BMJ Open Respiratory Research

Introduction: Although temporal variation is the hallmark of asthma, recommended diagnostic approaches largely rely on single clinic-based measurements. Ambulatory monitoring captures diurnal and day-to-day variability and may therefore enhance diagnostic accuracy. We evaluated the clinical feasibility and potential utility of home spirometry and fractional exhaled nitric oxide (FeNO) monitoring in asthma diagnosis. Methods: Symptomatic, untreated adults with GP-suspected asthma underwent diagnostic tests including bronchodilator reversibility, in-clinic FeNO, blood eosinophil counts and bronchial challenge. Participants measured spirometry and FeNO four times daily over one week; during the second week spirometry were measured twice daily. The reference standard was provided (asthma/not-asthma) by an expert panel of at least two asthma specialists based on clinical history and the results of all in-clinic testing; home spirometry (except for peak expiratory flow) and FeNO measurements were blinded to the panel. Results: Of 67 eligible participants, 51(76%) were recruited, and 38 had asthma confirmed or excluded by the panel. 1058 home spirometry measurements were obtained from 37(73%) participants; 848 home FeNO readings were obtained from 39(76%) participants. Among those completing at least one home measurement, median (IQR) adherence was 66.7(58.6-97.6)% for spirometry and 78.5(51.8-103.6)% for FeNO. Collection of health impact data for economic evaluation was feasible. In participants with a confirmed diagnostic outcome who completed home measurements (FeNO: n=32; spirometry: n=28), the putative home-testing metrics demonstrated high sensitivities at [≥]90% specificity, and outperformed peak expiratory flow diurnal variability. Incorporating home testing into the BTS/NICE/SIGN 2024 diagnostic pathway had the potential to reduce reliance on bronchial challenge testing by 57%. Conclusions: Home spirometry and FeNO testing and the prospective collection of health-economic data in the diagnostic setting were feasible. Home-based testing strategy showed early potential to improve asthma diagnosis and pathway efficiency. These findings support further evaluation through an adequately powered diagnostic accuracy study and health-economic assessment.

Background Recent guidelines differ in how fractional exhaled nitric oxide (FeNO) is used to diagnose school-age asthma, either as one of several tests with a cut-off at 25 ppb or as a single rule-in test at 35 ppb. Evidence on its diagnostic performance and clinical utility in subgroups remain limited. Methods We analysed data from 1,979 school-age children in the Swiss Paediatric Airway Cohort referred for suspected asthma. We investigated FeNO performance with diagnosis by paediatric pulmonologists as reference standard using receiver operating characteristics curves, selected cut-offs and simulated predictive values across different prevalence. Subgroup analyses considered allergic sensitisation with allergic rhinitis and current inhaled corticosteroid (ICS) use. Results In the overall cohort (asthma diagnosis 70%), FeNO showed poor discrimination for asthma (AUC 0.66; 95% CI 0.64-0.68) with an optimal cut-off at 22 ppb. At 25 and 35 ppb, sensitivity was low (43%, 95% CI 40-46; 31%, 95% CI 29-34) and specificity moderate to high (84%, 95% CI 77-84; 90%, 95% CI 87-92). Positive predictive value at 35 ppb was 88% and was 57% when simulated at a prevalence of 30%. FeNO had no diagnostic value in non-sensitised children and lower performance in sensitised children with allergic rhinitis than in those without (AUC 0.59 vs 0.68). Current ICS use did not influence performance. Conclusion FeNO has limited diagnostic performance as a stand-alone test for school-age asthma, and underlying asthma prevalence and allergic characteristics should be considered in the interpretation.

IntroductionIndividuals with COPD can be classified according to their levels of physical activity (PA) and physical capacity (PC). The relationship between nutrition and body composition within these classifications remains unclear. ObjectivesTo compare the body composition and food intake of people with COPD and verify the associations. MethodsCross-sectional exploratory analysis study in which body composition and food intake were assessed in individuals with COPD. Classification was based on six-minute walk test (PC) and accelerometry(PA): Quadrant "can do, dont do" (I-preserved PC, low PA); quadrant "can do, do do" (II-preserved PC, preserved PA). Results72 individuals with COPD, 39 in quadrant I and 33 in quadrant II, with mean ages of (69 {+/-} 6) (67 {+/-} 7), respectively. Group I had a higher proportion of males, whereas group II had a higher proportion of females. A positive trend in skeletal muscle mass (p=0.011) (B= 2.883) and a negative trend in basal metabolic rate (p=0.010) (B=-0.092) for group I. ConclusionBrazilians with COPD classified in quadrants I and II showed similar results in terms of body composition and food intake. A positive trend in skeletal muscle mass was observed for the group I. These findings align with the pathophysiological model of COPD, in which the preservation of muscle mass and adequate protein intake support functional capacity and the maintenance of higher physical activity levels.

