Corrigendum: Patients with juvenile idiopathic arthritis have decreased clonal diversity in the CD8+ T cell repertoire response to influenza vaccination.

[This corrects the article DOI: 10.3389/fimmu.2024.1306490.].

Patients with juvenile idiopathic arthritis have decreased clonal diversity in the CD8+ T cell repertoire response to influenza vaccination.

Recurrent exposures to a pathogenic antigen remodel the CD8+ T cell compartment and generate a functional memory repertoire that is polyclonal and complex. At the clonotype level, the response to the conserved influenza antigen, M158-66 has been well characterized in healthy individuals, but not in patients receiving immunosuppressive therapy or with aberrant immunity, such as those with juvenile idiopathic arthritis (JIA). Here we show that patients with JIA have a reduced number of M158-66 specific RS/RA clonotypes, indicating decreased clonal richness and, as a result, have lower repertoire diversity. By using a rank-frequency approach to analyze the distribution of the repertoire, we found several characteristics of the JIA T cell repertoire to be akin to repertoires seen in healthy adults, including an amplified RS/RA-specific antigen response, representing greater clonal unevenness. Unlike mature repertoires, however, there is more fluctuation in clonotype distribution, less clonotype stability, and more variable IFNy response of the M158-66 specific RS/RA clonotypes in JIA. This indicates that functional clonal expansion is altered in patients with JIA on immunosuppressive therapies. We propose that the response to the influenza M158-66 epitope described here is a general phenomenon for JIA patients receiving immunosuppressive therapy, and that the changes in clonal richness and unevenness indicate a retarded and uneven generation of a mature immune response.

Acute care utilization among individuals with sickle cell disease and related cardiopulmonary and renal complications.

Cardiopulmonary and renal end organ (CPR) complications are associated with early mortality among individuals with sickle cell disease (SCD). However, there is limited knowledge regarding acute care utilization for individuals with SCD and CPR complications. Our objective was to determine the prevalence of CPR complications in a state specific SCD population and compare acute care utilization among individuals with and without CPR complications. We leveraged 2017-2020 data for individuals with SCD identified by the Sickle Cell Data Collection program in Wisconsin. The prevalence of CPR complications is determined for distinct age groups. Generalized linear models adjusted for age compared the rate of acute care visits/person/year among individuals who had cardiopulmonary only, renal only, both cardiopulmonary and renal, or no CPR complications. There were 1378 individuals with SCD, 52% females, mean (SD) age 28.3 (18.5) years; 48% had at least one CPR complication during the study period. The prevalence of CPR complications was higher in adults (69%) compared to pediatric (15%) and transition (51%) groups. Individuals with SCD and cardiopulmonary complications had higher acute visit rates than those without CPR complications (5.4 (IQR 5.0-5.8) vs 2.4 (IQR 2.1-2.5), p <0.001)). Acute care visit rates were similar between individuals with SCD who had renal only complications and no CPR complications (2.7 (IQR 2.5-3.0) vs 2.4 (2.1-2.5), p = 0.24). The high acute care visit rates, especially for those with cardiopulmonary complications, warrant further investigation to understand risk factors for CPR complications, the underlying reasons and identify effective disease management strategies.

Birth Prevalence of Sickle Cell Disease and County-Level Social Vulnerability - Sickle Cell Data Collection Program, 11 States, 2016-2020.

Sickle cell disease (SCD) remains a public health priority in the United States because of its association with complex health needs, reduced life expectancy, lifelong disabilities, and high cost of care. A cross-sectional analysis was conducted to calculate the crude and race-specific birth prevalence for SCD using state newborn screening program records during 2016-2020 from 11 Sickle Cell Data Collection program states. The percentage distribution of birth mother residence within Social Vulnerability Index quartiles was derived. Among 3,305 newborns with confirmed SCD (including 57% with homozygous hemoglobin S or sickle ß-null thalassemia across 11 states, 90% of whom were Black or African American [Black], and 4% of whom were Hispanic or Latino), the crude SCD birth prevalence was 4.83 per 10,000 (one in every 2,070) live births and 28.54 per 10,000 (one in every 350) non-Hispanic Black newborns. Approximately two thirds (67%) of mothers of newborns with SCD lived in counties with high or very high levels of social vulnerability; most mothers lived in counties with high or very high levels of vulnerability for racial and ethnic minority status (89%) and housing type and transportation (64%) themes. These findings can guide public health, health care systems, and community program planning and implementation that address social determinants of health for infants with SCD. Implementation of tailored interventions, including increasing access to transportation, improving housing, and advancing equity in high vulnerability areas, could facilitate care and improve health outcomes for children with SCD.

