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.

Social determinants of health and treatment center affiliation: analysis from the sickle cell disease implementation consortium registry.

BACKGROUND: Adults with sickle cell disease (SCD) suffer early mortality and high morbidity. Many are not affiliated with SCD centers, defined as no ambulatory visit with a SCD specialist in 2 years. Negative social determinants of health (SDOH) can impair access to care. HYPOTHESIS: Negative SDOH are more likely to be experienced by unaffiliated adults than adults who regularly receive expert SCD care. METHODS: Cross-sectional analysis of the SCD Implementation Consortium (SCDIC) Registry, a convenience sample at 8 academic SCD centers in 2017-2019. A Distressed Communities Index (DCI) score was assigned to each registry member's zip code. Insurance status and other barriers to care were self-reported. Most patients were enrolled in the clinic or hospital setting. RESULTS: The SCDIC Registry enrolled 288 Unaffiliated and 2110 Affiliated SCD patients, ages 15-45y. The highest DCI quintile accounted for 39% of both Unaffiliated and Affiliated patients. Lack of health insurance was reported by 19% of Unaffiliated versus 7% of Affiliated patients. The most frequently selected barriers to care for both groups were "previous bad experience with the healthcare system" (40%) and "Worry about Cost" (17%). SCD co-morbidities had no straightforward trend of association with Unaffiliated status. The 8 sites' results varied. CONCLUSION: The DCI economic measure of SDOH was not associated with Unaffiliated status of patients recruited in the health care delivery setting. SCDIC Registrants reside in more distressed communities than other Americans. Other SDOH themes of affordability and negative experiences might contribute to Unaffiliated status. Recruiting Unaffiliated SCD patients to care might benefit from systems adopting value-based patient-centered solutions.

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.

Time to pain relief: A randomized controlled trial in the emergency department during vaso-occlusive episodes in sickle cell disease.

OBJECTIVE: Compare time to pain relief (minimum of a 13 mm and 30% reduction) during an Emergency Department (ED) visit among patients with sickle cell disease (SCD) experiencing severe pain associated with a vaso-occlusive episode who were randomized to receive either an individualized or weight-based pain protocol. METHODS: A randomized controlled trial in two EDs. Adults with sickle cell disease. Research staff recorded pain scores every 30 min during an ED visit (up to 6 h in the ED) using a 0-100 mm visual analogue scale. Analysis included 122 visits, representing 49 patients (individualized: 61 visits, 25 patients; standard: 61 visits, 24 patients). RESULTS: Pain reduction across 6-h was greater for the individualized compared to the standard protocol (protocol-by-time: p = .02; 6-h adjusted pain score comparison: Individualized: M = 29.2, SD = 38.8, standard: M = 45.3, SD = 35.6; p = .03, Cohen d = 0.43). Hazards models indicated a greater probability of 13 mm (HR = 1.54, 95% CI = 1.05, 2.27, p = .03) and 30% (HR = 1.71, 95% CI = 1.11, 2.63, p = .01) reduction in the individualized relative to the standard protocol. CONCLUSIONS: Patients who received treatment with an individualized protocol experienced a more rapid reduction in pain, including a 13 mm and 30% reduction in pain scores when compared to those that received weight-based dosing.

"The project did not come to us with a solution": Perspectives of research teams on implementing a study about electronic health record-embedded individualized pain plans for emergency department treatment of vaso-occlusive episodes in adults with sickle cell disease.

BACKGROUND: This study aimed to capture the implementation process of the ALIGN Study, (An individualized Pain Plan with Patient and Provider Access for Emergency Department care of Sickle Cell Disease). ALIGN aimed to embed Individualized Pain Plans in the electronic health record (E-IPP) and provide access to the plan for both adult patients with sickle cell disease (SCD) and emergency department providers when a person with SCD comes to the emergency department in vaso-occlusive crises. METHODS: Semi-structured interviews were conducted with research teams from the 8 participating sites from the ALIGN study. Seventeen participants (principal investigators and study coordinators) shared their perspectives about the implementation of ALIGN in their sites. Data were analyzed in three phases using open coding steps adapted from grounded theory and qualitative content analysis. RESULTS: A total of seven overarching themes were identified: (1) the E-IPP structure (location and upkeep) and collaboration with the informatics team, (2) the role of ED champion, (3) the role of research coordinators, (4) research team communication, and communication between research team and clinical team, (5) challenges with the study protocol, (6) provider feedback: addressing over-utilizers, patient mistrust, and the positive feedback about the intervention, and (7) COVID-19 and its effects on study implementation. CONCLUSIONS: Findings from this study contribute to learning how to implement E-IPPs for adult patients with SCD in ED. The study findings highlight the importance of early engagement with different team members, a champion from the emergency department, study coordinators with different skills and enhancement of communication and trust among team members. Further recommendations are outlined for hospitals aiming to implement E-IPP for patients with SCD in ED.

