Predictors of health-related quality of life in a large cohort of adult patients living with sickle cell disease in France: the DREPAtient study.

Background: Sickle cell disease (SCD) is an inherited autosomal recessive disorder exhibiting a range of symptoms and acute and/or chronic complications that affect the quality of life. This study aimed to assess health-related quality of life (HRQoL) and to identify the associated factors in adult patients with SCD in France. Methods: DREPAtient is a cross-sectional, multicenter study conducted from June 2020 to April 2021 in France and in certain French overseas territories where SCD is highly prevalent. Sociodemographic and clinical data were collected online. HRQoL was assessed by the French version of the 36-Item Short Form Survey (SF-36) questionnaire. HRQoL determinants were identified using multivariable linear regression analysis. Results: In total, 570 participants were included, mostly women (68.9%), with a mean age of 33.3 (±10.7) years. The highest mean score HRQoL was found in the Physical functioning domain (67.5 ± 21.8) and the lowest mean score in the General Health perception domain (37.7 ± 20.3). The mean score of the physical composite (PCS) and mental composite (MCS) of SF-36 summary scores was 40.6 ± 8.9 and 45.3 ± 9.8, respectively. Participants receiving oxygen therapy (ß = -3.20 [95%CI: -5.56; -0.85]), those with a history of femoral osteonecrosis (-3.09 [-4.64; -1.53]), those hospitalized for vaso-occlusive crisis (VOC) or acute chest syndrome (ACS) (-2.58 [-3.93; -1.22]), those with chronic complications (-2.33 [-4.04; -0.62]), female participants (-2.17 [-3.65; -0.69]), those with psychological follow-up (-2.13 [-3.59; -0.67]), older participants (-1.69 [-3.28; -0.09]), and those receiving painkillers (-1.61 [-3.16; -0.06]) reported worse PCS score. By contrast, those who had completed secondary or high school (4.36 [2.41; 6.31]) and those with stable financial situation (2.85 [0.94, 4.76]) reported better PCS scores. Worse MCS scores were reported among participants with psychological follow-up (-2.54 [-4.28; -0.80]) and those hospitalized for VOC/ACS in the last 12 months (-2.38 [-3.99; -0.77]), while those who had relatives' support (5.27 [1.92; 8.62]) and those with stable financial situation (4.95 [2.65; 7.26]) reported better MCS scores. Conclusion: Adults with major SCD reported poor physical and mental HRQoL scores. Hospitalization for VOC/ACS, chronic complications, use of painkillers, perceived financial situation, and support from relatives are important predictors of HRQoL in SCD patients. Interventions to improve HRQoL outcomes SCD should be considered.

Barriers and facilitators to community acceptability of integrating point-of-care testing to screen for sickle cell disease in children in primary healthcare settings in rural Upper East Region of Northern Ghana.

INTRODUCTION: Sickle cell disease (SCD) remains a public health problem especially in sub-Saharan Africa including Ghana. While pilot initiatives in Africa have demonstrated that neonatal screening coupled with early intervention reduces SCD-related morbidity and mortality, only 50-70% of screen-positive babies have been successfully retrieved to benefit from these interventions. Point-of-care testing (POCT) with high specificity and sensitivity for SCD screening can be integrated into existing immunization programs in Africa to improve retrieval rates. This study explored community acceptability of integrating POCT to screen for SCD in children under 5 years of age in primary healthcare facilities in Northern Ghana. METHOD: This was an exploratory study using qualitative research approach where 10 focus group discussions and 20 in-depth interviews were conducted with community members and health workers between April and June 2022. The recorded interviews were transcribed verbatim after repeatedly listening to the recordings. Data was coded into themes using QSR Nvivo 12 software before thematic analysis. RESULTS: Most participants (70.9%) described SCD as serious and potentially life-threatening condition affecting children in the area. Of 148 community members and health workers, 141 (95.2%) said the screening exercise could facilitate diagnosis of SCD in children for early management. However, discrimination, fear of being tested positive, stigmatization, negative health worker attitude linked with issues of maintaining confidentiality were reported by participants as key factors that could affect uptake of the SCD screening exercise. Most participants suggested that intensive health education (78.3%), positive attitude of health workers (69.5%), and screening health workers not being biased (58.8%) could promote community acceptability. CONCLUSION: A large majority of participants viewed screening of SCD in children as very important. However, opinions expressed by most participants suggest that health education and professionalism of health workers in keeping patients' information confidential could improve the uptake of the exercise.

