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.

Psychiatry referral and appointment attendance in a clinic for young adults with sickle cell disease.

Mental illness is a common sickle cell disease (SCD) comorbidity. This observational study evaluated psychiatry appointment attendance among 137 young adults with SCD. In their first year of adult SCD care, 43% of subjects were referred to psychiatry. Referral was associated with chronic transfusion therapy. Twenty-four percent of subjects attended a psychiatry appointment; attendance was associated with the appointment being scheduled within 6 weeks of referral and no subject characteristics. Ninety-one percent of subjects attending psychiatry appointments had a psychiatric disorder. Among young adults with SCD, psychiatric morbidity is high. Psychiatric services are, therefore, essential for this patient population.

Trainees' perspectives on sickle cell education: a qualitative needs assessment.

BACKGROUND: Sickle cell disease (SCD) exemplifies many of the social, racial, and healthcare equity issues in the United States. Despite its high morbidity, mortality, and cost of care, SCD has not been prioritized in research and clinical teaching, resulting in under-trained clinicians and a poor evidence base for managing complications of the disease. This study aimed to perform a needs assessment, examining the perspectives of medical trainees pursuing hematology/oncology subspecialty training regarding SCD-focused education and clinical care. METHOD: Inductive, iterative thematic analysis was used to explore qualitative interviews of subspecialty hematology-oncology trainees' attitudes and preferences for education on the management of patients with SCD. Fifteen trainees from six programs in the United States participated in 4 focus groups between April and May 2023. RESULTS: Thematic analysis resulted in 3 themes: 1. Discomfort caring for patients with SCD. 2. Challenges managing complications of SCD, and 3. Desire for SCD specific education. Patient care challenges included the complexity of managing SCD complications, limited evidence to guide practice, and healthcare bias. Skill-building challenges included lack of longitudinal exposure, access to expert clinicians, and didactics. CONCLUSIONS: Variations in exposure, limited formal didactics, and a lack of national standardization for SCD education during training contributes to trainees' discomfort and challenges in managing SCD, which in turn, contribute to decreased interest in entering the SCD workforce. The findings underscore the need for ACGME competency amendments, dedicated SCD rotations, and standardized didactics to address the gaps in SCD education.

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.

The Complex Association of Daily Opioid Dose with Visits for Pain in Sickle Cell Disease: Tolerance or Treatment-Refractory Pain?

INTRODUCTION: Opioids are used for acute and chronic pain in patients with sickle cell disease. How outpatient opioid regimens relate to acute care visits is of interest given the risks of high opioid doses and high hospital utilization. A prior study by our group suggested that outpatient opioid treatment for chronic pain could contribute to a vicious cycle of treatment-refractory acute pain, greater acute care utilization, and escalating opioid doses. The present larger naturalistic observational study was undertaken to determine whether the results were reliable across multiple acute care settings. METHODS: One year of clinical data on patients (n = 291) followed in the Sickle Cell Center for Adults (August 2018 to July 2019) were extracted, including visits to the emergency department, visits to the infusion center, and inpatient admissions. Outpatient opioid dosage was used to predict acute care treatment in generalized linear models that were controlled for patient, disease, and treatment characteristics. RESULTS: Outpatient opioid dosage predicted dosage during visits but did not predict visit length or pain relief. Higher outpatient opioid dosage was associated with greater number of visits. However, in post hoc analyses, this relationship was nonlinear, with a clear positive association only for those prescribed the lowest 50% of dosages. DISCUSSION: Higher outpatient opioid dosage predicted higher dosages during acute care visits to achieve the same pain score improvement, which is more consistent with opioid tolerance than with treatment-refractory pain. The relationship of outpatient opioid dosage with number of acute care visits was more complex, which suggests that opioid consumption at lower levels is driven by intermittent acute pain and opioid consumption at higher levels is driven by chronic pain.

Illness Intrusiveness in Adults with Sickle Cell Disease: The Role of Fatigue.

