Sex and frequency of pain episodes are associated with acute pain trajectories in adolescents with sickle cell disease.

Introduction/Objective: Acute pain episodes are a major cause of health care utilization (HCU) in sickle cell disease (SCD), and adolescence is associated with increased pain frequency. We sought to determine whether there were differences in acute pain trajectories by sex and frequency of pain episodes among adolescents with SCD who presented to the emergency department (ED). Methods: Retrospective review of electronic health records from a large, multicampus, pediatric SCD program. Results: Of the 113 adolescents included, the mean age was 16.6 (SD 0.9), 41.6% (n = 47) were female, 77.9% (n = 88) had HbSS or a similarly severe genotype, and 43.4% (n = 49) had ≥3 episodes of HCU for pain, which we defined as having history of high HCU for pain. Those with a history of high HCU for pain had higher mean pain intensity scores at presentation, were more likely to receive either intravenous or intranasal opioids, and were more likely to be hospitalized. In a model considering the 3-way interaction between sex, history of high HCU for pain, and follow-up time from the initial pain intensity score, adjusted for opioid per kilogram body weight, and prescription of hydroxyurea, adolescent female patients with high HCU for pain had the slowest decline in pain intensity during treatment for acute pain in the ED. Conclusion: Sex and history of high HCU for pain are associated with acute pain trajectories in adolescents with SCD presenting to the ED. These novel findings should be confirmed in future prospective studies.

Assessment of Hospital-Onset SARS-CoV-2 Infection Rates and Testing Practices in the US, 2020-2022.

Importance: Characterizing the scale and factors associated with hospital-onset SARS-CoV-2 infections could help inform hospital and public health policies regarding prevention and surveillance needs for these infections. Objective: To evaluate associations of hospital-onset SARS-CoV-2 infection rates with different periods of the COVID-19 pandemic, hospital characteristics, and testing practices. Design, Setting, and Participants: This cohort study of US hospitals reporting SARS-CoV-2 testing data in the PINC AI Healthcare Database COVID-19 special release files was conducted from July 2020 through June 2022. Data were collected from hospitals that reported at least 1 SARS-CoV-2 reverse transcription-polymerase chain reaction or antigen test during hospitalizations discharged that month. For each hospital-month where the hospital reported sufficient data, all hospitalizations discharged in that month were included in the cohort. SARS-CoV-2 viral tests and results reported in the microbiology files for all hospitalizations in the study period by discharge month were identified. Data analysis was conducted from September 2022 to March 2023. Exposure: Hospitalizations discharged in an included hospital-month. Main Outcomes and Measures: Multivariable generalized estimating equation negative-binomial regression models were used to assess associations of monthly rates of hospital-onset SARS-CoV-2 infections per 1000 patient-days (defined as a first positive SARS-CoV-2 test during after hospitalization day 7) with the phase of the pandemic (defined as the predominant SARS-CoV-2 variant in circulation), admission testing rates, and hospital characteristics (hospital bed size, teaching status, urban vs rural designation, Census region, and patient distribution variables). Results: A total of 5687 hospital-months from 288 distinct hospitals were included, which contributed 4 421 268 hospitalization records. Among 171 564 hospitalizations with a positive SARS-CoV-2 test, 7591 (4.4%) were found to be hospital onset and 6455 (3.8%) were indeterminate onset. The mean monthly hospital-onset infection rate per 1000 patient-days was 0.27 (95 CI, 0.26-0.29). Hospital-onset infections occurred in 2217 of 5687 hospital-months (39.0%). The monthly percentage of discharged patients tested for SARS-CoV-2 at admission varied; 1673 hospital-months (29.4%) had less than 25% of hospitalizations tested at admission; 2199 hospital-months (38.7%) had 25% to 50% of all hospitalizations tested, and 1815 hospital months (31.9%) had more than 50% of all hospitalizations tested at admission. Postadmission testing rates and community-onset infection rates increased with admission testing rates. In multivariable models restricted to hospital-months testing at least 25% of hospitalizations at admission, a 10% increase in community-onset SARS-CoV-2 infection rate was associated with a 178% increase in the hospital-onset infection rate (rate ratio, 2.78; 95% CI, 2.52-3.07). Additionally, the phase of the COVID-19 pandemic, the admission testing rate, Census region, and bed size were all significantly associated with hospital-onset SARS-CoV-2 infection rates. Conclusions and Relevance: In this cohort study of hospitals reporting SARS-CoV-2 infections, there was an increase of hospital-onset SARS-CoV-2 infections when community-onset infections were higher, indicating a need for ongoing and enhanced surveillance and prevention efforts to reduce in-hospital transmission of SARS-CoV-2 infections, particularly when community-incidence of SARS-CoV-2 infections is high.

