Mental health, pain and likelihood of opioid misuse among adults with sickle cell disease.

Depressive symptoms are prevalent in individuals living with sickle cell disease (SCD) and may exacerbate pain. This study examines whether higher depressive symptoms are associated with pain outcomes, pain catastrophizing, interference and potential opioid misuse in a large cohort of adults with SCD. The study utilized baseline data from the 'CaRISMA' trial, which involved 357 SCD adults with chronic pain. Baseline assessments included pain intensity, daily mood, the Patient Health Questionnaire (PHQ), the Generalized Anxiety Disorders scale, PROMIS Pain Interference, Pain Catastrophizing Scale, the Adult Sickle Cell Quality of Life Measurement Information System and the Current Opioid Misuse Measure. Participants were categorized into 'high' or 'low' depression groups based on PHQ scores. Higher depressive symptoms were significantly associated with increased daily pain intensity, negative daily mood, higher pain interference and catastrophizing, poorer quality of life and a higher likelihood of opioid misuse (all p < 0.01). SCD patients with more severe depressive symptoms experienced poorer pain outcomes, lower quality of life and increased risk of opioid misuse. Longitudinal data from this trial will determine whether addressing depressive symptoms may potentially reduce pain frequency and severity in SCD.

Mortality in adults with sickle cell disease: Results from the sickle cell disease implementation consortium (SCDIC) registry.

The cause of death in people affected by sickle cell disease (SCD) is often challenging to define as prior studies have used retrospective or administrative data for analysis. We used a prospective longitudinal registry to assess mortality and clinical co-morbidities among subjects enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. At enrollment, we collected the following data: patient-reported demographics, SCD phenotype, baseline laboratory values, comorbidities, and current medications. Subjects were followed for a median of 4.7 years before the present analysis. The relationship of clinical co-morbidities (at time of enrollment) to mortality was determined using survival analysis, adjusting for SCD phenotype and gender. There was a total of 2439 people with SCD enrolled in the SCDIC registry. One hundred and twenty-eight participants (5%) died during the observation period (2017-2022). Six people died from trauma and were excluded from further analysis. Proximate cause of death was unwitnessed in 17% of the deaths, but commonest causes of death include cardiac (18%), acute chest or respiratory failure (11%), sudden unexplained death (8%). Enrollment characteristics of the individuals who died (n = 122) were compared to those of survivors (n = 2317). Several co-morbidities at enrollment increased the odds of death on univariate analysis. All co-morbidities were included in a multivariable model. After backward elimination, iron overload, pulmonary hypertension, and depression, remained statistically significant predictors of the risk of death. SCD reduces life expectancy. Improved comprehensive and supportive care to prevent end-organ damage and address comorbidities is needed for this population.

Opioid Use Among Children and Adults With Sickle Cell Disease in North Carolina Medicaid Enrollees in the Era of Opioid Harm Reduction.

Adults and children with sickle cell disease (SCD) are predominantly African American, with pain-related health disparities. We examined opioid prescription fill patterns in adults and children with SCD and compared factors associated with fills in North Carolina Medicaid enrollees. Our retrospective cohort study included 955 enrollees diagnosed with SCD having at least one opioid fill. Associations were measured between two cohorts (12 and 24 mo of continuous enrollment) for the following characteristics: sex, age, enrollee residence, hydroxyurea adherence, comanagement, enrollment in Community Care North Carolina, prescription for short versus short and long-acting opioids, and emergency department reliance. The majority of individuals did not have an opioid claim over a 12 or 24-month period. Claims increased at ages 10 to 17, peaking at ages 18 to 30. The increased number of claims was associated with the following factors: increasing age, male, short versus long-acting opioids, and Medicaid enrollment for 24 versus 12 months. Community Care North Carolina enrollees in the 12-month cohort had higher opioid days of supply per month; the inverse was true of the 24-month cohort.

Characterising the prevalence of overweight and obese status among adults with sickle cell disease.

