Pediatrics

BackgroundPediatric long COVID is associated with substantial symptom burden, yet evidence-based pharmacologic treatments remain limited. Low-dose naltrexone (LDN) has been proposed as a potential symptomatic therapy, but data in pediatric populations is lacking. MethodsWe conducted a retrospective analysis of pediatric and young adult patients ([≤]25 years) with a clinical diagnosis of long COVID who were prescribed LDN between July 2020 and July 2025 at three multidisciplinary pediatric long COVID programs in the United States. Deidentified clinical data were extracted from medical records. Outcomes included symptom prevalence, dosing practices, treatment continuation or discontinuation, adverse effects, and available patient-reported quality-of-life measures (PedsQL and PROMIS(R)). FindingsThe study included 62 patients (mean age, 15.6 years [range, 8-23]; 53.2% male and 46.8% female). Fatigue was nearly universal (98.4%), followed by headaches (87.1%), brain fog (74.2%), dizziness/lightheadedness (67.7%), anxiety (66.1%), and post-exertional malaise (56.5%). LDN-treated patients demonstrated a higher prevalence of neurocognitive and autonomic symptoms, compared to general clinic cohorts. Most patients (71.0%) reported no adverse effects; the most common were vivid dreams (9.7%) and insomnia (9.7%). At follow-up, 66.1% of patients remained on LDN. Medication discontinuation was attributed to perceived lack of benefit (43.8%) or side effects (25.0%). Baseline quality-of-life measures at initiation showed marked impairment: PedsQL Physical Health (M=38.0, SD=20.9) and Multidimensional Fatigue (M=35.7, SD=15.8) scores were low. PROMIS scores indicated reduced physical functioning (M=36.8, SD=8.7) and cognitive functioning (M=40.8, SD=7.6), with elevated fatigue (M=68.0, SD=10.4) and pain interference (M=58.6, SD=8.2) relative to population norms. The study was not designed to assess efficacy. InterpretationLDN was primarily prescribed to patients with prominent fatigue, neurocognitive symptoms, and autonomic dysfunction, and was generally well tolerated. These findings provide descriptive evidence of real-world prescribing practices and support the need for clinical trials to systematically evaluate LDNs efficacy in pediatric long COVID.

ImportanceWhole genome sequencing (WGS) is increasingly used to diagnose severely ill children, yet the long-term impact of a genetic diagnosis on healthcare utilization and resource allocation remains poorly understood. ObjectiveTo determine the influence of a genetic diagnosis via WGS on long-term healthcare utilization metrics in severely ill children. DesignA retrospective cohort study using data from the Next Generation Children study (2016-2020) with record linkage and analysis of primary care records conducted between 2022 and 2024. SettingA multicenter study involving primary care and hospital records linked via the UK National Health Research Institute (NIHR) Rare Disease Bioresource, Cambridge, UK. ParticipantsA referred sample of 270 severely ill children who underwent WGS. Exposure(s)Receipt of a genetic diagnosis (87/270; 32%) compared to those who remained undiagnosed (183/270; 68%) following WGS. Main Outcome(s) and Measure(s)Comparison of 36 healthcare utilization parameters, including hospitalizations, primary care prescriptions, and diagnostic tests. ResultsAmong the 270 children analyzed, those receiving a genetic diagnosis (n=87) exhibited significantly higher overall healthcare utilization compared to undiagnosed peers (n=183). This included increased hospital admissions and outpatient visits, particularly for neurodevelopmental and seizure-related conditions. Diagnosed children received a higher volume of neurological, gastrointestinal, and nutritional prescriptions. The most pronounced differences in utilization were observed in children initially diagnosed in neonatal (NICU) or pediatric (PICU) intensive care settings. While genetic diagnosis was not associated with reduced healthcare costs during the study period, it was linked to more targeted, condition-specific medical care. Conclusions and RelevanceWGS diagnosis facilitates the integration of specialist care and the alignment of healthcare resources with the specific needs of children with complex disorders. These findings suggest that while costs may not decrease immediately, a diagnosis enables more precise and targeted clinical management. Key PointsO_ST_ABSQuestionC_ST_ABSDoes a genetic diagnosis through whole genome sequencing influence long-term healthcare utilization in severely ill children? FindingsIn this cohort study of 270 children, those who received a genetic diagnosis demonstrated significantly greater overall healthcare utilization, including more hospitalizations and targeted prescriptions, compared with undiagnosed children. MeaningA genetic diagnosis facilitates the integration of specialized, condition-specific care, helping to align healthcare resources with the individual needs of children with complex disorders.

