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Cover page of The contribution of community transmission to the burden of hospital-associated pathogens: A systematic scoping review of epidemiological models.

The contribution of community transmission to the burden of hospital-associated pathogens: A systematic scoping review of epidemiological models.

(2025)

Healthcare-associated infections (HAI), particularly those involving multi-drug resistant organisms (MDRO), pose a significant public health threat. Understanding the transmission of these pathogens in short-term acute care hospitals (STACH) is crucial for effective control. Mathematical and computational models play a key role in studying transmission but often overlook the influence of long-term care facilities (LTCFs) and the broader community on transmission. In a systematic scoping review of 4,733 unique studies from 2016 to 2022, we explored the modeling landscape of the hospital-community interface in HAI-causing pathogen transmission. Among the 29 eligible studies, 28 % (n = 8) exclusively modeled LTCFs, 45 % (n = 13) focused on non-healthcare-related community settings, and 31 % (n = 9) considered both settings. Studies emphasizing screening and contact precautions were more likely to include LTCFs but tended to neglect the wider community. This review emphasizes the crucial need for comprehensive modeling that incorporates the communitys impact on both clinical and public health outcomes.

Education Research: Rewarding Our Educators: Design and Evaluation of a Program to Fund Teaching in Neurology.

(2025)

BACKGROUND AND OBJECTIVES: Pressures on academic physician educators to generate clinical revenue or research grants may threaten faculty engagement as teachers. Neurology has historically prized its outstanding educators, but programs that provide financial support for teaching are lacking. We developed an opt-in, financial, teaching incentive program in an academic neurology department and evaluated its impact on faculty experience, motivation, and identity. METHODS: We applied a change management framework and conducted a National and local needs assessment before designing an education value unit (EVU) system using time-based metrics and rates reflecting impact on clinical revenue. Activities essential for graduation of students and residents that reduced clinical revenue generation were included. Faculty self-reported teaching through an online platform and received an incentive payment at the end of each year. Following a 6-month pilot, faculty participated in a 3-year implementation phase followed by an evaluation through faculty survey and semistructured interviews. RESULTS: In the first 3 years of the program, 42, 56, and 54 faculty enrolled, representing 28% of faculty by year 3. Faculty reported an average of 1,488 hours of teaching annually, drew from 13 divisions, and included all ranks (51% assistant, 29% associate, and 20% full). Fifty-five percent of participating faculty (N = 30) completed a survey to evaluate the incentive program. The majority agreed or somewhat agreed that the program had met its goals (80%-92%), reduced barriers to teaching (56%), and the department highly valued teaching (93%). Semistructured interviews with 11 participating faculty identified 5 themes regarding the impact of the program on faculty experience, including (1) supporting the choice of faculty to teach even when time is scarce, (2) making teaching visible to oneself and others, (3) directing faculty toward eligible teaching opportunities, (4) communicating the departments commitment to education, and (5) reinforcing educator identity and sense of belonging. DISCUSSION: The development of a teaching incentive program at an academic neurology center is feasible with benefits extending beyond the incentive payment itself. Although EVU programs are not without limitations, faculty experienced the program as reflective of the department valuing its educators, which reinforced their educator identity and engagement in teaching.

Cover page of Financial conflicts among physician speakers at the April 12, 2024 Oncology Drug Advisory Meeting: Who decided that MRD can be a novel regulatory endpoint in myeloma?

Financial conflicts among physician speakers at the April 12, 2024 Oncology Drug Advisory Meeting: Who decided that MRD can be a novel regulatory endpoint in myeloma?

(2025)

Background

In April 2024, the Oncology Drug Advisory Committee (ODAC) voted to approve minimal residual disease (MRD) as a new regulatory endpoint for multiple myeloma (MM) despite its poor trial-level surrogacy. This is expected to result in faster MM drug approvals, a potential boon for the pharmaceutical companies that make them. This study investigates the prevalence of financial conflicts of interest (FCOIs) with these companies among United States (US)-based physician speakers at the meeting.

Methods

Public data regarding the past 3 years of pharmaceutical company payments to US-based physician speakers at the ODAC meeting discussing MRD (available at https://openpaymentsdata.cms.gov/) were collected. For each general payment (GP), we recorded the amount, company payor, reason for payment, and associated products. Descriptive analyses were performed on payments from companies who manufacture MM therapeutics (MM payments).

Results

12 of the 20 physician speakers (60 %) eligible to have FCOIs recorded on the OpenPayments database received MM payments from 2021 to 2023, totaling more than $792,200. A majority of both voting and non-voting members had MM payments (median $11,800 and $764), most of which were consulting fees. Speakers earned more than 3.7 times as much from GPs associated with MM-related products compared to those associated with non-MM-related products.

Conclusion

Most US-based physician speakers at the April 2024 ODAC meeting had FCOIs from MM companies, including those with voting power.

Policy summary

Our findings highlight the need for greater policing of FCOIs among US-based physicians involved in cancer drug regulatory policy.