Background While a mobile lung cancer screening (mLCS) program can mitigate barriers to access, this study conducted a survey study to assess barriers and facilitators to mLCS which could inform the implementation of new mLCS programs or inform modifications to existing programs. Methods Patient eligibility included current age of 50 to 80 and had undergone any cancer screening at Moffitt Cancer Center (MCC) between January 1, 2023 and December 1, 2024. A web-based survey was administered from May 2025 to June 2025 which collected data on health behaviors, barriers, facilitators, screening preferences, and demographics. Descriptive statistics were used to quantify survey responses. Results Among participants who completed the survey, 73.4% reported no concerns about getting screened in a mobile screening unit, 67.9% reported concerned about the cost or if insurance covered mobile lung cancer screening, and 82.4% reported they would be screened if a voucher or insurance would pay for it. For preferences, 54.1% reported no preference for the time of year for a mobile screening event, 59.6% reported they will be willing to wait up to 30 minutes to get screened, and 44% would travel more than 20 minutes to get screened. There were no statistically significant differences in barriers and facilitators when the analyses were stratified by LCS eligibility. Conclusions We found acceptability of mobile lung cancer screening and preferences that are actionable including daytime weekday events, indoor waiting, short waits, proximity to home, clear cost coverage, and streamlined clinician recommendation.

OBJECTIVE This study investigates the long-term impacts of childhood exposure to voiding cystourethrogram (VCUG), a diagnostic procedure for vesicoureteral reflux. Primary outcomes include long-term health outcomes, mental health disorders, healthcare avoidance, and participation in risky behaviors compared to a control group. METHODS A 9-month retrospective cohort study was conducted with adults who received most of their medical care in the U.S. Respondents self-reported health metrics, behaviors, and outcomes via a 20-minute survey. Respondents were divided into two groups: those who remembered undergoing at least one VCUG in childhood (VCUG group), and those who did not (control group). RESULTS Of 334 respondents, 204 (61%) were in the VCUG group (mean age: 29, 70% female) and 130 (39%) were controls (mean age: 34, 70% female). Notable findings include: 47% of VCUG respondents were diagnosed with depression compared to 27% of controls. 15% of female-born VCUG respondents reported they would never visit a gynecologist compared to 2% of controls. 34% of VCUG respondents smoked regularly compared to 5% of controls, and 11% of VCUG respondents regularly missed work compared to 1% of controls. These findings highlight the need for further research and clinical consideration of VCUG's long-term consequences. CONCLUSIONS This study suggests that the effects of childhood VCUG extend into adulthood. Our findings underscore the need to reassess informed consent protocols and consider full-scale studies to minimize bias.

Background: Idiopathic pulmonary fibrosis (IPF) is a rare disease with a poor prognosis. Disease risk involves rare and common genetic variants. However, an inverse association have been described between them. Accordingly, IPF patients with a higher polygenic risk score (PRS) for IPF are less likely to carry rare deleterious variants and vice versa. Here, we evaluate weather PRS of IPF could serve as an additional criterion to patient prioritisation for rare variant discovery. Methods: We identified carriers based on the presence of rare qualifying variants (QVs) in genes linked to monogenic forms of pulmonary fibrosis in 888 IPF patients from the Pulmonary Fibrosis Foundation Patient Registry (PFF-PR). Genome-wide association study (GWAS) summary statistics from independent cohorts were used to construct a whole-genome PRS (WG-PRS) using a clumping and thresholding method (C+T) and a Bayesian method (SBayesRC). PRS were also derived from 19 known common sentinel IPF variants (Sentinel-PRS). Logistic regression models were used to evaluate associations between PRS and carrier status. Discriminatory performance was evaluated using area under the curve (AUC) analysis, and comparisons were made with DeLong test. Validation was performed in 472 IPF individuals from the UK PROFILE cohort. Results: IPF-PRS were strongly associated with the QVs carrier status: Odds Ratio [OR] 0.65 (95% Confidence Interval [CI] 0.53-0.79) for WG-PRSC+T, OR 0.71 (95% CI 0.59-0.86) for WG-PRSSBayesRC, and OR 0.77 (95% CI 0.63-0.94) for Sentinel-PRS. Adding WG-PRS to the patient personal clinical history improved the prediction of QVs carriers: AUC=0.62 for the clinical model, AUC=0.68 for WG-PRSC+T (DeLong test, p=9.54x10-4) and AUC=0.66 for WG-PRSSBayesRC (DeLong test, p=0.02). Adding of IPF-PRS to clinical variables correctly reclassified 22.8% of carriers when using WG-PRSC+T, 20.8% when using Sentinel-PRS, and 16.7% for WG-PRSSBayesRC. WG-PRSSBayesRC and the Sentinel-PRS also demonstrated improved prediction of QVs carriers in telomere-related genes in PROFILE. Conclusions: Incorporating IPF-PRS into a model based on the patient clinical history improves the identification of QVs carriers. Although the overall discriminatory power was moderate, these findings raise de the possibility of using WG-PRS as useful criterion for rare variant discovery in patients with IPF and enhance decision-making.

