homeopathy, 96 (1), pp. 46-48 http://dx.doi.org/10.1016/j.homp.2006.09.002 volk, h.a. et al. (2008) the efficacy and tolerability of levetiracetam in pharmacoresistant epileptic dogs. veterinary journal, 2008, 176 (3), pp. 310-319 http://dx.doi.org/10.1016/j.tvjl.2007.03.002 von klopmann, t., rambeck, b. and tipold, a. (2007) prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs. journal of small animal practice, 48 (3), pp. 134-138 http://dx.doi.org/10.1111/j.1748-5827.2006.00290. intellectual property rights authors of knowledge summaries submitted to rcvs knowledge for publication will retain copyright in their work, but will be required to grant to rcvs knowledge an exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. authors will be required to complete a licence for publication form, and will in return retain certain rights as detailed on the form. impacts of schmallenberg virus infection in early lambing sheep flocks following the second wave of virus circulation in south west england in 2012/2013: a mixed-methods descriptive study | veterinary evidence skip to main content article keywords: schmallenberg virus; mixed-methods; impacts; early lambing; malformations; welfare; reproductive performance impacts of schmallenberg virus infection in early lambing sheep flocks following the second wave of virus circulation in south west england in 2012/2013: a mixed-methods descriptive study mike j. glover, ba vetmb certshp frcvs1* neil blake, bvsc (hons) mrcvs1 clare j phythian, bsc(hons) bvsc certavp dipecsrhm dipecawbm(wel) phd mrcvs2, 3 1 torch farm and equine ltd, horsepond meadow, south molton, devon, ex36 4ej, uk 2 university of bristol, bristol veterinary school, langford bs4 4du, uk 3 norwegian university of life sciences, faculty of veterinary medicine, institute for production animal clinical sciences, small ruminant research and herd health, 4325 sandnes, norway * corresponding author email: mikeglover@torchfarmvets.com vol 8, issue 1 (2023) submitted 11 mar 2022; published: 08 feb 2023 doi: https://doi.org/10.18849/ve.v8i1.604 abstract background the first cases of schmallenberg virus (sbv) infection in the uk were confirmed in congenitally malformed lambs born in south east england in january 2012. epidemiological studies confirmed that sbv infection could have severe negative impacts on animal welfare and productivity in affected flocks of sheep (ovis aries), but there was a lack of specific research on the impacts of infection on recorded reproductive performance, animal welfare, financial performance, and farmers’ emotional well-being in some of the first affected early lambing flocks in south west england in 2012 / 2013. objectives this veterinary practice-based study aimed to describe the clinical signs observed by sheep farmers in the region experiencing outbreaks of disease due to sbv for the first time; to evaluate physical records (quantitative data) on reproductive performance in early lambing flocks prior to and during the affected 2012 / 2013 production year; and to gauge farmers’ perceptions (qualitative interview data and quantitative severity scores) of the impacts of sbv infection on animal welfare, financial performance, and their emotional well-being, and risks of future outbreaks of disease and preventive strategies including sbv vaccination. evidentiary value this mixed-methods descriptive study reported farmers’ detailed experiences, and recorded and perceived impacts, of sbv infection in six pedigree and purebred flocks in south west england, lambing early between november 2012 and january 2013. previous surveys were larger than the current study and assessed the impacts of sbv at farm rather than flock level and on a more diverse range of british sheep farms lambing over extended periods; impacts were compared between three categories of farms based on laboratory confirmation or farmers’ suspicions of infection i.e. ‘sbv confirmed’, ‘sbv suspected’ and ‘sbv not suspected’. this study was able to capture and compare the reproductive performance of these flocks in the sbv affected production year in 2012 / 2013 with up to three previous unaffected years; it found variable negative effects of sbv not only on ewe and lambs losses, stillbirths and abortions, levels of dystocia and need for variable levels of assistance to deliver lambs, but also on overall flock reproductive performance, barren rate, lambing percentage and lamb rearing percentage. the qualitative elements of the study enabled new insights into the variable effects of sbv infection in flocks on ewes and lambs and on farmers’ perceptions of the impacts on animal welfare, flock financial performance and their own emotional well-being. the findings suggest previous surveys may not have fully captured the impacts of sbv infection in high value pedigree and purebred early lambing flocks infected for the first time during the second wave of virus circulation and peak midge vector activity in the southwest region in summer and autumn 2012. the findings highlight the need for further research to explore factors influencing uptake of sbv vaccination by farmers to protect flocks against future waves of infection, and to develop more rational vaccination programmes based on ‘early warning’ surveillance systems. methods face-to-face semi-structured interviews were conducted in 2013. qualitative interview data were thematically analysed to gain an understanding of the perspectives, perceptions and lived experiences of sheep farmers. quantitative data in the form of (i) farmers’ self-appraised severity scores of the perceived impacts on flock welfare, financial performance and their emotional well-being; and (ii) flock records of pregnancy scanning results, lambing dates, and mortality records for ewes and lambs, were collected for the sbv affected 2012/2013 production year and for up to 3 previous years for comparison. results farmers perceived generally high but widely variable negative impacts of sbv infection on animal welfare (median score: 3.5/5, range: 2–5), financial performance (median score: 3.5/5, range: 2–5) and their own well-being (median score: 4/5, range: 2–5); variation between farmers in the severity of impacts appeared not to be directly related to recorded lamb losses (of all lambs born, an overall average of 21% (range: 13.7–42.6%) were stillborn or died within 7 days; 15% (range: 4.1–42.6%) were stillborn or died due to sbv), or to reductions in lamb rearing percentage (10–37% fewer lambs reared in the affected year compared to previous reproductive performance or an industry benchmark). the qualitative elements of the study enabled new insights into the variable effects of sbv infection in flocks on ewes and lambs and on farmers’ perceptions of the impacts on animal welfare, flock financial performance and their own emotional well-being. the semi-structure interviews captured narrative descriptions of the distressing clinical signs seen in ewes and lambs, the variable levels of dystocia, and the lived experiences of farmers caring for affected sheep including the increased workload during the lambing period, greater feelings of tiredness and anxiety than in ‘normal’ lambing periods, depression, and also more positive emotions of resilience and ability to cope with an unexpected and novel disease outbreak. three of the six farmers subsequently vaccinated with sbv vaccine to protect their early lambing flocks before the next early breeding season. of the three farmers who decided not to vaccinate: one delayed the start of the subsequent breeding season; the second felt uncertain about using the rapidly developed and authorised vaccine so close to the start of the breeding season but was reassured by veterinary advice that the risk of a further disease outbreak in the subsequent breeding season was low as flock sbv seroprevalence was high (~90% of ewe were seropositive) following the first outbreak; and the third experienced the lowest sheep losses of the six farmers in the first outbreak and perceived the severity of the impacts to be at the lowest level, but felt uncertain about the risks of repeat infections and future disease outbreaks. conclusion severity of farmer perceived impacts of sbv infection was generally high; farmers’ detailed descriptions of their experiences during the outbreak, and perceptions of the impacts on ewe and lamb welfare, financial performance and their emotional well-being, captured during semi-structured interviews, are reported for the first time. variation in severity of impacts appeared not to be directly related to the number and proportion of lambs stillborn or that died in the first week of life and the overall reduction in percentage of lambs reared for sale. qualitative interview data taken together with quantitative data on recorded flock performance suggested multiple factors and variable effects of sbv in flocks were likely to have contributed to, and variably influenced, the severity of impacts perceived by farmers. uncertainty about the safety, efficacy and use of the vaccine so close to the next early breeding season when it was first authorised in may 2013, and the risks of repeat sbv infections and future disease outbreaks for farmers who decided not to vaccinate their flocks may have added to the impact on farmers’ emotional well-being. reductions in lamb rearing percentage appeared to be higher in flocks that artificially inseminated ewes in synchronised oestrus in july 2012 than in those that mated ewes naturally in spontaneous oestrus in june 2012. these findings are important and suggest that recorded lamb losses and reduction in rearing percentage should not be used as proxy measures of the severity of impacts of sbv infection on farmers and sheep flocks. further outbreaks have occurred in the uk in 2016/2017 and 2021/2022 and it is expected this pattern of virus circulation and disease re-emergence will be repeated every 3–6 years. flocks remain at-risk of future sbv infection and, in high risk flocks, of severe impacts on animal health and welfare, flock financial performance and farmers’ emotional well-being. further research is needed to explore farmers’ future risk perceptions, uncertainty and decision-making around preventive vaccination, and to explore the potential for more rational vaccination programmes based on active arbovirus (sbv and bluetongue virus [btv]) surveillance systems. application these findings will be of interest to all stakeholders in the sheep industry e.g. farmers, veterinarians, advisers, researchers, welfare organisations, pharmaceutical companies, the uk government, industry levy boards and other research funding bodies. the study offers new insights into the impacts of sbv infection in sheep flocks, particularly in production systems dependent upon early breeding (so called ‘out of season breeding’) overlapping with periods of peak midge activity and circulation of sbv in which risks of high impacts appear to be greater. other studies are needed to investigate further possible associations between variability in reproductive outcomes and factors such as breed (not reported here) and timing and method of breeding (natural mating or artificial insemination; at a spontaneous or synchronised oestrus). research is needed to better understand farmers’ decision-making around sbv vaccination and to investigate the potential for more rational vaccination programmes based on early warning systems, such as national or europe-wide arbovirus surveillance systems. introduction in october 2011, schmallenberg virus (sbv), a novel orthobunyavirus, was identified as the cause of a mild acute infection in cattle that had emerged in summer and autumn 2011 in the border region between germany (north rhine-westphalia), the netherlands and belgium; clinical signs included reduced milk production, fever and diarrhoea (hoffmann et al., 2012). in november 2012, sbv infection of pregnant ruminants was associated with abortions, stillbirths and the birth of offspring with congenital malformations (gibbens, 2012; herder, wohlsein, peters, hansmann, & baumgärtner, 2012; lievaart-peterson, luttikholt, van den brom, & vellema, 2012). investigations identified that acute sbv infection in naïve ewes can go unnoticed, but may result in early embryonic death, repeat mating and increased proportion of barren ewes; whilst infection of the foetus at a critical stage of pregnancy (days 30–50 in sheep (parsonson, della-porta, & snowdon, 1977)) can cause abortions, stillbirths and a range of congenital malformations in newborn lambs known as the arthrogryposis and hydrancephaly syndrome (ahs) (afonso et al., 2014; anonymous, 2012a; lievaart-peterson et al., 2012). the spread of sbv throughout europe has been well documented (afonso et al., 2014; efsa, 2014). the first reports of sbv infection in lambs with congenital malformations were reported in the netherlands in late november 2011 (van den brom et al., 2012 cited by lievaart-peterson et al., 2012), in belgium in december 2011 (martinelle, dal pozzo, gauthier, kirschvink, & saegerman, 2014), and in france (dominguez et al., 2012) and the uk in january 2012 (anonymous, 2012b). however, with surveillance studies focused on identifying the spread of sbv, there was a lack of data on within-flock impacts of the first outbreaks of infection (afonso et al., 2014; efsa, 2014). despite a lack of data, in summer 2012 the uk government described schmallenberg as a ‘low impact disease’ (simmons, 2012a). this assessment did not fit well with our veterinary experience of outbreaks in early lambing flocks in south west england in november and december 2012 (m. glover & blake, 2012). subsequently, the uk government acknowledged that within-flock impacts had been variable and were likely to be higher in early lambing flocks (simmons, 2012b). this assessment was later supported by national impact studies carried out in the uk (harris et al., 2014; stokes et al., 2018), and elsewhere in northern europe (dominguez et al., 2012; luttikholt et al., 2014; saegerman, martinelle, dal pozzo, & kirschvink, 2014). this study aimed to add to research on within-flock impacts of sbv infection by: firstly, quantitatively describing the impacts perceived by farmers of the first outbreaks of sbv on reproductive performance and production outcomes in early lambing flocks in south west england; secondly, qualitatively describing perceptions and experiences of the physical signs of sbv that farmers observed at lambing time, and impacts on