Health-Related Quality of Life of Children and Adolescents with Sickle Cell Disease in the Middle East and North Africa Region A systematic review *Suthan Pandarakutty,1 Kamala Murali,2 Judie Arulappan,3 Sulaiman D. Al Sabei4 Sultan Qaboos University Med J, November 2020, Vol. 20, Iss. 4, pp. e280–289, Epub. 21 Dec 20 Submitted 2 Dec 19 Revision Req. 26 Feb 20; Revision Recd. 2 Apr 20 Accepted 15 May 20 1Department of Nursing, College of Health Sciences, University of Buraimi, Al Buraimi, Oman; 2Department of Paediatric Nursing, Rani Meyyammai College of Nursing, Annamalai University, Chidambaram, Tamil Nadu, India; Departments of 3Maternal & Child Health and 4Fundamentals & Administration, College of Nursing, Sultan Qaboos University, Muscat, Oman *Corresponding Author’s e-mail: suthan0912@gmail.com Sickle cell disease (scd) is a hereditary disorder that often results in complications incl- uding acute and chronic pain, severe anaemia, infection and stroke.1 The disease primarily affects the development of red blood cells, resulting in the formation of haemoglobin S (Hb S), an abnormal type of haemoglobin which causes red blood cells to become sickle-shaped and inflexible. These abnormal cells clump together in the arteries, blocking blood flow to various organs and causing various complications.1,2 The most common and severe form of SCD is sickle cell anaemia (SCA) which results when both parents inherit the Hb S variant; in contrast, sickle cell trait (SCT), which occurs when Hb S volume is <50%, is less severe.2,3 Overall, SCD is linked with high morbidity and mortality particularly among young children under the age of five and adolescents.4–9 In addition, it can have adverse social and economic consequences.10 As such, both the World Health Organization (WHO) and the review جودة احلياة املرتبطة بصحة األطفال واملراهقني املصابني بداء اخلالاي املنجلية يف منطقة الشرق األوسط ومشال افريقيا مراجعة منهجية �سوثان بانداركوتي، كاماال مورايل، جودي ارالبان، �سليمان داوؤود ال�سابعي abstract: Sickle cell disease (SCD) can significantly impair the health-related quality of life (HRQOL) of children and adolescents. This review aimed to assess current evidence regarding the HRQOL of children and adolescents with SCD in the Middle East and North Africa region. A systematic search of various databases was conducted to identify relevant articles, including MEDLINE® (National Library of Medicine, Bethesda, Maryland, USA), Scopus® (Elsevier, Amsterdam, the Netherlands), Cumulative Index to Nursing and Allied Health Literature®, Masader (Oman Virtual Science Library, Muscat, Oman) and EBSCOhost (EBSCO Information Services, Ipswich, Massachusetts, USA). A total of 533 articles were identified; however, only 10 were eligible for inclusion in the final analysis. Results from these studies showed that children and adolescents with SCD had compromised HRQOL compared to their healthy peers, particularly in terms of physical, psychosocial, familial, financial and academic functioning. Therefore, interventions are necessary to improve overall HRQOL outcomes for this population. Keywords: Sickle Cell Disease; Health-Related Quality Of Life; Infants; Children; Adolescents; Middle East; North Africa. امللخ�ص: ميكن لداء اخلاليا املنجلية اأن ي�سعف ب�سكل كبري جودة احلياة املرتبطة ب�سحة االأطفال واملراهقني. هدفت هذه املراجعة اإىل تقييم االأدلة احلالية املتعلقة باالأطفال واملراهقني امل�سابني بداء اخلاليا املنجلية يف منطقة ال�رشق االأو�سط و�سمال اإفريقيا. مت اإجراء بحث منهجي لقواعد البيانات املختلفة لتحديد املقاالت ذات ال�سلة، مبا يف ذلك ميدالين )املكتبة الوطنية للطب، بيثي�سدا، مرييالند، الواليات املتحدة االأمريكية(، �سكوب�ض )اأيل�سيفري، اأم�سرتدام، هولندا(، الفهر�ض الرتاكمي للتمري�ض واالأدب ال�سحي املتحالف، م�سادر )مكتبة عمان االفرتا�سية للعلوم، م�سقط، عمان(، وايبي�سكو )ايبي�سكو خلدمات املعلومات، اإب�سويت�ض، ما�سات�سو�ست�ض، الواليات املتحدة االأمريكية(. مت حتديد ما جمموعه 533 مقالة؛ ومع ذلك، كان فقط 10 منها موؤهلني لالإدراج يف التحليل النهائي. اأظهرت نتائج هذه الدرا�سات اأن االأطفال واملراهقني امل�سابني البدين االأداء حيث من �سيما ال االأ�سحاء، باأقرانهم مقارنة بال�سحة املرتبطة احلياة جودة يف لنق�ض تعر�سوا قد املنجلية اخلاليا بداء والنف�سي واالجتماعي والعائلي واملايل واالأكادميي. لذلك، فاإنه من ال�رشوري القيام بالتدخالت املنا�سبة لتح�سني النتائج االإجمالية جلودة احلياة املرتبطة بال�سحة لهذه الفئة من ال�سكان. الكلمات املفتاحية: داء اخلاليا املنجلية؛ جودة احلياة املرتبطة بال�سحة؛ الر�سع؛ اأطفال؛ مراهقني؛ ال�رشق االأو�سط؛ �سمال افريقيا. This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License. https://doi.org/10.18295/squmj.2020.20.04.002 https://creativecommons.org/licenses/by-nd/4.0/ Suthan Pandarakutty, Kamala Murali, Judie Arulappan and Sulaiman D. Al-Sabei Review | e281 United Nations General Assembly have confirmed that SCD represents a global public health problem.11 Worldwide, approximately 25 million people suffer from SCD; according to the WHO, more than 300,000 infants are born with a major haemoglobin disease every year, of which SCD accounts for 200,000 cases.4,12 Varying rates of SCD have been reported in different regions due to differences in Hb S gene prevalence (2– 30%). In the USA, approximately 100,000 are affected by SCD, with one in every 365 African-American and 16,300 Hispanic-American births, while the SCT is reported in one in 13 black or African-American babies.2 A recent survey reported that approximately 12,000–15,000 people were affected in the UK, equivalent to one in 4,600 people.13 In the Netherlands, 800 newborns are born with SCD every year.14 In contrast, the global burden of SCD is more pronounced in the Middle East and North Africa (MENA) region. In Africa, approximately 10–15 million people live with SCD, with Congo and Nigeria most affected.4,7,15–17 The high prevalence of SCD in this region is likely due to the increased frequency of consanguineous marriages particularly between first-degree relatives.11 High rates of consanguineous marriages have been reported in Saudi Arabia (42– 67%), Sudan (44–63%), Qatar (54%), the United Arab Emirates (40–54%), Jordan (29–64%), Yemen (40– 45%) and Egypt (21–33%).1,18,19 In the Middle East, the highest prevalence of SCD and SCT is in eastern Saudi Arabia (2.6% and 21%, respectively).20 In 2015, the incidence of paediatric SCA was 2,238 in Egypt and 25,375 in Iraq.21 Studies from Oman indicate that approximately 3,000 people live with SCD, with an estimated 118 new cases every year and SCT present in one in 370 live births.22–25 Young children and adolescents are more vulnerable to lifelong SCD complications such as vaso- occlusive crises (VOCs), acute splenic sequestration