Evaluating threshold for donor fraction cell-free DNA using clinically available assay for rejection in pediatric and adult heart transplantation.

BACKGROUND: The aims of the study were to assess the performance of a clinically available cell-free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection. METHODS: Observational, non-interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy-associated plasma samples were used for cfDNA measurements. Pre-determined cut points were tested for analytic performance. RESULTS: A total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df-cfDNA values between rejection [0.21% (IQR 0.12-0.69)] and healthy samples [0.05% (IQR 0.01-0.14), p < .0001]. The pediatric rejection group had a median df-cfDNA value of 0.93% (IQR 0.28-2.84) compared to 0.09% (IQR 0.04-0.23) for healthy samples, p = .005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection. CONCLUSION: The study suggests that pediatric patients with rejection show higher levels of circulating df-cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance.

Influence of the COVID-19 Pandemic on Health-Care Career Interests Among High School Students.

PURPOSE: This study investigates the influence of the COVID-19 pandemic on high school students' interest in health-care careers. METHODS: A voluntary web-based survey, approved by the Medical College of Wisconsin's Institutional Review Board, was administered across eight high schools in Milwaukee and its suburbs in Wisconsin. The survey collected students' demographic details, opinions on the health-care system's pandemic response, and their interest in health-care careers before and after the pandemic. RESULTS: Out of 2,949 respondents, 29.9% were already contemplating a health-care career before the pandemic, with 27.7% indicating increased interest thereafter. Students not previously interested in health-care careers registered an 11.5% increase in interest due to the pandemic. Notably, the pandemic significantly boosted health-care career interest among females and freshmen. DISCUSSION: The COVID-19 pandemic has distinctly influenced high school students' interest in health-care careers, notably among females and freshmen. This finding has implications for addressing projected health-care professional shortages.

Higher Weight-Based Doses Are Required to Achieve and Maintain Therapeutic Voriconazole Serum Trough Concentrations in Children.

OBJECTIVE: Children require weight-based voriconazole doses proportionately larger than adults to achieve therapeutic serum trough concentrations (1-6 mcg/mL). The objective of this quality improvement project was to determine the initial dose, proportion of patients achieving target concentrations with initial dosing, and subsequent therapeutic drug monitoring and dose modifications needed to achieve and maintain therapeutic voriconazole concentrations in children. METHODS: This retrospective study evaluated children aged <18 years treated with voriconazole during the study period. Dosing and therapeutic drug monitoring (TDM) values were collected and compared by age. Data are presented as median (IQR), unless otherwise stated. RESULTS: Fifty-nine patients, aged 10.4 (3.7-14.7) years and 49% female, met inclusion criteria; 42 had at least 1 steady-state voriconazole serum trough concentration measured. Twenty-one of 42 (50%) achieved the target concentration at the first steady-state measurement. An additional 13 of 42 (31%) achieved the target following 2 to 4 dose modifications. The dose required to first achieve a value in the target range was 22.3 (18.0-27.1) mg/kg/day in children aged <12 years and 12.0 (9.8-14.0) mg/kg/day in children aged ≥12 years. After reaching the target, 59% and 81% of repeated steady-state measurements were in the therapeutic range in patients aged <12 years and ≥12 years, respectively. CONCLUSIONS: Reaching therapeutic voriconazole serum trough concentrations required doses larger than currently recommended by the American Academy of Pediatrics. Multiple dose adjustments and TDM measurements were required to achieve and maintain therapeutic voriconazole serum concentrations.

Evaluating the Discriminatory Ability of the Sickle Cell Data Collection Program's Administrative Claims Case Definition in Identifying Adults With Sickle Cell Disease: Validation Study.