Background: Extreme-phenotype comparisons allowed the discovery of novel asthma genetic risk loci. However, this approach remains unexplored in epigenome-wide association studies (EWAS). We aimed to identify bulk and cell-specific methylation markers of asthma with severe exacerbations across diverse ancestry groups. Methods: We conducted a meta-EWAS of 739,543 CpGs in whole blood among 1,192 African American and Latino pediatric populations, comparing non-asthmatics and asthma exacerbators. Genome-wide CpGs were followed up for replication in a meta-analysis across 1,516 ethnically diverse participants and in a cross-tissue evaluation of 393 nasal samples. We conducted differentially methylated region (DMRs), cell-type-deconvoluted, and quantitative trait loci analyses (whole-genome sequencing n=1,668; RNA-seq n=1,209). We examined enrichment in traits, pathways, and druggable genes, and analyzed DNAm predictors of plasma proteins and aging. Results: DNAm at 505 CpGs and 119 DMRs in whole blood were associated with asthma exacerbations (p<9x10-8, {lambda}=1.05). We replicated 25 CpGs in blood cells, cross-validated 7 in nasal samples, and detected 42 cell-specific DNAm markers mainly driven by T cells. DNAm at 134 CpGs was associated with gene expression in whole blood, including 118 associations with T-cell receptor genes, and 446 CpGs were regulated by [&ge;]1 genetic variant. We found enrichment for previous associations with environmental exposures, immune disorders, immune and inflammatory pathways, and druggable genes by developmental drugs. 21 methylation-predicted plasma proteins, involved in host defense, and one lung aging clock were associated with asthma exacerbations. Conclusions: The first meta-EWAS of extreme asthma phenotypes identified hundreds of novel DNAm markers, suggesting novel methylation biomarkers and candidate drugs for asthma and supporting the role of T cells.

Background: Preterm births contribute to approximately 35% of neonatal deaths globally, with an estimated 13.4 million infants born prematurely each year. Despite this substantial burden, limited evidence exists on time to discharge and its determinants among preterm neonates admitted to Neonatal Intensive Care Units (NICUs), particularly in rural Ugandan settings. This study aimed to investigate time to discharge and associated factors among preterm neonates admitted to Kiwoko Hospital in Nakaseke District, Uganda. Methods: A retrospective cohort study was conducted using secondary data from Kiwoko Hospital on preterm neonates admitted to the Neonatal Intensive Care Unit (NICU) between 2020 and 2021 (n = 847). The cumulative incidence function was used to estimate the probability of discharge within 28 days of admission, accounting for competing events. A Fine and Gray sub-distribution hazard regression model was fitted to identify factors associated with time to discharge. Results: Of the 847 preterm admissions, 70.1% were discharged alive within 28 days. The median time to discharge was 14 days. The cumulative incidence of discharge by 28 days was 68%, accounting for competing events. During follow-up, 165 neonates did not complete the 28-day period, including 88 deaths. Factors significantly associated with time to discharge included place of delivery (SHR: 0.62; 95% CI: 0.53-0.73; p<0.001), maternal residence in other districts (SHR: 0.69; 95% CI: 0.48-0.99; p=0.044), extreme preterm (SHR: 0.05; 95% CI: 0.03-0.09; p<0.001), very preterm (SHR: 0.18; 95% CI: 0.14-0.25; p<0.001), moderate preterm (SHR: 0.59; 95% CI: 0.46-0.76; p<0.001), triplet births (SHR: 0.40; 95% CI: 0.23-0.68; p=0.001), 2-4 ANC visits (SHR: 0.70; 95% CI: 0.56-0.87; p=0.002), <=1 ANC visit (SHR: 0.64; 95% CI: 0.49-0.85; p=0.002), respiratory distress syndrome (SHR: 0.64; 95% CI: 0.48-0.74; p<0.001), and birth trauma (SHR: 2.62; 95% CI: 1.60-4.29; p<0.001). Conclusions: Respiratory distress syndrome, fewer antenatal care visits, out-of-district residence, and higher degrees of prematurity were associated with prolonged time to discharge among preterm neonates. Strengthening antenatal care utilization and improving access to quality neonatal care in underserved areas may enhance discharge outcomes.