crises, acute chest syndrome (ACS), central nervous system infarctions, haemolytic and aplastic crises and avascular hip necrosis.5,26,27 In children, the most common complication of SCD is painful VOCs.28,29 These occur when the irregularly-shaped red blood cells become stuck in the small vessels, causing multiple organ infarctions including kidney, spleen, bone and brain infarctions.30 Risk factors for VOC include exposure to cold, hypoxia, acidosis, inflamm- ation, fatigue, physical activity and emotional stress.31 A study of Omani children revealed that 22% of 240 children with SCD developed ACS, with 71% of cases preceded by painful VOCs.32 In another study of Omani children with SCD, VOCs constituted the main reason for admission in 83% of 316 hospital admissions over a 12-month period.33 Current management of SCD focuses primarily on the maintenance of health and treatment of acute and chronic complications. Several important modal- ities such as hydroxyurea (HU) therapy and blood trans- fusions, have been found to boost patient outcomes.34,35 In particular, HU therapy reduces the frequency of VOCs and ACS thereby reducing the need for blood transfusions and associated hospitalisation.36 While stem cell transplantation is the intervention most likely to be curative in nature, this option is often associated with several complications.37 Despite recent advances in SCD treatment, the health-related quality of life (HRQOL) of children and adolescents with SCD remains poor compared to their healthy peers particularly with regards to physical, mental, social and academic domains.38,39 Although many systematic reviews are available regarding HRQOL in children and adolescents with SCD, none focus specifically on the MENA region. As outlined earlier, the prevalence of SCD is much higher in this region; hence, understanding the impact of SCD on the HRQOL of children and adolescents in this region would be invaluable in order to inform future interventions such as premarital genetic counselling and potential lifestyle modification strategies, and to identify and prioritise patient-care decisions. Therefore, this systematic review aimed to summarise and analyse the existing empirical literature with regards to the HRQOL of children and adolescents living with SCD in the MENA region, discuss the implications of these findings on research and clinical practice and suggest strategies for improving HRQOL in this region. Methods This systematic review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.40 A systematic search of various electronic databases was performed to identify articles assessing the HRQOL of children and adolescents with SCD in the MENA region published between January 2010 and March 2020 including the MEDLINE® (National Library of Medicine, Bethesda, Maryland, USA), Scopus® (Elsevier, Amsterdam, the Netherlands), Cumulative Index to Nursing and Allied Health Literature®, Masader (Oman Virtual Science Library, Muscat, Oman) and EBSCOhost (EBSCO Information Services, Ipswich, Massachusetts, USA) databases. The search terms included the following in various combinations: “health-related quality of life”, “quality of life”, “sickle cell disease”, “sickle cell anaemia”, “Middle East”, “North Africa”, “infant,” “children” and Health-Related Quality of Life of Children and Adolescents with Sickle Cell Disease in the Middle East and North Africa Region A systematic review e282 | SQU Medical Journal, November 2020, Volume 20, Issue 4 “adolescents”. All full-text peer-reviewed articles were included in the final analysis if they met the following criteria: (1) the articles constituted research studies assessing the HRQOL of children and adolescents with SCD aged <21 years; (2) the population of interest was relevant to the MENA region; (3) the articles were published in English between January 2010 and March 2020; and (4) the population of interest included all SCD genotypes. Articles published before 2010 and in languages other than English were excluded, as were systematic reviews, meta-analyses, editorials, case studies, pilot studies and unpublished research, as well as studies focusing on the perspectives of adults, caregivers, parents or healthcare providers. Following the initial literature search, the authors screened the titles and abstracts of each relevant article to eliminate duplicate results. In addition, the reference lists of articles retrieved during the database search were reviewed to identify additional articles for inclusion in the analysis. Subsequently, two authors independently evaluated the full text of each article to determine its eligibility according to the inclusion criteria, with any disagreements settled by consensus. In the third step, the authors independently collected and consolidated relevant data from the articles as per Garrard’s matrix method including the name and profession of the authors, year of publication of the article, purpose, design and setting of the study, period of recruitment, age group, characteristics and size of the sample, type of HRQOL instrument, type of rater (i.e. self or proxy) and relevant outcomes from the study. A total of 533 articles were initially identified during the literature search. After removing duplicates, 176 unique articles were available for further screening. Of these, 146 articles were removed because they did not meet the criteria. After screening the full text of the remaining 30 articles, 10 articles met the inclusion criteria and were included in the final analysis [Figure 1]. Two reviewers independently assessed the methodological quality of each study using an adapted version of the Newcastle-Ottawa Quality Assessment Scale, except for mixed-method studies which were assessed using the Mixed Methods Appraisal Tool.41,42 Cross-sectional studies were scored out of 8 points, based on sample collection (four items), comparability (one item) and outcome calculation (two items). Case-control studies were scored out of 9, based on sample size (four items), comparability (one item) and outcome calculation (three items). Cohort studies were scored out of 6, based on sample selection (two items), comparability (one item) and outcome measurement (two items). Each item within the sample selection and outcome criteria received a maximum of one point, while items in the comparability criteria received a maximum of two points. In cases where there was a divergence in scoring, the reviewers discussed the item in question until a consensus was reached; if necessary, a third reviewer was consulted. Studies with final scores of <50% were considered to be of poor