flock welfare, production and financial performance, and on farmers’ emotional well-being (reported previously by c. j. phythian and glover (2019)); thirdly, quantitatively evaluating the farmer perceived severity of those impacts using a simple scoring system; and finally, describing farmers’ perceptions of the risk of future outbreaks of sbv disease and preventive strategies including sbv vaccination. methods & materials study design farmers of seven small pedigree and purebred early lambing sheep flocks in south west england (counties of devon, cornwall and somerset), with clinically confirmed cases of sbv infection in ahs affected lambs, who had previously participated in a serological sbv survey (mike glover & blake, 2013), and who we expected had maintained detailed lambing records, were invited to participate in the current study through contact with torch farm and equine ltd, a veterinary practice based in north devon. serological sampling in may and early june 2013 had identified that a substantial proportion of ewes (86.7%, range: 34.9–93.6%) in these flocks had been exposed to sbv infection in the second wave of virus circulation in the uk in summer 2012 and had seroconverted (mike glover & blake, 2013). they were considered to be amongst the first flocks in south west england to be affected by sbv infection. the small size of the flocks, nature of early lambing to achieve high prices for slaughter lambs and breeding stock, and loss of valuable pedigree breeding animals were of particular interest in understanding the perceived and recorded impacts of the first outbreaks of infection on these farms. a mixed-methods approach was used to gain new insights into farmers’ observations and perceived impacts of sbv infection. each farmer was invited to participate in a semi-structured face-to-face interview conducted at a time and a location of their choice. participation was voluntary; one of the seven farmers declined the invitation to be interviewed, not wishing to relive the experience. prior to undertaking the study, interview questions were pilot tested on one commercial sheep farmer to ensure interviews would take approximately 30 minutes. interviews were conducted during august to october 2013. before each interview, informed, written consent of participants was obtained. the study was approved by the university of bristol, faculty of medical and veterinary science research ethics committee (number 3283). data collection data were collected on participant demographics: farm type, and flock size, purpose and breed. farmers were asked the same series of open questions (see supplementary material s1 – interview questioning guide) to capture new insights (qualitative data) on their experiences of sbv infection, including what they had witnessed in their flocks during the early lambing period between november 2012 and january 2013; and what changes they had made following their first experiences of sbv infection including; had they changed the timing of their breeding season, and had they vaccinated all or part of their early lambing flocks, or considered vaccination, to prevent future outbreaks of sbv. all six interviews took place around the farmhouse kitchen table. interviews were conducted by a veterinary researcher (cjp) who was unfamiliar to the participants and had designed the interviews to capture useful data, and ensured the conversation avoided diverging into a veterinary clinical or advisory discussion (gill, stewart, treasure, & chadwick, 2008). a familiar veterinarian (mjg) was present to put respondents at ease, build confidence and rapport around discussing potentially sensitive topics with an unfamiliar visitor (cjp). at the end of the interview, each farmer was asked to score (quantitative data) the severity of perceived negative impacts on flock welfare, financial performance and their emotional well-being on a scale of 1 to 5 (1 = no impact, 5 = high impact) using the approach of harris et al. (2014). quantitative data on flock reproductive outcomes, based on farmer-maintained records, were collected at the end of the visit and during follow-up contact with the farmers, in order to evaluate flock reproductive performance and key production outcomes. flock data on the 2012/2013 early lambing production year, and where available for up to 3 years prior, were collected to ascertain; breeding and lambing start and end dates, ewe to ram ratio, number of ewes mated, number of barren ewes, number of lambs born alive and stillborn, number of ewes and lambs clinically affected by sbv, number of assisted lambings including embryotomies and caesarean sections, recorded ewe and lamb mortality rates, and rearing percentage (number of lambs reared relative to the numbers of ewes mated in the early lambing flock in 2012 expressed as a percentage). data analysis qualitative (interview) data were captured as individual digital voice recordings. recordings were transcribed verbatim. transcription responses were double-checked against the voice recording for consistency before responses were examined using a thematic analysis approach (braun & clarke, 2006). farmer responses were examined and manually coded by one researcher (cjp) to identify broad themes. coding was later checked by a second researcher (mjg). where any discrepancy was identified, the descriptions were reviewed and a consensus reached. farm records were descriptively analysed by a second researcher (mjg) to calculate key reproductive and production outcomes, including scanning percentage, rearing percentage, ewe and lamb overall mortality and mortality attributed to sbv infection. the approach of barrett, o'neill, sammin, clegg, and more (2015) was applied to calculate a rearing factor, the ratio of rearing percentage for 2012/2013 to the baseline rearing percentage for each flock. the baseline used for comparison was either a flock-specific average based on retrospective farm data prior to the 2012 / 2013 production year; or, if retrospective data were lacking, on an industry benchmarking figure for early lambing flocks (eblex, 2009). results all six participants were of white british ethnicity, three male and three female, aged between 30–60 years. the numbers of ewes mated on these farms in the 2012 / 2013 early breeding season varied from 27–320 as previously described (c. j. phythian & glover, 2019). study farms reared pedigree or purebred sheep breeds including charollais and polled dorset. to maintain anonymity, flock location and breed are not presented. recorded impacts on reproductive performance (quantitative element) key flock performance indicators and impacts of sbv infection on the 2012 / 2013 early lambing production year are presented in tables 1 and 2. compared to previous years, recorded barren ewe rates were higher in three flocks (a, b and f) and lower in one (e), lamb losses from pregnancy scanning to sale were higher in three flocks (b, e and f), and lamb rearing percentages were lower in five flocks (a, b, and d–f). two farmers (a and e) attributed higher ewe mortality rates around lambing to sbv. five farmers (a–d and e) reported that higher levels of lambing assistance were required to deliver sbv affected lambs; these observations were supported by farm records for four flocks (a, b, d and e). of all lambs born, an overall average of 21.2% (207/975; range: 13.7–42.6%) were either stillborn or died within a week of birth and 15.0% (146/975; range: 4.1–42.6%) were born dead or died due to sbv infection. rearing percentage was calculated for the 2012/2013 production year for five (a, b, and d–f) of the six flocks in which the relevant data had been recorded by farmers (see table 1). in comparison with baseline figures for earlier years, or an industry benchmark (eblex, 2009), rearing percentages were reduced in flocks b and d (by a factor of 0.91 and 0.88 respectively) and severely reduced in flocks a, e, and f (by a factor of 0.63). details of the breeding management used and reductions in rearing percentage are presented in table 1: rearing percentages in flocks b and d, where ewes were naturally mated to lamb in november, were reduced by ~10% compared to baseline figures; whereas, in flocks a, e, and f, where ewes were inseminated at a synchronised oestrus to lamb in december, rearing percentages were reduced by 37%. lack of recorded data for flock c prevented calculation of a rearing percentage. clinical signs of sbv infection (qualitative element) the main themes regarding the clinical signs of sbv infection reported by farmers in ewes and lambs were (i) lack of premonitory signs in pregnant ewes until around lambing, (ii) higher than normal levels of dystocia, protracted births and need for lambing assistance to deliver congenitally malformed lambs, and (iii) the high prevalence and severity of congenital deformities in lambs. individual quotes were selected to illustrate these broad themes, as presented below. lack of premonitory signs all participants reported an absence of premonitory signs of sbv infection in ewes from early to late stages of pregnancy: ‘i wouldn't have said anything was wrong with them. they were scanned normal. once we'd gone through scanning we didn’t even think of schmallenberg again.’ (farmer e). signs of infection were only apparent at the time of lambing as farmer c recalled: ‘i was the only one lambing the sheep. it was completely different. no signs whatsoever, you'd have a good one then a bad one. you can tell soon as you put your hand in and you get that back, you know something is not right’. retrospective analysis of farm records indicated that two flocks (c and f) had experienced repeat breeding during the 2012 early breeding season and three flocks (a, b, and f) had a considerably higher proportion of barren ewes (table 1) than in previous lambing seasons. a large proportion of ewes mated (n = 128, 47%) were barren at lambing in flock c, but no baseline figure could be calculated for comparison (table 1). in hindsight, two farmers (b and d) reported that ewes appeared to have been particularly affected by biting midges in the late summer of 2012, but recalled no apparent premonitory physical signs of sbv infection in ewes. dystocia and protracted lambings all but one farmer (f) recalled difficult or protracted lambings and the need for an unusually high degree of lambing assistance: ‘i think we lambed nearly everything. probably three of four of them we didn't lamb. most of them had something going on. normally we lamb, half a dozen at most. we wouldn't normally lamb many at all.’ (farmer e). farmers elected to give earlier assistance at lambing with increasing awareness of the issues: ‘i did pull out more than i normally did. suppose, perhaps i started going in more than i would normally, once i knew what was going on.’ (farmer c). rarely were malformed lambs born without assistance: ‘you had to try to get, well all of them out. there was some that you'd come down and there was a couple of deformed lambs born, which lambed themselves. ninety percent of affected ewes had to be lambed.’ (farmer d). a consistent feature reported by farmers was the observation that the birthing process took longer than normal: ‘they would quite take [sic.] a long time to lamb, they would probably take up to 24 hours to lamb, to get something presented correctly.’ (farmer e). the extent of dystocia, and their first experience of lambing ewes giving birth to malformed lambs, took farmers by surprise and gave cause for some self-doubt: ‘i mean the first ewe i lambed, i didn't realise what was happening and i thought what's wrong with me, i can't get this leg forward, i cannot and […] i'm usually not that bad i can get that leg forward but i thought what's wrong with me, and when it came out i knew it looked like something was wrong[...] that's my experience of it.’ (farmer d). almost all farmers dealt with dystocia cases by themselves. three farmers (b, c, and e) reported undertaking embryotomies and one (e) initially required veterinary assistance to manage cases of dystocia and deliver malformed lambs, including carrying out a caesarean section. farmer e later became reluctant to seek veterinary support as farm staff became familiar with the abnormal presentations of malformed lambs, and after experiencing poor outcomes even when dystocia cases received veterinary assistance: ‘we had the vet[...] probably say six[…] or seven times, can't remember now[…] we had one caesarean. had one we cut up, which was a disaster, ‘cause everything died then. we only lost one ewe[…] that was during one of these embryotomies[…] we'd leave them a fair while, once we knew what we were dealing with because one we didn't want vets visits, and we were trying to just see if we can deal with it ourselves.’ (farmer e). congenital deformities farmers described a range of severe congenital physical, behavioural and neurological abnormalities in newborn lambs; particularly striking features were spinal deviations (torticollis, kyphosis and scoliosis). ‘you'd occasionally put your hand around a jaw to pull it around and it, yeah, it was not pleasant. some of the worst ones had very, very roached backs[…] really arched so you were struggling to move them around. the necks were the things that were quite prominent. i would say about half of them had funny necks, and nearly all of them had odd limbs. i think virtually all of them had twisted or deformed legs in some way.’ (farmer e). commonly reported signs in sbv affected lambs, observed by at least five of the six farmers, were: arthrogryposis, torticollis, brachygnathia, deformed skulls and stillbirths (figure 1); less commonly reported, by three or fewer farmers, were kyphosis/scoliosis, and neurological signs including blindness, seizures and ‘dummy’ lambs; see figure 2a and 2b, and video clips of neurological signs shown by two liveborn sbv-affected lambs in flock d provided as supplementary material (clip 1 – liveborn schmallenberg affected lamb with seizures; clip 2 – liveborn schmallenberg affected blind ‘dummy’ lamb). figure 1. number of flocks (n = 6) reporting specific clinical signs associated with congenital sbv infection in lambs born during the early lambing season from november 2012 to january 2013   figure 2a. lamb with congenital malformations: arthrogryposis, kyphosis, skeletal muscle hypoplasia and brachygnathia   figure 2b. hypoplasia of the central nervous system: hydrancephaly   a wide variety of malformations and abnormalities were observed: ‘[we] had a whole range, screwed up, mummified ones, then big lambs lying there and didn't stand up. some had their necks bent around, some were just first, funny jaws and, they were like little aliens really. some were really big, some really small. they were all different. i had one that really sticks in [my] mind, i don't know if he was blind, but he went around the pen shouting and wouldn't suck.’ (farmer c). many of the affected lambs were born alive but with apparent reduced cognitive ability: ‘we had one or two that were erm, their brain didn't seem to be three-quarters there and we used to have to work quite hard to let them suck. we had half a dozen like that, not many. it was like we had some totally deformed ones, laying right back and around, totally still. a small percent were nearly there but not quite[...] there were a few born dead but i would say about three-quarters of them were born alive.’ (farmer d). however, not all lambs from the same litter were physically affected, which surprised even some of the most experienced shepherds: ‘very often the first lamb would be born fine, and then there'd be a longer than normal time before they tried to get settled and you know then that there's something happening don't you? then you'd erm, obviously examine the ewe and you'd find that the second lamb more often than not would be there, with legs all wrong, leg back. my dad couldn't believe when he came, he couldn't believe one could be born alright and the other could be born so wrong.’ (farmer d). farmers were not unfamiliar with the occasional birth of lambs with congenital malformations in previous years, but what struck them most was the intensity and regularity with which malformed lambs were born: ‘we weren't losing lamb after lamb[…] but we had deformed lambs every single day.’ (farmer b). perceived impact on flock welfare (qualitative element) the main themes identified regarding farmers’ concerns and perceptions for flock welfare, were; (i) the severe impact of dystocia and physical trauma, damage and death of ewes associated with the birth of malformed lambs and their own interventions in these cases, and (ii) the impact of congenital malformations and neurological deficits on the viability of lambs at birth and ability to survive the neonatal period. impact of dystocia on the welfare of ewes ewes in five of the six flocks (not on farm a) required varying levels of farmer and veterinary assistance to deliver malformed lambs leading to concerns about both short-term effects on ewe health and welfare, and long-term effects on future productivity: ‘it was traumatic, probably, ‘cause the lambings were so difficult. it will be interesting what the scanning comes out [with] this time, if it's affected them in the future. a lot of them were battered and bruised so it has got to have affected them the welfare side of it [sic.].’ (farmer e). ‘i did pull out more than i normally did. suppose, perhaps i started going in more than i would normally, once i knew what was going on. i got them all surprisingly easy, once i knew. some of the big ones they just fell apart.’ (farmer c). farmers were in a dilemma as to how best to deliver malformed lambs without causing unnecessary pain or suffering to ewes. ‘i just wanted to get lambs away without too much stress to the ewe, which was not easy. you can't draw the legs out [if] they are all twisted back.’ (farmer a). the higher level of dystocia resulted in an unusually high ewe mortality rate in two flocks (a and e): ‘you wouldn't lose that many sheep during the normal lambing process would you, not before they've lambed.’ (farmer a). impact of congenital malformations and neurological deficits on the welfare of lambs farmers evaluated the welfare of affected liveborn lambs weighing-up their ability to survive. severely affected liveborn lambs were euthanised on farm or at local hunt kennels. other farms had to deal with a higher than usual number of stillborn lambs: ‘[…] we had to put down some ‘cause they couldn't suck or survive or even get up. there would be more, the majority, that[…] had to be put down. nothing was ever similar. they were all completely different. [the…] only thing that compared to that [sbv] was abortion, but not in the later ones [the later lambing flock].’ (farmer c). affected liveborn lambs needed more care than expected: ‘we had one or two that were erm, their brain didn't seem to be three-quarters there and we used to have to work quite hard to let them suck. we had half a dozen like that, not many, but we tried to rear them all. a small percent were nearly there but not quite. most of the lambs were born alive, there were a few born dead but i would say about three-quarters of them were born alive.’ (farmer d). other farmers had less success and expressed disappointment that lambs died despite their best efforts to avoid euthanasia: ‘a couple [of lambs] never stood up, there was one single that we kept in the shed and he was fine as long as nothing disturbed him, and i let the ewe out into the main part of the shed and the lamb was totally lost and he, he didn't suck again and he just died.’ (farmer b). perceived financial impact (qualitative element) three main themes were identified regarding the perceived financial losses: (i) reduction in lamb sales compared to previous years; (ii) loss of genetic material; and (iii) higher rearing costs than in previous years. farmers in the study perceived the reduction in lamb sales to be approximately £100/lamb lost based on the value of lambs destined for slaughter: ‘it was horrific. for the sheep it would be as somewhere, if i was selling those fat, those 20 [lambs] that died, it would be £2000[…]’ (farmer e). ‘we lost 75 lambs – that's what we make isn't it, £7500.’ (farmer d). however, these pedigree and purebred sheep farmers also felt they had lost valuable genetic material, built up over many years, in breeding stock and potential ewe replacements that died due to sbv: ‘[...] but some of those would be breeding stock[…], so somewhere near £5000 [sic.] [in lost profit] and some of those would be ewe replacements, difficult to put a figure on those – part of a generation that we are going to miss.’ (farmer e). ‘the three ewes that i lost[…] it's not so much of the financial is it? it's the breeding[...]’ (farmer a). veterinary and medicine costs outweighed potential profits in 2012/2013: ‘probably spent £1500 on vet visits and drugs because we were giving a lot of drugs to make them live.’ (farmer e). whereas, feed costs were of more concern for others: ‘my costs of living lambs isn’t going to cover the costs for keeping lambs. not going to cover the feed bill. fat lambs[…] 70% less than normal. it's quite frightening really.’ (farmer c). workload and resources needed during lambing were increased but profits were reduced: ‘since we lost 24 [ewes] that year and not all because of the disease you still have to do the same amount of work to rear fewer lambs and employ the same staff.’ (farmer b). perceived impacts on farmers’ emotional well-being (qualitative element) results of thematic analysis of the qualitative interview data on perceived impacts on farmers’ emotional well-being have been reported in detail previously (c. j. phythian & glover, 2019). briefly, three themes emerged from the interviews: (i) emotional highs and lows are part of a normal lambing season, e.g. ‘when things are going great, there’s no better thing to be doing than lambing really’ (farmer b), and ‘to me that’s breeding, that’s what we do, they live or they don’t live[…]’ (farmer c); (ii) negative emotions and memories associated with the first outbreaks of this novel disease, e.g. ‘i was just upset, just upset about the losses isn’t it[…] any losses are, you know[...] especially when it’s the ewes. i think lambs[...] you lose lambs don’t you, but when it comes to the ewes you kind of feel a bit more touched.’ (farmer a); ‘i think i just remember feeling a little bit more stressed than normal. that’s how it works when you’re under a little bit of pressure, i mean normally you cope with things better at that time.’ (farmer d); and ‘it affects your mental health. it was difficult, you didn’t want to, you just knew you had to go outside again. it was very depressing at the end, cause you know every time, virtually, you would have a problem.’ (farmer e); and (iii) resilience and coping with these unexpected disease outbreaks, e.g. ‘i was just thinking it’s not in my children, thank goodness it’s not in my children.’ (farmer c), and ‘speaking to friends and neighbours they had something much worse than we had.’ (farmer b). severity of farmer-perceived impacts on flock welfare, financial performance, and farmers’ emotional well-being (quantitative element) farmer-perceived impacts are presented as self-appraised categorical severity scores in figure 3. all farmers perceived negative impacts on flock welfare, financial performance, and their own well-being. overall severity was generally high, although self-appraised scores varied widely between farmers: for the impact of sbv on animal welfare the median severity score was 3.5/5 (range: 2–5); on financial performance the median score was 3.5/5 (range: 2–5); and on farmers emotional well-being the median score was 4/5 (range: 2–5). farmers c and e, with the highest overall self-appraised severity scores, recorded the highest neonatal lamb losses (29.8% and 42.6% of all lambs born, respectively) due to sbv; whereas farmer b, with the lowest overall severity scores (level 2), recorded the lowest neonatal lamb losses (4.1% of all lambs born). farmers c, d, and e perceived the impact of sbv infection on flock welfare to be at the two highest levels (scores ≥4); flocks d and e (not recorded for flock c) had recorded a high proportion of ewes delivering sbv affected lambs and requiring assistance to give birth, and all three flocks (d, e and c) had recorded high proportions of lambs stillborn or dead due to sbv during the first week of life. figure 3. farmers’ self-appraised severity scores of the negative impact of schmallenberg virus on flock welfare, financial performance, and their emotional well-being (rated from 1 = no impact; to 5 = high impact (harris et al., 2014) by sbv lamb losses and rearing percentage reduction factor (nr = not recorded) in six pedigree or purebred flocks (labelled a to f) during the 2012/2013 early lambing season   severity of farmer perceived impacts on financial performance varied widely, even between farmers experiencing similar lamb losses due to sbv. for example, farmer f, who recorded losing 16.7% (7/42) of all lambs born due to sbv during the first week of life and losing 35.3% (18/51) of lambs between scanning and sale (tables 1 and 2), perceived the severity of the impact on financial performance to be at the lowest level (score 2) despite an overall reduction in percentage of lambs reared by a factor of 0.63 in 2012–13 (table 1); whereas, farmer a, with a similar level 12.5% (5/40) of recorded newborn lamb losses due to sbv , and the same reduction in percentage of lambs reared, perceived the financial impact to be high (score 4). in addition to similar lamb losses and reductions in lamb rearing percentage as flock f, flock a also lost three ewes at lambing due to sbv, 9.1% (3/33) of those mated, which flock f did not. there were two relative extremes in self-appraised severity scores for farmer-perceived impacts on emotional well-being ranging from the lowest level (score 2) of farmers a and b, to the two highest levels (score ≥4) of the four farmers, c–f. farmer b had experienced the lowest lamb losses of the six farmers and a low proportion of ewe losses due to sbv, no ewes required assistance to deliver malformed lambs, and perceived the negative impacts on animal welfare and flock financial performance to be at the lowest level (score 2); whereas farmers c–f had experienced higher lamb losses, and variable other effects of sbv e.g. on ewe mortality, dystocia and proportion of ewes requiring assistance to deliver malformed lambs (up to 92% of ewes [23/25] in flock e). perceived future risks of sbv infection and changes made to prevent future disease (qualitative element) farmers had weighed up the risk of repeat infection with sbv during subsequent pregnancies either independently or in consultation with their local veterinarian; and with the benefit of information on levels of flock immunity based on blood test results and flock sbv seroprevalence (mike glover & blake, 2013) following the first outbreaks of disease in these flocks, considered possible changes to the management of their flocks and deployment of sbv vaccine to help reduce risks of future outbreaks. three themes emerged during the interviews: (i) decision to continue sheep farming, (ii) commitment to the current breeding system and considerations around delaying the timing of the breeding season to avoid the critical period of pregnancy for congenital malformations coinciding with the peak of midge vector season in summer and early autumn, and (iii) use of flock sbv vaccination to prevent future disease outbreaks. decision to continue sheep farming all six farmers had decided to continue sheep farming despite their experiences during the first outbreaks of sbv infection, although one farmer suggested this decision would be reconsidered if repeat outbreaks of disease occurred in future: ‘it affected me a little bit, but not, not so bad, if it [sbv] was going to happen every year, i wouldn't do it [breed sheep] again.’ (farmer c). committed to the breeding system all six farmers were committed to breeding and lambing their pedigree and purebred flocks early to produce lambs in november and december to allow lambs time to be sufficiently well grown for the breeding stock sales (of ram and ewe lambs) in the summer and early autumn following birth, or for sale as ‘finished’ slaughter lambs when they would be most likely to achieve high prices: ‘kind of committed to the system now, you can't change the whole system just for one blip.’ (farmer c). ‘we haven't made any changes at all. we've carried on as normal. when i want to sell ram lambs, i want to sell around 8 to 9 months old so i have to lamb that time [early december].’ (farmer e). ‘no [we haven’t made any changes since that experience of sbv], we still lamb at the same time [november] and we didn’t vaccinate last year [prior to 2013 early breeding season].’ (farmer b). changing the timing of the breeding season farmers were aware that the first outbreaks of disease due to sbv in the uk had occurred in early lambing flocks; later (spring) lambing flocks had been largely unaffected, indeed five of the six farmers (not e) not only had an sbv affected early lambing flock but also had an unaffected spring lambing flock. it was understood that in the absence of a safe and effective sbv vaccine an option to reduce the risks of future disease outbreaks was to delay the start of the breeding season so as to avoid the peak midge-vector season and exposure of ewes to sbv infection coinciding with the critical stage of pregnancy in ewes (anonymous, 2013). one farmer (a), decided to delay the start of the subsequent breeding season for the early lambing flock by 1 month, rather than vaccinate: ‘no, i didn’t alter my decision [about vaccination] when i saw the blood results [around a quarter of ewes in the early lambing flock, and half of the yearling replacement ewes, were seropositive for sbv…] i had already decided to lamb 1 month later.’ use of flock sbv vaccination to prevent future disease outbreaks there had been an awareness of the rapid development, authorisation and introduction to the market of a sbv vaccine in may 2013, a short time before the subsequent early breeding season, offering farmers an immunological option to control sbv infection and prevent disease: ‘you have got the opportunity to vaccinate, and that is your choice, it’s not as if we are without vaccine, which is a plus because it was brought in on pretty fast speed [sic.]... you have the choice.’ (farmer b). three of the six farmers (c, d and f) had decided to vaccinate ewes and replacement females in their early lambing flocks: ‘we vaccinated the following year [prior to the 2013 early breeding season], that was the major thing [we changed after the experience of sbv].’ (farmer d). farmer c had vaccinated the early lambing flock but decided not to vaccinate the spring lambing flock, appearing to highlight the possibly one-off nature of the first outbreak and perceived lower risk of severe impacts in later lambing flocks: ‘i vaccinated the first ones [early lambing flock] i suppose, but i haven't bothered with the later flock.’ farmers who decided to vaccinate, vaccinated their breeding ewes but not their rams, most likely following advice from their veterinarian and the manufacturer that the safety and efficacy of the sbv vaccine had not been established in breeding males; one farmer had not considered vaccinating rams: ‘we just vaccinated the ewes, we didn't even think about doing the rams.’ (farmer f). three farmers (a, b, and e) decided not to vaccinate their flocks. farmer e had concerns about using the new vaccine so close to the start of the subsequent breeding season and the possibility of adverse effects on the outcome of an artificial insemination (ai) programme. this farmer had been somewhat reassured by veterinary advice, and the results of serological testing following the first outbreak indicating a high level of flock immunity, that there was a low risk of repeat infection during the subsequent pregnancy (mean flock sbv seroprevalence had been ~87%) (mike glover & blake, 2013): ‘we discussed it with the vet, it [sbv serological testing] indicated that we'd had it quite severely. he [the vet] said if the vaccine doesn't come in time the risks, hopefully, are minimal. when the vaccine came out it was quite close to our ai date. when they were saying 3 weeks, some saying do it up to 4 weeks before [breeding], i said i'm not even going to take the risk [of vaccinating],’ (farmer e). farmer a delayed the start of the subsequent breeding season by 1 month to reduce the risk of a further disease outbreak. farmer b had decided neither to vaccinate, nor to delay the start of the breeding season, but expressed some uncertainty about future risks of repeat sbv infections and disease outbreaks: ‘no, we still lamb at the same time and we didn’t vaccinate last year[…] it's [risk of future sbv infection] just a concern looking forward. again you have got the opportunity to vaccinate, and that is your choice.’ discussion two previous studies have assessed the impacts of sbv infection on british sheep farms following outbreaks of disease during the 2011/2012 (harris et al., 2014) and 2016/2017 (stokes et al., 2018) lambing seasons. however, to our knowledge, this is the first time that farmers’ detailed qualitative descriptions of sbv affected lambs and ewes; in-depth quantitative evaluations of key production indices for flocks experiencing outbreaks of disease during the 2012/2013 early lambing season in the uk; qualitative and quantitative analysis of farmers’ perceptions of the impacts of sbv on animal welfare, flock financial performance and their emotional well-being; and perceptions of the risk of future outbreaks of sbv disease and preventive strategies including sbv vaccination, have been presented in a mixed-methods study. the clinical signs most commonly observed in sbv affected lambs were; stillbirths, arthrogryposis, deformed heads and stiff necks (torticollis); other spinal deviations (kyphosis / scoliosis) and neurological signs were observed less commonly, as reported by others (dominguez et al., 2012; harris et al., 2014). farmers’ descriptions were consistent with a clinically-silent pattern of disease in ewes in the acute phase of sbv infection in sheep in summer 2012, as described elsewhere (peperkamp et al., 2015; saegerman et al., 2014). however, with the benefit of key flock reproductive performance indicators for the 2012/2013 early lambing season and similar data for previous seasons for comparison, there appears to have been evidence to suggest that there were effects of acute sbv infection in summer 2012 on reproductive events other than during the critical period of pregnancy for congenital malformations in lambs; e.g. scanning percentage was lower in three of the four flocks where data were available and similar in the other, percentage of ewes barren at scanning was higher in the same three flocks and similar in the other, and in five of the six flocks ewes that were scanned in-lamb lost lambs (aborted) after scanning and were barren at lambing. in this study, an overall average of 21.2% (207/975, range: 13.7–42.6%) of lambs born were either stillborn or died within a week of birth and 15.0% (146/975, range: 4.1–42.6%) were born dead or died due to sbv during the 2012/2013 early lambing season; substantially higher losses than an accepted industry benchmark of 5.2% for average lamb mortality in early lambing flocks (eblex, 2009), and higher than findings from other impact studies (harris et al., 2014; stokes et al., 2018; domingues et al., 2012; saegerman et al., 2014; and luttikholt et al., 2014). the first survey of the impacts of sbv on british sheep farms following the first wave of virus circulation in southern england in 2011 and outbreaks of disease during the 2011/2012 production year found an average of 10.4% of all lambs born died within 1 week of birth on sbv confirmed sheep farms and 5.5% of lambs were born malformed (harris et al., 2014). the second survey of british sheep farms, following recirculation of virus and recrudescence of disease during the 2016/2017 production year, similarly found 9.1% of all lambs born died within a week of birth on sbv confirmed farms (stokes et al., 2018). elsewhere, in france, almost 13% of lambs in sbv infected flocks were born dead or died within 12 hours of birth during the first outbreak, and 10% showed congenital malformations typical of sbv (dominguez et al., 2012); similarly, in belgium, 13.2% of lambs were stillborn or died at birth and 10.1% had deformities in sbv affected flocks (saegerman et al., 2014); and in the netherlands, in a case-control study, 13.9% of lambs were born dead or died prior to weaning in case flocks and 5.2% were born with congenital malformations (luttikholt et al., 2014). differences in findings between this and other impact studies are likely to reflect differences in the samples (sheep flocks or farms) surveyed, sample size and other methodological differences, and epidemiological differences between waves of sbv infection in the uk in 2011/2012, 2012/2013 and 2016/2017. the current study was small, farmers with pedigree and purebred early lambing flocks were purposively selected, recorded and perceived impacts were evaluated at flock level and compared reproductive performance in the affected year with previous years, and all flocks lambed early over a relatively short period between 5 november 2012 and 31 january 2013. the two previous british impact studies (harris et al., 2014; stokes et al., 2018) were larger, sbv confirmed sheep farms were purposively selected for inclusion whilst others responded to an online survey, impacts were estimated at farm rather than flock level and compared reproductive performance indicators between groups of farms on which sbv had been (laboratory) confirmed, was suspected or not suspected by farmers, and the sheep farms included lambed over extended periods from september 2011 to june 2012, and from october 2016 to june 2017 respectively. as a result, findings of the two previous studies and this study may not be directly comparable. neither of the previous studies was able to collect data from previous production years for comparison with performance in the sbv affected year, and neither was able to assess overall impacts on productivity and financial performance of affected flocks. acute sbv infection, whilst not clinically apparent in sheep, can have severe negative consequences on early reproductive events resulting in poor conception rates, early embryonic deaths, repeat mating, high barren rates and early abortions (dominguez et al., 2012; lievaart-peterson et al., 2012; luttikholt et al., 2014; saegerman et al., 2014); however, no evidence of early gestational effects were found in the two previous british studies that compared barren rate and lambing percentage between sbv confirmed, suspected and not suspected sheep farms (harris et al., 2014; stokes et al., 2018). stokes et al. (2018) suggested the lack of evidence for effects on barren rate and lambing percentage in their study was likely due to exposure of ewes in all three categories of farms to sbv infection during pregnancy, including in the sbv not suspected farms used as the reference category for comparison of reproductive performance with that of sbv confirmed and suspected farms. our post-outbreak analysis of farmer-maintained records was able to compare reproductive performance of early lambing flocks in the affected year with previous years, where data were available, and highlighted increased early embryonic losses in three early lambing flocks presenting as lower scanning percentages and higher ewe barren rates at pregnancy scanning in 2012/2013. an important factor determining productivity and financial performance of lowland flocks is lamb rearing percentage (c. phythian, phillips, wright, & morgan, 2014). although limited by small sample size, our results suggest there were greater lamb losses in sbv infected flocks that used oestrus synchronisation and artificial insemination (ai) as a breeding method than in those that naturally mated ewes in spontaneous oestrus. rearing percentages for the two naturally mated flocks (b and d) were reduced by a factor of 0.91 and 0.88 times respectively compared to their baseline figures prior to the 2012 early lambing season, and approximately the same as the reduction in weaning rate (by a factor of 0.9, 10% fewer lambs) reported by barrett et al. (2015) in sbv confirmed irish flocks. whereas, for three of the four flocks (a, e and f; not c) that artificially inseminated ewes at a synchronised oestrus, we were able to calculate a reduction in rearing percentage by a factor of 0.63 (37% fewer lambs reared); greater than that reported by barrett et al. (2015). others have suggested flocks that synchronise oestrus to facilitate early breeding appear to be at higher risk of greater lamb losses due to sbv infection than those mating ewes naturally in spontaneous oestrus (afonso et al., 2014; simmons, 2012b). in this study, it seems plausible that in the three flocks that synchronised oestrus for ai to facilitate early breeding in july, a larger proportion of naïve ewes were at the critical stage of pregnancy for congenital malformations when they were first infected with sbv in summer 2012 than in the two flocks that mated ewes naturally in spontaneous oestrus in june 2012. it is not possible to determine whether the greater impact of sbv infection on reproductive performance in the three inseminated flocks was due to synchronisation of breeding for ai, to timing of early breeding in july compared to june, to differences in breeds of sheep, or to a combination of these or other factors. previous british studies have used a questionnaire survey, as was also used here, to quantitatively investigate farmers’ perceptions of the impacts of sbv disease outbreaks on flock welfare, financial performance, and their emotional well-being. this approach is not able to fully reflect the extent and complexity of farmers’ emotions and their perceptions of the impacts of sbv. however, the semi-structured interviews, carried out as part of this study, offered an opportunity to capture farmers’ responses to a series of open questions (see supplementary material s1 – interview questioning guide) providing narrative descriptions of their lived experiences and perceptions of the impacts of sbv infection during the first outbreaks of disease in these early lambing flocks in 2012/2013. farmers’ responses included descriptions of the distressing clinical signs observed around lambing time in ewes and lambs (see supplementary material s2 – clip 1 – liveborn schmallenberg affected lamb with seizures; clip 2 – liveborn schmallenberg affected blind ‘dummy’ lamb), the sometimes damaging interventions required to assist ewes (up to 92% [23/25] on one farm) to give birth to malformed lambs, and their perceptions of the negative impacts of the effects of sbv on: the welfare of ewes and lambs, the financial costs associated with increased ewe and lamb losses and reductions in lamb rearing percentage, veterinary and medicine costs including those associated with caesarian section, and subsequent treatment of ewes damaged during assisted delivery of malformed lambs, increased costs of rearing lambs, and effects on farmers’ emotional