Background: Chest tube infection is one of the complications of the tube thoracostomy. Infectious complications may develop in 2% to 25% of patients who undergo thoracotomy tube placement. The use of prophylactic antibiotics to prevent infections associated with thoracostomy tubes remains a subject of debate. Current practices in managing infections related to tube thoracostomy are hindered by the lack of comprehensive and localised data on the microbial profile and their resistance patterns. Objective: To determine the prevalence of thoracostomy tube infections and associated clinical characteristics among patients treated with a thoracostomy tube at KCMC Zonal Referral Hospital. Methodology: Prospective cohort study done at KCMC Zonal Referral Hospital. Include all patients undergoing thoracostomy tube insertion from September 2024 to April 2025. Results: A total of 84 patients underwent tube thoracostomy during the study time. Of these 22 (26.2%) developed SSI. Out of the 22 samples collected, 17 (77.3%) had positive culture results. The most commonly identified pathogens were Pseudomonas aeruginosa (41.2%) and Staphylococcus aureus (29.4%). The highest overall susceptibility was observed with amikacin, effective against 10 (58.8%) of the tested organisms. The most common resistance was observed against ceftazidime (56.3%) and piperacillin-tazobactam (50.0%). Prolonged chest tube duration (>7 days) was the strongest independent predictor of tube thoracostomy infection. Conclusion: This study revealed a high prevalence of tube thoracostomy infection. Prolonged tube duration and admission to a non-surgical ward care emerge as key risk factors for SSI. These findings underscore the importance of limiting chest tube duration when clinically feasible and ensuring optimal postoperative care environments to minimise the risk of infection.

Background Tuberculosis (TB) remains a critical public health challenge, with two-thirds of the global TB burden in ten Asian countries. Social vulnerabilities, comorbidities, health inequity, multi-dimensional poverty, malnutrition, and barriers to healthcare access continue to fuel TB epidemic. Inability to detect asymptomatic and sub-clinical TB, combined with passive approach in service delivery and overreliance on smear microscopy, leads to delayed diagnosis, a substantial burden of undetected cases, and continuing TB transmission in the communities. In such a context, the introduction and scale-up of active case-finding approaches - including community-based TB screening using highly sensitive screening tools and novel rapid diagnostics - becomes a strategic priority to interrupt transmission. The growing availability of multiple screening and diagnostic options makes evidence-based decision-making increasingly complex. Methods To estimate the potential epidemiological impact and cost implications of scaling up TB diagnostics and community-based screening in ten high-burden Asian countries, we constructed a mathematical model and evaluated multiple intervention scenarios. We then assessed and compared four service delivery models: 1) digital ultraportable chest x-ray (UPCXR) & Xpert/Truenat in community, 2) digital UPCXR in community and Xpert/Truenat at health facilities, 3) digital UPCXR in community and near point of care (nPOC) at health facilities, 4) nPOC in community & Xpert/Truenat at health facilities - for total investment required and projected health benefits for their cost-effectiveness. Results and conclusions The modelling study indicated that strengthening health facility capacity (with enhanced TB screening, expanded molecular diagnostics, reduced loss to follow-up, private sector standard of care, leading to increased treatment coverage & quality of active disease treatment and reduced post-treatment relapse, scale-up of TB preventive treatment (TPT), and provision of nutritional support to 80% of TB patients and their household contacts) can significantly reduce TB incidence and mortality; however, community-wide mass screening remains essential to achieving TB elimination targets . Targeted screening of vulnerable populations demonstrated greater cost-effectiveness than untargeted screening approaches. Achieving the End TB goals will ultimately require an effective TB vaccine with high population-level coverage. AI-enabled digital UPCXR-based screening combined with Xpert/Truenat testing at the community level demonstrated maximum epidemiological impact potential, while the most cost-efficient model is Digital UPCXR in the community combined with nPOC testing at health facilities. An investment of USD 12.7 billion over the next five years in community-level implementation of digital UPCXR and molecular diagnostics could avert an additional 9.8 million TB cases and 1.9 million deaths across ten Asian countries over a ten-year horizon.

