High-impact chronic pain in sickle cell disease: insights from the Pain in Sickle Cell Epidemiology Study (PiSCES).

ABSTRACT: The US National Pain Strategy recommends identifying individuals with chronic pain (CP) who experience substantial restriction in work, social, or self-care activities as having high-impact chronic pain (HICP). High-impact chronic pain has not been examined among individuals with CP and sickle cell disease (SCD). We analyzed data from 63 individuals with SCD and CP who completed at least 5 months of pain diaries in the Pain in Sickle Cell Epidemiology Study (PiSCES). Forty-eight individuals met the definition for HICP, which was operationalized in this study as reporting pain interference on more than half of diary days. Compared with individuals without HICP, individuals with HICP experienced higher mean daily pain intensity, particularly on days without crises. They also experienced a greater proportion of days with pain, days with healthcare utilization, and days with home opioid use and higher levels of stress. They did not have a statistically significantly higher proportion of days with crises or experience higher mean daily pain intensity on days with crises. Individuals with HICP experienced worse physical functioning and worse physical health compared with those without HICP, controlling for mean pain intensity, age, sex, and education. The results of this study support that HICP is a severely affected subgroup of those with CP in SCD and is associated with greater pain burden and worse health outcomes. The findings from this study should be confirmed prospectively in a contemporary cohort of individuals with SCD.

Dysphagia in patients with sickle cell disease: An understudied problem.

Dysphagia which is defined as disordered swallowing is well known as one of the most common and dangerous symptoms of many diseases, including neurological disorders such as Parkinson's disease, amyotrophic lateral sclerosis, myasthenia gravis, and most commonly, stroke. Strokes are a potentially devastating complication of sickle cell disease (SCD), the most common genetic hemoglobinopathy worldwide, yet little is known about dysphagia as it relates to SCD. Thus, the purposes of this article are to review briefly the primary causes and health consequences of dysphagia, to highlight the relevance of dysphagia to SCD, to review what little is known about dysphagia in SCD, to recommend, based on our consensus and the available literature, when to screen, evaluate, and monitor dysphagia in patients with SCD, and to outline unanswered questions where research on dysphagia in SCD might improve health outcomes.

Impact of community health workers on quality of life in adolescents and young adults with sickle cell disease: The SHIP-HU study.

Health-related quality of life (HRQoL) is an important outcome for patients with sickle cell disease (SCD). It is often poor compared with other chronic medical conditions or measured as a multidomain disease-specific construct. We previously reported outcomes in the Start Healing in Patients with Hydroxyurea (SHIP-HU) randomized controlled trial in adolescents and adults with SCD at six clinical sites. Besides the primary outcomes, we also measured HRQoL as a secondary outcome. Patients in the intervention arm were each assigned community health workers (CHWs) who provided case management services. CHW services were independent of medical management, and medical managers were blinded to the study arm. Patients in the control arm received only standard of care. We hypothesized that having a CHW would improve HRQoL in patients enrolled in SHIP-HU. We did not find significant differences between domains of HRQoL in the two study arms. Possible explanations include selection bias of enrolled versus unenrolled patients, selection bias of sites, medical providers and medical management, enforced blinding, and a lack of cooperation between medical managers and CHWs. The importance of CHWs and HRQoL is nonetheless recognized based on the literature. Future interventions on HRQoL in SCD should consider alternative study designs and multimodal interventions.

Patient Motivation to Reduce or Discontinue Opioids for Chronic Pain: Self-efficacy, Barriers, and Readiness to Change.

OBJECTIVES: This study aimed to assess levels and predictors of self-efficacy and motivation to change opioid use among a community sample of patients using opioids for chronic pain, as well as patient-reported barriers to pursuing opioid discontinuation. METHODS: Participants with a variety of chronic pain conditions, recruited from ResearchMatch.org , completed a battery of electronic, self-report questionnaires assessing demographic and medical characteristics, pain treatment history, and levels of readiness, self-efficacy, and other attitudes toward reducing or discontinuing opioid use. Multiple regression analyses and analyses of variance were conducted to examine predictors of readiness and self-efficacy to change opioid use. A modified version of rapid qualitative analysis was utilized to analyze themes in participant responses to an open-ended item about "what it would take" to consider opioid discontinuation. RESULTS: The final sample included N=119 participants, the majority of whom were female (78.2%), Caucasian (77.3%), and well-educated. Readiness and self-efficacy to decrease or stop opioid use were fairly low on a 0 to 10 Visual Analog Scale (2.6 to 3.8) and significantly higher to decrease than stop ( P <0.01). Higher readiness to change was predicted by lower pain severity and higher concern about opioids, whereas higher self-efficacy was predicted by shorter pain duration. Results from the qualitative analyses revealed that the availability of an alternative treatment option was the most commonly cited requirement to consider opioid discontinuation. DISCUSSION: Patients with lower pain severity, shorter duration of pain, and higher concerns about opioids may be a prime target from a motivation standpoint for interventions addressing opioid tapering and discontinuation.