well-being. as has previously been reported in detail by c. j. phythian and glover (2019), and briefly here, farmers recalled their negative memories and emotions during that lambing period in terms such as: upset and touched by sheep losses, stressed, under pressure and tired, the difficulty, affect on mental health, depressing endings, and the ability to cope better normally at lambing time. however, those interviewed were experienced shepherds and some recalled experiencing both emotional ‘highs’ when things went well during lambing periods, and ‘lows’ when they did not e.g. during a previous abortion outbreak. half of these farmers also recalled more positive emotions including feelings of resilience and ability to cope with this unexpected disease outbreak. farmers were asked to quantitatively score the severity of those impacts on a scale of 1 to 5 (1 = no impact, 5 = high impact) using the approach of harris et al. (2014). all six farmers perceived negative impacts on animal welfare, flock financial performance, and their emotional well-being (figure 3). overall, the severity of impacts was perceived to be generally high, but self-appraised severity scores varied between farmers and, for five of the six farmers, between impacts. variation in severity scores appeared not to be directly related to the proportion of lambs lost by flocks, as was also reported by harris et al. (2014). there were indications from the qualitative interview data collected in this study that the severity of impacts perceived by farmers was variably influenced by multiple factors and effects of sbv infection including: increases in barren ewe rate; ewe and lamb mortality; reductions in lamb rearing percentage; births of living lambs with distressing clinical signs, particularly those with neurological abnormalities and requiring euthanasia; severe dystocia in a greater proportion of ewes requiring assistance to deliver malformed lambs; farmers’ experiencing both negative emotions of anxiety and depression associated with more intense feelings of tiredness and stress than during normal lambing periods, but also more positive emotions of resilience and ability to cope with the challenges and uncertainties of an unexpected and previously unknown disease outbreak. harris et al. (2014) suggested uncertainty about the final outcomes of this novel disease, for which there were no effective control measures at the time of these first outbreaks, contributed to the severity of the impacts perceived by farmers. in our study, concerns and uncertainty were expressed about use of the sbv vaccine by two farmers who had decided not to vaccinate to protect their flocks. one farmer, recalled feeling uncertain about the safety, efficacy and use of the sbv vaccine at the time it was rapidly authorised and introduced to the market in may 2013; and another, who had experienced the lowest ewe and lamb losses of the six flocks during the first outbreak, and having decided not to vaccinate acknowledged some uncertainty about the risks of repeat sbv infection and future disease outbreaks. some farmers gave approximate estimates of the direct financial costs associated with reduced rearing percentages and lost income from lamb sales based on the value of slaughter lambs in 2012/2013. however, these estimates did not include losses due to increased ewe mortality and veterinary and medical costs, nor could they reflect the true value of lost genetic potential in ewes and lambs that died due to sbv. farmer-perceived impacts on financial performance appeared high, irrespective of the number and proportion of lambs stillborn or that died in the neonatal period and irrespective of the reduction in rearing percentage. other observed effects of sbv infection on reproductive performance, ewe dystocia and associated morbidity and poor milk production of ewes, are likely to have contributed to the high financial impacts perceived by farmers. in these high value pedigree and purebred flocks, some farmers appeared to be more upset by the long-term loss of valuable genetic material in the ewes and lambs that died, than by any short-term financial ‘hit’. increased flock replacement costs associated with higher periparturient ewe mortality, and increased veterinary and medicine costs associated with dystocia and treatment of sick ewes, are also likely to have contributed to the perceived impact on financial performance, but are difficult to measure and were not assessed here, nor in previous british studies. models have been developed to estimate the economic impact of sbv infection in a range of uk sheep production systems, but these have not included pedigree and purebred early lambing flocks deriving a proportion of income from sales of high value breeding sheep, and in which flock replacement costs are high (alarcon et al., 2013). serological testing of these flocks following the first outbreaks of disease due to sbv infection in 2012/2013 indicated that within-flock seroprevalence was variable (34.9–93.6%) and natural immunity against sbv was likely to be incomplete (mike glover & blake, 2013). these farmers were mostly risk averse to repeat sbv infection and future disease outbreaks and therefore it might seem surprising that only three of the six farmers decided to vaccinate their flocks prior to the next breeding season. the study design offered an opportunity to investigate farmers’ decisions on use of vaccine during the semi-structured interviews. cost of vaccine did not appear to be a major factor influencing farmers’ decisions. uncertainty about the safety of the newly developed vaccine and concerns about vaccinating sheep so close to the start of the breeding season were mentioned by one farmer who decided not to vaccinate. this farmer had felt reassured by veterinary advice that a large proportion of the flock was immune, blood testing for sbv antibodies in the serum of ewes had shown ~90% were seropositive, and risks of repeat infection were likely to be low; it seemed the farmer did not feel the likely benefit to be gained in terms of reduced risk of sbv infection outweighed the perceived risks associated with vaccination. another farmer decided to delay the start of the subsequent breeding season by 1 month rather than vaccinate; an accepted management change to reduce the risk of disease outbreaks (wernike & beer, 2020). a third farmer did not offer a reason for not vaccinating; however, this flock lost the lowest proportion (4.1% [8/197]) of newborn lambs of the six flocks included in the current study, lost no ewes, and a low percentage of ewes (3.8% [4/105]) required lambing assistance to deliver affected lambs. this farmer perceived the severity of the impacts on flock welfare, financial performance and emotional well-being to be at the lowest level, and possibly did not perceive sufficient benefit in terms of disease risk reduction to justify the cost of whole flock sbv vaccination despite expressing some uncertainty about future risk. larger studies have included more diverse samples of sheep farmers; these have found that between 13.3–13.7% of british farmers vaccinated with sbv vaccine in 2013, reducing to 1.6% in 2014 (stokes, baylis, & duncan, 2016; stokes et al., 2018). stokes et al. (2018) suggested cost and previous experience of sbv were factors likely to influence vaccine uptake; following recrudescence of sbv in the uk in 2016/2017, a third of british farmers on sbv confirmed and suspected farms indicated they would consider vaccinating if the cost of vaccine was < £1, whereas fewer, around a quarter, would consider doing so on farms where sbv was not suspected; and < 10% of farmers would consider vaccinating if the cost of vaccine was £4–5. uncertainty due to the lack of reported data on efficacy and duration of immunity when the first sbv vaccine was released, vaccine cost and previous experience of disease (stokes et al., 2018), limited scientific knowledge about the disease, perceived isolated nature of the first disease outbreak and intermittent nature of future outbreaks, are likely to have influenced these and other farmers’ decisions on use of vaccination to prevent future outbreaks (stavrou, daly, maddison, gough, & tarlinton, 2017). follow-up serological testing of homebred lambs born in 2014 indicated exposure of these study flocks to sbv was very low or unlikely in 2014 (glover & blake, unpublished observations), and furthermore, a freedom of disease study based on serological testing of lambs born in southern england between october 2014 and april 2015 indicated that circulation of sbv in the region was also very low, or unlikely, in 2015 (stokes et al., 2016). the results of these two serological surveys, taken together with the absence of confirmed cases of sbv in the uk in 2015 (anonymous, 2016), indicated there was likely to be an increasing proportion of naïve animals in flocks in the uk in 2016 (stavrou et al., 2017). subsequently, recirculation of sbv and recrudescence of disease were confirmed in the uk in autumn 2016 (anonymous, 2016, 2017; stokes et al., 2018) and again in 2021 (anonymous, 2022), and it is expected this pattern of virus circulation and disease re-emergence will be repeated intermittently every 3–6 years (anonymous, 2021; stavrou et al., 2017). since the first outbreaks of disease were reported in 2012 the uk government has funded passive surveillance for sbv in the uk, including free of charge pcr testing of the brain in lamb submissions fitting the case description for sbv and antibody testing of serum from ewes. however, looking forward passive surveillance is of limited value to sheep farmers such as those included in the current study, who in high risk years when sbv begins to circulate, might want to deploy preventive measures such as vaccinating part or all of their flocks (assuming vaccine is available) ahead of the breeding and peak midge vector seasons, or delaying the start of mating. early warning systems would allow farmers to proactively deploy vaccine, or take other management decisions, to prevent disease outbreaks ahead of the breeding season (de regge, 2016; kirkland, 2015). a jointly funded cooperative initiative between the livestock industries and government (both national and state) established a national arbovirus monitoring system for arboviruses in australia in 1993 to monitor annual fluctuations in viruses and vectors (kirkland, 2004); this system could provide a model for a similar europe-wide arbovirus (sbv and bluetongue virus [btv]) surveillance system (stavrou et al., 2017). study strengths and limitations the small number of participating farmers, the nature of the farm visits and familiarity with the veterinarian, allowed us to collate good quality, detailed records, from almost all flocks, and to carry out the qualitative elements of this study. whilst farmers likely to have good records were selected, farmers’ records were not perfect and we were not able to determine baseline figures for comparison for all reproductive parameters in all flocks. we also recognise that this study did not capture a saturation of farmers’ beliefs across the region in the qualitative research elements, nor did we capture the diversity of beliefs about the risk of future circulation of sbv and outbreaks of disease, and intentions to vaccinate to protect flocks. these flocks were purposively selected, they were high value pedigree and purebred flocks on farms in the southwest of england, and they lambed early between early november and late january 2012. as a result, these findings may not be generalisable to commercial flocks lambing later in the spring in other parts of the uk, and may not be directly comparable to those of previous british impact studies that were larger and included farms with a more diverse range of lambing dates and production systems, and estimated impacts at farm rather than flock level. supplementary materials supplementary material s1 – interview questioning guide supplementary material s2 – video clip 1: liveborn schmallenberg affected lamb with seizures; video clip 2: liveborn schmallenberg affected blind ‘dummy’ lamb supplementary material s3 – table 1: farmer recorded flock-level reproductive performance data for the production year including the november 2012 to january 2013 lambing period supplementary material s4 – table 2: farmer recorded flock-level data on the impacts of sbv on ewes and lambs, reproductive performance and survival around lambing time during the november 2012 to january 2013 lambing period acknowledgements we are grateful to the farmers who participated in this study for candidly sharing their experiences and allowing us access to their farm management records. we would also like to thank the two reviewers for their helpful comments on the manuscript. author contributions mike j. glover: conceptualisation, methodology, funding acquisition, investigation, data curation (quantitative element), formal analysis (quantitative element), co-writing – first draft preparation, co-writing – review & editing. neil blake: conceptualisation, methodology, funding acquisition, co-writing – review & editing. clare j. phythian: conceptualisation, methodology, investigation, data curation (qualitative element), formal analysis (qualitative element), co-writing – first draft preparation, co-writing – review & editing. orcid mike j. glover: https://orcid.org/0000-0002-3454-0676 neil blake: https://orcid.org/0000-0002-1739-5120 clare j phythian: https://orcid.org/0000-0003-3140-4414 funding we are grateful to msd animal health, the south west healthy livestock initiative, and the directors of torch farm and equine ltd. for their encouragement and financial support. the funders played no role in the study design, conduct, analysis, interpretation or reporting of these findings. conflict of interest the authors declare no conflicts of interest. references afonso, a., abrahantes, j. c., conraths, f., veldhuis, a., elbers, a., roberts, h., van der stede, y., méroc, e., gache, k. & richardson, j. 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(2020). schmallenberg virus: to vaccinate, or not to vaccinate? vaccines (basel). 