Understanding patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease in Mulago and Kiruddu hospitals, Uganda, a qualitative study.

BACKGROUND: In 2016, Uganda added Hydroxyurea (HU) to the list of essential drugs to treat sickle cell disease SCD. However, Hydroxyurea utilization has been low for several countries in sub-Saharan Africa. This study examined patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease in Mulago and Kiruddu hospitals, in Uganda. METHODS: To understand the patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease, we conducted a parallel convergent mixed methods study at outpatient departments of two national referral hospitals in Uganda from October 2022 to January 2023. The cross-sectional mixed-methods study employed both quantitative and qualitative methods. We collected survey data from a systematic sample of 259 participants and conducted individual interviews with a purposive sample of 40 participants (20 adolescents or their caregivers and 20 adult patients with SCD) and interviewed them individually on their knowledge, perceptions, barriers, and facilitators of HU utilization. Descriptive data were analyzed using Stata 16, whereas qualitative data were analyzed thematically using an inductive approach supported by NVivo 12 software. We triangulated data to determine the concordance of qualitative and quantitative data. RESULTS: The study enrolled 40 participants for qualitative interviews and 259 patients for quantitative, with an average age of 16, over half being female, 46% having secondary education, and 96% unmarried. The prevalence of HU use was 78%. The study identified three themes as follows: Patient barriers at the individual including Inadequate knowledge about HU, Persistent pain, Poor adherence to HU, Poor communication with health care workers, and Psychosocial and emotional challenges. At the facility level, long queues and poor quality of care, drug-related side effects that affect HU, and drug stock-outs were reported. Myths, rumors, and misconceptions about HU, and gender-related barriers were reported to affect HU utilization at a community level. Facilitators for the use of HU and recommendations for improvement. Facilitators included perceived benefits, long duration on HU, information sharing by healthcare workers, availability of complementary drugs, confirmation of diagnosis, and availability of medication at public health facilities or private pharmacies. Patients suggested continuous adherence support, encouragement from healthcare workers, sensitization about benefits and risks, a peer-to-peer approach, and financial support for adolescents and women to start businesses to resolve financial problems. CONCLUSION: Implementing the use of HU has been challenging in Uganda and needs improvement. Facilitators to hydroxyurea use have been highlighted, though Patient-identified barriers at individual, facility, and community levels that need to be resolved. The experiences and insights shared by our participants provide invaluable guidance for increasing the uptake of HU. Further studies are needed to establish validated instruments to assess patients' pain communication and adherence to the HU regimen.

An assessment of the psychometric properties of the Coping Strategies Questionnaire - Sickle Cell Disease (CSQ-SCD) among adults in the United States.

BACKGROUND: Previous studies have reported conflicting factor structures of the Coping Strategies Questionnaire - Sickle Cell Disease (CSQ-SCD). This study examined the psychometric properties of the CSQ-SCD among adults with SCD in the United States. METHODS: This study implemented a cross-sectional study design with web-based self-administered surveys. Individuals with SCD were recruited via an online panel. Psychometric properties, including factorial and construct validity, and internal consistency reliability, of the CSQ-SCD were assessed. RESULTS: A total of 196 adults with SCD completed the survey. Confirmatory factor analysis (CFA), using maximum likelihood estimation and the 13 subscale scores as factor indicators, supported a three-factor model for the CSQ-SCD compared to a two-factor model. Model fit statistics for the three-factor model were: Chi-square [df] = 227.084 [62]; CFI = 0.817; TLI = 0.770; RMSEA [90% CI] = 0.117 [0.101-0.133]; SRMR = 0.096. All standardized factor loadings (except for the subscales isolation, resting, taking fluids, and praying and hoping) were > 0.5 and statistically significant, indicating evidence of convergent validity. Correlations between all subscales (except praying and hoping) were lower than hypothesized; however, model testing revealed that the three latent factors, active coping, affective coping, and passive adherence coping were not perfectly correlated, suggesting discriminant validity. Internal consistency reliabilities for the active coping factor (α = 0.803) and affective coping factor (α = 0.787) were satisfactory, however, reliability was inadequate for the passive adherence coping factor (α = 0.531). Given this overall pattern of results, a follow-up exploratory factor analysis (EFA) was also conducted. The new factor structure extracted by EFA supported a three-factor structure (based on the results of a parallel analysis), wherein the subscale of praying and hoping loaded on the active coping factor. CONCLUSIONS: Overall, the CSQ-SCD was found to have less than adequate psychometric validity in our sample of adults with SCD. These results provide clarification around the conflicting factor structure results reported in the literature and demonstrate a need for the future development of a SCD specific coping instrument.

