Poor Sleep Quality in Jamaican Adults With Sickle Cell Disease: Prevalence, Risk Factors, and Association With Quality of Life.

Poor sleep and chronic illnesses have a bidirectional relationship where presence of one can worsen the other. Sickle cell disease (SCD) is associated with significant morbidity and early mortality. In this study, we examine sleep quality, its predictors, and its association with quality of life in Jamaican adults with SCD. This cross-sectional study evaluated 177 well adult SCD patients for sleep quality using The Pittsburgh Sleep Quality Index (PSQI) and quality of life using the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me). Multiple linear regression models examined the predictors of poor sleep quality. The mean global PSQI score was 6.9 (SD 4.2) with 56.5% having poor sleep quality. Women had significantly worse scores for sleep efficiency (p 0.005), sleep latency (p 0.03) and higher use of sleeping medications (p 0.02). Those overweight/obese had significantly worse subjective sleep quality (p 0.001) and sleep efficiency (p 0.05). In multivariate regression analysis, overweight individuals had poorer sleep quality (OR: 2.9; 95% C.I.: 1.07, 7.88) than those with normal weight whereas those unemployed and looking for a job had lower prevalence of poor sleep quality (OR 0.2; 95% C.I.: 0.05, 0.77) compared to employed individuals. Participants with good sleep quality had significantly better functioning in all 5 domains of the ASCQ-Me. In conclusion, persons with SCD who are overweight or obese are at increased risk of poor sleep which can negatively affect quality of life. Patient populations and healthcare providers will need to manage the emerging burden of overweight/obesity.

Telehealth: Navigating the COVID-19 Pandemic and Beyond: The Sickle Cell Unit Experience.

Introduction: To examine the use of telehealth for delivery of health care in persons with sickle cell disease in a resource-constrained country during the COVID-19 pandemic. Methods: This study was a retrospective review of patient encounters at the Sickle Cell Unit (SCU), Jamaica during a 3-year period, March 10, 2019 to March 9, 2022 and a comparison of endpoints between 1 year before and 2 years during the pandemic. Primary endpoints of registration numbers, day-care admissions, and study visits were obtained from logbooks and the electronic medical records. Additional endpoints included well visits, hydroxyurea (HU) visits, and bone pain crisis. Results: Patients registered at the clinic on 17,295 occasions, with 7,820 in the pre-pandemic year decreasing by 43.8% and 35% in the 2 subsequent pandemic years. Overall, study visits increased by 4.9% and 1.3% in the pandemic years. They increased in adults by 13.1% and 8.9% but fell by 3.2% and 6.2% in children. Fewer people were seen in the pandemic years, with children showing a 20.7% decline in numbers. Tele-visits accounted for 31.4% of all study visits during the pandemic years and increased by 23.6% between the pandemic years. There were more well-visits and HU visits, but fewer pain visits and day-care admissions in the pandemic years. Conclusions: The SCU maintained health care delivery for a high-risk population during the pandemic, with tele-visits mitigating the short-fall from in-person visits. Tele-visits may be more acceptable to adults with a chronic illness and may be a suitable alternative for delivering health care.

Acute kidney injury in Jamaicans with sickle cell disease hospitalized with COVID-19 infection.

Despite a high occurrence of acute kidney injury (AKI) with COVID-19 infection, there are no data on its incidence in sickle cell disease (SCD). We performed a single-center retrospective chart review of persons aged >1 year with SCD, COVID-19 infection and no prior dialysis requirement hospitalized from June 1, 2020 to May 31, 2022. Demographics, clinical, laboratory characteristics and outcomes were abstracted. AKI was defined using Kidney Disease Improving Global Outcomes (KDIGO) criteria. Of 38 patients meeting study criteria (60.6% female, mean age ± SD 38.6 ± 15.9 years), 3 (7.9%) were COVID vaccinated. Fifty-five percent (55%) developed AKI with 7.9% (n = 3) requiring dialysis. Participants with AKI were older (44.9 versus 30.8 years, p = 0.005), with a higher proportion having baseline chronic kidney disease (52% versus 0%, p = 0.001). Severe COVID infection [age-adjusted odds ratio (aOR): 8.93, 95%CI: 1.73-45.99, p = 0.033], red cell transfusion (aOR 7.92, 1.47-42.69) and decrease in hemoglobin per unit from baseline (aOR 2.85, 1.24-2.28) were associated with AKI. Five persons died in hospital, with AKI resulting in higher median length of stay (12 versus 5 days, p = 0.007). Targeted COVID-19 preventative measures and multinational longitudinal studies to ascertain the impact of AKI and COVID-19 infection in SCD are needed.