BACKGROUND: Sickle cell disease (SCD) was first recognized in 1910 and identified as a genetic condition in 1949. However, there is not a universal clinical registry that can be used currently to estimate its prevalence. The Sickle Cell Data Collection (SCDC) program, funded by the Centers for Disease Control and Prevention, funds state-level grantees to compile data within their states from various sources including administrative claims to identify individuals with SCD. The performance of the SCDC administrative claims case definition has been validated in a pediatric population with SCD, but it has not been tested in adults. OBJECTIVE: The objective of our study is to evaluate the discriminatory ability of the SCDC administrative claims case definition to accurately identify adults with SCD using Medicaid insurance claims data. METHODS: Our study used Medicaid claims data in combination with hospital-based medical record data from the Alabama, Georgia, and Wisconsin SCDC programs to identify individuals aged 18 years or older meeting the SCDC administrative claims case definition. In order to validate this definition, our study included only those individuals who were identified in both Medicaid's and the partnering clinical institution's records. We used clinical laboratory tests and diagnostic algorithms to determine the true SCD status of this subset of patients. Positive predictive values (PPV) are reported overall and by state under several scenarios. RESULTS: There were 1219 individuals (354 from Alabama and 865 from Georgia) who were identified through a 5-year time period. The 5-year time period yielded a PPV of 88.4% (91% for data from Alabama and 87% for data from Georgia), when only using data with laboratory-confirmed (gold standard) cases as true positives. With a narrower time period (3-year period) and data from 3 states (Alabama, Georgia, and Wisconsin), a total of 1432 individuals from these states were included in our study. The overall 3-year PPV was 89.4% (92%, 93%, and 81% for data from Alabama, Georgia, and Wisconsin, respectively) when only considering laboratory-confirmed cases as true cases. CONCLUSIONS: Adults identified as having SCD from administrative claims data based on the SCDC case definition have a high probability of truly having the disease, especially if those hospitals have active SCD programs. Administrative claims are thus a valuable data source to identify adults with SCD in a state and understand their epidemiology and health care service usage.

Use of Clinical Practice Guideline to Improve Management of Osteoarticular Infections in Children.

OBJECTIVES: Osteoarticular infections (OAIs) in children pose significant risks if incorrectly managed. We introduced a clinical practice guideline (CPG) to decrease use of broad-spectrum and intravenous (IV) antibiotics for OAI treatment. The primary aims of our project were to decrease the percent of patients with empirical broad cephalosporin use to 10% and decrease IV antibiotic therapy on discharge to 20% while increasing narrow-spectrum oral antibiotic use to 80% within 24 months. METHODS: We used quality improvement methodology to study patients diagnosed with OAIs. Interventions included multidisciplinary workgroup planning, CPG implementation, education, information technology, and stakeholder feedback. Outcome measures were the percentage of patients prescribed empirical broad-spectrum cephalosporins, percent discharged on IV antibiotics, and percent discharged on narrow-spectrum oral antibiotics. Process measures included percent of patients hospitalized on medicine service and infectious diseases consultation. Balancing measures included rates of adverse drug reactions, disease complications, length of stay, and readmission within 90 days. The impact of the interventions was assessed with run and control charts. RESULTS: A total of 330 patients were included over 96 months. The percentage of patients with empirical broad cephalosporin coverage decreased from 47% to 10%, percent discharged on IV antibiotics decreased from 75% to 11%, and percent discharged on narrow-spectrum oral antibiotics increased from 24% to 84%. Adverse drug reactions decreased from 31% to 10%. Rates of complications, readmissions, and length of stay were unchanged. CONCLUSIONS: Through development and implementation of a CPG for OAI management, we demonstrated decreased use of empirical broad-spectrum antibiotics and improved definitive antibiotic management.

Comparison of CAT and short forms for PROMIS pain and physical health domains in children with sickle cell disease.