Disease-modifying therapies for sickle cell disease: Decisional needs and supports among adolescents and young adults.

BACKGROUND: Shared decision-making is one promising solution to addressing barriers in use of disease-modifying therapies for adolescents and young adults (AYAs) with sickle cell disease (SCD). A thorough understanding of decisional needs can guide the development of decisional supports and promote shared decision-making. PROCEDURE: Informed by the Ottawa Decision Support Framework (ODSF), we conducted a qualitative analysis to assess decisional needs and supports reported by AYAs with SCD, their caregivers, and healthcare providers. Semi-structured qualitative interviews were conducted with AYAs and their caregivers, and online crowdsourcing was used with SCD providers. Thematic and descriptive content analyses were used to summarize perspectives on decisional needs and supports regarding disease-modifying therapies. RESULTS: Fourteen AYAs (Mage  = 21 years, 57% male, 93% non-Hispanic Black, 79% HbSS), 11 caregivers (80% female, 100% non-Hispanic Black), and 40 healthcare providers (65% female, 65% non-Hispanic White, Myears in practice  = 14.8 years, 75% physicians) participated. Thematic analysis revealed needs related to: decisional conflict, inadequate knowledge, unclear expectations, and inadequate supports and resources. Six forms of support emerged as important for decision-making: establishing an open and trusting patient/family-provider relationship, providing information, accepting ambivalence and unreadiness, supporting implementation of a decision, addressing inadequate health and social services, and promoting adequate social, emotional, and instrumental help. CONCLUSIONS: This is the first study to assess decisional needs and supports for AYAs with SCD considering disease-modifying therapies. Additional research is needed to examine which decision supports are the most impactful to promote effective shared decision-making in this population.

A Systemic Review of the Psychosocial Aspects of Chronic Pain in Youth With Sickle Cell Disease.

OBJECTIVES: The psychosocial aspects of chronic pain among youth with sickle cell are poorly described and may be better understood within a biopsychosocial model of chronic pain as applied to youth living with sickle cell disease. DESIGN: A systematic literature review was performed to synthesize the psychosocial factors contributing to chronic pain in this population. Criteria for study inclusion were primary quantitative research studies focused on psychosocial aspects of chronic pain among youth with sickle cell disease. DATA SOURCES: PubMed, CINAHL, PsychINFO, and Scopus were searched for relevant articles. REVIEW/ANALYSIS METHODS: Articles selected for full-text review were appraised for quality using the Joanna Briggs Institute Quality Appraisal Tools. Thirteen articles were included. RESULTS: Depression, anxiety, pain catastrophizing, pain coping, executive functioning, and functional impairment were prevalent in youth living with sickle cell disease and chronic pain. Research gaps included the influence of stigma, injustice, peer interactions, and school and work on chronic pain. CONCLUSIONS: The biopsychosocial model of chronic sickle cell disease-related pain for youth was developed and modified based on the results of this systematic review to remind clinicians of the various factors to consider in clinical practice and spur additional research in this field.

Food insecurity and quality of life in patients with sickle cell disease.

Little is known about the relationship between quality of life (QOL) and food insecurity (FI) among patients with sickle cell disease (SCD). We hypothesized FI is associated with lower QOL in children and young adults with SCD. Overall (N = 99), 22% screened positive for FI. Supplemental Nutrition Assistance Program (SNAP) enrollment was 50 and 71% among people from food secure and FI households, respectively. A higher FI score was correlated with lower overall QOL (r = -0.22, p = .03), specifically lower QOL in worry and communication domains. Interventions for FI beyond SNAP may be important for QOL among people living with SCD.

The relationship between cumulative risk and health-related quality of life in youth with sickle cell disease: Moderating effects of secondary control engagement coping.