Hygiene Practices and Early Childhood Development in the East Asia-Pacific Region: A Cross-Sectional Analysis.

Poor hygiene might be a risk factor for early childhood development (ECD). This study investigated the associations of three hygiene practices ('wash hands before a meal,' 'wash hands after going to the toilet,' and 'brush teeth'), separately and combined, with ECD. Six thousand six hundred ninety-seven children (4 [0.8] years) from the East Asia-Pacific Early Child Development Scales validation study were included in this cross-sectional analysis. The hygiene variables were recoded to have comparable values as 'always,' 'sometimes,' and 'never.' These variables were then grouped to create combined categories. The binary outcome variables, poor ECD, were defined as a score < age-specific 25th centile. Modified Poisson regression models were used to analyse the associations. Data collection was performed between 2012 and 2014, and the analyses were conducted in April 2022. Compared with children who 'always' washed their hands before a meal, those who did it 'sometimes' (Prevalence Ratio [PR]: 1.30 [95% CI: 1.16-1.46]) or 'never' (PR: 1.35 [1.18-1.55]) had a higher likelihood of poorer overall development. Comparable results were identified for the other two hygiene practices and the other four domain-specific outcomes (p < 0.05). Compared with children who always followed the three hygiene practices, the likelihood of poor overall ECD increased as the combined hygiene practice decreased among children with poor hygiene practices (PRnever: 1.67 [1.40-2.00]; PRrarely: 1.49 [1.30-1.71]; PRsometimes: 1.30 [1.14-1.49]). Children who did not always follow good hygiene practices had a higher likelihood of poor ECD independently of sociodemographic factors. Considering these findings, future hygiene practice interventions and trials should consider including ECD outcomes.

Health-Related Quality of Life in Adolescents With Chronic Illness in Jamaica: Adolescent and Parent Reports.

PURPOSE: The aim of this study is to assess the level of agreement between adolescents' self-assessment and parent-proxy reports on health-related quality of life (HRQOL) in Jamaican adolescents with chronic illness. METHODS: A cross-sectional study was conducted, recruiting adolescents living with a chronic illness (ALCIs)-asthma, human immunodeficiency virus, insulin-dependent diabetes mellitus, or sickle cell disease and age/sex-matched healthy adolescents. Data were collected on HRQOL from adolescents and parents using the Pediatric Quality of Life Scale. Parent-adolescent agreement was determined at group level (Wilcoxon signed-rank test) and individual level (intraclass correlation coefficient). RESULTS: Two hundred twenty-six (226) parent/adolescent pairs participated: 130 ALCIs and 96 healthy peers; mean age 14.9 ± 2.8 years; 58% females. Adolescents with and without chronic illness reported similar HRQOL; parent-proxies reported better HRQOL for healthy adolescents compared to ALCIs. Intraclass correlation demonstrated higher levels of parent-adolescent correlation for ALCIs than healthy adolescents (ALCIs: 0.11-0.34; healthy adolescents: 0.01-0.10). At group level, analyses demonstrated better parent-proxy rating of QOL in all of the scores with the exception of the general health score. Parent-proxies overestimated QOL for asthma and insulin-dependent diabetes mellitus but not for sickle cell disease and human immunodeficiency virus. Linear regression modeling revealed that female sex and living with chronic illness were significant predictors of agreement. DISCUSSION: Parent-proxies overestimated adolescents' QOL compared to adolescents' report regardless of whether the adolescent was living with a chronic illness or not. As such, health care providers should elicit feedback from the adolescent wherever possible and proxy reports should be used as complementary information rather than primary source.

Stigma and quality of life in adults with sickle cell disease in Jamaica and the United States.