PurposeWhile genomic testing is integral to pediatric inborn errors of immunity (IEI) care, few studies have examined strategies to support its optimal delivery. This study aimed to characterize a pediatric IEI cohort and assess the impact of implementing a mainstream model-of-care (MoC). Materials/MethodsComprehensive chart audit was conducted for patients ([&le;]18y) who received IEI genomic testing in Queensland, Australia, from 2017-2025. Descriptive analyses captured demographic and clinical characteristics, genomic testing and results, and management outcomes. Inferential analyses assessed changes in genomic practices pre-MoC (<2021) and post-MoC ([&ge;]2021). Results322 patients met eligibility criteria (n=481 genomic test). Diagnostic yield (27.6%) varied by testing indication, with the highest rate among phagocytic defects (n=4/4;100%) and severe combined immunodeficiency (n=8/10;80%). Very-early-onset inflammatory bowel disease had the lowest diagnostic yield (n=3/68;4.4%), prompting changes to testing criteria. Molecular diagnosis resulted in management changes for 90.5% patients. Genomic testing was widely used pre-MoC (n=251 genomic tests). All outcomes significantly improved pre-and post-MoC (p<0.05): duplicate testing decreased (13.9% to 0%); variants of uncertain significance reduced (37.7% to 7.1%); informed consent documentation increased (70.5% to 88.4%); and diagnostic yield increased (16.2% to 27.4%). ConclusionTargeted interventions are needed to support delivery of genomic testing and strengthen service effectiveness.

BackgroundParticipating in research during medical school is supported by institutional programs and may influence subsequent professional development. ObjectiveWe aimed to describe the current status and heterogeneity of scholarly research programs for medical students in the United States, including expectations, support, and key structural features. MethodsWe conducted a cross-sectional web audit of official webpages for all accredited US MD- and DO-granting medical schools (search performed September 2024 to January 2025). Extracted variables included participation requirements, mentorship, timing and duration (overall and dedicated research time), expected scholarly outputs, funding sources, stipend information, and stated program goals. We compared Carnegie tier R1 (Very high research activity) versus other institutions, QS Top-50 versus other institutions, and MD versus DO schools using {chi}2/Fisher exact tests for 2x2 tables and exact trend or Freeman-Halton tests for multicategory variables. ResultsPrograms were identified for all 202 institutions. Funding was explicitly mentioned by 61.9% (125/202) of programs, 27.0% (51/189) were compulsory, 98.9% (188/190) reported faculty mentorship, and 91.0% (171/188) were exclusive for medical students. Program duration, dedicated time, expected outcomes, stipend reporting, funding sources, and stated goals varied widely. Carnegie R1 institutions had longer duration (P=.002) and tended to report external funding more often than other institutions (25/104, 24.0% vs 9/98, 9.2%; OR 3.13, 95% CI 1.38-7.10; P=.008). QS Top-50 institutions were more likely to require compulsory participation than other institutions (11/19, 57.9% vs 40/170, 23.5%; OR 4.47, 95% CI 1.68-11.87; P=.003). No significant differences were observed between MD and DO programs across most measured characteristics. ConclusionsScholarly research programs for medical students are ubiquitous across US medical schools but heterogeneous in structure, expectations, and support. Research-intensive and top-ranked institutions may have more external funding and sometimes may put together longer and compulsory programs Further evaluation of student experiences and outcomes is warranted.

Background and ObjectivesDecision-making about resuscitating a critically ill child is complex yet common. We aimed to study the survival thresholds at which physicians, compared to parents, decide to treat or withhold resuscitating a child. Moreover, we aimed to compare physicians survival estimates with those from a nationwide registry. MethodsWe conducted a cross-sectional survey-based study in the United States. Clinical vignettes based on hypothetical survival probabilities were used to study and compare the decision thresholds for parents and physicians. Vignettes developed using the Get-With-The-Guidelines-Resuscitation registry were used to explore physicians decision thresholds and compare their survival estimates with those from the data. Thresholds were determined using mixed-effect logistic regression models. ResultsWe had decisions for 501 and 257 vignettes from 167 parents and 43 physicians, respectively. The decision threshold for survival to discharge was 5.3% (95% CI: 3.7 to 7.0) for physicians and 1.2% (95% CI: -0.8 to 3.0) for parents. Whereas the decision threshold for survival to discharge with PCPC 1 or 2 was 3.5% (95% CI: 1.1 to 7.1) for physicians and 0.6% (95% CI: -1.2 to 1.8) for parents. About 58% of the physicians overestimated the likelihood of survival. ConclusionsThe study found that the decision threshold for the physicians was higher than that for the parents (5.3% vs. 1.2%). This illustrates that parents still want to attempt resuscitation at a survival probability where physicians would recommend withholding resuscitation. These findings have implications for clinical practice and counseling the parents of critically ill hospitalized children.