Individuals with sickle cell disease (SCD) have historically been considered underweight. Despite increasing body mass index (BMI) in the general population, the prevalence of overweight and obese status remains unclear in the adult SCD population. Our primary aim was to determine the prevalence of overweight and obese status and to identify associations between BMI, demographic, and clinical characteristics. We conducted an analysis of abstracted electronic health record data and patient-reported outcomes from the Sickle Cell Disease Implementation Consortium registry; individuals aged 20-45 years were included. The median (interquartile range) BMI for the 1664 adults in this analysis was 23.9 (21.1-28) kg/m2 . In this cohort, 42.9% had a BMI of >25 kg/m2 (Centers for Disease Control and Prevention definition of overweight/obese). In multivariable analysis, higher odds of being overweight or obese were associated with female gender, older age, college education, private insurance, and hypertension diagnosis. Higher odds of a BMI of >25 kg/m2 were observed in individuals with HbSC or HbSß+ thalassaemia regardless of hydroxycarbamide (hydroxyurea) exposure (odds ratio [OR] 3.4, p < 0.0001) and HbSS or HbSß0 thalassaemia exposed to hydroxycarbamide (OR 1.6, p = 0.0003) compared to those with HbSS or HbSß0 thalassaemia with no hydroxycarbamide exposure. These data highlight the importance of early identification, prevention, and intervention for increasing BMI to reduce obesity-related complications that may impact SCD-related complications.

Infertility and treatment-seeking practices among females and males with sickle cell disease in the Sickle Cell Disease Implementation Consortium registry.

OBJECTIVE: To describe the prevalence of infertility and infertility treatment seeking among people enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry and identify sociodemographic and clinical correlates of infertility. DESIGN: Cross-sectional. PARTICIPANTS: The study population included 2108 women and men (≥18 years of age) enrolled in the SCDIC registry who completed the fertility questionnaire. RESULTS: All participants who completed the infertility-specific questions were included in the analysis (1224 females; 884 males). Of these, 16.9% of males and 23.7% of females reported infertility, in contrast to rates in the general population (12% of males; 11% of females). Only 22.8% of this subgroup had sought a fertility consultation; of these, 41% received infertility testing and 58% received advice, yet only a few received specific treatment: ovulation medication (19.1%), fallopian tubal surgery (4.8%), other female treatment (17.5%), varicocelectomy (8.1%), or other male treatment (10.8%). Increasing age, employment status, and interaction between gender and single marital status are associated with reported infertility. We did not observe differences between groups relative to sickle cell disease (SCD) genotype, a broad category of self-reported hydroxyurea use any time during life, type of medical insurance, income, or education. CONCLUSION: To our knowledge, this is the first study to examine self-reported identification of and treatment for infertility among a large sample of people with SCD. These findings suggest that (a) infertility occurs at a higher rate, but fertility care treatment seeking is less frequent than in the general public; and (b) sociodemographic and clinical differences between individuals who report experiencing infertility and those who do not did not emerge in this study.

Consensus definition of essential, optimal, and suggested components of a pediatric sickle cell disease center.

Sickle cell disease (SCD) requires coordinated, specialized medical care for optimal outcomes. There are no United States (US) guidelines that define a pediatric comprehensive SCD program. We report a modified Delphi consensus-seeking process to determine essential, optimal, and suggested elements of a comprehensive pediatric SCD center. Nineteen pediatric SCD specialists participated from the US. Consensus was predefined as 2/3 agreement on each element's categorization. Twenty-six elements were considered essential (required for guideline-based SCD care), 10 were optimal (recommended but not required), and five were suggested. This work lays the foundation for a formal recognition process of pediatric comprehensive SCD centers.

Evaluating Associations between Average Pain Intensity and Genetic Variation in People with Sickle Cell Disease: An Exploratory Study.

BACKGROUND: Pain is one of the most common and deleterious symptoms experienced by individuals with sickle cell disease (SCD). There is a paucity of studies identifying potential genetic mechanisms of pain in this population. AIM: Examine associations between 11 functional single nucleotide polymorphisms in 9 candidate genes with reports of average pain intensity in individuals with sickle cell disease. METHOD: Cross-sectional analyses were performed on data and blood samples collected through the Duke SCD Implementation Consortium Registry. Participants were asked to rate their pain "on the average" using an 11-point numeric rating scale (0 = no pain; 10 = pain as bad as you can imagine). We genotyped 11 single nucleotide polymorphisms in 9 pain-related genes using TaqMan® Genotyping Assays. Associations between each polymorphism and reports of average pain were evaluated. RESULTS: The 86 participants (mean age: 28.7 years; 64% female) included in this study reported moderate pain on average (Mean = 4, Standard Deviation = 2.4). ICAM1 rs1799969 was the only genetic polymorphism that was significantly associated with pain (p = .01). Individuals with one or more minor alleles had lower average pain (Mean = 1.25, Standard Deviation = 1.50) than individuals without a minor allele (Mean = 4.13, Standard Deviation = 2.25). The effect size for ICAM1 rs1799969 was 1.30, which is considered large. The effect sizes for all other single nucleotide polymorphisms ranged from small to medium (range: 0-0.3). CONCLUSIONS: Our findings provide preliminary evidence that the minor allele in ICAM1 rs1799969 had protective effects against experiencing more severe pain in sickle cell disease.