methodological quality. Results s t u d y c h a r a c t e r i s t i c s A total of 10 articles were included in the systematic review [Table 1].21,43–51 Of these, nine were observational studies, including five cross-sectional, two case-control and two cohort studies.21,44–51 The Figure 1: Diagram showing the search process used to identify articles for inclusion in the systematic review. Suthan Pandarakutty, Kamala Murali, Judie Arulappan and Sulaiman D. Al-Sabei Review | e283 Table 1: Characteristics of studies assessing the health-related quality of life of children and adolescents with sickle cell disease in the Middle East and North Africa region (N = 10)21,43–51 Author and year of publication Purpose Study design Setting Type of participants Sample size Instrument Rater Relevant findings Quality of study* Boulassel et al.46 (2019) To investigate factors that affect HRQOL in children with SCA Cross- sectional Oman Children with SCA aged 2–16 years and their caretakers 123 PedsQL™ V4 SCD module Self and proxy • Children with SCA had reduced HRQOL scores. • The lowest scores fell on the pain impact subscale, with an average of 41 ± 21% (range: 2.5–100%), suggesting that HRQOL is adversely affected by pain. • In contrast, the highest score fell on the Worry II subscale, with an average of 70 ± 28% (range: 12.5–100%). 75% (6/8) Kambasu et al.43 (2019) To evaluate the HRQOL of adolesc- ents with SCD Mixed- method Uganda Children with SCD aged 8–17 years and their caretakers 140 PedsQL™ generic core scale and FGDs with adolescents and caretakers Self and proxy • HRQOL scores were low in the physical functioning, emotional functioning and academic functioning domains. 75% Salih51 (2019) To examine the impact of SCA on the QOL of school- aged children in three dimensions (psychological, social and academic) Cross- sectional Sudan Children with SCA aged 7–15 years 107 Structured questionnaire Self • SCD posed multiple social and psychological problems that need to be addressed. • Common problems included enuresis, depressive symptoms, school absenteeism and deterioration in school performance. 62.5% (5/8) Cevher et al.47 (2018) To evaluate QOL, clinical effective- ness and satisfac- tion in children and young adults with SCD receiving HU therapy Cohort Turkey Children aged 7–17 years and young adults aged 18–22 years with SCD who received HU therapy for ≥1 year 50 (34 children and 16 young adults) CHQ-PF50 Self and proxy • Both QOL and adherence to HU therapy were low, likely due to the lack of effectiveness of HU therapy, along with comorbidity, concomitant drug use and side-effects. 66.7% (4/6) Essawy et al.21 (2018) To evaluate the QOL of children with SCA Cross- sectional Iraq Children with SCA aged 6–12 years and their mothers 100 Structured questionnaire and interviews Self and proxy • SCA significantly affected the QOL of the children. • Two-thirds of the children had poor QOL, less than a quarter had neutral QOL and few had good QOL. • Severe pain was reported by 78% of the affected children. 75% (6/8) Senol et al.48 (2016) To evaluate QOL, clinical effective- ness and satisfac- tion in patients with BTM and SCA receiving DFX chelation therapy Cohort Turkey Children aged 5–18 years and adults with BTM or SCA who received DFX therapy for ≥6 months 72 (37 children and 35 adults) CHQ-PF50 Proxy • Patients with SCA had significantly lower HRQOL scores for general health, physical activity, role/social limitations, parental impact- time and family activities and higher scores for health transition compared to BTM patients (P <0.05). 83.3% (5/6) Alharbi et al.44 (2016) To assess the HRQOL of children with SCA Cross- sectional Saudi Arabia Children with SCD aged 6–12 years and their mothers 40 PedsQL™ generic core scale Self and proxy • SCD significantly affected most HRQOL domains, including physical, social, emotional and academic wellbeing domains. 87.5% (7/8) Sehlo and Kamfar45 (2016) To evaluate the association of social support, disease severity and depression on HRQOL in children with SCD Case- control Saudi Arabia Children with SCD aged 10–15 years and matched healthy controls aged 9–15 years 120 (60 cases and 60 controls) PedsQL™ generic core scale Self and proxy • Disease severity and depression were associated with poor QOL in children with SCD. 100% (9/9) HRQOL = health-related quality of life; SCA = sickle cell anaemia; PedsQL™ = Pediatric Quality of Life Inventory™; V4 = Version 4.0; SCD = sickle cell disease; FGDs = focus group discussions; QOL = quality of life; HU = hydroxyurea; CHQ-PF50 = Child Health Questionnaire - Parent Form 50; BTM = β-thalassemia major; DFX = deferasirox; WHOQ- OL-BREF = World Health Organisation Quality of Life Brief Version; SF-36 V2 = 36-item Medical Outcomes Study Short-Form Version 2. *Methodological quality was assessed using an adapted version of the Newcastle-Ottawa Quality Assessment Scale, except for mixed-method studies, which were assessed using the Mixed Methods Appraisal Tool.41,42 Cross-sectional, cohort and case-control studies were scored out of 8, 6 and 9, respectively, with scores of <50% considered to indicate poor methodological quality. Health-Related Quality of Life of Children and Adolescents with Sickle Cell Disease in the Middle East and North Africa Region A systematic review e284 | SQU Medical Journal, November 2020, Volume 20, Issue 4 final study used a mixed-method design involving both quantitative and qualitative measures.43 Most of the authors were nurses, medicine or health sciences faculty members, psychiatrists, haematologists, pharmacists or geneticists. Four studies were conducted in Saudi Arabia, two in Turkey and one each in Iraq, Sudan, Uganda and Oman.21,43–51 Most of the studies focused primarily on children and adolescents aged 2–18 years.21,43–46,48,50,51 However, two studies focused both on paediatric and young adult populations aged 18–22 years.47,49 In most cases, self-reported measures were applied to children over the age of 8 years who were literate and capable of comprehension, with caregiver proxy reports utilised for those between 2–8 years.21,43–47,49–51 The sample size for children and adolescents with SCD or SCA ranged from 37–180.21,43–51 m e a s u r e s o f h e a lt h-r e l at e d q u a l i t y o f l i f e Various tools were used to assess the HRQOL of children and adolescents with SCD. Two studies used self- designed structured questionnaires completed during interviews.21,51 Three studies utilised the generic core scale of the Pediatric Quality of Life Inventory™ (PedsQL™); in addition, another study applied the PedsQL™ SCD module