BACKGROUND: Pain and physical health domains included in Patient-Reported Outcomes Measurement Information System® (PROMIS®) can be administered as short forms (SF) or as computer adaptive tests (CAT). CAT is ideal in many settings but cannot be administered without specialized technology. We compared SF and CAT to identify items for customized SFs to improve the SF performance for children with sickle cell disease (SCD). METHODS: Eligible children 8-17 years old were administered CATs for 5 domains of physical health and 2 domains of pain, followed by any items on the corresponding SF that were not included in the CAT assessments. We describe the range of scores on the CAT and SFs, including the percentage of participants with floor or ceiling effects using the SF. The agreement and correlation between CAT and SF scores were assessed using Bland-Altman plots. Items frequently offered on CAT that had variable responses and were not already present on SF are recommended as additional items for customized SFs. RESULTS: Among 90 children with SCD, there were strong correlations between CAT and SF scores (Concordance Correlation Coefficient > 0.8) however, the SFs for fatigue, mobility, strength impact, pain behavior, and pain interference had substantial floor/ceiling effects. Fatigue, mobility, physical stress experience, and pain behavior domains had items that were frequently offered on CAT, variable responses, and were not present on the SF. CONCLUSIONS: Adding items to the SFs for the fatigue, mobility, physical stress experience, and pain behavior domains may improve these domains' SFs performance for children with SCD.

Validation of donor fraction cell-free DNA with biopsy-proven cardiac allograft rejection in children and adults.

OBJECTIVES: Donor-specific cell-free DNA shows promise as a noninvasive marker for allograft rejection, but as yet has not been validated in both adult and pediatric recipients. The study objective was to validate donor fraction cell-free DNA as a noninvasive test to assess for risk of acute cellular rejection and antibody-mediated rejection after heart transplantation in pediatric and adult recipients. METHODS: Pediatric and adult heart transplant recipients were enrolled from 7 participating sites and followed for 12 months or more with plasma samples collected immediately before all endomyocardial biopsies. Donor fraction cell-free DNA was extracted, and quantitative genotyping was performed. Blinded donor fraction cell-free DNA and clinical data were analyzed and compared with a previously determined threshold of 0.14%. Sensitivity, specificity, negative predictive value, positive predictive value, and receiver operating characteristic curves were calculated. RESULTS: A total of 987 samples from 144 subjects were collected. After applying predefined clinical and technical exclusions, 745 samples from 130 subjects produced 54 rejection samples associated with the composite outcome of acute cellular rejection grade 2R or greater and pathologic antibody-mediated rejection 2 or greater and 323 healthy samples. For all participants, donor fraction cell-free DNA at a threshold of 0.14% had a sensitivity of 67%, a specificity of 79%, a positive predictive value of 34%, and a negative predictive value of 94% with an area under the curve of 0.78 for detecting rejection. When analyzed independently, these results held true for both pediatric and adult cohorts at the same threshold of 0.14% (negative predictive value 92% and 95%, respectively). CONCLUSIONS: Donor fraction cell-free DNA at a threshold of 0.14% can be used to assess for risk of rejection after heart transplantation in both pediatric and adult patients with excellent negative predictive value.

The Burden of Neonatal Abstinence Syndrome, Opioids, and COVID-19 in Wisconsin.

INTRODUCTION: Wisconsin experienced overlapping and accelerating epidemics of opioid use and COVID-19 after March 2020. We hypothesized that Wisconsin neonatal abstinence syndrome rates increased after March 2020 alongside other markers of opioid burden. METHODS: Retrospective cohort analysis examined deidentified Wisconsin census, birth certificate, death certificate, hospital discharge, Prescription Drug Monitoring Program, emergency medical service run, and COVID-19 diagnosis records spanning January 1, 2019, through December 31, 2021. January 2019 through March 2020 was considered before the onset of COVID-19 (pre); April 2020 through December 2021 was considered post-onset of COVID-19 (post). Wisconsin Department of Health Services guidelines defined 5 Wisconsin regions. Rates pre- to post-onset were compared with P values < 0.05 considered statistically significant. RESULTS: Of 1362 patients, 83.3% completed a COVID-19 vaccination series. Younger patients had increased odds of not completing a COVID-19 vaccination series (mean [SD] 46.7 [14.7] vs 54.3 [15.8]; OR 1.03; 95% CI, 1.02-1.04; P < 0.001). Those who identified as non-White (1.88; 95% CI, 1.16-3.04; P = 0.010) or current smoker (1.85, 95% CI, 1.85-2.79; P = 0.004) had increased odds of not completing a COVID-19 vaccination series. Those who resided in rural ZIP codes (1.81; 95% CI, 1.35-2.43; P < 0.001), had not received a 2019-2020 influenza vaccine (5.13; 95% CI, 3.79-6.96; P < 0.001), or had lower comorbidity scores (2.95; 95% CI, 1.98-4.41; P < 0.001) had higher odds of not completing a COVID-19 vaccination series. CONCLUSIONS: Opioid-associated morbidity and mortality increased in Wisconsin during the study period, including among females age 15 to 44 years. Despite increased opioid burden, neonatal abstinence syndrome incidence decreased in the Southeastern Region. Ongoing neonatal abstinence syndrome and opioid analysis may benefit from region-based contextualization.