BackgroundCaregiver skills training programmes are well-researched in the fields of autism and intellectual disability, but children with motor disorders such as cerebral palsy remain underrepresented despite their high prevalence. These caregivers face unique challenges, and group programmes may provide family-centred care through information provision, problem-solving and peer support. MethodsSystematic searches of five databases (CINAHL, Medline, Embase, PsychINFO and ERIC) were conducted for interventional studies of group programmes aiming to improve the skills, confidence and wellbeing of caregivers of children with neurodisability focusing on motor disorders. Data were extracted on study and intervention characteristics and outcomes. Risk of bias was assessed, effect sizes calculated, and results summarised descriptively using forest plots. ResultsOf 6093 studies identified, 21 studies met inclusion criteria (nine randomised-controlled trials, two quasi-experimental and ten pre-post designs). Most reported on programmes developed in resource-constrained settings and addressed caregiver skills, coping strategies, or health-promoting behaviours. Outcomes were grouped according to caregiver wellbeing, caregiver skills and confidence, and social support and family functioning. Child outcomes were reported separately. Most caregiver outcomes showed positive effects, though most studies had high risk of bias due to self-reported outcomes and lack of blinding of intervention allocation and outcome measurement. DiscussionGroup-based training programmes show promise for improving caregiver skills and wellbeing. Clinicians and stakeholders in high-income countries may learn from these innovations in low-resource settings. Future research should strengthen protocol reporting, address attrition, control for confounding factors, and establish a core set of caregiver-reported outcomes to better capture programme impact. Systematic review registrationPROSPERO registration CRD42024595002

BackgroundEvidence supports the key role research mentors play in bolstering the success of early stage investigators (ESI). However, there are limited data about the impact of supplemental, cross-disciplinary career mentorship and professional development opportunities for ESIs seldom included during academic training. We assessed the perceived value of this approach among post-doctoral fellows and early career faculty who participated in a multi-component career mentoring program organized by the University of California, San Francisco Center for AIDS Research (UCSF CFAR). MethodsWe surveyed past program participants (2005-2020), assessing demographics, current career status, perceived impact of the program, and feedback on program elements. We performed thematic analysis on open-ended responses to explore program benefits. ResultsOf 146 program participants contacted, 102 responded (70% response rate). Over two thirds (65%) were female, and 38% self-identified as underrepresented minority (URM) investigators. A majority of respondents now dedicate >70% of their time to research. All would recommend the program to ESI colleagues, and over 80% reported that their CFAR mentors influenced their career trajectories in several ways, including help with grant writing, linkage to researchers sparking new collaborations, and support through personal challenges or navigating conflict with primary research mentors. While 90% of URM ESIs valued advice from CFAR mentors, only a third reported receiving specific support around challenges faced as minoritized investigators. ConclusionsA career mentoring program designed to complement the support offered by research mentors positively influenced the career trajectory of ESIs. Focused efforts are needed to support URM investigators who face ongoing structural barriers to success in academic settings.

BackgroundVision loss represents a significant public health concern according to the World Health Organisation, with increasing global age-standardised prevalence rates. Visual impairments are disproportionately distributed, occurring eight times more frequently in Sub-Saharan Africa and Southeast Asia compared to high-income regions. The Interprofessional Education (IPE) approach, utilizing the Arclight package as an implementation vehicle, offers promising potential for collaborative early detection and management of eye conditions in resource-constrained environments. This research aimed to implement validated Interprofessional Eye Health Education(IPEHE) in Rwanda, assess fundamental eye health knowledge and skills acquisition, evaluate medium to long-term learning retention, and explore IPEs role in developing these competencies. MethodsThe study employed a mixed-methods approach combining a Randomised Controlled Trial (RCT) with qualitative assessment at the University of Rwanda. Researchers invited 443 final-year students from diverse healthcare programs including nursing, pharmacy, midwifery, medicine, and ophthalmic clinical officers. With statistical power set at 0.80 and alpha error probability at 0.05, the design aimed to detect pre-post training score differences of 10% or greater. The calculated sample size of 54 participants per group was expanded to 280 total participants (180 intervention, 100 control) to accommodate potential attrition. ResultsIn the intervention group, 161 students (89.4%) attended the training, and 113 (70.2%) participated in the 10-month follow-up assessment (POST2). Of the control group, 90 participants (90%) attended assessments at 10 months post-intervention (POST2). Knowledge scores in the intervention group increased by 58.9% (SD=20.8, Z=10.82 p<0.001) immediately post-training, while skills improved by 49.7% (SD=14, Z=-8.382, P<0.001). At the 10-month follow-up, these gains remained significantly above baseline levels. Intervention participants significantly outperformed the control group at follow-up in both knowledge, with a 54.1% difference (SE= 2.0, df (201) = 27.3, P<0.001), and skills, with a 44% difference (SE=1.1, t(155)=38.7, p<0.001). Qualitative data from the intervention group indicated an appreciation for interprofessional collaboration, holistic patient care approaches, and the practical skills acquired. ConclusionThe IPEHE intervention significantly enhanced collaborative eye health knowledge and skills among Rwandan healthcare students, with demonstrated retention up to 10 months post-intervention. These findings suggest that pre-qualification interprofessional education effectively produces collaborative practice-ready professionals capable of addressing eye health challenges in resource-limited settings.