scale, Version 4.0.43–46 Two studies used the Child Health Questionnaire - Parent Form 50.47,48 Finally, the WHO Quality of Life Brief Version scale and 36-item Medical Outcomes Study Short-Form was applied in one study each.49,50 Apart from the self-designed questionnaires, all of these instruments have been previously validated for use in different populations and various languages.43–50 d o m a i n s o f h e a lt h-r e l at e d q u a l i t y o f l i f e Four distinct HRQOL domains were identified in the studies including physical wellbeing, psychological wellbeing, family/financial wellbeing and academic functioning.21,43–51 In certain cases, specific findings from the studies encompassed more than one of these domains because of the interconnected nature of HRQOL. p h y s i c a l w e l l-b e i n g Boulassel et al. reported that children with SCA in Oman demonstrated low HRQOL scores; in particular, the lowest scores were found on the pain impact scale thereby indicating that HRQOL in this cohort was Table 1 (cont’d): Characteristics of studies assessing the health-related quality of life of children and adolescents with sickle cell disease in the Middle East and North Africa region (N = 10)21,43–51 Author and year of publication Purpose Study design Setting Type of participants Sample size Instrument Rater Relevant findings Quality of study* Al Jaouni et al.49 (2013) To assess the HRQOL of patients with SCD and to measure the impact of treatment adher- ence on complic- ations, disease sev- erity, crises and out- comes Cross- sectional Saudi Arabia Patients with SCD aged 2–48 years 115 (including 23 children aged 1–12 years, 33 adolescents aged 13–18 years and 25 adults aged 18–48 years) WHOQOL- BREF Self and proxy • Extremely ill patients had significantly lower HRQOL scores (P = 0.002). • Pain was the main cause of hospitalisation (51.3%). • Patients with painful episodes (31.3%) and on regular narcotics had significantly lower HRQOL scores (P <0.001). • HRQOL scores decreased significantly as pain levels increased. • Patients with delayed treatment or those who did not adhere to treatment reported significantly lower HRQL scores (P = 0.001). 75% (6/8) Amr et al.50 (2011) To evaluate HRQOL deficiencies among adolescents with SCD Case- control Saudi Arabia Adolescents with SCD aged 14–18 years and age- and gender-matched healthy controls 382 (180 cases and 202 controls) SF-36 V2 Self • Adolescents with SCD reported poorer HRQOL scores compared to healthy adolescents, particularly in several HRQOL domains, including physical functioning, body pain and general health 88.9% (8/9) HRQOL = health-related quality of life; SCA = sickle cell anaemia; PedsQL™ = Pediatric Quality of Life Inventory™; V4 = Version 4.0; SCD = sickle cell disease; FGDs = focus group discussions; QOL = quality of life; HU = hydroxyurea; CHQ-PF50 = Child Health Questionnaire - Parent Form 50; BTM = β-thalassemia major; DFX = deferasirox; WHO- QOL-BREF = World Health Organisation Quality of Life Brief Version; SF-36 V2 = 36-item Medical Outcomes Study Short-Form Version 2. *Methodological quality was assessed using an adapted version of the Newcastle-Ottawa Quality Assessment Scale, except for mixed-method studies, which were assessed using the Mixed Methods Appraisal Tool.41,42 Cross-sectional, cohort and case-control studies were scored out of 8, 6 and 9, respectively, with scores of <50% considered to indicate poor methodological quality. Suthan Pandarakutty, Kamala Murali, Judie Arulappan and Sulaiman D. Al-Sabei Review | e285 adversely affected by pain.46 In Uganda, Kambasu et al. observed low scores in terms of physical, emotional and academic functioning among adolescents with SCD.43 According to Cevher et al., both quality of life and adherence to HU therapy was low among paediatric and young adult patients in Turkey; this was attributed to the lack of effectiveness of HU therapy, in addition to comorbidity, concomitant drug use and side-effects.47 In Iraq, Essawy et al. concluded that SCA significantly affects the quality of life of children, with more than two-thirds of the cohort noted to have poor quality of life; moreover, the majority (78%) reported being in severe pain.21 Among a cohort of SCD patients in Saudi Arabia, Al Jaouni et al. observed that those who were extremely ill demonstrated significantly lower HRQOL scores, with HRQOL scores decreasing significantly as pain levels increased.49 In addition, patients with delayed or low adherence to treatment reported lower HRQL scores.49 Finally, in another study set in Saudi Arabia, Amr et al. showed that adolescents with SCD had poorer HRQOL scores compared to healthy adolescents, particularly in terms of physical functioning, body pain and general health.50 p s y c h o l o g i c a l w e l l-b e i n g In Sudan, Salih confirmed that SCD caused multiple social and psychological problems among school- aged children, with enuresis, depressive symptoms, school absenteeism and deterioration in academic performance being most common.51 Additionally, Sehlo and Kamfar reported associations between poor quality of life and disease severity and depression among children with SCD in Saudi Arabia.45 fa m i ly a n d f i n a n c i a l w e l l-b e i n g In Turkey, Senol et al. reported significantly lower scores among a cohort of children and adolescents with SCA for various HRQOL-related subscales including general health, physical activity-related limitations, physical functioning, parental impact-time and family activities compared to patients with β-thalassaemia major.48 In addition, the former group demonstrated significantly higher scores in terms of health transition compared to the latter.48 a c a d e m i c f u n c t i o n i n g Alharbi et al. found that SCD significantly affected most HRQOL domains in a group of children in Saudi Arabia including physical, social, emotional and academic well-being domains.44 Discussion Children with SCD undergo frequent hospitalisation due to painful crises which can affect a myriad of other facets of life including academic achievement, school attendance, social activities and sleep quality.29,52 Moreover, SCD can affect familial relationships and the ability to engage in routine family activities; for caregivers, looking after a child with SCD can represent an emotional and financial burden.53 Individuals with SCD also encounter stigma for a variety of reasons such as race, disability status, socioeconomic status, chronic pain and delayed growth and puberty.54 This systematic review examined the existing empirical literature regarding the HRQOL of children and