Asthma Smarts Education: Increased Disease Knowledge and Reduced School Nurse Visits.

BACKGROUND: Worldwide, asthma is one of the most prevalent chronic diseases. Lack of asthma knowledge can lead to exacerbations, emergency room visits, absenteeism, and decreased quality of life. Asthma prevalence in Milwaukee Public Schools (MPS) is often 20% or higher, and among children ages 5 to 17, asthma is a leading cause of missed school days. A community collaboration created an asthma education program tailored to MPS needs. OBJECTIVE: The purpose of this study was to evaluate the efficacy of brief, school-based asthma education for students with asthma in grades three to five. METHODS: A prospective cohort study of students with asthma in third to fifth grades was developed to assess asthma knowledge improvements via survey (n = 2,066) before and after implementing three 30-minute Asthma Smarts lessons delivered one week apart. Additionally, MPS data was analyzed to explore impact on asthma-related school nursing visits (n = 110). RESULTS: Improvement upon post-testing was shown for all questions in each implementation year with highly significant results (all P < 0.0001). Students that participated in Asthma Smarts made fewer asthma-related visits to the school nurse with a significant difference in the mean number of visits pre and post program (P < 0.001). CONCLUSIONS: This project demonstrates potential for mutually beneficial partnerships addressing gaps in school-based nursing services, and successful support for students with asthma.

Relationship between donor fraction cell-free DNA and clinical rejection in heart transplantation.

BACKGROUND: Clinical rejection (CR) defined as decision to treat clinically suspected rejection with change in immunotherapy based on clinical presentation with or without diagnostic biopsy findings is an important part of care in heart transplantation. We sought to assess the utility of donor fraction cell-free DNA (DF cfDNA) in CR and the utility of serial DF cfDNA in CR patients in predicting outcomes of clinical interest. METHODS: Patients with heart transplantation were enrolled in two sequential, multi-center, prospective observational studies. Blood samples were collected for surveillance or clinical events. Clinicians were blinded to the results of DF cfDNA. RESULTS: A total of 835 samples from 269 subjects (57% pediatric) were included for this analysis, including 28 samples associated with CR were analyzed. Median DF cfDNA was 0.43 (IQR 0.15, 1.36)% for CR and 0.10 (IQR 0.07, 0.16)% for healthy controls (p < .0001). At cutoff value of 0.13%, the area under curve (AUC) was 0.82, sensitivity of 0.86, specificity of 0.67, and negative predictive value of 0.99. There was serial decline in DF cfDNA post-therapy, however, those with cardiovascular events (cardiac arrest, need for mechanical support or death) showed significantly higher levels of DF cfDNA on Day 0 (2.11 vs 0.31%) and Day 14 (0.51 vs 0.22%) compared to those who did not have such an event (p < .0001). CONCLUSION: DF cfDNA has excellent agreement with clinical rejection and, importantly, serial measurement of DF cfDNA predict clinically significant outcomes post treatment for rejection in these patients.

Surveillance for the Rare Condition of Sickle Cell Disease in Wisconsin.

