Project description:AbstractTo address acute vaso-occlusive episodes (VOEs), the leading cause of emergency department (ED) visits among individuals with sickle cell disease (SCD), we conducted the clinical study, ALIGN (An Individualized Pain Plan with Patient and Provider Access for Emergency Department care of SCD), across 8 sites. We hypothesized an improvement of 0.5 standard deviations in perceived quality of ED pain treatment of a VOE after implementing individualized pain plans (IPPs) accessible to both patients and providers. Patients with SCD were aged 18 to 45 years, owned a cell phone, and had an ED VOE visit within 90 days prior. Patients completed the perceived quality of care surveys at baseline and within 96 hours after an ED VOE visit. Providers completed surveys regarding comfort managing VOEs at baseline and after managing an enrolled patient. Most of the 153 patients were African American (95.4%), female (64.7%), and had Hb SS/Sβ0 genotype (71.9%). The perceived quality of ED pain treatment was high at both baseline and after implementation of IPPs; our primary outcome hypothesis was not met, because no statistically significant change in the patient-perceived quality of ED treatment occurred. A total of 135 providers completed baseline and follow-up surveys. On a scale of 1 to 7, with 7 being extremely comfortable managing VOEs, 60.5% reported a score ≥6 after IPP implementation vs 57.8% at baseline. Almost all (97.6%) ordered the recommended medication, and 94.7% intended to use IPPs. In this implementation protocol, all sites successfully implemented IPPs. Patients and ED providers both endorsed the use of IPPs. This trial was registered at www.ClinicalTrials.gov as # NCT04584528.

| S-EPMC11568751 | biostudies-literature

Nociceptors protect sickle cell disease mice from vaso-occlusive episodes and chronic organ damage.

Project description:Sickle cell disease (SCD) is a common hereditary hematologic disorder. SCD patients suffer from acute vaso-occlusive episodes (VOEs), chronic organ damage, and premature death, with few therapeutic options. Although severe pain is a major clinical manifestation of SCD, it remains unknown whether nociception plays a role in SCD pathogenesis. To address this question, we generated nociceptor-deficient SCD mice and found, unexpectedly, that the absence of nociception led to more severe and more lethal VOE, indicating that somatosensory nerves protect SCD mice from VOE. Mechanistically, the beneficial effects of sensory nerves were induced by the neuropeptide calcitonin gene-related peptide (CGRP), which acted on hematopoietic cells. Additionally, oral capsaicin consumption, which can activate somatosensory nerves by binding to TRPV1, dramatically alleviated acute VOE and significantly prevented chronic liver and kidney damage in SCD mice. Thus, the manipulation of nociception may provide a promising approach to treat SCD.

| S-EPMC7534906 | biostudies-literature

Association between baseline fetal hemoglobin levels and incidence of severe vaso-occlusive pain episodes in children with sickle cell anemia.

Project description:The ameliorating effect of high fetal hemoglobin (HbF) levels on the incidence of pain episodes in sickle cell anemia (SCA) is well-known; however, in children this relationship is less clearly established. We hypothesized that higher HbF levels in children with SCA are associated with fewer severe pain episodes. A meta-analysis of data from the Silent Infarct Transfusion Trial (n = 456) and the Cooperative Study of Sickle Cell Disease (n = 764), demonstrated that baseline HbF levels were associated with the incidence of severe pain, commonly defined across studies as an event requiring hospitalization (P-value = 0.02).

| S-EPMC4387562 | biostudies-literature

Pharmacotherapeutical strategies in the prevention of acute, vaso-occlusive pain in sickle cell disease: a systematic review.