IntroductionPhysician assistant (PA) programs face persistent challenges in recruiting and retaining clinical preceptors due to time constraints, administrative burden, lack of compensation, and limited training. Additional pressures, such as health care consolidation, program expansion, clinician burnout, and financial implications of paid clinical sites, further strain preceptorship capacity. This study examines motivators and barriers influencing clinicians willingness to precept PA students. MethodsThis mixed-methods study used snowball sampling to recruit current, former, and non-precepting PAs across North Carolina. Participants completed surveys with Likert-scale and open-ended items adapted from the 2011 National Survey of Physician Assistants. Four virtual focus groups, selected from survey respondents, underwent semi-structured interviews informed by Self-Determination Theory (SDT). Quantitative data were analyzed using descriptive statistics and ordinal logistic regression; qualitative data underwent thematic analysis with deductive SDT coding and inductive refinement. Triangulation integrated findings. ResultsRespondents (N = 158) represented diverse clinical experience. Top motivators included student quality (66%), program support (53%), and financial compensation (51%). Key barriers were student quality (61.29%), burnout (53.23%), and lack of compensation (46.77%). From the focused group discussion, four themes emerged: Student Quality, Financial Compensation, Non-Financial Incentives, and Administrative Support. Student preparedness acted as both motivator and barrier; compensation concerns focused on fairness. DiscussionPreceptorship relies on relational and professional factors, student quality, recognition, and institutional alignment, rather than financial incentives alone. System inefficiencies, inadequate preparation, and misaligned compensation hinder engagement. Improving student readiness, enhancing institutional support, and implementing transparent, layered incentives may strengthen recruitment and retention.

PurposeGenetic diseases often present and are first diagnosed in the neonatal intensive care unit (NICU). Accurate identification of neonates with genetic diagnoses (GDs) in electronic health records (EHR) would enable a more complete understanding of their phenotypic spectrum, advancing care and personalized medicine. Prior research has used International Classification of Diseases (ICD) billing codes as proxies for GDs, though their accuracy for detecting confirmed GDs is uncertain. We evaluate the ICD codes for neonates with confirmed GDs and compare ICD billing code patterns between neonates with and without GD in two independent NICU cohorts. MethodsRetrospective analysis of patients admitted to the Boston Childrens Hospital (BCH) level IV NICU (1,344 neonates) and Nationwide Childrens Hospital (NCH)s neonatal network (33,315 neonates, mixed Level III/IV). For both cohorts, GDs captured by phecodes, aggregates of ICD codes, were compared with confirmed GDs. Two separate phenome-wide association studies (PheWAS) compared phecode patterns between neonates with GDs and those without, adjusting for sex, age at admission, gestational age, and NICU length of stay. ResultsGenetic phecodes were able to correctly identify 43.5% of neonates that received a GD in the BCH or NCH NICUs. Among 719 individuals with two or more genetic phecodes at BCH or NCH, 566 (78.72%) had a true GD. The BCH PheWAS analysis revealed a statistically significant positive association with atrioventricular septal defects and a negative association with bronchopulmonary dysplasia. The NCH pheWAS revealed 179 significantly associated phecodes, including many congenital anomalies. ConclusionThe use of ICD codes to identify NICU infants with GDs is neither sensitive nor accurate, though phecode analysis demonstrated stronger accuracy than sensitivity. Our data highlight clinical features of NICU infants more commonly seen in those that receive a GD (congenital heart defects) and those that are not (BPD). Our results can help to better predict and identify NICU neonates that receive a GD.