INTRODUCTION: Despite universal newborn screening, there is no comprehensive surveillance system to understand the sickle cell disease population in Wisconsin. METHODS: We initiated the development of a sickle cell disease surveillance system by linking newborn screening data and electronic health records from 2 large tertiary health care institutions in Wisconsin: Children's Wisconsin and Froedtert Hospital. RESULTS: There were 1478 individuals within the 3 data sources. One hundred thirty-two (82%) of 159 identified by newborn screening from 2013 through 2019 received care at Children's Wisconsin. The majority of individuals with sickle cell disease at Children's Wisconsin and Froedtert Hospital resided in Milwaukee County. DISCUSSION: The new surveillance program will increase our understanding of the sickle cell disease population in Wisconsin and help improve quality of care and health outcomes.

Detection of changes of functioning over time after asthma exacerbation in children with the use of PROMIS domains.

OBJECTIVES: Patient reported outcome measures, such as the Patient Reported Outcomes Measurement Information System (PROMIS) may be utilized to understand experiences of patients. The purpose of this study was to determine the ability of PROMIS domains to detect changes in pain, physical functioning, and asthma impact over time for children experiencing asthma exacerbation. METHODS: Our prospective cohort study included children presenting to the emergency department (ED) for asthma exacerbation. Children completed PROMIS surveys in the ED, 7-10 days, and 1-3 months post-discharge. We used linear mixed models adjusted for age, gender, acute care utilization, and child global health to determine changes in PROMIS T-scores. We used self-reported child health response (Much better now versus a little better now or worse) at discharge as an anchor to determine if change in PROMIS scores corresponded with changes in health. A change was statistically significant if the 95% CI did not include 0. RESULTS: Our study included 63 children who presented to the ED for acute asthma exacerbation. We identified that children improved significantly in all domains over time. There was improvement over time following discharge from ED for all pain and physical functioning domains, and asthma impact. Using the clinical anchor, those with considerable improvement in asthma symptoms had improved T scores from 4-17. CONCLUSIONS: PROMIS domains of pain, physical functioning, depression, fatigue, peer relationships, and asthma impact are responsive to changes in health states over time. These domains may be used to measure clinically significant change in children experiencing asthma exacerbation.

Increase in nuclear cell-free DNA is associated with major adverse events in adult and pediatric heart transplant recipients.

BACKGROUND: Cell-free DNA is an emerging biomarker. While donor fraction may detect graft events in heart transplant recipients, the prognostic value of total nuclear cell-free DNA (ncfDNA) itself is largely unexplored. OBJECTIVE: Explore the relationship between ncfDNA and clinical events in heart transplant recipients. METHODS: We conducted a multi-center prospective study to investigate the value of cell-free DNA in non-invasive monitoring following heart transplantation. Over 4000 blood samples were collected from 388 heart transplant patients. Total ncfDNA and donor fraction were quantified. Generalized linear models with maximum likelihood estimation for repeated measures with subjects as clusters were used to explore the relationship of ncfDNA and major adverse events. Receiver operating characteristic curves were used to help choose cutpoints. RESULTS: A ncfDNA threshold (50 ng/ml) was identified that was associated with increased risk of major adverse events. NcfDNA was elevated in patients who suffered cardiac arrest, required mechanical circulatory support or died post heart transplantation as well as in patients undergoing treatment for infection. CONCLUSIONS: Elevated ncfDNA correlates with risk for major adverse events in adult and pediatric heart transplant recipients and may indicate a need for enhanced surveillance after transplant.

Comorbidities are risk factors for hospitalization and serious COVID-19 illness in children and adults with sickle cell disease.