Are children with sickle cell disease at particular risk from the harmful effects of air pollution? Evidence from a large, urban/peri-urban cohort.

INTRODUCTION: Pathophysiologic pathways of sickle cell disease (SCD) and air pollution involve inflammation, oxidative stress, and endothelial damage. It is therefore plausible that children with SCD are especially prone to air pollution's harmful effects. METHODS: Patient data were collected from a single-center, urban/peri-urban cohort of children with confirmed SCD. Daily ambient concentrations of particulate matter (PM2.5 ) were collected via satellite-derived remote-sensing technology, and carbon monoxide (CO), nitrogen dioxide (NO2 ), and ozone from local monitoring stations. We used multivariable regression to quantify associations of pollutant levels and daily counts of emergency department (ED) visits, accounting for weather and time trends. For comparison, we quantified the associations of pollutant levels with daily all-patient (non-SCD) ED visits to our center. RESULTS: From 2010 to 2018, there were 17,731 ED visits by 1740 children with SCD (64.8% HbSS/HbSß0 ). Vaso-occlusive events (57.8%), respiratory illness (17.1%), and fever (16.1%) were the most common visit diagnoses. Higher 3-day (lags 0-2) rolling mean PM2.5 and CO levels were associated with daily ED visits among those with SCD (PM2.5 incident rate ratio [IRR] 1.051 [95% confidence interval: 1.010-1.094] per 9.4 µg/m3 increase; CO 1.088 [1.045-1.132] per 0.5 ppm). NO2 showed positive associations in secondary analyses; ozone levels were not associated with ED visits. The comparison, all-patient ED visit analyses showed lower IRR for all pollutants. CONCLUSIONS: Our results suggest short-term air pollution levels as triggers for SCD events and that children with SCD may be more vulnerable to air pollution than those without SCD. Targeted pollution-avoidance strategies could have significant clinical benefits in this population.

Trends in blood transfusion, hydroxyurea use, and iron overload among children with sickle cell disease enrolled in Medicaid, 2004-2019.

BACKGROUND: There have been significant changes in clinical guidelines for sickle cell disease (SCD) over the past two decades, including updated indications for hydroxyurea, transfusions, and iron overload management. In practice however, there are few studies that examine SCD care utilization over time. METHODS: We conducted a serial cross-sectional cohort study of pediatric SCD patients from 2004 to 2019 using Georgia Medicaid claims data. For each year, we reported receipt of any transfusion, chronic transfusion, or three or more filled hydroxyurea prescriptions. For children receiving chronic transfusion (six or more annual transfusions), we evaluated iron overload diagnosis, monitoring, and chelation use. Among children with sickle cell anemia (SCA), we examined rates of transfusions and hydroxyurea use. The Cochran-Armitage test was used to assess trend. RESULTS: There were 5316 unique children 2-18 years old with SCD enrolled in Georgia Medicaid from 2004 to 2019. Children receiving any transfusion increased from 2004 to 2010, then stabilized. In SCA patients, chronic transfusions initially increased from 2004 to 2010, then stabilized from 2010 to 2019. For chronically transfused children, monitoring of iron burden and filled chelator prescriptions both increased significantly. Hydroxyurea use in SCA patients increased from 12% to 37%, with increases noted within each age group, most notably from 21% to 60% in the 13-18-year-old cohort. CONCLUSION: We demonstrated changes in SCD care utilization over time, including increased hydroxyurea use, changes in transfusion rates, and increased attention to iron overload management. While trends in clinical management do follow updates in treatment guidelines, there is still delayed and suboptimal uptake of guideline recommendations in pediatric SCD patients.