Biopsychosocial Factors Associated With Pain and Pain-Related Outcomes in Adults and Children With Sickle Cell Disease: A Multivariable Analysis of the GRNDaD Multicenter Registry.

Pain is the primary symptomatic manifestation of sickle cell disease (SCD), an inherited hemoglobinopathy. The characteristics that influence pain experiences and outcomes in SCD are not fully understood. The primary objective of this study was to use multivariable modeling to examine associations of biopsychosocial variables with a disease-specific measure of pain interference known as pain impact. We conducted a secondary analysis of data from the Global Research Network for Data and Discovery national SCD registry. A total of 657 children and adults with SCD were included in the analysis. This sample was 60% female with a median age of 34 (interquartile range 26-42 years) and a chronic pain prevalence of 64%. The model accounted for 58% of the variance in pain impact. Low social (P < .001) and emotional (P < .001) functioning, increasing age (P = .004), low income (P < .001), and high acute painful episodes (P = .007) were most strongly associated with high pain impact in our multivariable model. Additionally, multivariable modeling of pain severity and physical function in 2 comparable samples of registry participants revealed that increasing age and low social functioning were also strongly associated with higher pain severity and low physical functioning. Overall, the results suggest that social and emotional functioning are more strongly associated with pain impact in individuals with SCD than previously studied biological modifiers such as SCD genotype, hemoglobin, and percentage fetal hemoglobin. Future research using longitudinally collected data is needed to confirm these findings. PERSPECTIVE: This study reveals that psychosocial (ie, social and emotional functioning) and demographic (ie, age) variables may play an important role in predicting pain and pain-related outcomes in SCD. Our findings can inform future multicenter prospective longitudinal studies aimed at identifying modifiable psychosocial predictors of adverse pain outcomes in SCD.

Precision, integrative medicine for pain management in sickle cell disease.

Sickle cell disease (SCD) is a prevalent and complex inherited pain disorder that can manifest as acute vaso-occlusive crises (VOC) and/or chronic pain. Despite their known risks, opioids are often prescribed routinely and indiscriminately in managing SCD pain, because it is so often severe and debilitating. Integrative medicine strategies, particularly non-opioid therapies, hold promise in safe and effective management of SCD pain. However, the lack of evidence-based methods for managing SCD pain hinders the widespread implementation of non-opioid therapies. In this review, we acknowledge that implementing personalized pain treatment strategies in SCD, which is a guideline-recommended strategy, is currently fraught with limitations. The full implementation of pharmacological and biobehavioral pain approaches targeting mechanistic pain pathways faces challenges due to limited knowledge and limited financial and personnel support. We recommend personalized medicine, pharmacogenomics, and integrative medicine as aspirational strategies for improving pain care in SCD. As an organizing model that is a comprehensive framework for classifying pain subphenotypes and mechanisms in SCD, and for guiding selection of specific strategies, we present evidence updating pain research pioneer Richard Melzack's neuromatrix theory of pain. We advocate for using the updated neuromatrix model to subphenotype individuals with SCD, to better select personalized multimodal treatment strategies, and to identify research gaps fruitful for exploration. We present a fairly complete list of currently used pharmacologic and non-pharmacologic SCD pain therapies, classified by their mechanism of action and by their hypothesized targets in the updated neuromatrix model.

The Lives Lost to Inequities: Avertable Deaths From Neurologic Diseases in the Past Decade.