BackgroundObjective Structured Clinical Examination (OSCE; Clinical Performance Examination [CPX] in South Korea) is a high-stakes assessment of clinical performance, communication, and reasoning during time-limited patient encounters. As AI-enabled virtual standardized patient (VSP) simulation and automated scoring are introduced for OSCE-like training, prospective evidence is needed on how such systems perform and are perceived when embedded in real educational workflows. MethodsWe developed CPX with Medical students Assistant for Training and Evaluation (CPX-MATE), a web-based platform integrating (1) CPX with Virtual Standardized Patient (CPX-VSP), real-time voice dialogue with a VSP using speech-to-speech (STS) models, and (2) CPX with Real-Time Evaluator (CPX-RTE), automated transcription, checklist-based scoring, and feedback from encounter audio using a Speech-to-Text model and a large language model. During an emergency medicine clerkship (Nov 2025-Jan 2026), 60 senior medical students completed two 12-min CPX encounters (VSP with acute pancreatitis; HSP with ureteral stone) with immediate CPX-RTE feedback. For CPX-VSP, students were assigned to either a full-capacity or a resource-limited STS configuration (n=30 each). Dialogue fidelity was evaluated by turn-by-turn analysis of student-VSP exchanges, classifying responses into clinically meaningful error types (tangential, oversharing, role-breaking, off-script). CPX-RTE performance was assessed by agreement (Gwets AC1) with professor real-time and resident video-based ratings using a 45-item checklist. Usability of CPX-VSP and CPX-RTE, with overall system usability scale (SUS), were surveyed, and mean per-session costs for CPX-VSP and CPX-RTE were calculated. ResultsAcross 3,282 dialogue turns, overall error rates were 1.77% versus 9.43% for full-capacity versus resource-limited STS configurations (p<0.001), driven by fewer tangential and oversharing responses; no off-script errors were observed. The mean per-session cost was $0.12 for resource-limited configuration and $0.78 for full-capacity configuration. CPX-RTE showed high agreement with human ratings (AC1=0.916 vs professor; 0.916 vs resident), with slightly different levels of agreement across four sections, and high usability across all domains (mean scores, 4.65-4.92), with a per-session cost of $0.17. CPX-MATE demonstrated good overall usability (median [IQR] of 77.5 [70.0-85.0]). ConclusionsEmbedded within a prospective clinical clerkship, CPX-MATE demonstrated operational fidelity and human-level checklist agreement as an end-to-end, voice-based AI-assisted OSCE platform. This real-world deployment supports its scalable integration as a complementary assessment tool while highlighting the importance of systematic validation and context-aware implementation in medical education.

PurposeCaregivers of children with complex neurodisability frequently experience high caregiving demands, social isolation, unmet support needs, and reduced wellbeing. This paper explores caregivers perceptions of the impact of "Encompass", a ten-modular, community-based group support programme for caregivers of children under five with complex neurodisability, co-facilitated by an expert parent. Materials and methodsThis study formed part of a pilot and feasibility study conducted in two socially disadvantaged, ethnically diverse urban areas in the United Kingdom. Outcome measures were collected pre-intervention, post-intervention and at three-month follow-up to explore caregiver wellbeing, empowerment, activation, and quality of life. Semi-structured qualitative interviews were conducted within three months of programme completion. Interview data were analysed using deductive coding informed by the "Encompass" programme theory alongside inductive analysis to explore mechanisms and unanticipated benefits. Results and conclusionsSeven participating caregivers described improved wellbeing, increased confidence in caring for their child, navigating services, advocating for their family and engaging in the community. Peer support, shared learning and expert parent facilitation were key identified mechanisms of impact. Data from outcome measures showed patterns of improvement post-intervention, with less consistent eYects at follow-up. Findings confirmed the key change mechanisms, informing future iterations and other caregiver group programmes. Trial RegistrationClinicalTrials.gov Identifier: NCT06310681

BackgroundAsthma is a frequent comorbidity in children with sickle cell disease and has been associated with an increased risk of acute complications, particularly vaso-occlusive crises and acute chest syndrome. However, determinants of clinical severity among children with sickle cell disease and confirmed asthma remain poorly characterized, especially in tropical settings. This study aimed to identify factors associated with clinical severity in this population. MethodsWe conducted an observational study among children with sickle cell disease followed in French Guiana. The analysis was restricted to children with confirmed asthma. Clinical severity was defined as the occurrence of at least two hospitalizations during the 12 months preceding evaluation for vaso-occlusive crises and/or acute chest syndrome. Factors associated with severity were assessed using univariate and multivariate logistic regression analyses. ResultsA total of 138 children with sickle cell disease and confirmed asthma were included, of whom 49 (35.5%) presented a severe clinical form. In multivariate analysis, no variable was independently associated with clinical severity. However, a trend toward an increased risk of severe disease was observed among children living in rural areas (adjusted OR = 1.94; 95% CI: 0.77-4.86), while a trend toward a protective effect was observed for Strongyloides stercoralis infection (adjusted OR = 0.18; 95% CI: 0.02-1.51). Allergic sensitization, although frequent (64.5%), was not associated with clinical severity after adjustment (adjusted OR = 0.66; 95% CI: 0.31-1.44). ConclusionAmong children with sickle cell disease and confirmed asthma, more than one third experience severe clinical disease. Severity does not appear to be driven by allergy but may be influenced by environmental and contextual factors specific to tropical settings. These findings support a stratified approach to sickle cell-associated asthma to identify high-risk children and prevent avoidable acute complications.