Chronic illness experiences often interfere with daily functioning (a concept known as illness intrusiveness) and health-related quality of life (HRQoL). However, less is known about the role of specific symptoms in predicting illness intrusiveness in sickle cell disease (SCD). This exploratory study examined associations between common SCD-related symptoms (i.e., pain, fatigue, depression, and anxiety), illness intrusiveness, and HRQoL among adults with SCD (n = 60). Illness intrusiveness significantly correlated with fatigue severity (r = .39, p = .002), depression severity (r = .45, p < .001), anxiety severity (r = .41, p = .001), physical HRQoL (r = - .53, p < .001), and mental HRQoL (r = - .44, p < .001). Multiple regression revealed a significant overall model, (R2 = .28, F(4, 55) = 5.21, p = .001), with fatigue, but not pain, depression, or anxiety, significantly predicting illness intrusiveness (ß = .29, p = .036). Results suggest that fatigue may be a primary factor contributing to illness intrusiveness-a determinant of HRQoL-in individuals with SCD. Given the limited sample size, larger confirmatory studies are warranted.

Converting adults with sickle cell disease from full agonist opioids to buprenorphine: A reliable method with safety and early evidence of reduced acute care utilization.

Buprenorphine, a novel opioid with complex pharmacology, is effective for treating pain and is qualitatively safer than high-dose full agonist opioid therapy; but transitioning to buprenorphine can be technically complex and carries some risk of precipitated withdrawal. We report our clinic's experience converting 36 patients with sickle cell disease (SCD) from full agonist opioids to buprenorphine using a method developed in the past 10 years. Thirty of these patients were induced using a standard outpatient protocol and six were induced during medical admissions. Typically, patients were on high-dose chronic opioid therapy (COT) with inadequate response, and often with very high acute care utilization. Unlike prior case series, the method of induction, dosing, and management of withdrawal are detailed, as are post-induction adverse events. There were seven adverse events in the first 3 days following standard induction, and two of which were judged to be definitely related to the induction but none with any lasting sequelae. At 6 months follow-up, five participants had discontinued buprenorphine (16.67%), and overall acute care visits dropped from a mean of 10.50 (SD 11.35) in the 6 months pre-induction to 2.89 (SD 3.40) in the 6 months post-induction. In an appropriately interdisciplinary care setting, buprenorphine shows promise as a safe alternative to COT with early evidence of benefit for high-utilizing patients with SCD.

A Preliminary Investigation of the Underlying Mechanism Associating Daily Sleep Continuity Disturbance and Prescription Opioid Use Among Individuals With Sickle Cell Disease.

BACKGROUND: There are emerging data indicating that sleep disturbance may be linked with an increase in opioid use. The majority of sickle cell disease (SCD) patients experience sleep disturbances, which can elevate pain severity and pain catastrophizing, both of which are important predictors of opioid consumption. PURPOSE: We conducted a preliminary investigation on the association between previous night sleep disturbance and short-acting opioid use, as well as the potential mediating roles of pain severity and pain catastrophizing. Because sex is associated with sleep disturbance, pain-related experiences, and opioid use, we also explored the potential moderating role of sex. METHODS: Participants were 45 SCD patients who were prescribed opioids. For 3 months, sleep diaries were collected immediately upon participants' awakening. Daily pain severity, pain catastrophizing, and prescription opioid use measures were collected before bedtime. RESULTS: Multilevel structural equation modeling revealed that wake time after sleep onset (WASO) during the previous night (Time 1) predicted greater short-acting opioid use during the next day (Time 2). Pain severity and pain catastrophizing measured during the next day (Time 2) also mediated the association between the two. Sex moderation analysis showed that the positive association between WASO and pain severity was largely driven by women. CONCLUSION: These findings provide some preliminary evidence as to the mechanism linking sleep continuity disturbance and opioid requirement in SCD patients. Future studies should replicate and extend these findings with clearer temporal information and employing more refined measures of sleep continuity and prescription opioid use in a larger sample.

Psychological symptom screening in an adult sickle cell disease clinic and predictors of treatment follow up.

Absence of formal and systematic screening for mood and anxiety disorders among patients with sickle cell disease (SCD) can result in under-recognized psychological problems. This study examined the prevalence of psychological symptoms using a systematic screening process. Patients with SCD completed four self-report screening tools for measurement of depressive and anxiety symptoms, self-efficacy, and pain. The goal was to detect patients with psychological symptoms and identify predictors of follow-up treatment attendance. A total of 336 adult patients (57% female, mean age 33 years) completed validated screening instruments for major depressive disorder and generalized anxiety disorder. Patients recommended for mental health follow-up included higher proportions of women. Patients who accepted the mental health follow up had higher levels of education compared to groups that did not accept nor attend the follow-up appointment. Overall, 34% of patients who endorsed elevated distress scores and were referred for mental health care attended the follow-up appointment. Findings suggest patients with SCD and elevated psychological distress are likely to use mental health treatment resources, which notes this program's success in identifying needs and responding to them. However, further research is needed to understand ways to engage this population in mental health care.