8(2). doi: https://doi.org/10.3390/vaccines8020287 intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise 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systematic reviews of animal studies – report of an international symposium | veterinary evidence skip to main content article keywords: animal systematic review; evidence synthesis; evidence-based veterinary medicine; literature searching; ebvm systematic reviews of animal studies – report of an international symposium erik fausak, mslis ma rvt rlat1 melissa c. funaro, ms mlis2 andrea c. kepsel, mlis3 erin r.b. eldermire, mlis4 margaret foster, ms mph5 hannah f. norton, ms6 kim mears, mlis7 molly e. crews, mls8 marnie brennan, bsc(vb) bvms phd pgche dipl. ecvph(pm)9 gillian l. currie, phd10 megan r. lafollette, ms phd11 annette o’connor, bvsc mvsc dvsc fanzcvs12 adrian j. smith, ma vetmb phd dipl. eclam (retired) mdnv13 kimberley e. wever, msc phd14 suzanne fricke, dvm mlis15* 1uc davis library, 100 nw quad, university of california, davis, ca 95616 usa 2harvey cushing / john hay whitney medical library, yale university, 333 cedar st, new haven, ct 06510 usa 3michigan state university libraries, 366 w circle dr, east lansing, mi 48824 usa 4cornell university library, ithaca, ny 14853 usa 5center for systematic reviews and research syntheses, texas a&m university, tamu, college station, tx 77843–4474, usa 6university of florida health science center libraries, communicore building, 1600 sw archer rd, gainesville, fl 32610 usa 7robertson library, university of prince edward island, 550 university ave, charlottetown, pe c1a 4p3 canada 8department of small animal clinical sciences, texas a&m university school of veterinary medicine and biomedical sciences, tamu, college station, tx 77843–4474, usa 9centre for evidence-based veterinary medicine, school of veterinary medicine and science, university of nottingham, sutton bonington campus, leicestershire, le12 5rd, uk 10clinical brain sciences, 49 little france crescent, university of edinburgh, edinburgh, eh16 4sb, uk 11the 3rs collaborative, 1312 17th st. pmb 70570, denver, colorado, 80202, usa 12department of large animal clinical sciences, michigan state university, 736 wilson road, d202 east lansing, mi 48824, usa 13norecopa, c/o norwegian veterinary institute, p.o. box 64, n–1431 ås, norway 14department of anesthesiology, pain and palliative medicine, radboud institute for health sciences, radboud university medical center, post 717, p.o. box 9101, 6500 hb nijmegen, the netherlands 15washington state university libraries, po box 45610 pullman, wa 99164–5610, usa * corresponding author email: suzanne.fricke@wsu.edu vol 8, issue 3 (2023) submitted 18 oct 2022; published: 11 aug 2023 doi: https://doi.org/10.18849/ve.v8i3.653 abstract objective: the symposium on animal systematic reviews held 24 may 2022, sought to bring organisations working on animal literature searching and systematic reviews together into the same virtual space for introductions and discussion. background: groups working on animal research synthesis are often siloed into preclinical, veterinary, and one health settings. this symposium sought to define commonalities and differences in methodologies, resources, and philosophies and to discuss future needs. methods: the 3-hour virtual symposium for veterinarians, researchers, and information specialists began with introductions by panelists from organisations involved in searching the literature for animal studies and conducting systematic reviews. this was followed by a panel discussion and question and answer period. results: panelists identified a need to ensure planning and accurate description of primary animal studies as a precursor to quality systematic reviews. they acknowledged and discussed differences in evidence synthesis expectations and tools based on the type of review, the types of studies available on the topic, and the focus on preclinical, veterinary, or one health topics. conclusion: the need to increase the speed and quality of evidence reviews, and to automate updates, requires investing in the development of both skilled teams and platforms. the symposium provided a chance to identify existing resources, define challenges, and note gaps unique to systematic reviews of animal studies. application: this symposium acts as a baseline for ongoing discussions centred on improving the culture and pipeline for evidence syntheses of animal studies that inform decision-making. introduction systematic reviews and other evidence syntheses are important tools for summarising and synthesising research from multiple locations into a single, accessible source. in addition to their traditional use in human medicine, these methodologies are increasingly applied in other disciplines, including animal studies. systematic reviews are particularly important in animal studies due to small study sample sizes, bias associated with individual study populations, and publication silos associated with animal health literature (manlove et al., 2016). in turn, the creation of systematic reviews helps to identify gaps where further research is needed and drives the use of standardised reporting guidelines so that future studies can more easily be compared with one another. as more systems become available that incorporate evidence syntheses for veterinary practitioners and animal caregivers, it is crucial that there is a greater understanding of the underlying methodology used. this will enable proper evaluation of these resources for publication and application to policy and practice. while animal studies share many similarities with human studies, there are distinct factors that need to be considered when conducting and evaluating systematic reviews and meta-analyses of animal studies. the growing interest in systematic reviews supported the creation of a symposium on animal systematic reviews held on 24 may 2022. although the symposium focused on systematic reviews, other types of evidence syntheses were discussed. this article summarises discussion at the symposium with a goal of educating veterinary practitioners, animal researchers, systematic review authors, and journal editors and reviewers on current issues in animal evidence synthesis, and provides a curated list of related resources. methods the symposium on animal systematic reviews brought together a diverse panel of experts from international organisations and institutions working to advance research, information systems, and syntheses that impact policies and practices affecting the health and welfare of the environment, humans, and animals. this 3-hour virtual symposium included introductions from invited experts, a panel discussion, and an audience question and answer session. the invitation to register for the symposium was promoted through professional organisation listservs, which included veterinarians, animal researchers, and information specialists. objectives symposium panelists and participants met with the following objectives: to bring together a diverse group of organisations working on systematic reviews of animal studies into the same virtual space for introductions and discussion.  to define commonalities among groups working on systematic reviews of animal studies for differing purposes, e.g., drug development, toxicology, veterinary, animal welfare, food safety, sustainability and conservation. to identify how systematic review methodology differs across organisations. to discuss how information specialists, researchers and journal editors can create a culture that values the use of guidelines in primary animal studies and evidence syntheses. to identify and document resources for systematic reviews of animal studies. to identify and document common questions and unique problems that arise when searching for animal literature. panel members introduction ten panelists were invited to participate in the symposium. the panelists introduced themselves and their respective organisations and illustrated their support for animal literature searching and syntheses. marnie brennan, centre for evidence-based veterinary medicine (cevm), university of nottingham. jessie carder, animal welfare information center (awic), usda national agricultural library (nal). gillian currie, collaborative approach to meta analysis and review of animal data from experimental studies (camarades), university of edinburgh. erin eldermire, flower-sprecher veterinary library and evidence synthesis service, cornell university. margaret foster, center for systematic reviews and research syntheses, texas a&m university school of medicine. megan lafollette, north american 3rs collaborative (na3rsc). annette o’connor, department of large animal clinical sciences and systematic reviews for animals and food (syreaf), michigan state university. adrian smith, national consensus platform for the replacement, reduction and refinement of animal experiments (norecopa). norway. jesslyn thay, centre for agriculture and bioscience international (cabi). kim wever, preclinicaltrials.eu, international prospective register of systematic reviews (prospero) guidelines for registering a review of animal studies, and medical center meta-research team, radboud university, the netherlands. results why systematic reviews of animal studies are needed systematic reviews of animal studies are needed to improve clinical decision-making, to assess how research is conducted, and to inform current practice and policy. systematic reviews confirm, or conversely question, whether conclusions from any one primary study are generalisable and help to explore the heterogeneity between studies in a field. for animal research consumers (veterinary practitioners and policy-makers), this synthesis can serve as a short-cut for keeping up to date on current research; clinicians reading one well-conducted systematic review can gain insights from multiple primary studies and understand their results in context of one another. in the preclinical research setting, systematic reviews can help advance understanding of human and animal disease and management, and help recognise when research can move from preclinical studies to the next stage of research (wever et al., 2012). systematic reviews also highlight areas where laboratory research can be improved or identify systemic barriers to the implementation of interventions (sena et al., 2014; de vries et al., 2014; and lafollette et al., 2017). for example, in preclinical stroke research with animal models, early systematic reviews identified the need to improve research methods and reporting (banwell et al., 2009). this feedback resulted in advancements made transparent to researchers in subsequent systematic review updates (mccann et al., 2016).  systematic reviews and related methodologies of veterinary studies provide critical appraisal of the quality of the available evidence surrounding a clinical question, increase external validity, reduce the risk of bias, and identify gaps in the research. compared to human-directed research, there is relatively limited research support for agriculture, and even less for veterinary science and companion animal care, so there is an ethical obligation that researchers maximise the quality of primary studies.  panelists noted an increasing need for reviews to be rapid and nimble, engaging policy-makers in the process, citing work by chris whitty, chief medical officer for england and chief medical adviser to the uk government that examined the impact of evidence on real-time government decision-making during the pandemic (whitty & collet-fenson, 2021). oversight and funding for systematic reviews of animal studies some worry that the growth in systematic review production may involve duplication of efforts and waste of limited time and resources. panelists agreed on the need to focus future efforts on improving the quality and not the quantity of reviews, and to encourage researchers to ask if a review on that topic has already been done or if a protocol has been registered on their topic. in addition, researchers should demonstrate where their review fits into the canon of previous work on the topic. availability of funding, often influenced by institutional or country policies, can determine review topics, as well as whether researchers focus on preclinical, veterinary, global one health issues, or the united nations’ sustainable development goals. in the netherlands, national funding exists for researchers to conduct mentored systematic reviews, and most applicants for this funding are phd students. an impact study of this dutch program showed that students’ completion of a systematic review improved the quality of their future primary research, regardless of whether they participated in subsequent reviews (menon et al., 2021). while funding structures may exist for preclinical and one health evidence synthesis projects, panelists observe less funding available for projects focused on veterinary questions, environmental factors, conventional housing, facilities, husbandry, morbidity and mortality, and background genomic factors of species, breeds and strains, except when veterinary studies are tied to industry (wareham et al., 2017). one model that a large professional organisation can use to remedy this oversight is to adopt a systematic process whereby members or conference attendees are asked to submit questions, information specialists search to see what questions have already been answered, and working groups pursue those questions that remain. types of evidence synthesis types of evidence synthesis reviews have proliferated (grant & booth, 2009), with a 2019 article categorising 48 separate review types (sutton et al., 2019). some commonly used types include scoping reviews, systematic reviews, rapid reviews, umbrella reviews, and meta-analyses. panelists shared their perspectives on the continuum of evidence synthesis types with which they have engaged, from systematic reviews to the less rigorous critically appraised topics (brennan et al., 2020). preliminary stakeholder discussions about conducting higher levels of evidence synthesis like systematic reviews and meta-analyses can be challenging depending on the discipline, type of question, and study type availability. for instance, while randomised controlled trials are considered the most reliable type of evidence, this study design is not feasible or ethical in all fields of research. researchers may lack or underestimate the resources needed to conduct a systematic review. while selling the idea of evidence synthesis is easy, learning the process and defining the scope may be difficult for researchers that are new to the methodology. the large variety of types of evidence synthesis can create a hurdle for readers, as well as those conducting and reviewing evidence