BackgroundThe epidemiology of suspected pediatric meningoencephalitis has shifted in the era of conjugate vaccines and multiplex PCR diagnostics, with viral pathogens now predominating over bacterial causes. Updated epidemiologic data are essential to adapt diagnostic and therapeutic algorithms to current clinical practice. MethodsThis retrospective single-center study included children and adolescents <18 years who underwent lumbar puncture with cerebrospinal fluid multiplex PCR for suspected central nervous system infection at a tertiary-care pediatric hospital in Germany between 2016 and 2024. Clinical, laboratory, and outcome data were extracted from electronic medical records. Cerebrospinal fluid was analyzed using the BioFire(R) FilmArray(R) Meningitis/Encephalitis Panel. Statistical analyses included descriptive statistics, nonparametric group comparisons, receiver operating characteristic analyses. ResultsAmong 1,198 included children, definite bacterial meningitis was diagnosed in 13 (1.1%), definite viral meningitis in 80 (6.7%), aseptic meningitis of unknown etiology in 131 (11.0%), confirmed/probable encephalitis in 53 (4.4%), and possible encephalitis in 34 (2.8%). Bacterial meningitis accounted for 5.8% of all meningitis cases. A causative pathogen was identified in all bacterial meningitis cases, most commonly Streptococcus pneumoniae (n = 7). Enterovirus (n = 52) and parechovirus (n = 9) predominated in viral meningitis, whereas an infectious etiology was identified in only 13 of 53 confirmed/probable encephalitis cases. The Bacterial Meningitis Score showed a sensitivity of 80.0% and a specificity of 57.6%. The recently published UK-ChiMES-pre- and post-lumbar puncture scores demonstrated sensitivities of 84.6% and 76.9% and specificities of 86.3% and 92.7%, respectively. DiscussionBacterial meningitis was rare in this contemporary cohort, while viral and etiologically unresolved infections predominated despite routine multiplex PCR diagnostics. Clinical prediction scores supported risk stratification, with the UK-ChiMES-pre-lumbar puncture score showing the most favorable balance between sensitivity and specificity and potential to guide diagnostic decisions and antiinfective therapy.

BackgroundAdvanced Practice Providers (APPs) in emergency and urgent care settings experience high burnout rates, yet limited research examines cognitive factors influencing professional fulfillment. The Empowerment Dynamic framework suggests outcome-oriented thinking may protect against burnout compared to problem-oriented patterns. ObjectiveTo examine relationships between cognitive mindset orientation, professional fulfillment, and burnout among APPs while providing preliminary validation of a novel cognitive assessment instrument. MethodsCross-sectional survey of licensed APPs working in emergency departments and urgent care facilities across two health systems (July-October 2025). Professional fulfillment and burnout were measured using the Stanford Professional Fulfillment Index; cognitive orientation was assessed using a newly developed 22-item instrument. ResultsAmong 98 respondents (19.5% response rate), mean professional fulfillment was 5.8 and mean burnout was 4.5; 40.8% met burnout criteria. Professional fulfillment and burnout were inversely correlated (r = -0.62; P < .001). Problem orientation correlated positively with burnout (r = 0.56) and negatively with fulfillment (r = -0.36), while outcome orientation showed opposite patterns (burnout: r = -0.57; fulfillment: r = 0.44). In multivariable models, outcome orientation remained independently associated with lower burnout ({beta} = -1.51; P = .003) and higher fulfillment ({beta} = 1.73; P = .002). ConclusionsCognitive mindset orientation is associated with burnout and professional fulfillment among APPs. The novel assessment instrument demonstrates acceptable psychometric properties. Future longitudinal studies are needed to establish causality and evaluate cognitive interventions for burnout prevention.