Predictors of acute care utilization and acute pain treatment outcomes in adults with sickle cell disease: The role of non-hematologic characteristics and baseline chronic opioid dose.

Despite its rarity in the United States, sickle cell disease accounts for a disproportionate amount of healthcare utilization and costs. The majority of this is due to acute care for painful crises. A small subpopulation of patients accounts for most these costs due to frequent visits to emergency departments and acute care facilities. Previous investigations have found that these high utilizing patients are distinguished by both a more severe disease course and certain non-hematologic characteristics, which may include higher socioeconomic status and some psychiatric and psychological characteristics. This prospective observational cohort study was undertaken to test the ability of these characteristics to prospectively predict acute pain care outcomes, including visit frequency, total opioid doses, and pain improvement at the Johns Hopkins Sickle Cell Infusion Center (SCIC). Seventy-three participants were followed for 12 months and SCIC utilization and treatment outcomes were tabulated for 378 visits. Participants who visited the SCIC most frequently had markedly worse pain improvement despite higher within-visit opioid doses. Higher utilization was associated with indicators of greater illness severity, more aggressive treatment for sickle cell disease, higher baseline opioid doses, higher socioeconomic status, greater pain-related anxiety, and a history of psychiatric treatment. Overall, poor acute pain treatment response was associated with higher utilization and higher baseline opioid doses. The pattern of association between high utilization, poor acute care outcomes, and higher baseline opioid doses is discussed in terms of prior research and future directions.

Examination of the Patient and Hospitalization Characteristics of 30-Day SCD Readmissions.

OBJECTIVES: Sickle cell disease (SCD) is associated with a high level of emergency department and hospital utilization, as well as a high rate of hospital readmissions. At Johns Hopkins Hospital, as at other institutions, SCD accounts for a large proportion of readmissions. Our study examined patient and hospitalization factors involved in readmissions at Johns Hopkins Hospital. METHODS: Patients at the Johns Hopkins Sickle Cell Center for Adults with a readmission in fiscal year 2011 were compared with an age- and sex-matched sample of clinic patients for comorbidities, complications, and prior utilization. Hospitalizations that were followed by readmissions were compared with those that were not as to admitting service, length of stay, and average daily opioid dose. RESULTS: Patients with readmissions had more complications and comorbidities and much higher prior utilization than typical clinic patients, whereas hospitalizations that were followed by readmissions had a longer length of stay but similar opioid doses. CONCLUSIONS: For patients with SCD with a high volume of hospital use, readmissions may be a natural consequence of a high-admission frequency associated with greater disease severity and higher comorbidity.

Impact of a dedicated infusion clinic for acute management of adults with sickle cell pain crisis.

Most adults with sickle cell disease (SCD) receive care for their acute painful episodes in an emergency department (ED) setting. The purpose of this article is to describe the impact of opening a dedicated treatment center for adults with SCD [Sickle Cell Infusion Clinic (SCIC)] on patient outcomes and on hospital discharges for SCD. Descriptive data including demographics, time to first dose of narcotic, and pain scores were collected on patients presenting to the SCIC and ED. Maryland hospital discharge data were obtained from the Maryland Health Services Cost Review Commission. Analyses were conducted using T tests, χ(2) tests, and simple generalized estimating equation regression models accounting for the clustered nature of observations, as appropriate. There were 3,874 visits to the SCIC by 361 unique patients; 85% of those visits resulted in the patient being sent home. During the same time period, there were 3,408 visits to the ED by 558 unique patients with SCD. The overall admission rate from the ED for these patients was 35.9% but decreased significantly over the time period with a rate of 20% in December 2011. There was a significant decrease in readmissions over time for the entire Baltimore Metro area with the likelihood of readmission decreasing by 7% over time. The SCIC model provides adults with SCD access to high quality care that decreases the need for hospital admission. Further research needs to be done to evaluate the cost effectiveness of this model.

Perceived discrimination, patient trust, and adherence to medical recommendations among persons with sickle cell disease.