Sickle cell disease (SCD) is the most common inherited blood disorder in both Jamaica and the United States and is characterized by poor quality of life and debilitating complications, with the hallmark symptom being pain caused by acute and chronic conditions. Individuals with SCD often experience stigma due to their disease status, opioid use, and race. This study sought to understand the influence of perceived stigma and demographic/clinical characteristics on quality of life in adults with SCD in Jamaica (n = 50) and the United States (n = 50). Participants completed interviewer-administered surveys including demographic/clinical characteristics; the Measure of Sickle Cell Stigma (MoSCS); and the Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me). A set of general linear models for each country was built to examine the influence of explanatory variables on the quality of life outcomes. Overall, stigma scores were low for both countries, with the exception of the MoSCS disclosure concerns and expected discrimination subscales, where scores averaged medium and high, respectively. In both countries, being employed was associated with better quality of life; and reports of stigma (internalized stigma and expected discrimination) was associated with worse quality of life. These findings have several implications for healthcare providers caring for individuals with SCD, policy makers, and researchers. Specifically, findings can be used to advocate for improved access to mental health care for individuals with SCD and inform stigma reduction intervention approaches in SCD.

Maternal mortality among women with sickle cell disease in Jamaica over two decades (1998-2017).

BACKGROUND: Sickle cell disease (SCD) affects 2.8% of Jamaican antenatal women. Between 1998-2007 their maternal mortality ratio was 7-11 times higher than women without these disorders. We aim to determine if outcomes improved between 2008 and 17 amid declining fertility and changes in referral obstetric care. METHODS: Maternal deaths in Jamaica's maternal mortality surveillance database (assembled since 1998) with SCD reported as underlying or associated cause of death were compared to those without known SCD, over two decades from 1998 to 2017. Social, demographic and health service variables were analysed using SPSS and EpiInfo Open. FINDINGS: Over the two decades from 1998 to 2017, 806 (74%) of the 1082 pregnancy-associated deaths documented by the Jamaican Ministry of Health and Wellness were maternal deaths. The maternal mortality ratio (MMR) did not statistically change over the two periods for women with (p = 0.502) and without SCD (p = 0.629). The MMR among women with and without SCD in 2008-17 was 378.1 (n = 41) and 89.2/100,000 live births (n = 336) respectively, an odds ratio of 4.24 (95% CI: 3.07-5.87). When deaths due to their blood disorders were excluded, risk remained elevated at 2.17 (95% CI: 1.36-3.32). There was an upward trend in direct deaths over the two decades (p [trend]=0.051). INTERPRETATION: MMRs were unchanged over two decades for Jamaicans with SCD. The high contribution to maternal mortality by women with SCD may explain some of the persistently higher mortality experience of women in the African diaspora. Multi-disciplinary evidence-based strategies need to be developed and tested which improve survival for women with SCD who want to have children. FUNDING: No external funding was provided.

External validation of the priapism impact profile in a Jamaican cohort of patients with sickle cell disease.

BACKGROUND: Priapism impairs quality of life and has a predilection for males with sickle cell disease (SCD). The Priapism Impact Profile (PIP) is a novel 12-item instrument designed to measure general health-related impact of priapism. The aim of the study was to evaluate the validity and reliability of the PIP in a Jamaican cohort of SCD patients experiencing priapism. METHODS: One hundred SCD patients with a history of priapism were recruited from a sickle cell clinic in Kingston, Jamaica and administered the PIP questionnaire. Patients rated each item of the PIP for clarity and importance. Statistical testing was employed to evaluate the psychometric performance of the PIP. Content validation was assessed based on patient descriptive rating of the items based on clarity, and importance and criterion-oriented validity were assessed by evaluating the PIP's ability to distinguish between patient subgroups. Test-retest repeatability was assessed in 20 of the 100 patients. RESULTS: Patients were stratified into active (54) and remission (46) priapism groups based on their experience of priapism within the past year. Patients in the active priapism group were younger (p = 0.011), had a shorter duration of disease (p = 0.023), and had more frequent priapism episodes (p = 0.036) than the remission group. PIP questionnaire scores differed significantly with respect to priapism activity (p < 0.001) and prevalence of erectile dysfunction (p < 0.05) but not by priapism severity (p = 0.62). The PIP questionnaire had good content validity, with questions rated as having medium or high clarity and importance by an average of 82.8% and 69.2% of patients, respectively. CONCLUSION: The PIP questionnaire was successfully validated in a Jamaican cohort of SCD patients and adequately discriminated patients with active priapism from those in remission. The instrument may be utilized in routine clinical management of patients with SCD-associated priapism. Further clinical investigations are warranted in other populations.

Reliability of self-reported data from the 2011 Ja-Kids birth cohort study: demographic, social, obstetric history, medical and outcome indicators.

