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ABSTRACT Background Risk for medication error increases during care transitions. Error susceptibility increases in pediatrics due to age and weight‐based dosing. Governing bodies acknowledge errors endanger patients, and transplant pharmacotherapy experts are mandated by the Center for Medicare and Medicaid Services (CMS). Pharmacist‐led medication histories reduce errors; however, pharmacists' roles in the transitions of care between transplant centers are unaddressed by CMS. We assessed the impact of transplant pharmacist involvement in medication histories for pediatrics transitioning between transplant centers. Methods Pediatric patients pre‐ or post‐heart transplant transitioning to our center were proactively identified. Transplant pharmacists conducted medication histories by phone with caregivers and tracked discrepancies between existing medication lists and interview responses. Descriptive statistical analyses were completed. Results Of 27 patients identified, seven caregivers were uncontactable, one declined participation, and 19 underwent transplant pharmacist medication history. Medication list errors were detected in 100% of patients ( n = 19), with a median [IQR] of 5 [3–11] issues per patient. Of 122 issues, 72 (59%) were inaccurate or missing data, 17.2% ( n = 21) listed stopped drugs, 9.8% ( n = 12) revealed incorrect administration routes, 7.4% ( n = 9) were duplicate medications, and 6.6% ( n = 8) of errors were medications needing to be added. Corrections included updating 84 inaccuracies (68.8%); removing/adding drugs (30 [24.6%] and 8 [6.6%], respectively); and team communication. Conclusions Complex dosing strategies in pediatrics confer error vulnerability. Designing transition of care processes with transplant pharmacist involvement in medication histories can assist in ensuring medication list accuracy, thereby improving pediatric patient safety.

Nonmedical stimulant use (NMSU) among adolescents poses significant public health concerns. Using cross-sectional design, this study examined risk and protective factors for NMSU among 20,576 Florida high school students using the 2020 Florida Youth Substance Abuse Survey, with 925 students reporting NMSU. Guided by Hawkins and Catalano’s Social Development Model, we employed multivariate logistic regression analyses to estimate adjusted odds ratios while controlling for demographics. Students engaged in extracurricular activities were 50% less likely to report NMSU. Higher academic performance was associated with lower NMSU likelihood. Students with friends who used stimulants nonmedically were significantly more likely to engage in NMSU (AOR, 7.60; 95% CI: 6.35, 9.10), as were those living with relatives who used substances (AOR, 3.54; 95% CI: 2.94, 4.26). Findings highlight the importance of extracurricular involvement and positive social networks in mitigating NMSU. Interventions addressing family, peers, and extracurricular involvement are crucial for prevention and evidence-based policies.

Abstract Background Methylation class pleomorphic xanthoastrocytoma (mcPXA) comprises tumors with the DNA methylation signature of classical PXA but with a wider histologic spectrum, including overlap with glioblastoma (GBM). Methods To clarify the histologic and molecular scope of mcPXA and characterize its clinical behavior, a cohort of 469 tumor samples from 458 patients matching to mcPXA by the DKFZ classifier (v12.6 score ≥0.85) was interrogated. Results Patient median age was 23 years (range 1-73 years) with a female predominance (259 female/199 male). CDKN2A/B homozygous deletion was observed in 406 of 469 (87%) samples. In samples tested for BRAF p.V600E mutations (n = 279), 240 (86%) harbored the mutation. A chr7+/chr10− pattern was observed in 103 of 469 (22%) samples. Among samples tested for TERT promoter mutations (n = 143), 32 (22%) harbored the mutation. Progression-free and overall survival of patients with mcPXA were comparable to patients with methylation class IDH-mutant astrocytoma, low grade, but a GBM-like subset (ie, cases with a pre-methylation working diagnosis of GBM) showed shorter survival. Histologic features of high grade, including palisading necrosis and microvascular proliferation, were prognostic in mcPXA. Compared to patients with BRAF p.V600E-altered GBM, patients with mcPXA were younger and had a lower frequency of TERT promoter mutations. Conclusion Tumors in mcPXA share molecular characteristics with histologically defined PXA, and high-grade histologic features can help predict their clinical behavior. The use of an epigenetic classification of PXA reveals that this group of tumors is more common than previously appreciated and warrants in-depth study to identify efficacious therapeutic options.