BACKGROUND AND OBJECTIVES: Mortality rates for neurologic diseases are increasing in the United States, with large disparities across geographical areas and populations. Racial and ethnic populations, notably the non-Hispanic (NH) Black population, experience higher mortality rates for many causes of death, but the magnitude of the disparities for neurologic diseases is unclear. The objectives of this study were to calculate mortality rates for neurologic diseases by race and ethnicity and-to place this disparity in perspective-to estimate how many US deaths would have been averted in the past decade if the NH Black population experienced the same mortality rates as other groups. METHODS: Mortality rates for deaths attributed to neurologic diseases, as defined by the International Classification of Diseases, were calculated for 2010 to 2019 using death and population data obtained from the Centers for Disease Control and Prevention and the US Census Bureau. Avertable deaths were calculated by indirect standardization: For each calendar year of the decade, age-specific death rates of NH White persons in 10 age groups were multiplied by the NH Black population in each age group. A secondary analysis used Hispanic and NH Asian populations as the reference groups. RESULTS: In 2013, overall age-adjusted mortality rates for neurologic diseases began increasing, with the NH Black population experiencing higher rates than NH White, NH American Indian and Alaska Native, Hispanic, and NH Asian populations (in decreasing order). Other populations with higher mortality rates for neurologic diseases included older adults, the male population, and adults older than 25 years without a high school diploma. The gap in mortality rates for neurologic diseases between the NH Black and NH White populations widened from 4.2 individuals per 100,000 in 2011 to 7.0 per 100,000 in 2019. Over 2010 to 2019, had the NH Black population experienced the neurologic mortality rates of NH White, Hispanic, or NH Asian populations, 29,986, 88,407, or 117,519 deaths, respectively, would have been averted. DISCUSSION: Death rates for neurologic diseases are increasing. Disproportionately higher neurologic mortality rates in the NH Black population are responsible for a large number of excess deaths, making research and policy efforts to address the systemic causes increasingly urgent.

Use of Community-Engaged Research Approaches in Clinical Interventions for Neurologic Disorders in the United States: A Scoping Review and Future Directions for Improving Health Equity Research.

BACKGROUND AND OBJECTIVES: Evidence suggests a significant prevalence of race and ethnic disparities in the United States among people with neurologic conditions including stroke, Alzheimer disease and related dementia (ADRD), Parkinson disease (PD), epilepsy, spinal cord injury (SCI), and traumatic brain injury (TBI). Recent neurologic research has begun the paradigm shift from observational health disparities research to intervention research in an effort to narrow the disparities gap. There is an evidence base that suggests that community engagement is a necessary component of health equity. While the increase in disparities focused neurologic interventions is encouraging, it remains unclear whether and how community-engaged practices are integrated into intervention design and implementation. The purpose of this scoping review was to identify and synthesize intervention studies that have actively engaged with the community in the design and implementation of interventions to reduce disparities in neurologic conditions and to describe the common community engagement processes used. METHODS: Two databases, PubMed and CINAHL, were searched to identify eligible empirical studies within the United States whose focus was on neurologic interventions addressing disparities and using community engagement practices. RESULTS: We identified 392 disparity-focused interventions in stroke, ADRD, PD, epilepsy, SCI, and TBI, of which 53 studies incorporated community engagement practices: 32 stroke studies, 15 ADRD, 2 epilepsy studies, 2 PD studies, 1 SCI study, and 1 TBI study. Most of the interventions were designed as randomized controlled trials and were programmatic in nature. The interventions used a variety of community engagement practices: community partners (42%), culturally tailored materials and mobile health (40%), community health workers (32%), faith-based organizations and local businesses (28%), focus groups/health need assessments (25%), community advisory boards (19%), personnel recruited from the community/champions (19%), and caregiver/social support (15%). DISCUSSION: Our scoping review reports that the proportion of neurologic intervention studies incorporating community engagement practices is limited and that the practices used within those studies are varied. The major practices used included collaboration with community partners and utilization of culturally tailored materials. We also found inconsistent reporting and dissemination of results from studies that implemented community engagement measures in their interventions. Future directions include involving the community in research early and continuously, building curricula that address challenges to community engagement, prioritizing the inclusion of community engagement reporting in peer-reviewed journals, and prioritizing and incentivizing research of subpopulations that experience disparities in neurologic conditions.

Structural Racism and Impact on Sickle Cell Disease: Sickle Cell Lives Matter.