BackgroundPatent ductus arteriosus (PDA) is a common and potentially serious cardiovascular condition in preterm infants, particularly those with low gestational age and birth weight. Its management remains controversial due to variability in screening, diagnostic criteria, and treatment strategies. This study aimed to evaluate risk factors, outcomes, and management strategies for PDA in preterm infants, and to identify predictors of clinical and echocardiographic response to therapy. MethodsWe conducted a retrospective cohort study over a 4-year period (2016-2019) in the neonatal intensive care unit (NICU) of a tertiary care center. All consecutive preterm infants admitted during the study period were eligible. Infants with echocardiographically confirmed PDA who received pharmacological treatment with intravenous paracetamol or ibuprofen were included in the analysis. Missing data were minimal and handled using available-case analysis. Statistical analyses included descriptive statistics, Pearsons chi-square test, and multivariable logistic regression. ResultsAmong 2154 preterm infants admitted to the NICU, 60 were diagnosed with PDA (incidence : 2.8%). The mean gestational age was 29 {+/-} 2.6 weeks, and the median birth weight was 1200 g. Respiratory distress occurred in 95% of cases, mainly due to hyaline membrane disease (86.7%). PDA was symptomatic in 80% of infants. First-line treatment resulted in clinical improvement in 77% and ductal closure in 83.3% of cases, most within 3 days. Predictors of successful closure included gestational age [&ge;] 28 weeks (OR = 5.9; 95% CI : 1.7-20.2) and antenatal corticosteroid exposure (OR = 1.2; 95% CI : 1.0-1.6). Overall mortality was 35% and was significantly higher in infants < 28 weeks (OR = 5.0; 95% CI : 2.4-10.3). Clinical improvement (OR = 3.7) and echocardiographic closure (OR = 4.5) after first-line treatment were associated with reduced mortality. ConclusionsPDA in preterm infants is associated with substantial morbidity and mortality, particularly in those born before 28 weeks of gestation. Early diagnosis, antenatal corticosteroid exposure, and timely pharmacological treatment may improve outcomes. Systematic echocardiographic screening in high-risk neonates should be considered.

ImportanceAge-related eye diseases, such as cataract, glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR), are leading causes of irreversible vision loss globally. Chronic inflammation is a shared pathogenic pathway, but the role of systemic inflammatory drivers like clonal hematopoiesis of indeterminate potential (CHIP) is unknown. ObjectiveTo investigate the association of CHIP, including its major genetic subtypes and clone sizes, with the risk of four major age-related eye diseases. Design, Setting, and ParticipantsThis was a prospective cohort study conducted using data from the UK Biobank, a large-scale, population-based cohort. A total of 436,469 participants free of the four eye diseases at baseline were included in the analysis. Data were collected from 2006 to 2010, with follow-up extending to March 2022. ExposuresCHIP status was ascertained from whole-exome sequencing data, defined by the presence of a somatic driver mutation with a variant allele fraction of 2% or greater. Main Outcomes and MeasuresThe primary outcomes were incident cases of cataract, glaucoma, AMD, and DR, identified through linked electronic health records. Associations were assessed using multivariable Cox proportional hazards regression models. ResultsOf 436,469 participants (mean [SD] age, 56.4 [8.1] years; 54.5% women), 14,110 (3.2%) had CHIP. Over a median follow-up of 13.1 years, CHIP was significantly associated with an increased risk of incident cataract (Hazard Ratio [HR], 1.08; 95% CI, 1.03-1.14), AMD (HR, 1.12; 95% CI, 1.04-1.21), and DR (HR, 1.41; 95% CI, 1.20-1.64). No significant association was found with glaucoma (HR, 1.08; 95% CI, 0.99-1.17). The risk for AMD was primarily associated with smaller clones (VAF <10%), while the risk for DR was highest with non-DNMT3A mutations. Systemic inflammation, particularly neutrophil count, partially mediated the associations. Conclusions and RelevanceIn this study, CHIP was independently associated with a higher risk of developing cataract, AMD, and DR, but not glaucoma. These findings establish a link between hematopoietic somatic mutations and the pathogenesis of several major age-related eye diseases, suggesting that CHIP-driven inflammation is a potential target for risk stratification and prevention. Key PointsO_ST_ABSQuestionC_ST_ABSIs clonal hematopoiesis of indeterminate potential (CHIP) associated with the risk of major age-related eye diseases? FindingsIn this cohort study of 436,469 participants, CHIP was associated with an increased risk of incident cataract (HR, 1.08; 95% CI, 1.03-1.14), age-related macular degeneration (HR, 1.12; 95% CI, 1.04-1.21), and diabetic retinopathy (HR, 1.41; 95% CI, 1.20-1.64), but not glaucoma. MeaningThese findings identify CHIP as an independent, non-ocular risk factor for cataract, AMD, and diabetic retinopathy, suggesting that systemic inflammation driven by CHIP contributes to the pathogenesis of these conditions and may represent a novel target for preventive strategies.