adolescents with SCD in the MENA region. Overall, this population demonstrated poor HRQOL in all domains compared to their healthy peers including physical, psychological, familial, academic, social and financial functioning.21,43–51 Palermo et al. reported similar findings in a case-control study comparing 120 healthy children to 58 children with SCD.55 Using the Child Health Questionnaire, the researchers found that the physical, psychological and social wellbeing of children with SCD was reduced in comparison to the healthy control group.55 After applying the PedsQL™ instrument, Dale et al. found that 63%, 28% and 55% of 124 children and adolescents with SCD were at risk of physical disability, poor social functioning and reduced academic performance, respectively.39 Such findings highlight the need for urgent strategies to improve the HRQOL of children and adolescents with SCD. Pain is a significant predictor for poor HRQOL among children and adolescents with SCD and a primary indicator of impaired physical and psychological functioning.56 Thornburg et al. found that children with SCD undergoing HU therapy demonstrated better physical and cognitive function compared to those who could not take the drug due to the extent of the disorder.57 Panepinto et al. revealed that poor physical HRQOL scores were correlated with clinical comorbidities, older age and lower family income.58 Pain has also been positively associated with increased maternal and caregiver stress and impaired family functioning, thereby leading to poor HRQOL outcomes.56 These findings are supported by those of other studies.46,59 As such, careful pain assessment at home and prompt management is recommended in order to promote resilience among children with SCD and increase their quality of life. Menezes et al. observed statistically significant gender differences in most HRQOL domains.52 Health-Related Quality of Life of Children and Adolescents with Sickle Cell Disease in the Middle East and North Africa Region A systematic review e286 | SQU Medical Journal, November 2020, Volume 20, Issue 4 However, contradictory findings have been reported regarding the effect of gender on pain sensation among children and adolescents with SCD. According to Andong et al., adolescent girls with SCD demonstrated significantly lower levels of physical activity and physical pain; in contrast, Kambasu et al. found that pain rates were higher in female children with SCD compared to their male counterparts.43,60 Therefore, further studies are needed to better understand gender differences in pain perception among children and adolescents with SCD so as to tailor pain management strategies accordingly. Various studies have reported poor cognitive and psychosocial performance in children and adolescents with SCD.58,61,62 In a study conducted in India, Patel and Pathan reported that children with SCD demonstrated low HRQOL scores in in physical, psychosocial and cognitive areas.61 These results are supported by other studies which revealed that children with SCD had lower self-esteem than healthy children.58,62 With regards to family, Wonkam et al. found that mothers of children with SCD had a higher risk of depression compared to mothers with healthy children.59 Families with children affected by SCD often face financial challenges. In many developing countries, national health insurance or social welfare programmes are lacking, thus placing the financial burden of care for children with chronic diseases on the individual family. In Nigeria, Lagunju et al. observed that families of children with SCD often experienced severe hardship due to the child’s medical expenses, adversely affecting the family’s basic needs such as housing and food; moreover, loss of employment resulting from time spent caring for a child with SCD also contributed significantly to this burden.34 Therefore, countries in the MENA region should take steps to help improve existing financial support systems for families affected by paediatric SCD, perhaps through the provision of social welfare subsidies or programmes. Various studies have shown that children with SCD exhibit poor academic functioning compared to healthy children, with pain once again found to be a significant predictor of such outcomes.44,52,56 Indeed, children and adolescents with SCD are often absent from school, thereby missing out on important educational experiences and daily social activities due to frequent hospitalisation secondary to pain crises, depression, social stigma and poor social support systems.44,52 Thus, it is necessary for educators to take necessary steps to improve the academic functioning of children with SCD, for instance by establishing school- or peer-led support groups and special extracurricular classes for affected children, or by allowing special leeway with regards to high rates of absenteeism for medical reasons. Lack of awareness of the disease has been linked with poor HRQOL outcomes among children and adolescents with SCD, especially as awareness is usually poor among both affected patients and caregivers. Shahine et al. found that an increase in awareness on the part of the caregiver was significantly associated with a decrease in the frequency of hospitalisation among children with SCD.38 Another study carried out by Al-Azri et al. indicated that the quality of life of children with SCD in Oman remained low primarily because of a lack of awareness of the disease.63 Therefore, health promotion and educational programmes are recommended to increase awareness of SCD and promote mandatory premarital screening to reduce the incidence of the disease in the MENA region. Social support can have a major impact on the resilience of children with SCD such as that offered by family members, teachers, peers and friends. Several studies have concluded that greater parental support and involvement is significantly linked to decreased depressive symptoms and better quality of life in children with SCD.45,64 Play therapy is a potential option to help children with SCD to express their emotions, improve communication with caregivers and peers and encourage socialisation. Similarly, Pandarakutty et al. reported that a nurse-led filial therapy and educational intervention resulted in a significant improvement in HRQOL scores among a group of children with SCD in Oman, particularly in terms of reducing emotions, improving knowledge, enhancing parental support and reinforcing family relationships.65 i m p l i c at i o n s f o r f u t u r e r e s e a r c h The findings of this systematic review underline an urgent need for practical