Wealth begets health: the health care system in the United States is run by and benefits the groups that have traditionally held power. Systems of structural racism and health care disparities persist. Patients with sickle cell disease (SCD) remain particularly vulnerable to disparities. They suffer from stigmas, lack of well-trained providers, and from misalignment of their needs with the priorities of their health care teams. These critically important burdens may actually be worsening rather than improving mortality for individuals living with SCD. Changes must be made at the federal, state, and local levels in order to address these systems of inequity and save vulnerable lives.

Targeting TRPV1 activity via high-dose capsaicin in patients with sickle cell disease.

Evidence suggests neuropathic pain (NP) develops over time in sickle cell disease (SCD), contributing to a complex, difficult-to-treat phenotype, with management based on scant evidence. One characteristic of NP found is hyperalgesia caused by nervous system sensitization, but risk factors for this have not been identified within the SCD population, as exact mechanisms leading to its development are not well defined. The SPICE (Sickle cell Pain: Intervention with Capsaicin Exposure) trial was a pilot safety and feasibility trial of high-dose (8%) topical capsaicin for patients with SCD and recurrent/chronic pain with neuropathic features, aimed at exploring capsaicin's utility as a mechanistic probe and adjunctive pain treatment for this population. Ten participants identifying "target" sites of pain with NP-type qualities consented to treatment. The primary endpoint was safety/tolerability. The novel Localized Peripheral Hypersensitivity Relief score (LPHR) was developed to determine improvement in sensitivity attributable to TRPV1 neutralization. There were no severe treatment-related adverse events. Higher baseline pain sensitivity at a given body site was associated with self-reported history of more frequent localized vaso-occlusive pain episodes at that site. There was a statistically significant improvement in the mean LPHR, evidencing TRPV1's importance to the development of hypersensitivity and a potential therapeutic benefit of capsaicin for SCD.

Satisfaction and access to care for adults and adolescents with sickle cell disease: ASCQ-Me quality of care and the SHIP-HU study.

A lack of adult sickle cell providers has long been blamed for poor satisfaction and access to specialty care for adults with sickle cell disease (SCD). We were interested in comparing how adolescent and adult patients already in established SCD centers perceived access and quality of care. Hydroxyurea-eligible patients aged 15 years and older were enrolled in the Start Healing in Patients with Hydroxyurea trial, which required them to be affiliated with a SCD specialist. Patients were seen in one of three adult-oriented specialty clinic sites or one of three pediatric-oriented sites. At baseline, patients completed the Adult Sickle Cell Quality of Life Measurement Information System measure as part of a survey battery. Patients treated at adult clinic sites reported being less able to get timely ambulatory appointments (p = .004). They reported emergency department (ED) wait times of >1 h far more often (47.7 vs. 19.3%, p = .0048). They reported less overall satisfaction with care (7.47 vs. 8.77, p < .0001), and less satisfaction with care in the ED (2.88 vs. 3.4, p = .0068. Ambulatory satisfaction was no different between pediatric site versus adult site patients. Poorer systems of care appeared to underlie reported differences, rather than differences in biopsychosocial determinants. Even among specialty-care-affiliated SCD patients, those seen in adult clinics reported worse access to care and lower satisfaction with care than patients seen in pediatric clinics. In addition to increasing the number of adult SCD providers and better preparing pediatric SCD patients to transfer to adult programs, SCD clinical caregivers must also improve aspects of adult care quality to meet reasonable patient expectations of timeliness and interpersonal aspects of care quality.

Feasibility and Quality Validation of a Mobile Application for Enhancing Adherence to Opioids in Sickle Cell Disease.