Opposing global change drivers counterbalance trends in breeding North American monarch butterflies.

Many insects are in clear decline, with monarch butterflies (Danaus plexippus) drawing particular attention as a flagship species. It is well documented that, among migratory populations, numbers of overwintering monarchs have been falling across several decades, but trends among breeding monarchs are less clear. Here, we compile >135,000 monarch observations between 1993 and 2018 from the North American Butterfly Association's annual butterfly count to examine spatiotemporal patterns and potential drivers of adult monarch relative abundance trends across the entire breeding range in eastern and western North America. While the data revealed declines at some sites, particularly the US Northeast and parts of the Midwest, numbers in other areas, notably the US Southeast and Northwest, were unchanged or increasing, yielding a slightly positive overall trend across the species range. Negative impacts of agricultural glyphosate use appeared to be counterbalanced by positive effects of annual temperature, particularly in the US Midwest. Overall, our results suggest that population growth in summer is compensating for losses during the winter and that changing environmental variables have offsetting effects on mortality and/or reproduction. We suggest that density-dependent reproductive compensation when lower numbers arrive each spring is currently able to maintain relatively stable breeding monarch numbers. However, we caution against complacency since accelerating climate change may bring growing threats. In addition, increases of summer monarchs in some regions, especially in California and in the south, may reflect replacement of migratory with resident populations. Nonetheless, it is perhaps reassuring that ubiquitous downward trends in summer monarch abundance are not evident.

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.

An evaluation of patient-reported outcomes in sickle cell disease within a conceptual model.

PURPOSE: To examine the relations between patient-reported outcomes (PROs) within a conceptual model for adults with sickle cell disease (SCD) ages 18 - 45 years enrolled in the multi-site Sickle Cell Disease Implementation Consortium (SCDIC) registry. We hypothesized that patient and SCD-related factors, particularly pain, and barriers to care would independently contribute to functioning as measured using PRO domains. METHODS: Participants (N = 2054) completed a 48-item survey including socio-demographics and PRO measures, e.g., social functioning, pain impact, emotional distress, and cognitive functioning. Participants reported on lifetime SCD complications, pain episode frequency and severity, and barriers to healthcare. RESULTS: Higher pain frequency was associated with higher odds of worse outcomes in all PRO domains, controlling for age, gender and site (OR range 1.02-1.10, 95% CI range [1.004-1.12]). Reported history of treatment for depression was associated with 5 of 7 PRO measures (OR range 1.58-3.28 95% CI range [1.18-4.32]). Fewer individual barriers to care and fewer SCD complications were associated with better outcomes in the emotion domain (OR range 0.46-0.64, 95% CI range [0.34-0.86]). CONCLUSIONS: Study results highlight the importance of the biopsychosocial model to enhance understanding of the needs of this complex population, and to design multi-dimensional approaches for providing more effective interventions to improve outcomes.

Recent climate change is creating hotspots of butterfly increase and decline across North America.

Some insect populations are experiencing dramatic declines, endangering the crucial ecosystem services they provide. Yet, other populations appear robust, highlighting the need to better define patterns and underlying drivers of recent change in insect numbers. We examined abundance and biodiversity trends for North American butterflies using a unique citizen-science dataset that has recorded observations of over 8 million butterflies across 456 species, 503 sites, nine ecoregions, and 26 years. Butterflies are a biodiverse group of pollinators, herbivores, and prey, making them useful bellwethers of environmental change. We found great heterogeneity in butterfly species' abundance trends, aggregating near zero, but with a tendency toward decline. There was strong spatial clustering, however, into regions of increase, decrease, or relative stasis. Recent precipitation and temperature appeared to largely drive these patterns, with butterflies generally declining at increasingly dry and hot sites but increasing at relatively wet or cool sites. In contrast, landscape and butterfly trait predictors had little influence, though abundance trends were slightly more positive around urban areas. Consistent with varying responses by different species, no overall directional change in butterfly species richness or evenness was detected. Overall, a mosaic of butterfly decay and rebound hotspots appeared to largely reflect geographic variability in climate drivers. Ongoing controversy about insect declines might dissipate with a shift in focus to the causes of heterogeneous responses among taxa and sites, with climate change emerging as a key suspect when pollinator communities are broadly impacted.