BACKGROUND: Youth with sickle cell disease (SCD) often experience low health-related quality of life (HRQOL). Engagement in resilience-promoting processes, such as secondary control engagement (SCE) coping, or adapting to stressors, may be linked to contextual risk factors (e.g., poverty status). This study aims to illuminate relationships between a cumulative risk index (CRI), SCE coping, and HRQOL in youth with SCD and test whether SCE coping moderates the relationship between CRI and HRQOL. PROCEDURE: Participants in this cross-sectional study included 63 youth ages 8-18 with SCD. Participants completed measures to assess SCE coping use (Responses to Stress Questionnaire) and HRQOL (PedsQL SCD Module). Six variables from the electronic medical record were compiled in a CRI. Correlational and regression analyses examined relationships between primary variables and moderating effects of SCE coping, respectively. RESULTS: Model results show that SCE coping and CRI explain variation in HRQOL (p = .001), and a significant interaction exists between SCE and CRI (ß = -.29, p = .02), with a stronger inverse relationship between CRI and HRQOL for higher SCE values. This suggests that lower CRI is associated with greater HRQOL for those with higher SCE coping relative to lower SCE coping. CONCLUSIONS: SCE coping may selectively benefit children with SCD experiencing lower cumulative risk, warranting encouragement of this strategy in clinical settings. Findings do not support SCE coping benefits for youth with higher risk, suggesting that the strategy may not be useful when risk-related stressors are especially pervasive; alternative protective factors should be identified for this risk group.

Pain screening in youth with sickle cell disease: A quality improvement study.

BACKGROUND: Youth with sickle cell disease (SCD) face several challenges as they age, including increased pain frequency, duration, and interference. The purpose of this study was to (i) determine the feasibility of routine pain screening; (ii) identify and describe various clinical pain presentations; and (iii) understand preferences/resources related to engaging in integrative health and medicine (IHM) modalities within an outpatient pediatric SCD clinic. METHODS: During routine outpatient visits, patients aged 8-18 completed measures of pain frequency, duration, and chronic pain risk (Pediatric Pain Screening Tool [PPST]). Participants screening positive for (i) persistent or chronic pain or (ii) medium or high risk for persistent symptoms and disability on the PPST were asked to complete measures of pain interference, pain catastrophizing, and interest in/resources for engaging in IHM modalities. RESULTS: Between March 2022 and May 2023, 104/141 (73.8%) patients who attended at least one outpatient visit were screened. Of these 104 (mean age 12.46, 53.8% female, 63.5% HbSS), 34 (32.7%) reported persistent or chronic pain, and 48 (46.2%) reported medium or high risk for persistent symptoms and disability. Patients completing subsequent pain screening measures reported a mean pain interference T-score of 53.2 ± 8.8 and a mean pain catastrophizing total score of 24.3 ± 10.2. Patients expressed highest interest in music (55.6%) and art therapy (51.9%) and preferred in-person (81.5%) over virtual programming (22.2%). CONCLUSIONS: Comprehensive pain screening is feasible within pediatric SCD care. Classifying patients by PPST risk may provide a means of triaging patients to appropriate services to address pain-related psychosocial factors.

Sleep experiences of parents of children 18 years or younger with sickle cell disease during the COVID-19 pandemic: a qualitative study.

STUDY OBJECTIVES: The coronavirus disease pandemic has highlighted disparities in health care. Parents assist in sickle cell disease management in children. Understanding sleep in parents of children who are diagnosed with sickle cell disease is an important facet of disease management. Our objectives were to identify sleep characteristics of parents of children with sickle cell disease age 18 years or younger during the coronavirus disease pandemic, to investigate measures used by parents to achieve restful sleep, and to discuss how sleep may be improved in parents of children diagnosed with sickle cell disease. METHODS: This study conducted 14 face-to-face semistructured interviews with parents of children diagnosed with sickle cell disease. A majority of the interviews (93%) were conducted at a hematology clinic. Qualitative thematic analysis was used to analyze data. RESULTS: All parents reported that their child experienced pain because of sickle cell disease. Most parents (86.7%) reported that their child was diagnosed with sickle cell anemia. Four themes were identified: difficulty obtaining restful sleep during their child's sickle cell crisis, sleep during the coronavirus disease pandemic, factors affecting sleep, and effects of sleep disturbance and deprivation on parental performance. CONCLUSIONS: This research has highlighted some of the difficulties experienced by parents of children who are diagnosed with sickle cell disease and allows for additional insight into the sleep experiences of parents as they attempt to manage their child's disease. CITATION: Osborne JC, Odlum M, Sedrak A. Sleep experiences of parents of children 18 years or younger with sickle cell disease during the COVID-19 pandemic: a qualitative study. J Clin Sleep Med. 2024;20(5):777-782.