Can subjective pain be inferred from objective physiological data? Evidence from patients with sickle cell disease.

Patients with sickle cell disease (SCD) experience lifelong struggles with both chronic and acute pain, often requiring medical interventMaion. Pain can be managed with medications, but dosages must balance the goal of pain mitigation against the risks of tolerance, addiction and other adverse effects. Setting appropriate dosages requires knowledge of a patient's subjective pain, but collecting pain reports from patients can be difficult for clinicians and disruptive for patients, and is only possible when patients are awake and communicative. Here we investigate methods for estimating SCD patients' pain levels indirectly using vital signs that are routinely collected and documented in medical records. Using machine learning, we develop both sequential and non-sequential probabilistic models that can be used to infer pain levels or changes in pain from sequences of these physiological measures. We demonstrate that these models outperform null models and that objective physiological data can be used to inform estimates for subjective pain.

Pregnancy outcomes with hydroxyurea use in women with sickle cell disease.

Hydroxyurea reduces pain crises, acute chest syndrome, and blood transfusions in sickle cell disease (SCD), but potential detrimental effects on fertility and birth outcomes impede its use. Data on the effects of hydroxyurea taken for SCD during conception and pregnancy are scarce. The Sickle Cell Disease Implementation Consortium collected self-reported pregnancy history, corresponding hydroxyurea use, and pregnancy outcomes in women with SCD in the clinical setting. Among 1285 women 18-45 years of age, 737 (57.4%) reported 1788 pregnancies (1079 live births, 394 miscarriages, 40 stillbirths, 207 abortions, 48 current pregnancies, and 20 missing outcomes) of which 241 (15.9%) live births, miscarriages or stillbirths were conceived while on hydroxyurea. In univariate analyses, pregnancy number more than three, severe sickle genotype, history of stillbirth or miscarriage, and chronic kidney disease at enrollment were covariates significantly associated with a pregnancy ending in miscarriage or stillbirth. After adjustment for covariates and additional SCD severity markers in multivariate analyses, hydroxyurea use during conception and pregnancy, but not during conception only, was associated with an increase in the odds ratio (OR) of miscarriage or stillbirth (OR 2.21, 95% confidence interval [CI] 1.40-3.47). In analyses of live birth outcomes, hydroxyurea use during conception and pregnancy was associated with birth weight < 5.5 pounds in full-term infants (OR 2.98, 95% CI 1.09-7.38) but not with prematurity or serious medical problems at birth. These findings suggest that hydroxyurea use may be safe up to the time of conception, but that clinicians should continue to advise caution regarding use during pregnancy.

Transitioning Adolescents With Sickle Cell Disease From Pediatric to Adult Care: Results From a New Survey of Health Care Professionals.

Transition from pediatric to adult care for adolescents and young adults (AYA) with sickle cell disease (SCD) comes at a time when a range of biopsychosocial issues occur simultaneously. A new survey sought information from physicians who treat AYA with SCD about their practices in how they transition pediatric patients to adult care. An online survey to physicians who treat SCD was conducted using SurveyMonkey between November 2019 and January 2020. Of 209 physicians who were contacted, 58 completed the survey; 62.1% treated primarily pediatric patients and 37.9% treated adults. Patient education on transition was regarded as "important" or "very important" by 94.2% of the physicians. Patients' knowledge about their disease and their ability to navigate the health care system were identified as 2 primary barriers to transition (mean 1.30 and 1.67 on a 3-point scale, respectively). Most physicians employ established models to facilitate the transition, including Got Transition (41.3%) and a biopsychosocial model (34.8%), with 34.8% using a mix of models and 23.9% not using an established model. Fewer than half (34.8%) rated their program as "very successful" or "successful." Transition protocols from pediatric to adult care should be re-examined to facilitate successful transition for AYA with SCD.