Patient-reported neurocognitive symptoms influence instrumental activities of daily living in sickle cell disease.

Individuals with sickle cell disease (SCD) experience neurocognitive decline, low medication adherence, increased unemployment, and difficulty with instrumental activities of daily living (IADL). The relationship between self-perceived cognitive difficulties and IADLs, including employment, school enrollment, independence, engagement in leisure activities, and medication adherence is unknown. We hypothesized that self-reported difficulties across neurocognitive areas would predict lower IADL skills. Adolescent and adult participants of the multi-site Sickle Cell Disease Implementation Consortium (SCDIC) (n = 2436) completed patient-reported outcome (PRO) measures of attention, executive functioning, processing speed, learning, and comprehension. Cognitive symptoms were analyzed as predictors in multivariable modeling. Outcome variables included 1) an IADL composite that consisted of employment, participation in school, reliance on others, and leisure pursuits, and 2) hydroxyurea adherence. Participants reported cognitive difficulty across areas of attention (55%), executive functioning (51%), processing speed (57%), and reading comprehension (65%). Executive dysfunction (p < 0.001) and sometimes or often experiencing learning difficulties (p < 0.001 and p = 0.04) and poor comprehension (p = 0.000 and p = 0.001), controlled for age (p < 0.001), pain (p < 0.001), and hydroxyurea use (p = 0.001), were associated with poor IADL skills. Executive functioning difficulties (p = 0.021), controlled for age (p = 0.013 for ages 25-34), genotype (p = 0.001), and hemoglobin (p = 0.004), predicted hydroxyurea non-adherence. Analysis of PRO measures indicated that cognitive dysfunction is prevalent in adolescents and adults with SCD. Cognitive dysfunction translated into clinically meaningful outcomes. PRO of cognitive symptoms can be used as an important adjunct clinical tool to monitor symptoms that impact functional skills, including engagement in societal activities and medication adherence.

System Level Informatics to Improve Triage Practices for Sickle Cell Disease Vaso-Occlusive Crisis: A Cluster Randomized Controlled Trial.

BACKGROUND: National Heart Lung and Blood Institute guidelines for the treatment of vaso-occlusive crisis among people with sickle cell disease in the emergency department recommend assigning an emergency severity index of 2 at triage. However, patients with sickle cell disease often do not receive guideline-concordant care at triage. To address this gap, a decision support tool was developed, in the form of a text banner on the triage page in the electronic health record system, visible to triage nurses. METHODS: A prospective quality improvement initiative was designed where the emergency severity index clinical decision support tool was deployed to a stratified random sample of emergency department triage nurses to receive the banner (n = 24) or not to receive the banner (n = 27), reminding them to assign the patient to emergency severity index category 2. The acceptability of the emergency severity index clinical decision support tool was evaluated with the Ottawa Acceptability of Decision Rules Instrument. Descriptive and bivariate (chi-square test) statistics were used to characterize the study's primary outcome, proportion of visits assigned an emergency severity index of 2 or higher. A generalized linear mixed model with clustering at the level of the triage nurse was performed to test the association between the banner intervention and triage practices. RESULTS: A total of 384 ED visits were included for analysis. Before study initiation, the percentage of sickle cell disease patients' visits with the proper emergency severity index assignment at triage was 37.04%. After initiation, the proportion of sickle cell disease patients' visits with an emergency severity index of 2 or higher triaged by nurses in the intervention group was markedly higher in the intervention group than in the control group (64.95% vs 35.05%; χ2 = 8.79, P ≤ .003). Accounting for clustering by nurse, the odds ratio for proper triage emergency severity index assignment was 3.22 (95% confidence interval 1.17-8.85; P ≤ .02) for the intervention versus control. Surveyed triage nurses reported the emergency severity index clinical decision support tool to be moderately acceptable (nurses' mean Ottawa Acceptability of Decision Rules Instrument scores ranged from 4.13 to 4.90 on the 6-point scale; n = 11). There were no differences in ED experience outcomes including time to first analgesic or length of stay between the control and intervention groups. CONCLUSION: Substantial improvements in triage guideline concordance were achieved and sustained without direct nursing education.

Patient-reported outcomes in sickle cell disease and association with clinical and psychosocial factors: Report from the sickle cell disease implementation consortium.