BACKGROUND: Adults with sickle cell disease (SCD) report experiencing discriminatory behavior from some healthcare providers. The impact of discrimination on health outcomes in SCD, including adherence to physician recommendations, is not known. OBJECTIVE: Our aim was to evaluate the association between perceived discrimination from healthcare providers and nonadherence to physician recommendations among persons with SCD, and to test the potentially mediating role of patient trust. PARTICIPANTS: Patients with SCD (age 15 years and older) participating in the Improving Patient Outcomes with Respect and Trust (IMPORT) Study. MAIN MEASURES: Perceived discrimination from healthcare providers and reported adherence to physician recommendations were assessed by patient self-report using items from the 2001 Commonwealth Fund Health Survey. Interpersonal trust in medical professionals was assessed using the short form of the Wake Forest Trust in Medical Professionals instrument. DESIGN: We used a cross-sectional analysis of IMPORT participant data. Multivariable Poisson regression models were used to test the independent association of discrimination with adherence and to test patient trust as a potential mediator. KEY RESULTS: Among 273 SCD patients with complete data on all variables of interest, patients reporting experiences of discrimination in the healthcare system were 53% more likely to also report being nonadherent to physician recommendations. Trust in medical professionals appeared to mediate the discrimination/nonadherence relationship, accounting for 50% of the excess prevalence of nonadherence among those experiencing discrimination. CONCLUSION: SCD patient perceptions of discriminatory experiences from healthcare providers are associated with greater nonadherence to physician recommendations, and may be a potential factor contributing to disparities in health and health quality among this patient population. Perceived discrimination appears to affect adherence behaviors through the pathway of patient trust. Improving relationships between healthcare providers and SCD patients may improve the trust that SCD patients have in medical professionals, which in turn may improve other outcomes among this underserved patient population.

"Buprenorphine, It Works so Differently": Adults with Sickle Cell Disease Describe Transitioning to Buprenorphine for Treatment of Chronic Pain.

A growing body of literature describes the use of buprenorphine for the treatment of chronic pain in people with sickle cell disease. The experiences of people with sickle cell disease who have tried buprenorphine have not yet reported. This qualitative descriptive study was conducted to explore perspectives on buprenorphine for chronic pain in sickle cell disease. We interviewed 13 participants with sickle cell disease who had been prescribed buprenorphine and had a clinic visit between December 1, 2020, and April 2022 in our Sickle Cell Center for Adults. Interviews were recorded, transcribed, and analyzed using thematic analysis. Eleven out of 13 participants were taking buprenorphine at the time of the interview, with a mean treatment duration of 33 months (SD 18, range 7-78 months). Five major themes were identified: 1) dissatisfaction with full agonist opioids; 2) navigating uncertainty with autonomy in deciding to try buprenorphine; 3) functional and relational changes after starting buprenorphine, 4) enduring systemic barriers to pain treatment, and 5) trusting treatment relationships are necessary when approaching patients about buprenorphine. The experience of adulthood living with sickle cell disease before and after starting buprenorphine is qualitatively different with significant improvements in social functioning. PERSPECTIVE: This study examined the experience of adults with sickle cell disease and chronic pain transitioning from full agonist opioids to buprenorphine. It is the first qualitative study of buprenorphine in people with sickle cell disease, contributing to a small but growing literature about buprenorphine and sickle cell disease.

An Observational Study of Proactive and On-Request Psychiatry Consultation Services: Evidence for Differing Roles and Outcomes.

BACKGROUND: Proactive psychiatric consultation services rapidly identify and assess medical inpatients in need of psychiatric care. In addition to more rapid contact, proactive services may reduce the length of stay and improve staff satisfaction. However, in some settings, it is impractical to integrate a proactive consultation service into every hospital unit; on-request and proactive services are likely to coexist in the future. Prior research has focused on changes in outcomes with the implementation of proactive services. OBJECTIVE AND METHODS: This report describes differences between contemporary proactive and on-request services within the same academic medical center, comparing demographic and clinical data collected retrospectively from a 4-year period from the electronic medical record. RESULTS: The proactive service saw patients over four times as many initial admissions (7592 vs. 1762), but transitions and handoffs between services were common, with 434 admissions involving both services, comprising nearly 20% of the on-request service's total contacts. The proactive service admissions had a shorter length of stay and a faster time to first psychiatric contact, and the patients seen were more likely to be female, of Black race, and to be publicly insured. There were over three times as many admissions to psychiatry from the proactive service. The on-request service's admissions had a longer length of stay, were much more likely to involve intensive care unit services, surgical services, and transfers among units, and the patients seen were more likely to die in the hospital or to be discharged to subacute rehabilitation. CONCLUSIONS: Overall, the results suggest that the two services fulfill complementary roles, with the proactive service's rapid screening and contact providing care to a high volume of patients who might otherwise be unidentified and underserved. Simultaneously, the on-request service's ability to manage patients in response to consult requests over a much larger area of the hospital provided important support and continuity for patients with complex health needs. Institutions revising their consultation services will likely need to consider the best balance of these differing functions to address perceived demand for services.