The burden of respiratory syncytial virus infections among children with sickle cell disease.

BACKGROUND: Although respiratory syncytial virus (RSV) is the leading cause of pediatric lower respiratory tract infections, the burden of RSV in children with sickle cell disease (SCD) is unknown. METHODS: We conducted a retrospective, nested, case-control study of children with SCD <18 years who had respiratory viral panels (RVPs) performed at Children's Healthcare of Atlanta from 2012 to 2019. We abstracted the medical records to describe the demographics, clinical features, and outcomes of children who tested positive for RSV (cases) versus children who tested negative (controls). We calculated the annual incidence of RSV and related hospitalization rates with 95% confidence intervals (CIs) and used multivariate logistic regression to evaluate associations. RESULTS: We identified 3676 RVP tests performed on 2636 patients over seven respiratory seasons resulting in 219/3676 (6.0%) RSV-positive tests among 160/2636 (6.1%) patients. The average annual incidence of laboratory-confirmed RSV infection among children with SCD was 34.3 (95% CI 18.7-49.8) and 3.8 (95% CI 0.5-7.0) cases per 1000 person-years for those <5 years and 5-18 years, respectively. The RSV-related hospitalization rate for children <5 years was 20.7 (95% CI 8.5-32.8) per 1000 person-years. RSV-positive cases were significantly younger than RSV-negative patients (3.8 years vs 7.6 years, P < .001). Of RSV-positive cases, 22 (13.8%) developed acute chest syndrome and nine (5.6%) required intensive care, which was not significantly different from RSV-negative children with SCD. CONCLUSION: RSV infections are common in children with SCD with higher burden in younger patients. RSV is associated with considerable morbidity, including higher rates of hospitalization compared to the general population.

Microbiology and radiographic features of osteomyelitis in children and adolescents with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk for bacterial infections including osteomyelitis (OM). Fever and bone pain, key presenting symptoms of OM, are common in SCD, thus complicating diagnosis. We reviewed presentation, imaging features, and microbiologic etiologies of children with SCD treated for OM. METHODS: The comprehensive SCD clinical database of children and adolescents with SCD followed at a single, large tertiary pediatric center were searched to identify all diagnostic coding for potential cases of osteomyelitis in children ages 6 months to 21 years from 2010 to 2019. Medical charts were reviewed to determine OM diagnostic probability based on radiographic and microbiologic findings and the duration of prescribed antibiotic treatment for OM. RESULTS: Review of 3553 patients (18 039 person-years) identified 20 episodes of probable OM in 19 children. Magnetic resonance imaging (MRI) findings to support OM were definitive in 4/19 (21%), probable in 10/19 (53%), suspected in 5/19 (26%), based on blinded radiologist review. Blood and/or operative cultures from bone and tissue debridement isolated Salmonella species in seven (35%) cases and methicillin-susceptible Staphylococcus aureus (MSSA) in two (10%). Six patients received antibiotic treatment prior to obtainment of cultures. Of culture-positive cases, MRI findings for OM were definitive or probable in six of nine (67%), suspected in three of nine (33%). CONCLUSIONS: Distinction between OM and sickle-related bone infarct or vasoocclusion is difficult based on imaging findings alone. Early attainment of blood and operative cultures increases the likelihood of identifying and adequately treating OM.