Prescription opioid nonadherence, specifically opioid misuse, has contributed to the opioid epidemic and opioid-related mortality in the US. Popular methods to measure and control opioid adherence have limitations, but mobile health, specifically smartphone applications, offers a potentially useful technology for this purpose. We developed, tested, and validated the OpPill application using the Mobile Applications Rating Scale (MARS), a validated tool for assessing the quality of mobile health apps. The MARS contains four scales (range of each scale = 0-4) that rate Engagement, Functionality, Aesthetics, and Information Quality. It also assesses subjective quality, relevance, and overall application impact. Our application was built to be a mobile monitoring and reporting system intended to enhance opioid adherence by collecting data and providing systematic feedback on pain and opioid use. Patients (n = 28) all had one of various SCD genotypes, were ages 19 to 59 years (mean 36.56), 53.6% were female, and 39.3% had completed some college. Patients rated the OpPill application highly on all four scales: Engagement, 3.93 ± 0.73; Functionality, 4.54 ± 0.66; Aesthetics, 3.92 ± 0.81; Information, 3.91 ± 0.87. The majority of patients found the application to be relevant for their care. A total of 96% reported the information within the app was complete, while 4% estimated the information to be minimal or overwhelming. Patients (91.7%) overwhelmingly reported that the quality of information as it pertained to SCD patients was relevant; only 8.3% found the application to be poorly relevant to SCD. Similarly, patients (91.7%) overwhelmingly rated both the application's performance and ease of use positively. The large majority of participants (85.7%) found the application to be interesting to use, while 74% found it entertaining. All users found the application's navigation to be logical and accurate with consistent and intuitive gestural design. We conclude that the OpPill application, specifically targeted to monitor opioid use and pain and opioid behavior in patients with Chronic Non-Cancer Pain, was feasible and rated by SCD patients as easy-to-use using a validated rating tool.

Urgent use of voxelotor in sickle cell disease when immediate transfusion is not safe.

The use of blood transfusions to improve anemia resulting from sickle cell disease (SCD) is often limited by alloimmunization, which occurs due to exposure to incompatible antigen present on donor red blood cells (RBCs). This complication occasionally manifests as delayed hemolytic transfusion reactions (DHTRs) that cause hemolysis of the recipient's own RBCs and can lead to fatal anemia. In this case study, we report a patient with SCD who experienced a DHTR following chronic transfusion and was successfully treated with voxelotor, an orally administered sickle hemoglobin (HbS) polymerization inhibitor for the treatment of SCD. Laboratory tests following admission indicated pan-reactivity in antigens, and a rare donor registry was used to locate acceptable units. The patient experienced the DHTR 3 days after admission, which limited laboratory tests due to profound hemolysis. Alternative treatments were limited, and phenotypically matched units were incompatible, so voxelotor was selected as a last-resort treatment. Following initiation of voxelotor 1500 mg, the patient's hemoglobin levels returned to baseline (6 g/dl) within 10 days, with clinical improvements. This report provides evidence regarding the use of voxelotor in the treatment of profound anemia where other treatments could be unsafe or unavailable.

Early Initiation of Sub-Anesthetic Ketamine Infusion in Adults with Vaso-Occlusive Crises Is Associated with Greater Reduction in Sickle Cell Pain Intensity: A Single Center's Experience.

OBJECTIVES: Recurrent, severely painful episodes, known as vaso-occlusive crises (VOCs) are the hallmark of sickle cell disease (SCD) and the primary reason for hospitalization. Opioids have been the gold standard for VOC treatment without significant improvement pain outcomes. To aid analgesia and combat opioid related adverse effects (ORAEs), some SCD clinicians have trialed infusions of sub-anesthetic ketamine along with opioids to treat VOCs. In this retrospective analysis, we compared adult SCD patients who received early vs late adjunctive sub-anesthetic ketamine infusions for VOCs. METHODS: We identified adult SCD patients (age 18-50 years) who presented to Duke University with a VOC and received sub-anesthetic ketamine infusions from July 2015 to June 2019. We assessed both daily opioid consumption (measured as oral morphine milligram equivalents (MME)) and self-reported 0-10 numeric pain ratings (NPR) at 1, 2, and 3 days after infusion initiation, as well as 1 day after discontinuation. RESULTS: A total of 56 patients were identified with a median age of 30 years. Compared to late administration, early infusion of sub-anesthetic ketamine was associated with a 24.5% (P = .0003) and 25.9% (P = .0006) reduction, respectively, in median NPR at 1 day and 2 days after infusion initiation but did not persist at 3 days following initiation of the infusion. A statistically significant reduction in MME was not observed. CONCLUSIONS: In a nonrandomized study of sickle cell patients with VOCs, early sub-anesthetic ketamine infusion led to greater reduction in subjective pain intensity than late initiation of the infusion. Randomized studies should further explore whether early vs late ketamine infusion improves management of acute SCD pain.

Development and validation of the sickle cell stress scale-adult.