ImportanceIdentifying factors associated with resilience during the COVID-19 pandemic can inform targeted interventions and resource allocation for groups disproportionately affected by systemic inequities.ObjectiveTo examine factors associated with self-reported resilience during the COVID-19 pandemic in racially and ethnically diverse, community-dwelling US adults.Design, Setting, and ParticipantsThis cross-sectional study was conducted as part of the Collaborative Cohort of Cohorts for COVID-19 Research (C4R) study, which assessed the associations of the pandemic with self-reported resilience of participants from 14 established US prospective cohorts since January 2021. This report includes participants who responded to the self-reported resilience question on C4R questionnaires. Data was initially analyzed from October 2023 to May 2024, with updated analyses performed from August 2024 to April 2025.ExposureRace and ethnicity, behavior factors, health conditions, and social determinants of health measurements accessed before and during the COVID-19 pandemic through cohort visits and C4R questionnaires.Main Outcomes and MeasuresSelf-reported resilience was collected via 1 question (from the Brief Resilience Scale) in C4R questionnaires, “I tend to bounce back quickly after hard times.” Participants who answered agree or strongly agree were classified as resilient, and those who reported neutral, disagree, or strongly disagree were classified as not resilient. Modified Poisson regression was performed to estimate prevalence ratios (PRs) and access multivariable-adjusted associations with resilience.ResultsOf 31 045 participants (18 672 [60%] women; 10 746 [34.6%] aged <65 years), 1185 (3.8%) identified as American Indian, 6728 (21.7%) as Black, 293 (0.9%) as East Asian, 6311 (20.3%) as Hispanic, 565 (1.8%) as South Asian, and 15 961 (51.3%) as White; a total of 23 103 participants (74.4%) self-identified as resilient. Compared with White participants, Black and Hispanic participants had higher prevalence of self-reported resilience (adjusted PR [aPR], 1.04; 95% CI, 1.02-1.06; aPR, 1.08; 95% CI, 1.06-1.11; respectively) and American Indian and East Asian participants had lower prevalence (aPR, 0.90; 95% CI, 0.86-0.94; aPR, 0.76; 95% CI, 0.68-0.84; respectively). Higher education, being married or living as married, higher income, and overweight were also associated with higher prevalence of resilience. Being female, having diabetes, and being unemployed were associated with lower prevalence of self-reported resilience. Compared with participants with public insurance only, participants with private insurance had higher prevalence of resilience (aPR, 1.07; 95% CI, 1.03-1.10). COVID-19 vaccination and infection statuses were not significantly associated with resilience. Modification analyses showed important racial and ethnic differences in how factors such as hypertension, marital status, and insurance status were associated with resilience.Conclusions and RelevanceIn this cross-sectional study of 31 045 adults, self-reported resilience varied by race, ethnicity, and sociodemographic factors. These findings highlight the complex interplay of individual and social factors in shaping the perception of resilience.

Abstract Twenty percent of patients with follicular lymphoma relapse early with poor outcomes; however, the molecular mechanisms underlying this aggressive behavior are unknown. Using a multiomic approach, we show that patients with follicular lymphoma with elevated IRF4 expression (IRF4hi) have increased transformation risk, dysregulated immune signaling, and a suppressive tumor microenvironment. Loss- and gain-of-function experiments in IRF4hi lymphoma cells, along with chromatin profiling, demonstrate that IRF4 impairs their interaction with T cells by repressing antigen presentation and co-receptor gene modules while promoting the expression of cytokines that antagonize T-follicular helper cell and regulatory T-cell functions. Additionally, IRF4 rewires tumor metabolism and restricts glucose availability to immune cells. Silencing of IRF4 inhibits tumor cell growth and restores immune surveillance mechanisms, thus representing a promising target for therapy. Our data suggest that IRF4hi lymphoma cells co-opt a developmental mechanism used to exit the germinal center response in promoting a more aggressive cancer via engagement of multiple immune-evasive mechanisms. Significance: We show that IRF4 controls immune and metabolic signaling with functional effects on the cross-talk between B and T cells, resulting in a suppressive immune microenvironment when IRF4 is overexpressed in lymphoma. This underscores the importance of IRF4 as a pivotal therapeutic target to restore antitumor immunosurveillance for IRF4-associated lymphomas.