Project description:Sickle-cell disease (SCD) is characterized by frequent and painful vaso-occlusive crises (VOCs). Various treatments have been evaluated over the years. However, a clear overview is lacking. The objective of this study was to systematically review all pharmacotherapeutical strategies in the prevention of VOCs beyond hydroxyurea. We performed a systematic literature search (MEDLINE, Embase, CENTRAL). Eligible studies were controlled clinical trials evaluating pharmacotherapeutical interventions targeting the reduction of VOCs in patients with SCD. Primary outcomes were the number or duration of SCD-related pain days, VOCs, or hospital admissions for VOCs. Secondary outcomes included time to first VOC or hospital admission for a VOC. A standardized data extraction sheet was used. The methodological quality of studies was assessed using Cochrane's risk-of-bias tool. A total of 36 studies were included in this review, covering 26 different prophylactic interventions. The most promising interventions for reducing the frequency of either VOCs or hospitalizations were the oral antioxidants l-glutamine and ω-3 fatty acids and the IV antiadhesive agent crizanlizumab. Twenty-three studies did not show any beneficial effect of the intervention under investigation, and 6 studies were either too small or methodologically inadequate to draw conclusions. Because of the heterogeneity of interventions, no meta-analysis was performed. In conclusion, this review identified 3 promising pharmacotherapeutical strategies in the prevention of VOCs in SCD. Importantly, this study highlights the discrepancy between the significant burden of SCD worldwide and the low number of adequate trials performed. This review was registered at PROSPERO (CRD42015025250).

| S-EPMC5728463 | biostudies-literature

Simvastatin reduces vaso-occlusive pain in sickle cell anaemia: a pilot efficacy trial.

Project description:Sickle cell anaemia (SCA) is a progressive vascular disease characterized by episodic vaso-occlusive pain. Despite the broad impact of inflammation on acute and chronic clinical manifestations of SCA, no directed anti-inflammatory therapies currently exist. Statins are cholesterol-lowering agents shown to confer protection from vascular injury by suppressing inflammation. We previously documented a reduction in soluble biomarkers of inflammation in patients with sickle cell disease treated with simvastatin. To determine the potential clinical efficacy of simvastatin, we treated 19 SCA patients with single daily dose simvastatin for 3 months and assessed changes from baseline in the frequency and intensity of diary-reported pain and levels of circulating nitric oxide metabolites (NOx), high sensitivity C-reactive protein (hs-CRP), vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), ICAM-3, E-selectin, and vascular endothelial growth factor (VEGF). Treatment with simvastatin resulted in a significant reduction in the frequency of pain (P = 0·0003), oral analgesic use (P = 0·003) and circulating hs-CRP (P = 0·003), soluble (s)E-selectin (P = 0·01), sICAM-1 (P = 0·02), sICAM-3 (P = 0·02) and sVEGF (P = 0·01). Simvastatin had no effect on pain intensity or levels of NOx, sP-selectin and sVCAM-1. The observed reductions in pain rate and markers of inflammation were greatest in subjects receiving hydroxycarbamide (HC), suggesting a synergistic effect of simvastatin. These results provide preliminary clinical data to support a larger trial of simvastatin in SCA.

| S-EPMC5435522 | biostudies-literature

Crizanlizumab for the Prevention of Vaso-Occlusive Pain Crises in Sickle Cell Disease.

Project description:Objective: To review the efficacy and safety of crizanlizumab (Adakveo) in the prevention of vaso-occlusive pain crises in sickle cell disease. Data Sources: An English-language literature search of PubMed, MEDLINE, and Ovid (1946 to January 2021) was completed using the terms crizanlizumab, SEG101, SelG1, and sickle cell disease. Manufacturer prescribing information, article bibliographies, and data from clinicaltrials.gov were incorporated in the reviewed data. Study Selection/Data Extraction: All studies registered on clinicaltrials.gov were incorporated in the reviewed data. Data Synthesis: Crizanlizumab is the first monoclonal antibody approved for sickle cell disease to reduce the frequency of vaso-occlusive crises. One phase 2 clinical trial and a post hoc analysis of the trial have been published. Relevance to Patient Care and Clinical Practice: Crizanlizumab is a monthly intravenous infusion approved by the Food and Drug Administration for patients with sickle cell disease 16 years of age and older to reduce the frequency of vaso-occlusive crises. Conclusion: Crizanlizumab appears to be an efficacious therapy for patients with sickle cell disease to reduce the frequency of vaso-occlusive crises. Concerns include drug cost and administration. Long-term benefits and risks have not been determined.

| S-EPMC8255978 | biostudies-literature

A polygenic score for acute vaso-occlusive pain in pediatric sickle cell disease.