Importance: Sleep-wake disturbances in midlife are common and potentially modifiable contributors to long-term brain health, yet primary care lacks a brief, validated tool that reliably identifies adults with early cognitive vulnerability. Objective: To evaluate associations between commonly used sleep questionnaires and cognitive impairment among midlife primary care patients. Design, Setting, and Participants: Cross-sectional analysis of baseline data from the MidCog cohort, an observational study of English-speaking adults aged 35 to 64 years receiving primary care at academic practices or federally qualified health centers in the Chicagoland area. Exposures: Five validated sleep questionnaires were used to assess distinct sleep-wake disturbance phenotypes: (A) unsatisfactory sleep (PROMIS Sleep Disturbance T-score >55), (B) short sleep duration (<6 hours; Munich Chronotype Questionnaire), (C) obstructive sleep apnea (OSA) risk (STOP-Bang [&ge;]3), (D) insomnia symptoms (Insomnia Severity Index [&ge;]15), and (E) poor multidimensional sleep health (RU-SATED [&le;]6). Main Outcomes and Measures: The primary outcome was cognitive impairment defined as an age- and education-adjusted NIH Toolbox Cognition Battery (NIHTB-CB) Fluid Composite T-score <40 ( >1 SD below the population mean). Cognitive impairment defined by the Montreal Cognitive Assessment (MoCA) score <23 served as the secondary outcome. Logistic regression estimated adjusted odds ratios (aOR), controlling for age, sex, education, body mass index, hypertension, hypercholesterolemia, diabetes, smoking, depressive symptoms, and recruitment site. Results: Among 646 participants (mean [SD] age, 52.3 [8.1] years; 62.4% female; 38.0% non-Hispanic Black, 38.4% non-Hispanic White, 16.0% Hispanic), cognitive impairment was present in 18.7% by NIHTB-CB and 22.3% by MoCA. Among five sleep-wake disturbance phenotypes evaluated, only poor multidimensional sleep health was consistently associated with cognitive impairment after multivariable adjustment (NIHTB-CB: adjusted OR [95% CI] = 2.03 [1.25-3.26]; MoCA: 1.98 [1.20-3.26]). Conclusions and Relevance: Poor multidimensional sleep health was associated with cognitive impairment in midlife primary care patients. Brief multidimensional sleep health screening may identify individuals with early cognitive vulnerability and represent a potential strategy for targeting sleep-focused interventions to promote long-term brain health.

Introduction: Solitary plasmacytomas (SP) are rare neoplasm of localised proliferation of clonal plasma cells. It can be classified based on site of involvement and bone marrow involvement. It is an indolent disease in the majority of patients. Primary modality of treatment is radiotherapy and surgical excision. Materials and methods: This was a retrospective audit of SP who were treated and followed up at a tertiary care center in eastern India from January 2012 to December 2025. Patients who has solitary plasma cytoma with more than 10% plasma cells, POEMS syndrome, have been excluded from analysis. Results: We identified 46 patients of SP. The median age of the studied population was 53 years (23-75 years). Males were more commonly affected than females (M:F=2.2:1). Most common chief complaints were bony pain (67.4%). SBP was seen in 39 (84.8%) cases whereas SEP was seen in 7 (15.2%) cases. Vertebra was the most common site of involvement (61.4%). Median M band concentration 0.24 g/dL (0.1 to 1.95 gm/dL). IgG was the most common isotype accounting for 60.6% cases. Six cases (13%) had minimal bone marrow involvement. The majority of the patients received local radiotherapy (89.1%). With a median follow up of 5.4 years (95% CI: 1.8 - 9.0), median OS was not reached, median PFS was 9.22 years (95% CI: 5.8-12.6), median time to next treatment (TTNT) was 9.86 years (95% CI: 6.8 - 12.9). Conclusion: Solitary plasmacytoma commonly affects young males. Bones are more commonly affected than extramedullary sites. SP has a lower rate of progression and excellent prognosis when treated with local radiotherapy.

Background: Hereditary transthyretin amyloidosis (hATTR) manifests as cardiomyopathy and/or polyneuropathy. The V142I variant predominantly causes cardiac disease in African Americans, though neurological involvement may be underrecognized. We characterized neuropathy documentation and treatment patterns in a predominantly V142I cohort. Methods: Retrospective review of 54 hATTR patients at a major academic medical center. Neuropathy was classified as: objective (abnormal EMG), possible polyneuropathy (documented symptoms suggestive of polyneuropathy), symptoms only (neuropathic symptoms without specialist evaluation), or unclear. Treatment with stabilizers (tafamidis, acoramidis, diflunisal) and gene silencers (patisiran, vutrisiran, eplontersen) was assessed. Results: Of 54 patients (88.9% African American, 85.2% V142I), 51 (94.4%) had confirmed cardiac involvement. Among cardiac patients, 40/42 eligible (95.2%) received stabilizers. Overall, 16 patients (29.6%) received gene silencers, with 13 (24.1%) receiving both a stabilizer and gene silencer concurrently. Possible neuropathy (objective, possible polyneuropathy, or symptoms) was documented in 30 patients (55.6%). Gene silencer use was highest among those with objective neuropathy (8/17, 47.1%) versus symptoms only (1/10, 10.0%). All three patients without confirmed cardiac disease received gene silencers. Conclusions: In this V142I-predominant cohort with 94.4% cardiac involvement, stabilizer use was high (95.2%) among eligible patients. Over half had possible neuropathy based on clinical documentation, though EMG completion was limited (57.4%). Gene silencer use was associated with objective neuropathy documentation and non-cardiac phenotype. These findings support systematic neurological assessment in hATTR, even when cardiac disease predominates.