syntheses. several excellent articles explaining the meaning and purpose of various types of reviews have been published for veterinarians (o’connor & sargeant, 2015; and sargeant & o’connor, 2014). however, some of the burden falls squarely on authors and journals to better identify review types. even centre for evidence-based veterinary medicine (cevm) expert researchers experience difficulty determining what publications qualify as a systematic review for inclusion in vetsrev (centre for evidence-based veterinary medicine, 2021), a database that indexes veterinary systematic reviews identified from cab abstracts and medline. reporting guidelines: ensuring quality of primary studies high-quality evidence synthesis starts with assuring the quality of the primary animal studies that will later be included in syntheses. to improve animal welfare and make use of the limited funding focused on outcomes for animals, planning of the research study design is vital. the prepare (planning research and experimental procedures on animals: recommendations for excellence) guidelines include a two-page checklist available in over 30 languages for planning animal studies (smith, 2018). planning is aided by a culture that encourages the pre-registration of animal primary study protocols (baker, 2019; and moore et al., 2021). preclinicaltrials.eu (van der naald et al., 2022) and animalstudyregistry.org (bert et al., 2019) are dedicated registries for primary animal studies, or authors may use general study registries identified in s1 table 1. for veterinary studies, the american veterinary medical association maintains the animal health studies database (murphey, 2019), modeled on clinicaltrials.gov (us national library of medicine, 2000), for recruiting participants. the use of reporting guidelines for primary studies, that define the information that is necessary to include based on study design, is crucial for comparing one animal study to another in systematic reviews. well-known preclinical reporting guidelines for animal research are the arrive 2.0 (animal research: reporting of in vivo experiments) guidelines (percie du sert et al., 2020). other reporting guidelines can be found through the enhancing the quality and transparency of health research (equator) network (uk equator centre, 2019), menagerie of reporting guidelines involving animals (meridian) network (meridian network, 2023), and norecopa (norecopa, n.d.), which collect and provide links to a broader number of reporting guidelines applicable to other types of animal research. authors of primary animal studies should be aware that the design impacts whether a study is included in larger evidence synthesis projects. for instance, a study may not be included in a systematic review if it does not meet the required inclusion / exclusion standards or risk of bias assessment criteria. while arrive 2.0 and other guidelines include recommendations related to abstracts, the panel highlighted abstracts as a major area where further improvement is needed. abstracts of primary animal studies are often vague in both technical and plain language. improvements in abstracts and reporting standards for conference proceedings would also help with efficiency in identifying studies appropriate for inclusion in evidence synthesis projects, since veterinary research is often reported in conference proceedings. preparation for conducting evidence synthesis evidence synthesis training  an array of toolkits and templates are available to introduce the preclinical systematic review process to first-time evidence synthesis authors. panelists recommend both the camarades preclinical systematic review wiki (camarades berlin, n.d.) and the systematic review center for laboratory animal experimentation (syrcle) course (syrcle, 2023). rcvs knowledge evidence-based veterinary medicine (ebvm) learning (rcvs knowledge, n.d.[a]) and veterinary evidence ‘how to write a knowledge summary’ (veterinary evidence, n.d.[a]) are good starting points for veterinarians. the veterinary systematic review process has been further described in a special issue of the journal zoonoses and public health (torrence (ed), 2014). once familiar with systematic review methodologies, researchers exploring more advanced automated aspects of reviews may start with the evidence synthesis hackathon and the accompanying evidence synthesis & meta-analysis in r conference (westgate & haddaway, 2017; and haddaway et al., 2022). selecting a review type choosing the appropriate review type is a pivotal first step for researchers, as it helps to determine the scope and focus of the review, as well as the methodology and analysis that will be used. cornell university library’s evidence synthesis service review methodology tree (cornell university library, n.d.), for deciding on a review type, can be a helpful tool to aid researchers in their decision. the flowchart helps researchers understand the basics of each review type and why one might be chosen over another. search development to assure transparency in the study selection process, prisma 2020 guidelines (page et al., 2021) and the prisma-s extension (rethlefsen et al., 2021) call for authors to identify all information sources searched or consulted, and to provide full search strategies for each. since animal research is published in a variety of disciplines and half of veterinary research is published outside of core veterinary journals (grindlay et al., 2012; and page et al., 2014), this requires searches across multiple databases and platforms with differing features and filters. also, articles found through citation searching may not be in journals indexed in larger databases, raising concerns that the journal might be predatory. panelists voiced how difficult it is to create concise database search strategies, specifically for studies about animal health, versus animal models of human disease. acronyms or terms that have context outside of animal studies can also be problematic in searches, returning irrelevant results. registration of animal evidence syntheses prospective registration of evidence syntheses contributes to methodological transparency and minimises duplication of effort. panelists addressed what elements of a review should be pre-registered and where they should be registered. protocol registration requirements developed for human study platforms often do not accommodate animal studies. for instance, clinical trials with small enrollments of six animals, or without controls, would not fulfill cochrane inclusion requirements. two tools specifically designed to register protocols for systematic reviews of animal studies include the guidelines developed for preclinical systematic review registration (uk crd, n.d.) in the human-centric international prospective register of systematic reviews (prospero) (booth et al., 2012), and systematic reviews for animals and food (syreaf) protocols (syreaf, 2023). prospero registers systematic reviews, rapid reviews or umbrella reviews of preclinical animal research studies that are of ‘direct relevance to human health’. prospero does not register scoping reviews. developed with input from researchers, prospero’s preclinical form includes more mandatory fields than the clinical form. the prospero team does not perform formal peer-review of protocols, but checks for transparency of methods and completeness of information. systematic review protocols of animal studies without a direct relevance to human health, such as those in veterinary or agricultural sciences, can be registered with syreaf protocols or open science foundation (osf) registries (center for open science, n.d.). the syreaf team currently considers strict guidelines as a barrier to veterinary researchers submitting protocols, therefore few protocol elements are mandatory. some additional conversation among attendees highlighted researchers' hesitancy to pre-register protocols due to concerns related to intellectual property. panel members felt that researchers fearful of protocol registration were in the minority. they asserted that pre-registration serves as a means to 'claim' a particular topic and that many journals and reviewers expect and reward this practice. pre-registration of animal systematic review protocols also encourages the pre-registration of primary animal study protocols.  study types types of studies to include in animal evidence synthesis projects depends both on the available research in a particular discipline and the type of question being asked in the review. there may be an abundance of clinical trials in some disciplines, and in others the body of evidence may be much more qualitative or rely heavily on observational studies. for instance, preclinical research questions, focused on mechanisms of disease, therapeutic targets, and safety, translate best to randomised and controlled experimental studies, while research questions in clinical veterinary settings concerned with the aetiology, prevention, or prognosis of a disease translate best to observational studies (veterinary evidence ‘guidance for writing the clinical bottom line,’ n.d.[b]). broader one health synthesis projects may include multiple questions with multiple variables, often incorporating mixed-method studies that address the role of human attitudes and behaviour. what might be evidence in one discipline does not always apply to all disciplines. tools and resources panelists noted that there are many tools for conducting systematic reviews. however, tools are only a means to an end and selecting an effective tool will depend on funding, familiarity, and unique needs of the review topic and / or field. preclinical animal researchers, in particular, value traditional systematic review screening tools such as covidence (covidence, n.d.), rayyan (rayyan, n.d.), and distillersr (distillersr, n.d.). however, some screening tools designed for human studies cannot handle common animal study protocols. for example, many popular screening tools such as covidence, do not support veterinary studies that include multiple primary studies in one publication. to facilitate the creation of preclinical in vivo systematic reviews, systematic review facility (syrf) was created to decrease the time needed for reviews and the need to use multiple software programs (bahor et al., 2021). a question was raised about whether the differences between animal and human systematic reviews are distinct enough to justify the need for different tools and resources. panel member opinions varied about the degree to which different tools are required across preclinical, veterinary, and human studies, however all panelists agreed that, at this point in time, human-centric tools do not adequately support evidence synthesis of animal studies. this may be an important consideration as the number of one health studies continues to grow. living systematic reviews as the amount of evidence grows and as global questions become more complex and incorporate multiple variables, more organisations are pursuing continuously updated living systematic review platforms, which have an a priori plan to incorporate new evidence over time.  camarades and syreaf have both explored living systematic reviews made available via r shiny web applications. camarades has implemented living systematic reviews on transgenic mice models of alzheimer’s disease and covid-19 research (hair et al., 2021b), and syreaf has a living systematic review looking at the impact that multiple effects of animal production have on the health of surrounding communities (fonseca & o’connor, 2021 and syreaf, 2023). camarades developed systematic online living evidence summaries (soles) for different research areas by implementing automation and crowd sourcing (hair et al., 2021b). automation adds the ability to analyse data at a level that surpasses that of human screeners (bannach-brown et al., 2019). living systematic reviews are greatly facilitated when workflows and platforms are created that minimise a need to transfer records from one tool to another. educating the next generation of practitioners on evidence synthesis panelists acknowledged a distinction between authors and consumers of systematic reviews and approach each audience differently. practitioners and students may not conduct research or become authors of reviews, but they need to know about different review types and how to apply their findings to practice. because of this, it is important to integrate instruction on using systematic reviews into the curricula of healthcare professions. the rcvs knowledge ebvm learning course teaches veterinary practitioners how to apply evidence to answer clinical questions, which is important foundational knowledge when engaging in the review process. students and first-time authors can engage first with ‘mini reviews’ called critically appraised topics (cats), a type of rapid review (brennan et al., 2020). clinical examples include knowledge summaries published in veterinary evidence (rcvs knowledge, n.d.[b]) and bestbets for vets (university of nottingham, 2023) made available online through the cevm. these are inexpensive, time efficient and simple ways of doing reviews that are useful for both learners and clinicians.  depending on their availability, students across a variety of disciplines and levels of education can contribute significantly to a larger synthesis project. involving a few undergraduates in phases of a synthesis review (as opposed to the entire process) can provide substantive experience and perhaps material for an honours degree thesis. graduate students, or professional students enrolled in concurrent degree programmes such as public health, will dive deeper into scholarly writing as part of their curriculum. by forming a cohort, these students can peer-review each other’s work to strengthen the learning process and to learn to apply reviews across different questions and topics. this then requires fewer one-on-one consultations by mentors or advisors. building capacity for conducting systematic reviews among the next generation is vital to the continued evolution and improvement of review methods. artificial intelligence and the future of systematic reviews evidence synthesis projects rely increasingly upon machine learning and artificial intelligence (ai). it may become harder to perform evidence synthesis without automation tools that create and translate searches, citation search, deduplicate citations, screen both title / abstracts and full-text, extract data, assess risk of bias, and manage workflows. ai tools are needed to decrease the time required to complete a systematic review. rapid completion of reviews is critical for policy change, as policy-makers will not often tolerate long timelines. in the health and social sciences, detailed manuals and handbooks, such as the cochrane handbook for systematic reviews of interventions and the campbell collaboration’s guidelines, contain rigorous methodological guidance on the process of conducting evidence syntheses. however, researchers using ai in evidence syntheses are likely to come from diverse research fields where detailed guidance may not exist. with this in mind, a network of organisations, the international collaboration for the automation of systematic reviews (icasr), works to create open tools for automating evidence synthesis (beller et al., 2018). the panelists outlined some of the synthesis review tasks where ai tools have been deployed for evidence synthesis projects involving animal studies. not all available tools were discussed in the symposium, and further recommendations for ai use in evidence synthesis are defined elsewhere (bersani et al., 2022).  