The Ja-Kids Longitudinal Study (JA-Kids) aims to improve the health and development of Jamaican children by identifying social, demographic, environmental and clinical factors that help or hinder these processes. As clinical indicators relied on maternal reporting, we aim to evaluate the quality of the self-reported data. Women were recruited across Jamaica during pregnancy or at delivery from July 1-30 September 2011. Indicators were compared between women recruited while pregnant and at delivery to understand possible differences between the sub-populations. Variables reported more than once between pregnancy and delivery were assessed to evaluate level of agreement (reliability). Clinical indicators from the literature were contrasted with study findings to determine how maternal reporting align with published prevalence (validity). Intra-class correlation and the kappa (κ) statistic were used to assess reliability while chi-squared, Fisher's-exact or students-t were used to compare differences over time; p values ≤0.05 were considered statistically significant. Women recruited during pregnancy (n = 3970) were younger, less parous and possibly more socially disadvantaged than those recruited at delivery (n = 5803). Socio-demographic and selected clinical indicators showed good to moderate (0.421 < κ < 0.681) reporting consistency between pregnancy and delivery for previous C-section (κ = 0.681), pre-existing diabetes mellitus (κ = 0.616) and prior twin gestations (0.580). Most conditions however showed only fair agreement (0.21 < κ < 0.40) including previous gestational hypertension (κ = 0.387), asthma (κ = 0.365), premature rupture of membranes (κ = 0.324), eclampsia (κ = 0.257) and essential hypertension (κ = 0.213). Infectious conditions had poor reliability. Prevalence rates for most conditions, except sickle cell disease, were lower than the published literature. Complications and outcomes which were well defined for women were better reported than those requiring clinical judgment (e.g. prior C-section versus specific hypertensive disorders of pregnancy). NCDs with only episodic acute effects were not well reported, e.g. asthma, hypertension and sickle cell disease. Maternal reporting of pregnancy complications needs to be interpreted with caution.

Integrating a problem-solving intervention with routine care to improve psychosocial functioning among mothers of children with sickle cell disease: A randomized controlled trial.

OBJECTIVE: To assess the feasibility of a problem-solving skills training intervention in improving psychological outcomes in mothers of infants with sickle cell disease (SCD). DESIGN AND METHODS: This parallel randomized controlled trial recruited 64 babies with SCD, 6 to 12 months of age, and their mothers. Baseline measurements assessed mothers' coping and problem-solving skills, depression, and parental stress before random assignment to intervention or control groups (n = 32 each). Problem-solving skills intervention was delivered through 6 monthly sessions, when babies attended for routine penicillin prophylaxis. All measurements were repeated for both groups at the end of the intervention period. Intention to treat analysis used repeated measures mixed models with the restricted estimation maximum likelihood approach. RESULTS: The problem-solving intervention had no significant effect on mothers' problem-solving skills (adjusted treatment effect: -1.69 points (95% CI:-5.62 to 2.25)), coping behaviours (adjusted treatment effect: 0.65 points (95% CI:- -7.13 to 8.41)) or depressive symptoms (adjusted treatment effect: -0.41 (95% CI: -6.00 to 5.19)). It reduced mothers' level of difficulty in managing stressful events by 9.5 points (95% CI (-16.86 to -2.16); effect size: 0.21 SD). In the subgroup of mothers at risk of depression (n = 31 at baseline), the intervention reduced depression scores with treatment effect of 10.4 points (95%CI: -18.83 to -1.88; effect size: 0.67 SD). CONCLUSION: This problem-solving skills intervention study suggests feasibility and possible efficacy in improving some maternal outcomes. Further refinement and culturally appropriate adaptations of the intervention could lead to stronger effects.

How Free Is Free Health Care? An Assessment of Universal Health Coverage Among Jamaicans with Sickle Cell Disease.