Disease-specific stress can partly explain Sickle Cell Disease (SCD) healthcare utilization. We developed and validated two measures of adult SCD-specific stress for research and clinical care. A large cohort of adults with SCD completed both the 3-item Likert-scale adapted from a previous disease stress measure and a 10-item Likert-scale questionnaire drafted specifically to measure SCD stress. They concurrently completed a psychosocial and health-related quality of life scale battery, then subsequently daily pain diaries. Diaires measured: daily intensity, distress and interference of pain; self-defined vaso-occlusive crises (VOC), opioid use, and types of healthcare utilization for up to 24 weeks. Analyses tested Cronbach's alpha, correlation of the three-item and 10-item stress scales with the concurrent battery, with percentages of pain days, VOC days, opioid use days, and healthcare utilization days, and correlation of baseline stress and 6-month stress for the 10-item scale. Cronbach's alpha was high for both the 3-item (0.73) and 10-item (0.83) SCD stress scales, test-retest correlation of 0.55, expected correlation with the concurrent battery, and correlation with diary-measured healthcare utilization over 6 months. The correlations with the 3-item scale were stronger, but only statistically significant for depression-anxiety. The correlation between the two stress scales was 0.59. Both the 3-item and the 10-item stress scales exhibited good face, construct, concurrent, and predictive validity as well as moderate test-retest reliability. Further scale validation should determine population norms and response to interventions.

Moving Toward a Multimodal Analgesic Regimen for Acute Sickle Cell Pain with Non-Opioid Analgesic Adjuncts: A Narrative Review.

Purpose of Review: Sickle cell disease (SCD) is an inherited hemoglobinopathy with potential life-threatening complications that affect millions of people worldwide. Severe and disabling acute pain, referred to as a vaso-occlusive crisis (VOC), is a fundamental symptom of the disease and the primary driver for acute care visits and hospitalizations. Despite the publication of guidelines for VOC management over the past decade, management of VOCs remains unsatisfactory for patients and providers. Recent Findings: Acute SCD pain includes pain secondary to VOCs and other forms of acute pain. Distinguishing VOC from non-VOC pain may be challenging for both patients and clinicians. Further, although opioids have been the gold-standard for VOC pain management for decades, the current highest standard of care for all acute pain is a multimodal approach that is less dependent on opioids, and, instead incorporates analgesics and adjuvants from different mechanistic pathways. In this narrative review, we focus on a multimodal pharmacologic approach for acute SCD pain management and explore the evidence for existing non-opioid pharmacological adjuncts. Moreover, we present an explanatory model of pain, which is not only novel in its application to SCD pain but also captures the multidimensional nature of the SCD pain experience and supports the need for such a multimodal approach. This model also highlights opportunities for new investigative and therapeutic targets - both pharmacological and non-pharmacological. Summary: Multimodal pain regimens that are less dependent on opioids are urgently needed to improve acute pain outcomes for individuals with SCD. The proposed explanatory model for SCD pain offers novel opportunities to improve acute pain management for SCD patients.

How Would You Treat This Patient With Acute and Chronic Pain From Sickle Cell Disease? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Sickle cell disease is prevalent in large numbers of patients in the United States and has a significant global impact. Its complications span numerous organs and lead to reduced life expectancy. Acute and chronic sickle cell pain is a common cause of patient suffering. The American Society of Hematology published updated guidelines on management of acute and chronic pain from sickle cell disease in 2019. Several of the recommendations are conditional and leave specific decisions to the treating physician. These include conditional recommendations about the use of ketamine for acute pain and the initiation and discontinuation of long-term opioid therapy for chronic pain. Here, 2 hematologists discuss these guidelines and make contrasting recommendations for the management of acute and chronic pain for a patient with sickle cell disease.

A randomised controlled provider-blinded trial of community health workers in sickle cell anaemia: effects on haematologic variables and hydroxyurea adherence.