BackgroundThe influence of genetic and environmental factors, especially during early development, is critical in the pathogenesis of autism. Maternal autoantibodies that recognize specific fetal brain proteins can be strong predictors of autism risk. These antibodies cross the placenta and bind to their target antigens, which play critical roles in neurodevelopment, thereby increasing autism risk. This etiologically defined subtype is now referred to as Maternal Autoantibody-Related Autism (MARA). The newly developed MAR-AutismTM test is an indirect multi-ELISA assay designed to detect specific combinations of these maternal antibodies, which strongly predicts increased autism risk. ObjectiveTranslation of the indirect ELISA assays for the eight relevant antibodies (LDH-A, LDH-B, GDA, STIP1, CRMP1, CRMP2, NSE and YBOX) from an academic laboratory to a clinical development laboratory for optimization and determination of the analytical performance of the individual antibody assays. MethodsFeasibility assays were transferred from the academic laboratory and their performance confirmed prior to optimization of all steps from target protein production to preliminary threshold determination. Validation to rigorous standards was conducted. The ELISAs are qualitative assays using an internal continuous response and a cutoff to define positivity and negativity for each analyte. Analytical performance metrics of linearity, sensitivity, specificity, precision, and stability were determined by standard testing methodologies. ResultsThe optimized ELISAs all performed at acceptable standards for analytical performance. All of the assays except one were demonstrated to be linear upon dilution with buffer and with non-reactive plasma, however, recovery was overestimated with buffer diluent. The precision profile results demonstrated that the Lower Limit of Quantification (LOQ) was greater than the Limit of Detection (LOD) and below the preliminary thresholds determined from a general population cohort distribution. Precision studies showed coefficients of variation less than 15% with two minor exceptions. Common interfering substances, apart from whole human IgG, did not affect assay performance. The microtiter assay plates were stable for at least 6 months without significant drift. ConclusionOverall, the individual antibody assays demonstrated high sensitivity, specificity, and robustness sufficient to enable extension to clinical validation. These assays enable evaluation of specific antibody combinations that were previously reported to strongly and specifically correlate with autism risk, particularly in settings of suspected diagnosis or in families with an older sibling with a confirmed autism diagnosis.

Introduction"Encompass" is a participatory group-based intervention originating from low- and middle-income countries, co-developed with parents and professionals to enhance the wellbeing, health literacy and empowerment of caregivers of young children with complex neurodisability. We aimed to assess feasibility and acceptability of a) intervention delivery in two socially deprived United Kingdom (UK) urban areas and b) evaluation methods including data collection on programme outcomes and costs. MethodsWe conducted a mixed-methods pilot and feasibility study with caregivers of children under five years with complex neurodisability. Feasibility and acceptability of intervention delivery were assessed based on recruitment rates, group attendance, fidelity checklists and qualitative interviews with caregivers and facilitators. Feasibility and acceptability of evaluation methods were explored through follow-up rates, questionnaire completeness, and caregiver feedback on outcome measures. Data relating to implementation at organisational and system levels were explored through interviews with facilitators and key partners. Results were compared to predefined traffic light criteria (green, amber, red) to determine whether a larger scale evaluation was warranted. ResultsEight caregivers participated in the programme. Fidelity of delivery and follow-up questionnaire completion met green criteria, while recruitment and attendance met amber criteria, indicating that minor adaptations are required before scaling up. Qualitative findings demonstrated high acceptability of the programme among caregivers and facilitators, particularly valuing the co-facilitation model, participatory approach, and peer support. Flexible delivery, including online participation and communication support, enhanced accessibility for families with diverse needs. Capturing programme delivery costs was feasible and provided preliminary estimates to inform future economic evaluation. ConclusionsOur findings provide proof of principle that "Encompass" can feasibly and acceptably be delivered and evaluated with caregivers of children with complex neurodisability in an ethnically diverse UK community health setting. The findings support progression to a larger-scale evaluation, with refinements to recruitment strategies and delivery logistics. Patient or Public ContributionCaregivers with lived experience were central to developing the "Encompass" programme and this study. Four local mothers of children with complex neurodisability contributed to planning, recruitment, and sense-checking the findings.

BackgroundChest radiograph interpretation is a foundational skill in physician associate (PA) education, and competence in diagnostic imaging is an accreditation standard. While a larger body of research on radiology education exists in undergraduate medical education, considerable variability in instructional approaches limits clear conclusions regarding the most effective method. Growing evidence supports the use of active learning strategies in radiology instruction. However, little published research specifically addresses radiology education within PA programs. Team-Based Learning (TBL), an active learning approach grounded in social constructivism that emphasizes preparation, collaboration, and application, may be well suited to teaching image interpretation. This study evaluates the effectiveness of TBL compared with traditional lecture-based instruction for chest radiograph interpretation. MethodsA mixed-methods, quasi-experimental cohort comparison using a pre-post design was conducted with two consecutive PA student cohorts at a single institution. One cohort received a 90-minute lecture-based session; another cohort participated in a 90-minute TBL session. Academic performance was assessed using validated pre- and post-tests. Student satisfaction and self-efficacy were evaluated using post-session surveys derived from the Kirkpatrick model and Banduras self-efficacy theory. Independent sample t-tests compared quantitative outcomes, and qualitative responses were analyzed thematically. ResultsBoth cohorts demonstrated improvement in chest radiograph interpretation scores, with no statistically significant differences between groups in post-test performance or score improvement (p = 0.841). Survey results indicated favorable perceptions of both instructional approaches. The TBL cohort reported significantly higher ratings for engagement and peer interaction (p = <0.001). Self-efficacy ratings were higher among TBL participants for selected confidence-related items (p=0.003, p = 0.021, p = <0.001). Qualitative responses on what contributed most to self-efficacy emphasized peer discussion in the TBL group and structured explanations in the lecture group. ConclusionsTBL produced academic performance comparable to lecture-based instruction while supporting greater learner engagement and confidence. These findings support TBL as a feasible instructional approach for chest radiograph interpretation in PA education.