Purpose: In an effort to transition toward universal health coverage (UHC), Jamaica abolished user fees at all public health facilities in 2008. We aimed to determine the extent of out-of-pocket payments (OPPs) and the other cost barriers to UHC among patients with sickle cell disease (SCD). Methods: Patients presenting to the Sickle Cell Unit in Kingston, Jamaica, for routine care between October 2019 and August 2020 were consecutively recruited and interviewed about their latest hospitalization within the previous 4 weeks. Parents or guardians completed the questionnaire on behalf of pediatric patients. The questionnaire included the Patient Satisfaction Questionnaire Short Form (PSQ)-18 and the health module of the Jamaica Survey of Living Conditions. Results: There were 103 patients with ages ranging from 7 months to 56 years (51.5% female, 60.2% public hospitalizations, and 54.4% pediatric). The modal income (J$6200-$11,999 per week) was similar to the minimum wage and 48.5% lived in overcrowded households. Government drug-subsidy cards were owned by 39.8%. OPPs were made by 19.4% of persons for items and tests that were unavailable at public facilities. There were no costs reported by 69.6%, who visited public pharmacies. Similarly, the cost of admission to public hospitals was free for 95.4% of subjects. Using public transportation, private hospitalization, and having more disease complications were predictive of a perception that health care is unaffordable. Conclusion: Most SCD subjects reported no expense with public hospitalizations; however, approximately one in five reported OPPs. Efforts are needed to increase the availability of subsidized items, and the use of drug-subsidy cards, to improve UHC.

2020 family medicine postgraduate examinations at The University of the West Indies: successes and challenges in the time of COVID-19 pandemic.

Little has been published regarding postgraduate assessments during the COVID-19 pandemic. There is an urgent need to graduate well-trained specialists including family physicians who play a key role in patient care. The successes and challenges encountered in mounting qualifying 2020 Family Medicine examinations during the COVID-19 pandemic at the University of the West Indies are described in this paper. Human resource, planning, use of technology and virtual environments are discussed, which enabled successful examinations at this multicampus regional site.

Priapism in Sickle Cell Disease: An Evaluation of the Knowledge of an at Risk Population in Jamaica.

INTRODUCTION: Ischemic priapism is characterized by painful erections that may lead to erectile dysfunction. Men with sickle cell disease (SCD) are particularly prone to this condition, however, the knowledge among this population with respect to possible complications is not well known. AIM: The objective of this study was to evaluate the knowledge of males with SCD about priapism and its possible consequences. METHODS: A cross-sectional study was carried out among consecutive consenting males aged 12 years and older with SCD presenting to the Sickle Cell Unit between September 2018 and August 2019. All participants completed a questionnaire detailing knowledge on the definition of priapism, its association with SCD, consequences of untreated priapism and treatment strategies. The responses were used to generate a total priapism knowledge score for each of the participants. MAIN OUTCOME MEASURES: Main outcomes included knowledge of the term priapism, its association with SCD as well as the total priapism knowledge score. RESULTS: 219 patients of mean age 29.8 ± 13 years completed the questionnaire. 38.4% of patients were familiar with the term priapism and of these 68.8% were aware of the association between SCD and priapism. There was a significant association between knowledge of association of priapism with SCD and increasing educational level (P = .036) and history of prior priapism episodes (P = .02). There was a significant association between knowledge of the term "priapism" and history of priapism (P = .002). The mean total priapism knowledge score among the participants was 5.16 out of a maximum score of 12, with 70.8% of participants being categorized as having "poor knowledge." CONCLUSION: There is a general lack of knowledge among patients with SCD with respect to the term priapism. Education campaigns geared toward addressing the identified knowledge gaps may prove beneficial in increasing awareness among this population and potentially decrease the risk of complications. Whyte N, Morrison-Blidgen B, Asnani M, Priapism in Sickle Cell Disease: An Evaluation of the Knowledge of an at Risk Population in Jamaica. Sex Med 2021;9:100339.

Sickle Cell Disease and Pain: Is it all Vaso-occlusive Crises?

OBJECTIVES: Acute pain is the main complication of sickle cell disease. Chronic pain (CP) and neuropathic pain (NP) may also be experienced, but have not been formally described in Jamaican patients. A cross-sectional study was conducted to determine their prevalence and characteristics, and to determine the common pain locations and modalities of management. MATERIALS AND METHODS: All well individuals with sickle cell disease patients 14 years and older, not pregnant and without a history of clinical stroke were consecutively recruited. Anthropometric measurements, hematology studies, an analgesia checklist, and the Adult Sickle Cell Quality of Life Measurement Information System questionnaire were completed. The painDETECT questionnaire was completed to describe NP and pain patterns-from which CP was defined. RESULTS: There were 257 patients in total, with 55.6% being females; the mean age of the patients was 31.7±12 years, and 75% had the SS genotype. Almost all patients (92.6%) had had an acute pain crisis in their lifetime and 72.4% in the last year. The mean severity at last attack was 6.8±3.1 on a scale of 0 to 10. The prevalences of CP and NP were 21.5% and 17.9%, respectively. Female sex, the presence of current leg ulcers, and the use of a strong opioid in the last 4 weeks produced higher odds of NP, whereas older age, milder genotypes, and daily analgesic use had the highest odds of CP. Opioids were used by 40.1% of the patients in the previous 4 weeks, whereas nonpharmacological treatments such as physiotherapy was less used, but reported to be very effective. DISCUSSION: CP and NP should be assessed during routine care of sickle cell pain so that targeted therapies can be applied.