tools include those for:  search strategy development text mining and keyword co-occurrence networks (kcns) using r package litsearchr can help automate identification of keywords for search strategy development, particularly in fields where standard controlled terminologies do not exist (grames et al., 2019). the sr-accelerator polyglot search translator can help translate search strings into the syntax of other databases (clark et al., 2020a; and clark et al., 2020b). the use and accessibility of generative ai search tools has exploded since this symposium was held in 2022, and information specialist authors caution that with many of these new tools the search is not replicable and relies on simple searches that can perpetuate existing silos within the literature. they do not adequately capture the semantic search combinations of controlled vocabulary and keywords needed to comprehensively search literature across the various disciplines, databases, and indexing and metadata conventions associated with animal studies. therefore, these tools should be seen as accessories to collaborative search strategy development by human teams familiar with both the topic and database querying. citation searching  several ai tools for backwards and forwards citation searching exist, including distillersr, citation chaser and sr accelerator spidercite (distillersr, n.d.; haddaway et al., 2021; and institute for evidence-based healthcare, n.d.).  deduplication  the camarades team uses automated systematic search deduplicator (asysd), a tool for deduplication that they developed themselves (hair et al., 2021a). other software such as covidence, rayyan, and distillersr also have a built-in deduplication function. screening  effective tools that facilitate screening of articles for inclusion or exclusion at the title and abstract level have been developed for many platforms including syrf, distillersr, sr-accelerator, covidence and others. systematic review screening standards dictate that more than one reviewer evaluates citations in order to eliminate bias. however, screening can be time consuming. organisations have approached the time barrier that screening presents in a variety of ways. camarades has crowdsourced and trained a large pool of reviewers, while others have explored the potential of ai to replace some human reviewers. confirming the difficulty in identifying study design, the camarades and syreaf teams have both tried to automate the detection of study design in biomedical research and were not successful (o’connor et al., 2018). however, the camarades team has developed an algorithm hosted by the evidence for policy and practice information and coordinating centre (eppi-centre) at university college london to classify studies based on title and abstract screening as ‘primary’ or ‘other’ (hair et al., 2021b). extraction the syreaf team and other panelists highlighted text extraction from pdfs as one of the most difficult automation steps. syrf has worked on a graphical data extraction tool to aid in meta-analysis of preclinical studies (bahor et al., 2021).  risk of bias assessment automated tools that assess the actual risk of bias are difficult to develop, since performing a risk assessment is much more complex than extracting experimental variables. the reporting of measures to reduce bias, such as the term ‘blinded experimenter’ or ‘random allocation’ can be more readily assessed with automated techniques. the syrcle risk of bias (rob) tool was developed to assess risk of bias for preclinical trials (hooijmans et al., 2014). evidence on the efficacy of ai tools in evidence synthesis for assessing quality of publications is lacking. discussion systematic reviews are useful tools for synthesising the results of studies, identifying research gaps, informing future research, and reducing research waste. as such, they are beneficial for health practitioners, researchers, and policy-makers. systematic reviews based on studies of animals are increasingly being recognised as a critical part of knowledge translation frameworks by preclinical, veterinary and one health groups that have not formally come together to discuss evidence synthesis. what constitutes a high-quality systematic review is an evolving metric. those working on synthesis of animal studies face common barriers of search strategy terminology and studies with small sample size, though the symposium uncovered distinct differences across disciplines in supporting infrastructures, required steps of the review, and included study designs. while much has already been done to define appropriate methodologies and create freely available tools, there are areas where development is still needed in order to further animal-focused evidence syntheses (e.g., inclusion of observational studies in reviews, ai). automation of steps has the potential to make conducting systematic reviews more accessible to smaller research teams.  when looking at the breadth of topics under the 'evidence synthesis of animal studies' umbrella, recognising the value of having teams with individual skill sets involved in reviews (e.g., information specialists, subject expert researchers and clinicians) is key. capturing discussions like this between various organisations, teams and individuals working to synthesise heterogenous studies contributes to a culture aiming to strengthen both evidence synthesis and primary research design and reporting. the symposium on animal systematic reviews provided a unique opportunity for preclinical and clinical researchers, and information specialists, to collectively assess the state of systematic reviews focused on animals. while the underlying symposium objectives served to guide discussion, the time limited format did not allow for complete stakeholder representation or consensus building, particularly in the area of one health. this was instead a forum for varied stakeholders, both panelists and attendees, to identify common challenges and opportunities unique to evidence synthesis of animal studies, including the use of existing resources or the need to develop new resources. resources discussed in the symposium are compiled and shared in s1 table 1. conversations and discussions should continue to further address some of the issues and barriers identified, including abstracts, indexing and reporting guidelines for primary studies, pre-registration, roles for ai, and types of studies to include, in order to improve the speed and quality of evidence synthesis of animal studies. supplementary materials supplementary material s1 – table 1: list of selected resources for evidence synthesis of animal studies discussed in the symposium. acknowledgements the authors credit the medical library association (mla), and members of the animal and veterinary information specialist caucus (avis) of mla, the united states agricultural information network (usain), the european veterinary libraries group (evlg) of the european association for health information and libraries (eahil), the evidence-based veterinary medical association (ebvma), and multiple research organisations and institutions for promoting the event. the authors would like to thank elizabeth tobey and jessie carder with usda awic, and jesslyn thay with cabi, for their help with the symposium. author contributions erik fausak: conceptualisation, methodology, writing – original draft preparation, writing – review and editing. melissa c. funaro: conceptualisation, methodology, writing – original draft preparation, writing – review and editing. andrea c. kepsel: conceptualisation, methodology, writing – original draft preparation, writing – review and editing.  erin r.b. eldermire: conceptualisation, methodology, investigation, writing – review and editing. margaret foster: conceptualisation, methodology, investigation, writing – review and editing. hannah f. norton: conceptualisation, methodology, writing – original draft preparation, writing – review and editing. kim mears: conceptualisation, methodology, writing – review and editing. molly e. crews: conceptualisation, methodology, writing – review and editing. marnie brennan: investigation, writing – review and editing. gillian l. currie: investigation, writing – review and editing. megan r. lafollette: investigation, writing – review and editing. annette o’connor: investigation, writing – review and editing. adrian j. smith: investigation, writing – review and editing. kimberley e. wever: investigation, writing – review and editing. suzanne fricke: conceptualisation, methodology, writing – original draft preparation, writing – review and editing, funding acquisition, supervision, project administration. orcid erik fausak: https://orcid.org/0000-0002-0510-0153 melissa c. funaro: https://orcid.org/0000-0001-6846-4846 andrea c. kepsel: https://orcid.org/0000-0002-9651-6700 erin r.b. eldermire: https://orcid.org/0000-0001-5846-4041 margaret foster: https://orcid.org/0000-0002-4453-7788 hannah f. norton: https://orcid.org/0000-0001-8062-2763 kim mears: https://orcid.org/0000-0001-6461-9054 molly e. crews: https://orcid.org/0000-0002-4960-5591 marnie brennan: https://orcid.org/0000-0002-4893-6583 gillian l. currie: https://orcid.org/0000-0003-3052-2929 megan r. lafollette: https://orcid.org/0000-0003-0643-2210 annette o’connor: https://orcid.org/0000-0003-0604-7822 adrian j. smith: https://orcid.org/0000-0002-8375-0805 kimberley e. wever: https://orcid.org/0000-0003-3635-3660 suzanne fricke: https://orcid.org/0000-0002-4412-9717 funding the symposium on animal systematic reviews received funding from the medical library association. conflict of interest participants were approached to be on the discussion panel based on their personal or organisational involvement with evidence synthesis of animal studies. as part of the discussion, participants were encouraged to mention resources or initiatives familiar to them, which included those originating from themselves or their organisations. references bahor, z., liao, j., currie, g., ayder, c., macleod, m., mccann, s.k., bannach-brown, a., wever, k., soliman, n., wang, q., doran-constant, l., young, l., sena, e.s. & sena, c. 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(2021). formal and informal science advice in emergencies: covid-19 in the uk. interface focus. 11(6), 20210059. doi: https://doi.org/10.1098/rsfs.2021.0059 contribute to the evidence there are two main ways you can contribute to the evidence base while also enhancing your cpd: tell us your information need write a knowledge summary either way, you will be helping to add to the evidence base, and strengthen the decisions that veterinary professionals around the world make to give animals the best possible care. learn more here: https://veterinaryevidence.org/index.php/ve/guidelines-for-authors licence copyright (c) 2023 erik fausak, melissa c. funaro, andrea c. kepsel, erin r.b. eldermire, margaret foster, hannah f. norton, kim mears, molly e. crews, marnie brennan, gillian l. currie, megan r. lafollette, annette o’connor, adrian j. smith, kimberley e. wever & suzanne fricke. this work is licensed under a creative commons attribution 4.0 international license. veterinary evidence uses the creative commons copyright creative commons attribution 4.0 international license. that means users are free to copy and redistribute the material in any medium or format. remix, transform, and build upon the material for any purpose, even commercially – with the appropriate citation. intellectual property rights authors of articles submitted to rcvs knowledge for publication will retain copyright in their work, and will be required to grant to rcvs knowledge a non-exclusive licence of the rights of copyright in the materials including but not limited to the right to publish, re-publish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to licence or permit others to do so. disclaimer any opinions expressed in articles and other publication types published in veterinary evidence are the author's own and do not necessarily reflect the view of the rcvs knowledge. veterinary evidence is a resource to help inform, and the content herein should not override the responsibility of the practitioner. practitioners should also consider factors such as individual clinical expertise and judgement along with patient’s circumstances and owners’ values. authors are responsible for the accuracy of the content. while the editor and publisher believe that all content herein are in accord with current recommendations and practice at the time of publication, they accept no legal responsibility for any errors or omissions, and make no warranty, express or implied, with respect to material contained within. for further information please refer to our terms of use.   veterinary evidence is an rcvs knowledge initiative. issn: 2396-9776 first floor, 10 queen street place, london ec4r 1be resources student awards staff login policies privacy policy accessing information policy cookie declaration terms of use copyright notices stay connected podcasts twitter facebook instagram linkedin back to top royal college of veterinary surgeons trust (trading as rcvs knowledge) is a registered charity no. 230886. registered as a company limited by guarantee in england and wales no. 598443.