Project description:Individuals with monogenic disorders can experience variable phenotypes that are influenced by genetic variation. To investigate this in sickle cell disease (SCD), we performed whole-genome sequencing (WGS) of 722 individuals with hemoglobin HbSS or HbSβ0-thalassemia from Baylor College of Medicine and from the St. Jude Children's Research Hospital Sickle Cell Clinical Research and Intervention Program (SCCRIP) longitudinal cohort study. We developed pipelines to identify genetic variants that modulate sickle hemoglobin polymerization in red blood cells and combined these with pain-associated variants to build a polygenic score (PGS) for acute vaso-occlusive pain (VOP). Overall, we interrogated the α-thalassemia deletion -α3.7 and 133 candidate single-nucleotide polymorphisms (SNPs) across 66 genes for associations with VOP in 327 SCCRIP participants followed longitudinally over 6 years. Twenty-one SNPs in 9 loci were associated with VOP, including 3 (BCL11A, MYB, and the β-like globin gene cluster) that regulate erythrocyte fetal hemoglobin (HbF) levels and 6 (COMT, TBC1D1, KCNJ6, FAAH, NR3C1, and IL1A) that were associated previously with various pain syndromes. An unweighted PGS integrating all 21 SNPs was associated with the VOP event rate (estimate, 0.35; standard error, 0.04; P = 5.9 × 10-14) and VOP event occurrence (estimate, 0.42; standard error, 0.06; P = 4.1 × 10-13). These associations were stronger than those of any single locus. Our findings provide insights into the genetic modulation of VOP in children with SCD. More generally, we demonstrate the utility of WGS for investigating genetic contributions to the variable expression of SCD-associated morbidities.

| S-EPMC8341359 | biostudies-literature

Opioid Use in Adults With Sickle Cell Disease Hospitalized During Vaso-Occlusive Crisis: A Systematic Review.

Project description:BackgroundWhile pain is the hallmark of sickle cell disease (SCD), healthcare personnel are often ill-equipped to adequately treat patients who present in vaso-occlusive crisis (VOC). Although symptom severity varies from individual to individual, SCD is characterized by intervallic pain as a result of oxygen deprivation in tissues and organs. Regardless of pain severity, SCD patients are often viewed as drug seekers by healthcare personnel who have concerns regarding patients' dependence on opioids which may lead to addiction. The objective was to assess the types and amount of opioids used to treat VOC in comparison to Centers for Disease Control opioid prescription guidelines.MethodsLiterature search was conducted using CINAHL, PubMed, the Cochrane Library, Web of Science and hand search. Data were analyzed from 1999 to 2018. Randomized trials, observational, and case studies involved hospitalized adults with SCD who were prescribed opioids to treat VOC. Quality assessment was conducted using Downs and Black checklist. Meta-analysis was not conducted.ResultsFive studies were conducted in the USA, Arabia and the Netherlands, and the USA and Canada were included. Participants were treated with either morphine or morphine milligram equivalent (MME). No study used the same method of opioid administration.ConclusionsPatients with SCD who are hospitalized secondary to VOC mostly received opioids for pain well within the Centers for Disease Control and Prevention prescription guidelines. No uniform method exists. Additional research is warranted.

| S-EPMC8110229 | biostudies-literature

Safety of intravenous arginine therapy in children with sickle cell disease hospitalized for vaso-occlusive pain: A randomized placebo-controlled trial in progress.

Project description: Not available

| S-EPMC8722015 | biostudies-literature