The terms personalized, individualized and precision medicine are increasingly used to describe health interventions, yet their operational meaning in clinical research remains unclear. Despite extensive conceptual discussion, there is limited empirical evidence on how these labels are applied in randomized controlled trials (RCTs) and whether such trials meet standards of transparency and methodological rigor. We systematically examined 262 RCTs published between 2020 and 2022 that used the terms "personalized", "individualized", or "precision" in the title to describe an intervention. The term "personalized" was used most frequently (49.2%), followed by "individualized" (45.8%) and "precision" (5.0%). In most trials, personalization involved behavioral, digital, or pharmacological interventions, with few studies employing -omics approaches. Personalization was most often based on individual lifestyle factors, psychological characteristics, or disease classification. We also found that in most trials, personalization consisted of tailoring a single intervention to individuals (82.8%), often through individualized dosage (73.2%). Most included RCTs were judged to be at high risk of bias and showed limited transparency with respect to data and code sharing. Our study suggests that, in contemporary RCTs, the labels "personalized", "individualized", and "precision" are applied interchangeably to a wide range of heterogeneous interventions that are predominantly non-genomic. Greater conceptual clarity and stronger methodological standards are needed to ensure that claims of personalization in clinical research are empirically meaningful and reliable.

BackgroundClinical research coordinators play a crucial role in ensuring the scientific rigor, regulatory compliance, and operational integrity of clinical trials. However, in Africa, they often lack access to structured, competency-based training, especially in operational, regulatory, and trial management domains. This study evaluated the effectiveness of a comprehensive training intervention designed to standardize and enhance core competencies of clinical trial coordinators. MethodsWe conducted a prospective pre-post interventional study among cohorts of clinical research professionals completing a 10-week, internationally-accredited, Moodle-based clinical trial operations training program aligned with the Joint Task Force Core Competency Framework, covering 10 lessons and 25 domains. Self-reported competence was evaluated at baseline and post-training. Data analyses included paired t-tests for aggregate scores, McNemars exact test for domain-level proportions, multivariable logistic regression for predictors of improvement, and Cohens d for effect size. ResultsAmong the 166 participants enrolled from 19 African countries and completed the pre-training survey, 152 who completed the program and post-training survey were included. The training significantly increased the mean aggregate competence from 12.24{+/-}7.85 (out of a maximum of 25) to 23.35{+/-}2.73 (mean difference: 11.11; 95% CI 9.86-12.36; p<0.001; Cohens d=1.41). Score variance decreased, with the median score increasing from 12.0 (IQR: 6.0-19.0) to 24.5 (IQR: 23.0-25.0). All 25 domains improved (p<0.001), with the largest gains in complex, low-baseline domains: managing external partners (+59.2%), project management (+58.6%), financial management (+55.3%), and trial close-out (+57.2%). (+57.2%). Ethical principles and informed consent that had high baseline competence reached near-universal levels at 99.3% and 98.7%, respectively. No differences were observed by country or gender (p>0.05). ConclusionStructured, competency-based training strengthens clinical trial coordinators capabilities, particularly in technical and administrative domains that are often overlooked. Accredited, framework-aligned clinical trial training programs promote consistent trial quality, strengthen research capacity, and sustain excellence in clinical trial delivery. WHAT IS ALREADY KNOWN ON THIS TOPIC- Clinical research coordinators play a crucial role in ensuring the scientific rigor, regulatory compliance, and operational integrity of clinical trials WHAT THIS STUDY ADDS- The study evaluated the effectiveness of a comprehensive training intervention designed to standardize and enhance core competencies of clinical trial coordinators in Africa, where they often lack access to structured, competency-based training HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY- This study should encourage the design and delivery of internationally-accredited, Moodle-based clinical trial operations training programs in Africa that enhance clinical trial competency.