Understanding patient experiences, quality of life, and treatment needs in individuals with sickle cell disease (SCD) is essential in promoting health and well-being. We used measures from the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me), Patient Reported Outcomes Measurement Information System (PROMIS), and Quality of Life in Neurological Disorders (NeuroQol) to evaluate pain impact, sleep impact, social functioning, depressive symptoms, tiredness, and cognitive function (collectively, patient reported outcomes [PROs]) and to identify associated demographic and clinical characteristics. Participants (n = 2201) between 18 and 45 years were recruited through the eight Sickle Cell Disease Implementation Consortium (SCDIC) sites. In multivariate models, PROs were significantly associated with one another. Pain impact was associated with age, education, employment, time since last pain attack, hydroxyurea use, opioid use, sleep impact, social functioning, and cognitive function (F = 88.74, P < .0001). Sleep impact was associated with household income, opioid use, pain impact, social functioning, depressive symptoms, and tiredness (F = 101.40, P < .0001). Social functioning was associated with employment, pain attacks in the past year, autoimmune/inflammatory comorbidities, pain impact, sleep impact, depressive symptoms, tiredness, and cognitive function (F = 121.73, P < .0001). Depressive symptoms were associated with sex, sleep impact, social functioning, tiredness, and cognitive function (F = 239.51, P < .0001). Tiredness was associated with sex, education, sleep impact, social functioning, depressive symptoms, and cognitive function (F = 129.13, P < .0001). These findings reflect the baseline PRO assessments among SCDIC registry participants. Further research is needed to better understand these outcomes and new targets for interventions to improve quality of life and function in people with SCD.

A Survey-Based Needs Assessment of Barriers to Optimal Sickle Cell Disease Care in the Emergency Department.

STUDY OBJECTIVE: Guided by an implementation science framework, this needs assessment identifies institutional-, provider-, and patient-level barriers to care of sickle cell disease (SCD) in the emergency department (ED) to inform future interventions conducted by the multicenter Sickle Cell Disease Implementation Consortium. METHODS: The consortium developed and implemented a validated needs assessment survey administered to a cross-sectional convenience sample of patients with SCD and ED providers caring for them. In total, 516 adolescents and adults with SCD and 243 ED providers from 7 and 5 regions of the United States, respectively, responded to the ED care delivery for SCD survey. RESULTS: Survey results demonstrated that 84.5% of respondents with SCD have an outpatient provider who treats many patients with SCD. In the ED, 54.3% reported not receiving care fast enough and 46.0% believed physicians did not care about them and believed similarly of nurses (34.9%). Consequently, 48.6% of respondents were "never" or "sometimes" satisfied with their ED care. Of surveyed ED providers, 75.1% were unaware of the National Heart, Lung, and Blood Institute recommendations for vaso-occlusive crises, yet 98.1% were confident in their knowledge about caring for patients with SCD. ED providers identified the following factors as barriers to care administration: opioid epidemic (62.1%), patient behavior (60.9%), crowding (58.0%), concern about addiction (47.3%), and implicit bias (37.0%). CONCLUSION: The results underscore that many patients with SCD are dissatisfied with their ED care and highlight challenges to optimal care on the practice, provider, and patient levels. Exploring these differences may facilitate improvements in ED care.

Inhaled steroids associated with decreased macrophage markers in nonasthmatic individuals with sickle cell disease in a randomized trial.

Inhaled mometasone was shown to improve pain scores and decrease soluble vascular cell adhesion molecule (sVCAM) concentration in a randomized controlled trial of nonasthmatic patients with sickle cell disease. We sought to explore potential changes in systemic inflammation as a mechanism underlying this effect. Serum samples from 41 trial participants (15 placebo- and 26 mometasone-treated) were analyzed using a 92 inflammatory marker panel at baseline and after 8 weeks of mometasone therapy. Individual marker analysis and correlation analysis were conducted. Adjusted for age, the mometasone-treated group decreased the concentration of CXCL9, CXCL11, CD40, IL-10, and IL-18 relative to placebo-treated participants. Hierarchical clustering and correlation analysis identified additional evidence for a decrease in cytokines linking to macrophage signaling and migration. There was no statistically significant change in markers of asthma and allergy, indicating that the improvement was unlikely mediated by modulation of occult reactive airway disease. This analysis of inflammatory markers suggests that decrease in macrophage activity may be involved in the mediation of the clinical benefit seen with use of inhaled mometasone in nonasthmatic patients with sickle cell disease.Trial registration: clinicaltrials.gov identifier: NCT02061202.