Trend of sales revenue by year for top selling cancer drugs in the US and the effect of loss of market exclusivity

(2025)

Biosimilars and generics have led to reduced cancer drug prices. The effect of biosimilar or generic drug competition on drug manufacturer revenue has not been previously described. In this study, the majority of top selling cancer drugs had a greater than 50 % decline in sales revenue within 2 years of generic or biosimilar market entry, reflecting both the decline in market share and reduction in unit drug price. This results in important drug manufacturer incentives, which may shape clinical trial agendas. The market structure incentives are unique for pharmaceutical companies due to the relatively short and limited duration of profitability. Policy changes such as patent reform leading to shorter duration of exclusivity may lead to greater incentive to expand low value indications in oncology.

Trajectories and patterns of US counties policy responses to the COVID-19 pandemic: A sequence analysis approach.

(2025)

Background

It is increasingly recognized that policies played a role in mitigating or exacerbating health inequities during the COVID-19 pandemic. While US counties were particularly active in policymaking, limited work has characterized geographic and temporal variation in pandemic-era policymaking at the local level, a prerequisite for later studies examining the health effects of these policies. This paper fills this gap by characterizing county-level COVID-19-related policy trajectories over time using a novel national policy database and innovative methods.

Methods

Data came from the US COVID-19 County Policy (UCCP) Database, including 309 counties in 50 states plus Washington DC during January 2020 to December 2021. We examined measures of overall policy comprehensiveness, as well as three domains including containment and closure, economic response, and public health. We applied sequence analysis to characterize county-level trajectories overall and within each policy domain, and cluster analysis to group similar trajectories.

Results

There was wide variation in policymaking, with nearly half of counties demonstrating consistently comprehensive policymaking, about 15-20% with consistently low comprehensiveness, and the remainder exhibiting intermittent comprehensiveness. Economic policies were less comprehensive than containment/closure and public health policies. There was also substantial variation within and across states, and associations with county characteristics.

Conclusion

This study is among the first to document substantial geographic and temporal variation in a variety of US county-level COVID-19-related policies, which likely contributed to health disparities during and after the pandemic. Future work should evaluate how these different policy trajectories differentially affected health and social outcomes.

Cover page of Whole-genome automated assembly pipeline for Chlamydia trachomatis strains from reference, in vitro and clinical samples using the integrated CtGAP pipeline.

Whole-genome automated assembly pipeline for Chlamydia trachomatis strains from reference, in vitro and clinical samples using the integrated CtGAP pipeline.

(2025)

Whole genome sequencing (WGS) is pivotal for the molecular characterization of Chlamydia trachomatis (Ct)-the leading bacterial cause of sexually transmitted infections and infectious blindness worldwide. Ct WGS can inform epidemiologic, public health and outbreak investigations of these human-restricted pathogens. However, challenges persist in generating high-quality genomes for downstream analyses given its obligate intracellular nature and difficulty with in vitro propagation. No single tool exists for the entirety of Ct genome assembly, necessitating the adaptation of multiple programs with varying success. Compounding this issue is the absence of reliable Ct reference strain genomes. We, therefore, developed CtGAP-Chlamydia trachomatisGenome Assembly Pipeline-as an integrated one-stop-shop pipeline for assembly and characterization of Ct genome sequencing data from various sources including isolates, in vitro samples, clinical swabs and urine. CtGAP, written in Snakemake, enables read quality statistics output, adapter and quality trimming, host read removal, de novo and reference-guided assembly, contig scaffolding, selective ompA, multi-locus-sequence and plasmid typing, phylogenetic tree construction, and recombinant genome identification. Twenty Ct reference genomes were also generated. Successfully validated on a diverse collection of 363 samples containing Ct, CtGAP represents a novel pipeline requiring minimal bioinformatics expertise with easy adaptation for use with other bacterial species.

Cover page of Efficacy and safety of lemborexant in subjects with insomnia disorder receiving medications for depression or anxiety symptoms.

Efficacy and safety of lemborexant in subjects with insomnia disorder receiving medications for depression or anxiety symptoms.

(2025)

AIM: Individuals with insomnia frequently have comorbid depression or anxiety. This study sought to provide a preliminary indication of the effects of lemborexant (LEM) in subjects treated for mild depression/anxiety symptoms. METHODS: E2006-G000-303 (NCT02952820; EudraCT 2015-001463-39; SUNRISE-2) was a 12-month, phase 3, randomized, placebo-controlled, double-blind study where subjects with insomnia disorder were randomized (1:1:1) to placebo, LEM 5 mg (LEM5), or LEM 10 mg (LEM10) for 6 months. During the second 6 months (not reported), placebo-treated subjects were re-randomized to LEM5 or LEM10. In this post hoc analysis, changes from baseline (CFB) in subject-reported (subjective) sleep onset latency (sSOL), sleep efficiency (sSE), wake after sleep onset (sWASO), total sleep time (sTST), Fatigue Severity Scale, and Insomnia Severity Index were evaluated in subjects treated with medications for symptoms of depression/anxiety (subpopulation). RESULTS: Of 949 randomized subjects, 61 treated with medications for symptoms of depression/anxiety were included. In the subpopulation, CFB comparing LEM with placebo were generally smaller than the overall population due to a larger placebo response in the subpopulation. However, the magnitudes of CFB within the active treatment groups for sSOL, sWASO, sTST, and sSE were similar between the subpopulation and the overall population. No new safety signals were observed in the subpopulation. CONCLUSION: LEM treatment benefited subjects with insomnia treated with medications for depression/anxiety symptoms, with no new safety signals. A greater placebo response in the subpopulation than in the overall population decreased the drug versus placebo effect size for LEM, as has been reported for other insomnia medications.