ABSTRACT Clinical and Laboratory Standards Institute (CLSI) recommends a blood culture contamination (BCC) threshold of <3%, with ≤1% considered optimal. However, there is not a standardized definition of BCC, and the effect of multiple definitions on BCC rates or what definitions laboratories use remain unknown. We surveyed 52 hospitals and analyzed 362,078 blood cultures (BCx) collected 1 September 2019 to 31 August 2021 from 62 intensive care units (ICUs) and 231 wards from 48 of these hospitals. We calculated and compared BCC rates using the College of American Pathologists (CAP) or CLSI criteria (both utilize a limited number of skin commensals to define BCC) and the comprehensive National Healthcare Safety Network (NHSN) commensal list. We characterized factors associated with BCC and related outcomes (central-line associated bloodstream infection [CLABSI] and vancomycin use). BCC, BCx positivity, and single BCx rates were monitored by 100%, 39%, and 21% of hospitals, respectively. Hospitals used CAP (65%), CLSI (17%), and NHSN (17%) criteria to define BCC. Mean BCC rate by CAP (CAP-BCC) was 1.38% for ICUs and 0.96% for wards. BCC rates remained similar by CLSI criteria but increased when using NHSN list. Sharing BCC data outside of the laboratory, measuring additional BCx quality indicators, and limiting central catheter-drawn BCx were associated with lower BCC rates. BCC was associated with higher CLABSI rates in ICUs. This study demonstrated variability in laboratory practices and opportunities to optimize BCx stewardship. IMPORTANCE Blood culture contamination (BCC) is associated with patient harm and unnecessary use of healthcare resources. BCC thresholds have been established; however, multiple BCC definitions exist. There is limited data on how BCC rates differ depending on the BCC definition used, what definitions laboratories most commonly use, or their approach to other blood cultures (BCx) quality indicators such as single rates or BCx positivity. A cross-sectional multicenter survey and analysis of BCx data from intensive care unit and wards revealed that most laboratories did not track single BCx or BCx positivity rates and that there was variability in how BCC was defined. Additionally, BCC rates were influenced by the definition used. BCC was associated with increased central-line associated bloodstream infection rates.

Background: Musculoskeletal disorders (MSKDs) are the leading cause of disability worldwide. The associations between socioeconomic and lifestyle factors and MSKDs have been widely studied in Europe and North America. However, little data are available about their relationship in Latin America. Objectives: To estimate the prevalence of chronic MSKDs in Brazil and assess their relationship with socioeconomic and lifestyle factors. Design: This is a cross-sectional study, based on a subanalysis of the open-access database from the Brazilian National Health Survey 2019. This survey was a nationwide, cross-sectional, door-to-door study that included 87,648 adults and was conducted between 2019 and 2020. Methods: Prevalence estimates were based on weighted sample strata, and the relationship between MSKD and socioeconomic and lifestyle factors was examined through network analysis and weighted Poisson regression models with robust variance. Results: The weighted prevalence of chronic MSKDs was estimated at 26.1% (95% confidence interval, 25.5%–26.8%). In the network analysis, including all socioeconomic and lifestyle variables, MSKDs prevalence was notably linked to higher body mass index, drinking, smoking, and low income. In the regression models, MSKD prevalence was associated with obesity, sleep disorders, smoking, alcohol consumption, and depression, and inversely associated with physical activity, even after controlling for the sociodemographic disparities. Conclusion: This study identifies specific socioeconomic and lifestyle factors associated with MSKDs and highlights the need for immediate national health promotion programs focused on MSKDs prevention through targeted lifestyle modifications, especially in populations belonging to the lower-income strata in Brazil.