Psychosocial and mental profile of children with sickle cell disease and their caregivers.

Sickle cell disease (SCD), a chronic debilitating disorder that may negatively affect health-related quality-of-life (HRQoL). In this observational, case-control study, we aim to assess the prevalence of impaired psychosocial profile and poor HRQoL among SCD patients and their caregivers as well as to determine the association of such impairment with parameters of disease severity. Sixty-five children and adolescents with SCD and 65 age- and sex-matched healthy controls and their caregivers were recruited. Demographic and clinical characteristics were collected, and a thorough clinical and psychiatric assessments and HR QoL were conducted. Recruited children and adolescents with SCD were 34 (52.3%) boys and 31 (47.7%) girls, and their mean age was 11.40 ± 3.55. Most of them (n = 44, 67.7%) had sickle HbSß+, and vaso-occlusive crises were the most common causes for hospital admission (n = 24, 36.9%). Children with SCD and their caregivers had depression and anxiety symptoms scores higher than reported in the control group. Children with SCD had significantly less self-esteem and less QoL scores with the least scores were in the communication domain. This adverse psychological profile was significantly negatively correlated with the age of the child, duration of illness, number and duration of hospitalizations, disease severity score, and occurrence of complications. We conclude that HRQoL of children suffering from SCD, and their caregivers are adversely affected necessitating implementation of interventions which focus on reducing depressive symptoms, enhancing self-esteem and QoL.

Daily Loneliness Affects Quality of Life in Sickle Cell Disease.

BACKGROUND: Loneliness is related to psychosomatic challenges in chronic illnesses; however, very little research focuses on loneliness in sickle cell disease (SCD), the most common genetic blood disorder. This study used a daily diary method to illustrate how loneliness and quality of life co-occur in the day-to-day lives of people living with SCD. METHOD: Seventy-nine adults living with SCD (63 women; mean age = 31.76 years) completed daily electronic surveys comprised of a brief loneliness scale and a single-item measure of quality of life. Participants completed each survey once per day for up to 42 consecutive days. We evaluated the effects of daily changes in loneliness on next-day quality of life through multilevel regression models. RESULTS: Central findings indicated that there were significant between-person (b = - .993, p < .001, 95% CI = - 1.26, - .725) and within-person (b = - .202, p < .005, 95% CI = .327, - .089) effects. Specifically, participants who reported higher mean levels of loneliness also reported lower quality of life. Further, days on which participants reported higher loneliness were followed by days on which they reported lower quality of life. CONCLUSIONS: These results may be the first to suggest a connection between loneliness and psychological outcomes in adults living with SCD. Daily fluctuations in loneliness appear to be associated with decrements in next-day quality of life. Future studies should elucidate the clinical relevance and broader health-related implications of these findings.

Social adjustment in children diagnosed with sickle cell disease: A retrospective study.

BACKGROUND: Children with sickle cell disease (SCD) are at risk for physical, psychological, and social adjustment challenges. This study sought to investigate social adjustment and related factors in children living with SCD. METHODS: Data from 32 children (50% male, mean age = 10.32 years, SD = 3.27) were retrospectively collected from a neuropsychology clinic at a tertiary care pediatric hospital. Social adjustment was measured using the Behavior Assessment System for Children (BASC-3) parent-proxy, withdrawal subscale, and the Pediatric Quality of Life Inventory (PedsQL) Generic Module Social Functioning self- and parent-proxy subscales. Other measures captured executive functioning (i.e., Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) Parent Form) and non-disease-related associations with social adjustment, including number of years in Canada and family functioning (i.e., PedsQL Family Impact Module). RESULTS: Sixteen percent of patients reported elevated social adjustment difficulties. Multiple linear regression found better family functioning [B = .48, t = 2.65, p = .016], and higher executive functioning [B = -.43, t = -2.39, p = .028] were related to higher scores on the PedsQL parent-proxy ratings of social adjustment [F(4,18) = 5.88, p = .003]. Male sex [B = .54, t = 3.08, p = .005], and having lived more years in Canada [B = .55, t = 2.81, p = .009], were related to higher PedsQL self-reported social adjustment [F(4,23) = 3.75, p = .017]. The model examining the BASC-3 withdrawal subscale was not statistically significant [F(4,16) = 1.63, p = .22]. IMPLICATIONS: Social adjustment in children diagnosed with SCD warrants future research to understand the influence of executive function, and non-disease-related factors, particularly focusing on sociocultural factors.