Hydroxyurea (hydroxycarbamide) (HU) for sickle cell anaemia (SCA) is underutilised. Case management is an evidence-based health management strategy and in this regard patient navigators (PNs) may provide case management for SCA. We hypothesised that HU-eligible patients exposed to PNs would have improved indicators of starting HU and HU adherence. We randomised 224 HU-eligible SCA adults into the Start Healing in Patients with Hydroxyurea (SHIP-HU) Trial. All patients received care from trained physicians using standardised HU prescribing protocols. Patients in the Experimental arm received case management and education from PNs through multiple contacts. All other patients were regarded as the Control arm and received specialty care alone. Study physicians were blinded to the study arms and did not interact with PNs. At baseline, 6 and 12 months we assessed and compared laboratory parameters and HU adherence indicators. Experimental patients had higher 6-month mean fetal haemoglobin (HbF) levels than controls. But at 12 months, mean HbF was similar, as were white blood cell count, absolute neutrophil count, total haemoglobin, platelet count and mean corpuscular volume. At 12 months there were fewer experimental patients missing HU doses than controls (mean 1·8 vs. 4·5, P = 0·0098), and more recent HU prescriptions filled than for controls (mean 53·8 vs. 92 days, median 27·5 vs. 62 days, P = 0·0082). Mean HU doses were largely similar. We detected behavioural improvements in HU adherence but no haematological improvements by adding PNs to specialty care.

Intraindividual pain variability and phenotypes of pain in sickle cell disease: a secondary analysis from the Pain in Sickle Cell Epidemiology Study.

ABSTRACT: Mean pain intensity alone is insufficient to describe pain phenotypes in sickle cell disease (SCD). The objective of this study was to determine impact of day-to-day intraindividual pain variability on patient outcomes in SCD. We calculated metrics of pain variability and pain intensity for 139 participants with <10% missing data in the first 28 days of the Pain in Sickle Cell Epidemiology Study. We performed Spearman rank correlations between measures of intraindividual pain variability and outcomes. We then used k-means clustering to identify phenotypes of pain in SCD. We found that pain variability was inversely correlated with health-related quality of life, except in those with daily or near-daily pain. Pain variability was positively correlated with affective coping, catastrophizing, somatic symptom burden, sickle cell stress, health care utilization, and opioid use. We found 3 subgroups or clusters of pain phenotypes in SCD. Cluster 1 included individuals with the lowest mean pain, lowest temporal instability and dependency, lowest proportion of days with pain and opioid use, and highest physical function. Cluster 2 included individuals with the highest mean pain, highest temporal dependency, highest proportion of days with pain and opioid use, and lowest physical function. Cluster 3 included individuals with high levels of mean pain, highest temporal instability, but with lower temporal dependency, proportion of days with pain and opioid use, and physical function compared with cluster 2. We conclude that intraindividual pain variability is associated with patient outcomes and psychological characteristics in SCD and is useful in delineating phenotypes of pain in SCD.

Telehealth acceptability and opioid prescribing patterns of providers of painful chronic diseases during the COVID-19 pandemic: A survey of sickle cell providers.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) has led to a rapid transition to telehealth services. It is unclear how subspecialists managing painful chronic diseases-such as sickle cell disease (SCD), an inherited hemoglobinopathy with significant disparities in access and outcomes-have viewed the transition to tele-health or altered their pain management practices. This study elicits the views of sickle cell providers regarding their transition to telehealth and their opioid prescribing patterns during the COVID-19 pandemic. DESIGN: An anonymous online survey was sent to eligible sickle cell providers. SETTING: Comprehensive sickle cell centers and/or clinics across the United States. PARTICIPANTS: Physicians and advanced practice providers providing care to SCD patients. MAIN OUTCOME MEASURES: Respondents answered questions regarding their (1) views of telehealth compared to in-person encounters and (2) opioid prescribing practices during the early months of the pandemic. RESULTS: Of the 130 eligible participants, 53 respondents from 35 different sickle cell centers completed at least 90 percent of the survey. Respondents reported a significant increase in telehealth encounters for routine and acute appointments (mean difference and standard deviation: 57.6 ± 31.9 percent, p < 0.001 and 24.4 ± 34.1 percent, p < 0.001, respectively) since COVID-19. The overwhelming majority of respondents reported no changes in their opioid prescribing patterns since COVID-19, despite increased telehealth use. Only a minority copre-scribed naloxone as a risk mitigation strategy. CONCLUSION: The rapid uptake of telehealth has not suppressed ambulatory providers' prescribing of opioids for SCD. Studies assessing the impact of the COVID-19 pandemic and telehealth on opioid prescribing practices in other painful chronic diseases are needed to ensure health equity for vulnerable pain patients.