A randomized controlled trial comparing two vaso-occlusive episode (VOE) protocols in sickle cell disease (SCD).

Limited evidence guides opioid dosing strategies for acute Sickle Cell (SCD) pain. We compared two National Heart, Lung and Blood (NHBLI) recommended opioid dosing strategies (weight-based vs. patient-specific) for ED treatment of acute vaso-occlusive episodes (VOE). A prospective randomized controlled trial (RCT) was conducted in two ED's. Adults ≥ 21 years of age with SCD disease were eligible. Among the 155 eligible patients, 106 consented and 52 had eligible visits. Patients were pre-enrolled in the outpatient setting and randomized to one of two opioid dosing strategies for a future ED visit. ED providers accessed protocols through the electronic medical record. Change in pain score (0-100 mm VAS) from arrival to ED disposition, as well as side effects were assessed. 52 patients (median age was 27 years, 42% were female, and 89% black) had one or more ED visits for a VOE (total of 126 ED study visits, up to 5 visits/patient were included). Participants randomized to the patient-specific protocol experienced a mean reduction in pain score that was 16.6 points greater than patients randomized to the weight-based group (mean difference 95% CI = 11.3 to 21.9, P = 0.03). Naloxone was not required for either protocol and nausea and/or vomiting was observed less often in the patient-specific protocol (25.8% vs 59.4%, P = 0.0001). The hospital admission rate for VOE was lower for patients in the patient-specific protocol (40.3% vs 57.8% P = 0.05). NHLBI guideline-based analgesia with patient-specific opioid dosing resulted in greater improvements in the pain experience compared to a weight-based strategy, without increased side effects.

Hospital Admissions, Mortality and Comorbidities Among New York State Sickle Cell Patients, 2005-2013.

Analyses of administrative and large data sources in Sickle Cell Disease (SCD) can answer questions not suitable for prospective study but have been hampered by lack of validated methods to adjust for individual comorbidities and lack of baseline utilization data over time. We sought to develop a database to characterize inpatient SCD care across New York State and generate a re-weighted sickle-cell specific Charlson Comorbidity index (S-CCI) for use in future large data SCD research. We identified 18,541 individual SCD patients admitted to New York State hospitals between 2005 and 2013 from the SPARCS database. We present data from both a randomly selected derivation cohort, used to develop the S-CCI and a validation cohort, The S-CCI resulted in small improvements in model fit and discrimination while using fewer covariates, allowing a more parsimonious model. Despite being the most common comorbidity, chronic pulmonary disease was not predictive of mortality. Mortality per hospitalization was 0.61%. Many patients (32%) were admitted only once during the nine year period. However, the majority was admitted more frequently with over 15% of patients being admitted more than once per year.

Inhaled steroids reduce pain and sVCAM levels in individuals with sickle cell disease: A triple-blind, randomized trial.

Clinical and preclinical data demonstrate that altered pulmonary physiology (including increased inflammation, increased blood flow, airway resistance, and hyper-reactivity) is an intrinsic component of Sickle Cell Disease (SCD) and may contribute to excess SCD morbidity and mortality. Inhaled corticosteroids (ICS), a safe and effective therapy for pulmonary inflammation in asthma, may ameliorate the altered pulmonary physiologic milieu in SCD. With this single-center, longitudinal, randomized, triple-blind, placebo controlled trial we studied the efficacy and feasibility of ICS in 54 nonasthmatic individuals with SCD. Participants received once daily mometasone furoate 220 mcg dry powder inhalation or placebo for 16 weeks. The primary outcome was feasibility (the number who complete the trial divided by the total number enrolled) with prespecified efficacy outcomes including daily pain score over time (patient reported) and change in soluble vascular cell adhesion molecule (sVCAM) levels between entry and 8-weeks. For the primary outcome of feasibility, the result was 96% (52 of 54, 95% CI 87%-99%) for the intent-to-treat analysis and 83% (45 of 54, 95% CI 71%-91%) for the per-protocol analysis. The adjusted treatment effect of mometasone was a reduction in daily pain score of 1.42 points (95%CI 0.61-2.21, P = 0.001). Mometasone was associated with a reduction in sVCAM levels of 526.94 ng/mL more than placebo (95% CI 50.66-1003.23, P = 0.03). These results support further study of ICS in SCD including multicenter trials and longer durations of treatment. www.clinicaltrials.gov (NCT02061202).

Rapidly progressive acute chest syndrome in individuals with sickle cell anemia: a distinct acute chest syndrome phenotype.