Patients with sickle cell disease (SCD) are at high risk of developing serious infections, therefore, understanding the impact that severe acute respiratory syndrome coronavirus 2 infection has on this population is important. We sought to identify factors associated with hospitalization and serious COVID-19 illness in children and adults with SCD.We established the international SECURE-SCD Registry to collect data on patients with SCD and COVID-19 illness. We used multivariable logistic models to estimate the independent effects of age, sex, genotype, hydroxyurea, and SCD-related and -nonrelated comorbidities on hospitalization, serious COVID-19 illness, and pain as a presenting symptom during COVID-19 illness. As of 23 March 2021, 750 COVID-19 illness cases in patients with SCD were reported to the registry. We identified history of pain (relative risk [RR], 2.15; P < .0001) and SCD heart/lung comorbidities (RR, 1.61; P = .0001) as risk factors for hospitalization in children. History of pain (RR, 1.78; P = .002) was also a risk factor for hospitalization in adults. Children with history of pain (RR, 3.09; P = .009), SCD heart/lung comorbidities (RR, 1.76; P = .03), and SCD renal comorbidities (RR, 3.67; P < .0001) and adults with history of pain (RR 1.94, P = .02) were at higher risk of developing serious COVID-19 illness. History of pain and SCD renal comorbidities also increased risk of pain during COVID-19 in children; history of pain, SCD heart/lung comorbidities, and female sex increased risk of pain during COVID-19 in adults. Hydroxyurea showed no effect on hospitalization and COVID-19 severity, but it lowered the risk of presenting with pain in adults during COVID-19.

Risk of pulmonary emboli after removal of an upper extremity central catheter associated with a deep vein thrombosis.

Standard treatment of catheter-associated upper extremity deep vein thrombosis (UE-DVT) is anticoagulation, although catheters are often removed for this indication. The optimal time for catheter removal and whether the act and/or timing of catheter removal is associated with pulmonary embolism (PE) remain unknown. A retrospective cohort study was performed at 8 participating institutions through the Venous thromboEmbolism Network US. Patients with hematologic malignancies and central venous catheter (CVC)-associated UE-DVT were included from 1 January 2010 through 31 December 2016. The primary outcome was objectively confirmed PE within 7 days of UE-DVT diagnosis in anticoagulated patients comparing early (≤48 hours) vs delayed (>48 hours) catheter removal. A total of 626 patients were included, among whom 480 were treated with anticoagulation. Among anticoagulated patients, 255 underwent early CVC removal, while 225 had delayed or no CVC removal; 146 patients received no anticoagulation, among whom 116 underwent CVC removal alone. PE within 7 days occurred in 2 patients (0.78%) with early removal compared with 1 patient (0.44%) with delayed or no CVC removal (P > .9). PE or any cause of death within 7 days occurred in 3 patients in both the early removal (1.18%) and delayed/no removal (1.33%) groups (P > .9). In patients treated with CVC removal only (no anticoagulation), there were no PEs but 3 deaths within 7 days. In patients with hematological malignancy and CVC-associated UE-DVT, early removal of CVCs was not associated with an increased risk of PE compared with delayed or no removal.

Blastomycosis in 64 Wisconsin Children: Unanticipated Infection Risk and Severity in Urban Residents.

BACKGROUND: Blastomycosis, an endemic mycosis of immunocompetent individuals, is typically seen after exposure to waterways within rural wooded regions. It is not considered a disease of urban environments. Infection can be solely pneumonic or disseminate to skin, bone or central nervous system. Unknown factors influence disease acquisition and severity in children. METHODS: We analyzed acquisition risks and disease characteristics of blastomycosis in children seen at a tertiary care center from 1998 to 2018 to identify potential exposure sources, measure disease severity and assess the effect of race upon disease severity. RESULTS: Of 64 infected children, mean age was 12.9 years, with median time to diagnosis 38.5 days. About 72% were male, 38% resided in urban counties and 50% had typical environmental exposure. Isolated pulmonary infection occurred in 33 (52%). The remainder had evidence of dissemination to skin (N = 13), bone (N = 16; 7 clinically silent) and cranium (N = 7; 3 clinically silent). Infection was moderate/severe in 19 (30%). Two children (3%) died. About 79% of children with moderate/severe disease (P = 0.008) and 71% of urban children (P = 0.007) lacked typical environmental exposure. Comparing children from urban counties to other residences, 63% versus 5% were black (P < 0.001) and 71% versus 35% developed extrapulmonary dissemination (P = 0.006). Moderate/severe disease was seen in 7/17 (42%) black children but only 12/47 (26%) children of other races (P = 0.23). CONCLUSIONS: Blastomycosis, can be endemic in urban children in the absence of typical exposure history, have frequent, sometimes clinically silent, extrapulmonary dissemination and possibly produces more severe disease in black children.