Background: Ethnic minorities and socioeconomically disadvantaged populations in the UK are at increased risk of obesity. We modelled longitudinal body mass index (BMI) trajectories through infancy, childhood, and adolescence to identify at-risk groups and modifiable risk factors. Methods: This cohort sampled 10,350 White and South Asian children born in Leicestershire, 1985-1997. We included 5,571 participants with [&ge;]3 BMI measurements between 0-18 years collected from healthcare records, questionnaires, and study visits. We used Group-Based Trajectory Modelling of BMI, separately by sex and ethnicity, and combined. We identified at-risk groups and modifiable risk factors using multinomial logistic regression, with inverse probability weighting to reduce selection bias. Results: We identified similar five BMI trajectories across sex and ethnicity: stable normal BMI (47%); persistent low BMI (30%); early overweight resolving (8%); childhood onset obesity (4%); and adolescent onset overweight (11%). Childhood onset obesity deviated from stable normal BMI at 2-4 years of age, adolescent onset overweight at 4-6 years. South Asians were at higher risk of childhood onset obesity (aOR: 1.66 [95%CI 1.08-2.53]) and adolescent onset overweight (1.29 [0.98-1.71]) than Whites. Children from deprived backgrounds (1.66 [0.92-2.82], most vs least deprived quintile) and those with less educated parents (1.67 [1.08-2.63], compulsory vs higher education) were at increased risk of childhood onset obesity. Smoking during pregnancy (1.50 [0.88-2.54]) and absence of breastfeeding (1.56 [1.07-2.29]) increased risk of childhood onset obesity. Physical activity decreased risk of childhood onset obesity (0.64 [0.44-0.93], [&ge;]4 vs 0-3 hours/week) and adolescent onset overweight (0.75 [0.59-0.94]). Conclusion: BMI trajectories diverge as early as age 2 years, revealing ethnic and social inequalities. Obesity strategies in the UK should intervene during critical windows in early life and prioritise South Asian children and those from socioeconomically deprived backgrounds.

AimWe examined associations between smoking and HbA1c among U.S. adults, and whether these associations vary by diabetes status. MethodsWe analyzed NHANES data from 2015-2018 for adults aged [&ge;]20 years. Smoking was assessed by self-report and serum cotinine. Survey-weighted multivariable linear regression was used to evaluate the association between smoking and HbA1c in the full population (N=9,214) and in adults without diabetes (N=7,328), adjusting for demographics, blood pressure, waist circumference, lipids, and C-reactive protein. ResultsAfter adjustment for cardiometabolic covariates, there was no significant association between smoking and HbA1c in the full population (former: {beta}=0.029%, p=0.30; current: {beta}=0.053%, p=0.13). Among adults without diabetes, former smoking was not associated with HbA1c, whereas current smoking remained significantly associated (former: {beta}=-0.001%, p=0.923; current: {beta}=0.067%, p<0.001). These findings were similar when cotinine was used as the exposure measure, with active smoking ([&ge;]3.0 ng/mL) associated with higher HbA1c among non-diabetic adults (p<0.001), but not in the full population. ConclusionsAmong adults without diabetes, current but not former smoking was associated with higher HbA1c. The absence of an association in former smokers suggests that this effect may attenuate following cessation. These findings support early cessation interventions and may inform cessation counseling and diabetes screening.