Health-related quality of life and neuropathic pain in sickle cell disease in Jamaica.

BACKGROUND: Health related quality of Life (HRQOL) is an important consideration when managing chronic diseases, like sickle cell disease (SCD). Assessment of neuropathic pain (NP) and its association with HRQOL in SCD are rarely reported. OBJECTIVES: To examine the prevalence of NP and its association with HRQOL in adult Jamaicans with SCD. METHODS: Adult SCD patients were recruited consecutively and data were collected on socio-demographics, NP using Douleur Neuropathique 4 (DN4), and HRQOL using the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me). Means, medians, t-tests, ANOVA tests, Wilcoxon Rank-sum tests, Kruskal-Wallis tests, Pearson's correlation and multivariate linear regression analyses were performed using STATA 14.2. RESULTS: There were 236 respondents, with 56.8% female, mean age 33.2 years (SD: 11.6; range: 18-67 years), and 75% had homozygous SS genotype. NP was likely present in 26.7% of the population. The standardized ASCQ-Me (mean ± SD; ordered from lowest to best HRQOL domain scores) were: emotional impact 53.3 ± 10.1; sleep impact 56.1 ± 9.7; social function 57.7 ± 10.6; pain impact 58.6 ± 7.8; and stiffness impact 61.0 ± 7.3. On multivariate analyses, NP significantly reduced emotional and social functioning and worsened sleep and stiffness. Higher acute pain scores significantly worsened all HRQOL domains, while higher disease severity worsened all except stiffness. Obesity was associated with worse sleep and greater stiffness. Females with leg ulcers reported lower social functioning and unemployed females had greater pain impact. CONCLUSIONS: NP is increasingly prevalent in SCD and worsens HRQOL. Gender specific studies are needed to understand the significantly poorer HRQOL in women.

Numb chin syndrome in sickle cell disease: a case series of Jamaican patients.

Numb chin syndrome is an uncommon presentation that has been reported as secondary to metastatic disease, trauma, and infections of the maxilla, mandible, or oral cavity. The hypoesthesia, paraesthesia, or pain are a result of injury to the inferior alveolar nerve, which is particularly vulnerable as it exits the mandible through the mandibular foramen as the mental nerve. In persons with sickle cell disease, it has been reported as a manifestation of mandibular vaso-occlusive crisis. This case series presents 13 patients with sickle cell disease who presented with numb chin syndrome, the largest number of cases that has been described in the literature to date. The report illustrates the wide variety of presentations and therefore possible differential diagnoses to consider. In this case series, the symptoms were associated with vaso-occlusive crises, allergic reactions, dental infections, malignancy, rheumatoid arthritis, and pregnancy. Most appeared to be self-limiting; however, one patient was having his second episode, and the numbness has persisted in three patients. The series illustrates that it is important not only to ensure that the source of the local vaso-occlusive crisis is treated, but also to not miss important differentials such as metastatic disease, where this can be the first presentation of malignancy and would represent a very poor prognosis. There is no reported successful treatment for the hypoesthesia in this case series, and this presents an area for further research.

Sickle cell disease is a global prototype for integrative research and healthcare.

Differences in health outcomes and treatment responses within and between global populations have been well documented. There is growing recognition of the need to move beyond simple inventories and descriptions of these differences and our linear explanations for them, and gain a better understanding of the multifaceted systems and networks underlying them in order to develop more precise and effective remedies. Typical targets for such integrative research have been common multifactorial diseases. We propose sickle cell disease, one of the most common monogenic diseases, as an ideal candidate for elucidating the complexity of the influences of endogenous and exogenous factors on disease pathophysiology, phenotypic diversity, and variations in responses to treatments at both the individual and population levels. We provide data-informed representations of diverse contributors to sickle cell disease complications that could guide innovative efforts to advance scientific knowledge, clinical practice, and policy formulation related to the disease; help improve outcomes for people worldwide with sickle cell disease; and inform approaches to studying and addressing other diseases.