Current definitions of acute chest syndrome (ACS) in sickle cell anemia (SCA) do not account for rapid progression of respiratory compromise. In this two-center retrospective cohort study, we tested the hypothesis that in children and adults with ACS and respiratory failure (≤24 hours after onset of respiratory symptoms) have a distinct ACS phenotype associated with multiorgan failure when compared to those with ACS that have a more subacute and protracted course. We identified 173 individuals (97 children <20 years and 76 adults ≥20 years) with SCA and at least one episode of ACS. Only one ACS episode was considered per individual. Rapidly progressive ACS occurred in 21% (n = 16) of adults, but only 2.1% (n = 2) of children. Compared to adults without rapidly progressive ACS, adults with rapidly progressive ACS more frequently developed acute kidney injury (68.8% vs. 3.3%, P < 0.001), hepatic dysfunction (75.0% vs. 15.0%, P < 0.001), altered mental status (43.8% vs. 11.7%, P < 0.001), multiorgan failure (93.8% vs. 10%, P < 0.001), and death (6.3% vs. 0%, P = 0.05). Clinical and laboratory covariates that were evaluable on the first day of respiratory symptoms were evaluated to identify predictors of rapidly progressive ACS. On multivariable analysis, decline in platelet count at presentation was the only predictor of rapidly progressive ACS [odds ratio 4.82 (95% CI 1.20-19.39), P = 0.027]. In conclusion, rapidly progressive ACS is a distinct phenotype that occurs more frequently in adults, is preceded by thrombocytopenia, and is associated with multiorgan failure. Am. J. Hematol. 91:1185-1190, 2016. © 2016 Wiley Periodicals, Inc.

Derivation and preliminary validation of a risk score to predict 30-day ED revisits for sickle cell pain.

BACKGROUND: Emergency department (ED) revisits and 30-day readmissions have been proposed as markers for quality of ED care for sickle cell disease (SCD). OBJECTIVE: To create a scoring system that quantifies the risk of 30-day revisit after ED discharge for SCD vaso-occlusive pain METHODS: This was a dual-center retrospective derivation and validation cohort study. The derivation was performed at an academic, tertiary care center and the validation at an urban community hospital. The primary outcome was revisit to the ED within 30 days after an ED discharge for SCD pain. Recursive partitioning was used to derive a scoring system to predict 30-day revisits. RESULTS: Of a total of 1456 ED visits for SCD pain, there were 680 ED discharges (admission rate of 53%) in 193 unique individuals included in the derivation cohort. There were 240 (35.3%) 30-day revisits. Of a total of 126 ED visits for SCD, there were 79 ED discharges in 41 unique individuals in the validation cohort. The final risk score included 4 variables: (1) age, (2) insurance status, (3) triage pain score, and (4) amount of opioids administered during the ED visit. Possible scores range from 0 to 6. The areas under the receiver operating characteristic curves were 0.746 (95% confidence interval, 0.71-0.78-derivation cohort) and 0.753 (95% confidence interval, 0.65-0.86-validation cohort). A cutoff of 4 or greater identified 60% of 30-day ED revisits in the derivation cohort and 80% of revisits in the validation cohort. CONCLUSIONS: A risk score can identify ED visits for SCD pain with high risk of 30-day revisit.

Wheezing in children with sickle cell disease.

PURPOSE OF REVIEW: The purpose of this article is to provide a comprehensive review of wheezing in sickle cell disease (SCD), including epidemiology, pathophysiology, associations between wheezing and SCD morbidity and finally the clinical approach to evaluation and management of individuals with SCD who wheeze. RECENT FINDINGS: Wheezing is common in SCD and in some individuals represents an intrinsic component of SCD-related lung disease rather than asthma. Emerging data suggest that, regardless of the cause, individuals with SCD and with recurrent wheezing are at increased risk for subsequent morbidity and premature mortality. We believe individuals who acutely wheeze and have respiratory symptoms should be managed with a beta agonist and short-term treatment of oral steroids, typically less than 3 days to attenuate rebound vaso-occlusive disease. For those who wheeze and have a history or examination associated with atopy, we consider asthma treatment and monitoring per National Heart, Lung and Blood Institute asthma guidelines. SUMMARY: Wheezing in SCD should be treated aggressively both in the acute setting and with controller medications. Prospective SCD-specific clinical trials will be necessary to address whether anti-inflammatory asthma therapies (leukotriene antagonists, inhaled corticosteroids) can safely mitigate the sequelae of wheezing in SCD.