measures to improve the HRQOL of children and adolescents with SCD in the MENA region. Such initiatives should focus on increasing knowledge and awareness of SCD, developing support groups to enhance the psychological wellbeing of children and adolescents with SCD and their caregivers, mitigating the economic burden of care on the families of children with SCD and strengthening existing family, social and academic support systems. Further studies are therefore necessary to help design, implement and assess the effectiveness of such strategies in this region. l i m i tat i o n s This research was subject to certain limitations. A meta-analysis could not be conducted to determine correlations between variables due to the differences Suthan Pandarakutty, Kamala Murali, Judie Arulappan and Sulaiman D. Al-Sabei Review | e287 in statistical analyses across studies. In addition, articles focusing on HRQOL outcomes of children and adolescents with SCD in the MENA region which were published in other languages could not be included in the final analysis, possibly resulting in the lack of inclusion of relevant non-English language studies. Conclusion A systematic review of studies assessing the HRQOL of children and adolescents with SCD in the MENA region revealed that the HRQOL of this population was poor in comparison to healthy children in all domains including physical, psychological, familial, academic, social and financial functioning. As such, healthcare providers, educators and policymakers should implement strategies to improve the HRQOL of this group. The authors recommend the implementation of mandatory awareness and premarital screening programmes, thereby increasing understanding, reducing stigma and minimising the incidence of hereditary diseases such as SCD. In addition, interventions such as play therapy may help to encourage socialisation, reduce psychological stress and strengthen familial bonds. Finally, existing financial support systems should be strengthened so as to alleviate the economic burden of medical care on affected families. c o n f l i c t o f i n t e r e s t The authors declare no conflicts of interest. f u n d i n g No funding was received for this research. References 1. Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, et al. Management of sickle cell disease: Summary of the 2014 evidence-based report by expert panel members. JAMA 2014; 312:1033–48. https://doi.org/10.1001/jama.2014.10517. 2. Centers for Disease Control and Prevention. Data & statistics on sickle cell disease. From: www.cdc.gov/ncbddd/sicklecell/ data.html Accessed: Apr 2020. 3. Lemanek KL, Ranalli M. Sickle cell disease. In: Roberts MC, Steele RG, Eds. Handbook of Pediatric Psychology, 4th ed. New York, USA: Guilford Press, 2009. Pp. 303–18. 4. McGann PT, Hernandez AG, Ware RE. Sickle cell anaemia in sub-Saharan Africa: Advancing the clinical paradigm through partnerships and research. Blood 2017; 129:155–61. https://doi. org/10.1182/blood-2016-09-702324. 5. Quinn CT. Sickle cell disease in childhood: From newborn screening through transition to adult medical care. Paediatr Clin North Am 2013; 60:1363–81. https://doi.org/10.1016/j. pcl.2013.09.006. 6. Aygun B, Odame I. A global perspective on sickle cell disease. Pediatr Blood Cancer 2012; 59:386–90. https://doi.org/10.1002/ pbc.24175. 7. Makani J, Cox SE, Soka D, Komba AN, Oruo J, Mwamtemi H, et al. Mortality in sickle cell anemia in Africa: A prospective cohort study in Tanzania. PloS One 2011; 6:e14699. https://doi. org/10.1371/journal.pone.0014699. 8. Sack FF, Njangtang DM, Chemegni BC, Djientcheu VD. Prev- alence of sickle cell disease in newborns in the Yaounde Central Hospital. J Med Res 2017; 3:277–9. https://doi.org/10.31254/ jmr.2017.3607. 9. Macharia AW, Mochamah G, Uyoga S, Ndila CM, Nyutu G, Makale J, et al. The clinical epidemiology of sickle cell anemia in Africa. Am J Hematol 2018; 93:363–70. https://doi.org/10.1002/ ajh.24986. 10. Kauf TL, Coates TD, Huazhi L, Mody-Patel N, Hartzema AG. The cost of health care for children and adults with sickle cell disease. Am J Hematol 2009; 84:323–7. https://doi.org/10.1002/ ajh.21408. 11. Piel FB, Hay SI, Gupta S, Weatherall DJ, Williams TN. Global burden of sickle cell anaemia in children under five, 2010- 2050: Modelling based on demographics, excess mortality, and interventions. PLoS Med 2013; 10:e1001484. https://doi. org/10.1371/journal.pmed.1001484. 12. World Health Organization. Sickle-cell anaemia: Report by the secretariat. From: https://apps.who.int/gb/archive/pdf_files/ WHA59/A59_9-en.pdf Accessed: Apr 2020. 13. Dormandy E, James J, Inusa B, Rees D. How many people have sickle cell disease in the UK? J Public Health (Oxf ) 2018; 40:e291–5. https://doi.org/10.1093/pubmed/fdx172. 14. Bouva MJ, Mohrmann K, Brinkman HB, Kemper-Proper EA, Elvers B, Loeber JG, et al. Implementing neonatal screening for haemoglobinopathies in the Netherlands. J Med Screen 2010; 17:58–65. https://doi.org/10.1258/jms.2010.009075. 15. Carey PJ. Addressing the global health burden of sickle cell disease. Int Health 2014; 6:269–70. https://doi.org/10.1093/ inthealth/ihu045. 16. Piel FB, Patil AP, Howes RE, Nyangiri OA, Gething PW, Dewi M, et al. Global epidemiology of sickle haemoglobin in neonates: A contemporary geostatistical model-based map and population estimates. Lancet 2013; 381:142–51. https://doi. org/10.1016/S0140-6736(12)61229-X. 17. Mulumba LL, Wilson L. Sickle cell disease among children in Africa: An integrative literature review and global recomm- endations. Int J Africa Nurs Sci 2015; 3:56–64. https://doi. org/10.1016/j.ijans.2015.08.002. 18. Tadmouri GO, Nair P, Obeid T, Al Ali MT, Al Khaja N, Hamamy HA. Consanguinity and reproductive health among Arabs. Reprod Health 2009; 6:17. https://doi.org/10.1186/1742- 4755-6-17. 19. Memish ZA, Saeedi MY. Six-year outcome of the national premarital screening and genetic counseling program for sickle cell disease and β-thalassemia in Saudi Arabia. Ann Saudi Med 2011; 31:229–35. https://doi.org/10.4103/0256-4947.81527. 20. Jastaniah W. Epidemiology of sickle cell disease in Saudi Arabia. Ann Saudi Med 2011; 31:289–93. https://doi.org/10.4103/0256- 4947.81540. 21. Essawy MA, El Sharkawy A, Al Shabbani Z, Aziz AR. Quality of life of children with sickle cell anemia. IOSR J Nurs Health Sci 2018; 7:29–39. https://doi.org/10.9790/1959-0702102939. 