Smoking as a risk factor for choroidal neovascularization secondary to presumed ocular histoplasmosis syndrome.

PURPOSE: To investigate the relationship of smoking to choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis syndrome (POHS). DESIGN: Retrospective, case-control study. PARTICIPANTS: A total of 568 patients 18 to 50 years of age, 142 of whom were diagnosed with CNV secondary to POHS in a private retina practice between July 1, 2000, and August 1, 2010. Four hundred twenty-six were controls selected from a private comprehensive ophthalmology practice at the same location. METHODS: A retrospective medical record review was performed for all participants. Age, gender, zip code, CNV diagnosis date, insurance status, and smoking status at CNV diagnosis date were collected first for the POHS patients. For each of these 142 patients, 3 randomly selected comprehensive clinic patients, whose visit date fell within 3 months of the corresponding POHS patient's CNV diagnosis date, served as controls. Age, gender, zip code, visit date, reason for visit, insurance type, and smoking status were recorded. Descriptive statistics were calculated for cases and controls. MAIN OUTCOME MEASURES: Logistic regression analyses were performed for both univariate and multivariate models, with CNV secondary to POHS as the main outcome variable and smoking as the main predictor variable, while adjusting for age, gender, insurance type, median household income, and education level. RESULTS: The mean age of patients with CNV secondary to POHS was 39.0±7.1 years, whereas that of the control patients was 35.7±9.1 years. Of the patients with CNV secondary to POHS, 47.2% were current or former smokers (42.3% current, 4.9% former). Of the control patients, 22.5% were current or former smokers (21.8% current, 0.7% former). Age, insurance type, median income, educational attainment, and smoking status were significant in the univariate models. In the final adjusted logistic regression model, only age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.07; P = 0.001), level of educational attainment by zip code (OR, 0.95; 95% CI, 0.92-0.98; P = 0.001) and smoking status (OR, 2.83; 95% CI, 1.86-4.31; P<0.0001) were significant. CONCLUSIONS: The odds of a smoker having CNV secondary to POHS are almost 3 times that of a nonsmoker. In this study, the odds of having CNV secondary to POHS increased with age and decreased with increasing level of educational attainment.

Examining the characteristics and beliefs of hydroxyurea users and nonusers among adults with sickle cell disease.

The attitudes of patients with sickle cell disease (SCD) toward the use of hydroxyurea (HU) therapy may contribute to the underutilization of HU in the United States, yet our understanding of these attitudes is limited. We examined the attitudes and beliefs of 94 adult SCD patients, comparing those who never used HU (n 5 37), formerly used HU (n 5 23), and were currently using HU (n 5 34). Seventy percent of current HU users reported some level of improvement from the drug ("average" or "very much") and 80% reported little or no trouble from side effects. Fifty-seven percent of former users reported taking HU for less than 6 months, with "doctor"s recommendation," or "not liking the way it made me feel" given as the most commonly reported reasons for stopping HU. Fifty percent of the never users reported receiving no information about HU from any source, and 85% of the never users thought that they would receive no improvement if they were to take HU. A deeper understanding of patient perspectives toward HU utilization is required as part of multipronged efforts to combat its underutilization in the treatment of SCD.

Maladaptive opioid use behaviors and psychiatric illness: what should we do with what we know?

It is well established that opioids are broadly effective for chronic pain. Although there is some agreement that stable, moderate dosing is desirable; longer-term management of patients with chronic pain often confronts clinicians with difficult decisions regarding when to intensify opioid treatment and when to declare failure. Under these circumstances the concern for addiction arises with uncomfortable frequency in specialty settings. An emerging literature has defined a number of plausible markers of risk for aberrant opioid use behaviors in clinical chronic pain populations. Some of these risk factors involve the presence of comorbid psychiatric illnesses, which puts clinicians in the difficult position of deciding whether or not to limit treatment to patients who are more complex. The authors discuss the issues of bad behavioral outcomes in opioid therapy, the implications of this emerging literature for clinicians, and suggest broad areas in which researchers can improve the knowledge base with which clinicians operate.