Education Liaison improves implementation of school accommodations for students with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) have lower academic attainment than healthy peers. Many benefit from neuropsychological testing (NPT) and educational accommodations, including Individualized Education Programs (IEPs) and Section 504 plans (504s). Despite medical barriers to academic attainment, many children with SCD do not receive indicated NPT or accommodations. OBJECTIVE: We hypothesize that a dedicated Education Liaison (EL) embedded in the SCD team increases implementation of NPT and accommodations. STUDY DESIGN: This retrospective study included children aged 5-20 years with SCD receiving care at a single center from 2017 through 2020. Univariate analysis and multiple logistic regression were performed. RESULTS: Total 316 children with SCD were included. At baseline, 52.8% had accommodations (IEP: 24.4%, 504: 38.0%). The EL interacted with 62.0% of children. Children with EL contact were more likely to undergo NPT (odds ratio [OR]: 5.385), have an IEP (OR: 4.580), and have a 504 (OR: 2.038) (p < .001 for all). At the end of the study period, 64.6% had accommodations (IEP: 33.5%, 504: 54.4%), which increased from baseline (p < .001 for all). EL interaction was associated with overt or silent stroke history (OR: 1.911), acute chest syndrome history (OR: 2.257), hospitalizations since age 5 (OR: 3.216), and hospitalization for vaso-occlusive pain since age 5 (OR: 2.226) (p < .001 for all). CONCLUSION: EL interaction improves access to NPT and educational accommodations among children with SCD. SCD centers should incorporate ELs in comprehensive care teams to improve access to appropriate educational accommodations.

Examining the influence of pain and fatigue on neurocognitive functioning in adolescents and young adults with sickle cell disease.

Pain and fatigue are among the most common and impactful complications of sickle cell disease (SCD). Individuals with SCD are also more likely to have neurocognitive deficits. Previous studies have suggested that pain and fatigue might influence neurocognitive functioning in patients with SCD. However, these studies are limited by small sample sizes and inadequate measurement of cognitive performance. The present study aimed to investigate the relationship between pain and fatigue with neurocognitive functioning using performance-based measures of neurocognition. Pain and fatigue were not associated with neurocognitive performance. Implications and directions for future research are discussed.

Psychiatric comorbidities in adults with sickle cell disease: A narrative review.

Although descriptions of quality of life and patient reports of mood in sickle cell disease (SCD) have become more common in the literature, less is known about psychiatric illness prevalence, presentation, and treatment, particularly for adults. We provide a narrative review of what is known about common and debilitating psychiatric conditions such as depression, anxiety, and cognitive impairment, specifically for adults with SCD. We discuss the limitations of the current evidence, make provisional recommendations, and identify opportunities for research and improved care.

Fatigue, Stress Appraisal, and Emotional Functioning Among Youth With Sickle Cell Disease: A Daily Diary Study.

OBJECTIVE: The aim of this study was to assess how fatigue is related to mood among youth with sickle cell disease (SCD) by evaluating if the cognitive appraisal of stress moderates the impact of fatigue on emotional functioning consistent with the Risk-and-Resistance Model of Chronic Illness. METHODS: Daily diaries assessing fatigue (Numerical Rating Scale), pain intensity (Numerical Rating Scale), mood (Positive and Negative Affect Schedule for Children), and cognitive appraisal of stress (Stress Appraisal Measure for Adolescents) were collected from 25 youth with SCD (ages 11-18 years) for 8 consecutive weeks resulting in 644 daily diaries for analyses. RESULTS: When measured concurrently, higher fatigue was associated with higher negative mood controlling for pain and prior-night sleep quality. Fatigue predicted next-day negative mood through its interaction with primary and secondary appraisal of stress, consistent with stress appraisal as a protective factor. A similar pattern was observed for pain, which, like fatigue, is a common SCD-related stressor. CONCLUSION: Fatigue and negative mood are inter-related when concurrently assessed, but their temporal association in SCD suggests that mood changes are not an inevitable sequalae of increased fatigue; fatigue influenced subsequent levels of negative mood, but only in the presence of less adaptive cognitions about stress; specifically, a higher perceived threat from stress and a lower belief in the ability to manage stress. The results suggest specific cognitive targets for reducing the negative impact of fatigue on mood in SCD.