Background/Objectives: Inflammatory bowel disease (IBD) is a chronic inflammatory condition encompassing ulcerative colitis (UC) and Crohn’s disease (CD). The role of environmental factors in the pathogenesis of IBD remains elusive. Nevertheless, evidence suggests a pivotal role of viruses, specifically Epstein–Barr virus (EBV), in the progression of IBD through mechanisms such as molecular mimicry and bystander activation. Our previous findings demonstrate EBV DNA’s significant role in exacerbating colitis symptoms and elevating the levels of the pro-autoimmune cytokine interleukin-17A (IL-17A) in an IBD mouse model via toll-like receptor 9 (TLR9). Therefore, we aimed to examine the role of EBV particles in the pathogenesis of IBD, and the potential role of TLR9 inhibition in ameliorating disease outcomes. Methods: Three days post colitis induction, EBV particles were intra-rectally injected into female C57BL/6J mice, followed by the intra-peritoneal administration of TLR9 inhibitor. Thereupon, mice were monitored daily and the disease activity index (DAI), colon lengths, and damage scores, as well as the number of cells, double-positive for IL-17A+ and IFN-γ+, and triple-positive for IL-17A+, IFN-γ+, and FOXP3+, were evaluated. Results: Our findings revealed a significant role of TLR9 inhibition in mitigating colitis features in an EBV-injected IBD mouse model compared to the control group. Conclusions: These results indicate an essential role of TLR9 in initiating immune responses against recurrent EBV reactivation events, which ultimately contributes to inflammation aggravation in IBD patients. Consequently, TLR9 could serve as a potential therapeutic target to alleviate the severe symptoms of IBD in EBV-infected individuals.

OBJECTIVE In many individuals, type 2 diabetes (T2D) remains poorly controlled despite taking multiple glucose-lowering therapies. Several studies have demonstrated that endogenous hypercortisolism is prevalent among these individuals. We tested whether cortisol-directed therapy improves their glycemic control. RESEARCH DESIGN AND METHODS In this prospective, multicenter, double-blind study, 136 individuals with T2D (hemoglobin A1c [HbA1c] 7.5%–11.5% [58–102 mmol/mol] on multiple medications) and hypercortisolism (by dexamethasone suppression test) were randomized 2:1 to the glucocorticoid receptor antagonist mifepristone (300–900 mg once daily; n = 91) or placebo (n = 45) for 24 weeks, with stratification by presence/absence of an adrenal imaging abnormality. The primary end point was the change in HbA1c. Secondary end points included changes in glucose-lowering medications, weight, and waist circumference and safety. RESULTS Mean baseline HbA1c in the study cohort was 8.55% (69.9 mmol/mol). At 24 weeks, the least squares mean (LSM) difference from placebo in HbA1c was −1.32% (95% CI −1.81 to −0.83; P &lt; 0.001). Participants receiving mifepristone experienced reductions in body weight and waist circumference (placebo-adjusted LSM differences of −5.12 kg [95% CI −8.20 to −2.03] and −5.1 cm [−8.23 to −1.99], respectively). Of participants on mifepristone, 46% discontinued therapy, compared with 18% on placebo. Adverse events with mifepristone (&gt;10% of participants) included hypokalemia, fatigue, nausea, vomiting, headache, peripheral edema, diarrhea, and dizziness, consistent with mifepristone’s known tolerability profile. Increases in blood pressure also occurred. CONCLUSIONS In individuals with inadequately controlled T2D and hypercortisolism, cortisol-directed medical therapy with mifepristone reduced HbA1c, with a manageable tolerability profile.