22. El-Hazmi MA, Al-Hazmi AM, Warsy AS. Sickle cell disease in Middle East Arab countries. Indian J Med Res 2011; 134:597–610. https://doi.org/10.4103/0971-5916.90984. https://doi.org/10.1001/jama.2014.10517 https://doi.org/10.1182/blood-2016-09-702324 https://doi.org/10.1182/blood-2016-09-702324 https://doi.org/10.1016/j.pcl.2013.09.006 https://doi.org/10.1016/j.pcl.2013.09.006 https://doi.org/10.1002/pbc.24175 https://doi.org/10.1002/pbc.24175 https://doi.org/10.1371/journal.pone.0014699 https://doi.org/10.1371/journal.pone.0014699 https://doi.org/10.31254/jmr.2017.3607 https://doi.org/10.31254/jmr.2017.3607 https://doi.org/10.1002/ajh.24986 https://doi.org/10.1002/ajh.24986 https://doi.org/10.1002/ajh.21408 https://doi.org/10.1002/ajh.21408 https://doi.org/10.1371/journal.pmed.1001484 https://doi.org/10.1371/journal.pmed.1001484 https://doi.org/10.1093/pubmed/fdx172 https://doi.org/10.1258/jms.2010.009075 v v https://doi.org/10.1016/S0140-6736%2812%2961229-X https://doi.org/10.1016/S0140-6736%2812%2961229-X https://doi.org/10.1016/j.ijans.2015.08.002 https://doi.org/10.1016/j.ijans.2015.08.002 https://doi.org/10.1186/1742-4755-6-17 https://doi.org/10.1186/1742-4755-6-17 https://doi.org/10.4103/0256-4947.81527 https://doi.org/10.4103/0256-4947.81540 https://doi.org/10.4103/0256-4947.81540 https://doi.org/10.9790/1959-0702102939 https://doi.org/10.4103/0971-5916.90984 Health-Related Quality of Life of Children and Adolescents with Sickle Cell Disease in the Middle East and North Africa Region A systematic review e288 | SQU Medical Journal, November 2020, Volume 20, Issue 4 23. Rajab A, Al Rashdi I, Al Salmi Q. Genetic services and testing in the Sultanate of Oman: Sultanate of Oman steps into modern genetics. J Community Genet 2013; 4:391–7. https://doi.org/10.10 07/s12687-013-0153-1. 24. Alkindi S, Al Zadjali S, Al Madhani A, Daar S, Al Haddabi H, Al Abri Q, et al. Forecasting hemoglobinopathy burden through neonatal screening in Omani neonates. Hemoglobin 2010; 34:135–44. https://doi.org/10.3109/03630261003677213. 25. Rajab AG, Patton MA, Modell B. Study of hemoglobinopathies in Oman through a national register. Saudi Med J 2000; 21:1168–72. 26. Potoka KP, Gladwin MT. Vasculopathy and pulmonary hyper- tension in sickle cell disease. Am J Physiol Lung Cell Mol Physiol 2015; 308:L314–24. https://doi.org/10.1152/ajplung.00252.2014. 27. Brousseau DC, Owens PL, Mosso AL, Panepinto JA, Steiner CA. Acute care utilization and rehospitalizations for sickle cell disease. JAMA 2010; 303:1288–94. https://doi.org/10.1001/jama.2010.378. 28. Jastaniah W, Abrar MB, Khattab T. Treatment related mortality of AML pediatric patients in a single center in Saudi Arabia. Blood 2011; 118:4291. https://doi.org/10.1182/blood.V118.21.4291.4291. 29. Meier ER, Miller JL. Sickle cell disease in children. Drugs 2012; 72:895–906. https://doi.org/10.2165/11632890-000000000-00000. 30. Manwani D, Frenette PS. Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies. Blood 2013; 122:3892–8. https://doi.org/10.1182/blood-2013-05-498311. 31. Yale SH, Nagib N, Guthrie T. Approach to the vaso-occlussive crisis in adults with sickle cell disease. Am Fam Physician 2000; 61:1349–56. 32. Jaiyesimi O, Kasem M. Acute chest syndrome in Omani children with sickle cell disease: Epidemiology and clinical profile. Ann Trop Paediatr 2007; 27:193–9. https://doi.org/10.1179/1465328 07X220307. 33. Jaiyesimi F, Pandey R, Bux D, Sreekrishna Y, Zaki F, Krishnamoorthy N. Sickle cell morbidity profile in Omani children. Ann Trop Paediatr 2002; 22:45–52. https://doi.org/10.1179/027249302125000148. 34. Lagunju IA, Brown BJ, Sodeinde OO. Chronic blood transfusion for primary and secondary stroke prevention in Nigerian child- ren with sickle cell disease: A 5-year appraisal. Pediatr Blood Cancer 2013; 60:1940–5. https://doi.org/10.1002/pbc.24698. 35. Ballas SK, Bauserman RL, McCarthy WF, Castro OL, Smith WR, Waclawiw MA. Hydroxyurea and acute painful crises in sickle cell anemia: Effects on hospital length of stay and opioid utilization during hospitalization, outpatient acute care cont- acts, and at home. J Pain Symptom Manage 2010; 40:870–82. https://doi.org/10.1016/j.jpainsymman.2010.03.020. 36. Voskaridou E, Christoulas D, Bilalis A, Plata E, Varvagiannis K, Stamatopoulos G, et al. The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: Results of a 17-year, single-center trial (LaSHS). Blood 2010; 115:2354–63. https://doi.org/10.11 82/blood-2009-05-221333. 37. Angelucci E, Matthes-Martin S, Baronciani D, Bernaudin F, Bonanomi S, Cappellini MD, et al. Hematopoietic stem cell trans- plantation in thalassemia major and sickle cell disease: Indic- ations and management recommendations from an international expert panel. Haematologica 2014; 99:811–20. https://doi.org/1 0.3324/haematol.2013.099747. 38. Shahine R, Badr LK, Karam D, Abboud M. Educational inter- vention to improve the health outcomes of children with sickle cell disease. J Pediatr Health Care 2015; 29:54–60. https://doi. org/10.1016/j.pedhc.2014.06.007. 39. Dale JC, Cochran CJ, Roy L, Jernigan E, Buchanan GR. Health- related quality of life in children and adolescents with sickle cell disease. J Pediatr Health Care 2011; 25:208–15. https://doi. org/10.1016/j.pedhc.2009.12.006. 40. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta- analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015; 4:1. https://doi.org/10.1186/2046-4053-4-1. 41. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. From: www.ohri.ca/programs/clinical_epidemiology/oxford.asp Accessed: Apr 2020. 42. Pace R, Pluye P, Barlett G, Macaulay AC, Salsberg J, Jagosh J, et al. Testing the reliability and efficiency of the pilot Mixed Methods Appraisal Tool (MMAT) for systematic mixed studies review. Int J Nurs Stud 2012; 49:47–53. https://doi. org/10.1016/j.ijnurstu.2011.07.002. 43. Kambasu DM, Rujumba J, Lekuya HM, Munube D, Mupere E. Health-related quality of life of adolescents with sickle cell disease in sub-Saharan Africa: A cross-sectional study. BMC Hematol 2019; 19:9. https://doi.org/10.1186/s12878-019-0141-8. 44. Alharbi EA, Alamri RF, AlJerayan ES, Salawati HS, Al-Mjershi SM. Quality of life assessment for children with sickle cell disease (SCD) in Mecca region. Int J Med Sci Public Health 2016; 5:901–5. https://doi.org/10.5455/ijmsph.2016.29122015310. 45. Sehlo MG, Kamfar HZ. Depression and quality of life in children with sickle cell disease: The effect of social support. BMC Psychiatry 2015; 15:78. https://doi.org/10.1186/s12888- 015-0461-6. 46. Boulassel MR, Al-Badi A, Elshinawy M, Al-Hinai J, Al-Saadoon M, Al-Qarni Z, et al. Hemoglobin F as a predictor of health-related quality of life in children with sickle cell anemia. Qual Life Res 2019; 28:473–9. https://doi.org/10.1007/s11136-018-2031-0. 