ImportanceGuideline-concordant care for young children with attention-deficit/hyperactivity disorder (ADHD) includes recommending parent training in behavior management (PTBM) as first-line treatment. However, assessing guideline adherence through manual chart review is time-consuming and costly, limiting scalable and timely quality-of-care measurement. ObjectiveTo evaluate the accuracy and explainability of large language models (LLMs) in identifying PTBM recommendations in pediatric electronic health record (EHR) notes as a scalable alternative to manual chart review. Design, Setting, and ParticipantsThis retrospective cohort study was conducted in a community-based pediatric healthcare network in California consisting of 27 primary care clinics. The study cohort included children aged 4-6 years with [&ge;] 2 primary care visits between 2020-2024 and ICD-10 diagnoses of ADHD or ADHD symptoms (n=542 patients). Clinical notes from the first ADHD-related visit were included. A stratified subset of 122 notes, including all cases with model disagreement, was manually annotated to assess model performance in identifying PTBM recommendations and rank model explanations. ExposuresAssessment and plan sections of clinical notes were analyzed using three generative large language models (Claude-3.5, GPT-4o, and LLaMA-3.3-70B) to identify the presence of PTBM recommendations and generate explanatory rationales and documentation evidence. Main Outcomes and MeasuresModel performance in identifying PTBM recommendations (measured by sensitivity, positive predictive value (PPV), and F1-score) and qualitative explainability ratings of model-generated rationales (based on the QUEST framework). ResultsAll three models demonstrated high performance compared to expert chart review. Claude-3.5 showed balanced performance (sensitivity=0.89, PPV=0.95, and F1-score=0.92) and ranked highest in explainability. LLaMA3.3-70B achieved sensitivity=0.91, PPV=0.89, and F1-score=0.90, ranking second for explainability. GPT-4o had the highest PPV [0.97] but lowest sensitivity [0.82], with an F1-score of 0.89 and the lowest explainability ranking. Based on classifications from the best-performing model, Claude-3.5, 26.4% (143/542) of patients had documented PTBM recommendations at their first ADHD-related visit. Conclusions and RelevanceLLMs can accurately extract guideline-concordant clinician recommendations for non-pharmacological ADHD treatment from unstructured clinical notes while providing clear explanations and supporting evidence. Evaluating model explainability as part of LLM implementation for medical chart review tasks can promote transparent and scalable solutions for quality-of-care measurement.

Objectives: Acute gastroenteritis is a leading cause of pediatric emergency department (ED) visits. While ondansetron reduces vomiting, intravenous rehydration, and hospital admissions, its efficacy when initiated at triage remains unclear. We aimed to evaluate whether triage nurse-initiated administration of ondansetron in children with suspected gastroenteritis reduces the proportion of patients requiring observation following initial physician assessment. Methods: We conducted a randomized, double-blind, placebo-controlled trial in a tertiary pediatric ED in Canada. Children aged 6 months to 17 years presenting with morae than 3 episodes of vomiting in the preceding 24 hours (including 1 within 2 hours of arrival), were eligible. At triage, we randomized participants to receive liquid ondansetron or a color- and taste-matched placebo. The primary outcome was the proportion of patients requiring observation after the first physician evaluation. Secondary outcomes included post-intervention vomiting, ED length of stay, patient comfort, and 48-hour return visits. The trial was registered at ClinicalTrials.gov (NCT03052361). Results: Recruitment was stopped prematurely due to the COVID-19 pandemic. Ninety-one participants were randomized to ondansetron (n= 44) or placebo (n= 47). Overall, 40 patients (45%) were discharged immediately after the initial physician assessment, with no difference between the ondansetron and placebo groups (44% vs. 45%; absolute difference -1%, 95% CI: -20% to 19%). No significant differences were observed in all secondary outcomes. Conclusion: In this trial, triage nurse-initiated ondansetron administration did not reduce the need for ED observation in children with presumed gastroenteritis. While being underpowered, this study could inform researchers planning larger clinical trials.

Objective Cerebral palsy (CP) affects approximately 1 million Americans and 18 million individuals worldwide, yet contemporary US epidemiologic data remains limited. We aimed to use Cerebral Palsy Research Network (CPRN) clinical registry to describe demographics and clinical characteristics of individuals with CP across the US and determine associations with gross motor function and genetic etiology. Methods Registry subjects were included if they had clinician-confirmed CP and prospectively entered data for Gross Motor Function Classification System (GMFCS) Level, gestational age, genetic etiology, CP distribution, and tone/movement types. Logistic regression was used to determine which of these variables plus race, sex, ethnicity, and age were associated with GMFCS level and genetic etiology. Results A total of 9,756 children and adults with CP from 22 CPRN sites met inclusion criteria. Participants were predominantly White (73.0%), male (57.3%), non-Hispanic (87.8%), and younger than 18 years (73.7%). Most were classified as GMFCS levels I-III (55.6%), born preterm (52.8%), had spasticity (83.8%), and had quadriplegia (41.9%); 12.2% were identified as having a genetic etiology. Tone/movement types, CP distribution, and gestational age were significantly associated with both GMFCS level and genetic etiology (p<0.001). Compared to White individuals, Black individuals were more likely to have greater gross motor impairment (p<0.001). Conclusion In this large US cohort, clinical and demographic factors, including race, were associated with gross motor function and genetic etiology in CP. These findings highlight persistent disparities and demonstrate the value of a national clinical registry for informing prognostication, quality improvement efforts, and targeted genetic testing strategies.