47. Cevher F, Ünal S, Küçükkavruk ŞP, Taşdelen B, Tunçtan B. Quality of life, clinical effectiveness, and satisfaction in pediatric and young adult patients with sickle cell disease receiving hydroxyurea therapy. Turk Klin J Med Sci 2018; 38:30–9. https://doi.org/10.5336/medsci.2017-57070. 48. Senol SP, Tiftik EN, Unal S, Akdeniz A, Tasdelen B, Tunctan B. Quality of life, clinical effectiveness, and satisfaction in patients with beta thalassemia major and sickle cell anemia receiving deferasirox chelation therapy. J Basic Clin Pharm 2016; 7:49–59. https://doi.org/10.4103/0976-0105.177706. 49. Al Jaouni SK, Al Muhayawi MS, Halawa TF, Al Mehayawi MS. Treatment adherence and quality of life outcomes in patients with sickle cell disease. Saudi Med J 2013; 34:261–5. 50. Amr MA, Amin TT, Al-Omair OA. Health related quality of life among adolescents with sickle cell disease in Saudi Arabia. Pan Afr Med J 2011; 8:10. https://doi.org/10.4314/pamj.v8i1.71057. 51. Salih KM. The impact of sickle cell anemia on the quality of life of sicklers at school age. J Family Med Prim Care 2019; 8:468–71. https://doi.org/10.4103/jfmpc.jfmpc_444_18. 52. Menezes AS, Len CA, Hilário MO, Terreri MT, Braga JA. Quality of life in patients with sickle cell disease. Rev Paul Pediatr 2013; 31:24–9. https://doi.org/10.1590/s0103-05822013000100005. 53. Adegoke SA, Kuteyi EA. Psychosocial burden of sickle cell disease on the family, Nigeria. Afr J Prim Health Care Fam Med 2012; 4:380. https://doi.org/10.4102/phcfm.v4i1.380. 54. Bhatt-Poulose K, James K, Reid M, Harrison A, Asnani M. Incr- eased rates of body dissatisfaction, depressive symptoms, and suicide attempts in Jamaican teens with sickle cell disease. Pediatr Blood Cancer 2016; 63:2159–66. https://doi.org/10.1002/pbc.26091. 55. Palermo TM, Schwartz L, Drotar D, McGowan K. Parental report of health-related quality of life in children with sickle cell disease. J Behav Med 2002; 25:269–83. https://doi.org/10.1 023/a:1015332828213. 56. Smith KE, Patterson CA, Szabo MM, Tarazi RA, Barakat LP. Predictors of academic achievement for school age children with sickle cell disease. Adv Sch Ment Health Promot 2013; 6:5–20. https://doi.org/10.1080/1754730X.2012.760919. 57. Thornburg CD, Calatroni A, Panepinto JA. Differences in health-related quality of life in children with sickle cell disease receiving hydroxyurea. J Pediatr Hematol Oncol 2011; 33:251–4. https://doi.org/10.1097/MPH.0b013e3182114c54. https://doi.org/10.1007/s12687-013-0153-1 https://doi.org/10.1007/s12687-013-0153-1 https://doi.org/10.3109/03630261003677213 https://doi.org/10.1152/ajplung.00252.2014 https://doi.org/10.1001/jama.2010.378 https://doi.org/10.1182/blood.V118.21.4291.4291 https://doi.org/10.2165/11632890-000000000-00000 https://doi.org/10.1182/blood-2013-05-498311 https://doi.org/10.1179/146532807X220307 https://doi.org/10.1179/146532807X220307 https://doi.org/10.1179/027249302125000148 https://doi.org/10.1002/pbc.24698 https://doi.org/10.1016/j.jpainsymman.2010.03.020 https://doi.org/10.1182/blood-2009-05-221333 https://doi.org/10.1182/blood-2009-05-221333 https://doi.org/10.3324/haematol.2013.099747 https://doi.org/10.3324/haematol.2013.099747 https://doi.org/10.1016/j.pedhc.2014.06.007 https://doi.org/10.1016/j.pedhc.2014.06.007 https://doi.org/10.1016/j.pedhc.2009.12.006 https://doi.org/10.1016/j.pedhc.2009.12.006 https://doi.org/10.1186/2046-4053-4-1 https://doi.org/10.1016/j.ijnurstu.2011.07.002 https://doi.org/10.1016/j.ijnurstu.2011.07.002 https://doi.org/10.1186/s12878-019-0141-8 https://doi.org/10.5455/ijmsph.2016.29122015310 https://doi.org/10.1186/s12888-015-0461-6 https://doi.org/10.1186/s12888-015-0461-6 https://doi.org/10.1007/s11136-018-2031-0 https://doi.org/10.5336/medsci.2017-57070 https://doi.org/10.4103/0976-0105.177706 https://doi.org/10.4314/pamj.v8i1.71057 https://doi.org/10.4103/jfmpc.jfmpc_444_18 https://doi.org/10.1590/s0103-05822013000100005 https://doi.org/10.4102/phcfm.v4i1.380 https://doi.org/10.1002/pbc.26091 https://doi.org/10.1023/a:1015332828213 https://doi.org/10.1023/a:1015332828213 https://doi.org/10.1080/1754730X.2012.760919 https://doi.org/10.1097/MPH.0b013e3182114c54 Suthan Pandarakutty, Kamala Murali, Judie Arulappan and Sulaiman D. Al-Sabei Review | e289 58. Panepinto JA, O’Mahar KM, DeBaun MR, Loberiza FR, Scott JP. Health-related quality of life in children with sickle cell disease: Child and parent perception. Br J Haematol 2005; 130:437–44. https://doi.org/10.1111/j.1365-2141.2005.05622.x. 59. Wonkam A, Mba CZ, Mbanya D, Ngogang J, Ramesar R, Angwafo FF. Psychosocial burden of sickle cell disease on parents with an affected child in Cameroon. J Genet Couns 2014; 23:192–201. https://doi.org/10.1007/s10897-013-9630-2. 60. Andong AM, Ngouadjeu ED, Bekolo CE, Verla VS, Nebongo D, Mboue-Djieka Y, et al. Chronic complications and quality of life of patients living with sickle cell disease and receiving care in three hospitals in Cameroon: A cross-sectional study. BMC Hematol 2017; 17:7. https://doi.org/10.1186/s12878-017-0079-7. 61. Patel AB, Pathan HG. Quality of life in children with sickle cell hemoglobinopathy. Indian J Pediatr 2005; 72:567–71. https://doi.org/10.1007/BF02724180. 62. Malheiros CD, Lisle L, Castelar M, Sá KN, Matos MA. Hip dys- function and quality of life in patients with sickle cell disease. Clin Pediatr (Phila) 2015; 54:1354–8. https://doi.org/10.1177/00 09922815586051. 63. Al-Azri MH, Al-Belushi R, Al-Mamari M, Davidson R, Mathew AC. Knowledge and health beliefs regarding sickle cell disease among Omanis in a primary healthcare setting: Cross-sectional study. Sultan Qaboos Univ Med J 2016; 16:e437–44. https://doi. org/10.18295/squmj.2016.16.04.006. 64. Hijmans CT, Fijnvandraat K, Oosterlaan J, Heijboer H, Peters M, Grootenhuis MA. Double disadvantage: A case control study on health-related quality of life in children with sickle cell disease. Health Qual Life Outcomes 2010; 8:121. https://doi. org/10.1186/1477-7525-8-121. 65. Pandarakutty S, Murali K, Arulappan J, Thomas DS. Effect- iveness of nurse led intervention on health related quality of life among children with sickle cell disease in Oman: A pilot study. Adv Hematol 2019; 2019: 6045214. https://doi.org/10.11 55/2019/6045214. https://doi.org/10.1111/j.1365-2141.2005.05622.x https://doi.org/10.1007/s10897-013-9630-2 https://doi.org/10.1186/s12878-017-0079-7 https://doi.org/10.1007/BF02724180 https://doi.org/10.1177/0009922815586051 https://doi.org/10.1177/0009922815586051 https://doi.org/10.18295/squmj.2016.16.04.006 https://doi.org/10.18295/squmj.2016.16.04.006 https://doi.org/10.1186/1477-7525-8-121 https://doi.org/10.1186/1477-7525-8-121 https://doi.org/10.1155/2019/6045214 https://doi.org/10.1155/2019/6045214