Cover page of Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) Study

Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) Study

(2025)

Purpose

To describe progression of best-corrected visual acuity (BCVA), full-field stimulus thresholds (FST), and electroretinography (ERG) over 4 years in the USH2A-related Retinal Degeneration study and to assess their suitability as clinical trial endpoints.

Design

Prospective natural history study.

Participants

Participants (n = 105) with biallelic disease-causing sequence variants in USH2A and BCVA letter scores of ≥54 were included.

Methods

BCVA, FST, fundus-guided microperimetry, static perimetry, and spectral domain OCT were performed annually and ERG at baseline and 4 years only. Mixed effects models were used to estimate annual rates of change with 95% confidence intervals. Associations of change from baseline to 4 years between BCVA, FST, ERG, and other metrics were assessed with Spearman correlation coefficients (r_s).

Main outcome measures

Best-corrected visual acuity, FST, and ERG.

Results

The annual rate of decline in BCVA was 0.83 (95% confidence interval: 0.65-1.02) letters/year. For FST, the change was 0.09 (0.07-0.11) log cd.s/m²/year for white threshold, 0.10 (0.08-0.12) log cd.s/m²/year for blue threshold, and 0.05 (0.04-0.06) log cd.s/m²/year for red threshold. Changes were 22.6 (17.4-28.2)%/year for white threshold, 26.0 (20.3-32.1)%/year for blue threshold, and 12.3 (8.7-16.0)%/year for red threshold. The high percentage of eyes with undetectable ERGs at baseline limited assessment of change.

Conclusions

Best-corrected visual acuity was not a sensitive measure of progression over 4 years. Full-field stimulus threshold was a more sensitive measure; however, additional information on the clinical relevance of changes in FST is needed before this test can be adopted as an endpoint for clinical trials.

Financial disclosures

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Atopic dermatitis and tobacco smoke exposure during childhood and adolescence

(2025)

Background

Tobacco smoke may affect atopic dermatitis (AD) because of its known effects on humoral and cellular immunity, but prior studies lack data on disease severity and biomarkers over time.

Objective

We investigated the association between passive and active tobacco smoke exposure (TSE) during childhood and adolescence and the activity and severity of AD.

Methods

A birth cohort of 10,521 individuals was followed through adolescence as part of the Avon Longitudinal Study of Parents and Children. We used mixed-effect models to determine the risk of AD (based on repeated assessments) with passive smoke exposure during childhood, active TSE during adolescence, and using a serum biomarker of tobacco exposure (cotinine) at 3 time points.

Results

After adjusting for confounding factors, there was no evidence of a relationship between passive TSE and concurrent AD activity in childhood (adjusted odds ratio, 0.95; 95% confidence interval, 0.83, 1.07) or of an increased risk between active smoking and AD activity in adolescence (adjusted odds ratio, 0.57; 95% confidence interval, 0.44, 0.75). Secondary analyses demonstrated no dose-response relationship and no increased severity of AD with passive or active TSE. Furthermore, we found no increased risk of AD with a cumulative measure of passive TSE across childhood (adjusted relative risk ratio, 0.98; 95% confidence interval, 0.96, 1.00).

Conclusion

Neither active nor passive TSE was associated with AD during childhood and adolescence.

Cover page of Severe Adult-Onset Non-Dystrophic Myotonia With Apnea and Laryngospasm Due to Digenic Inheritance of <i>SCN4A</i> and <i>CLCN1</i> Variants: A Case Report.

Severe Adult-Onset Non-Dystrophic Myotonia With Apnea and Laryngospasm Due to Digenic Inheritance of SCN4A and CLCN1 Variants: A Case Report.

(2025)

Objectives

To report a case of adult-onset non-dystrophic myotonia complicated by recurrent episodes of laryngospasm.

Methods

The patient is a 35-year-old man who was admitted to our hospital for recurrent episodes of apnea requiring endotracheal intubation with mechanical ventilation. He underwent extensive evaluation, including EMG, laryngoscopy, muscle biopsy, and genetic testing, which revealed a diagnosis of non-dystrophic myotonia.

Results

His myotonic disorder was due to the synergistic effects of a pathogenic CLCN1 variant and a newly reported SCN4A variant. His muscle biopsy demonstrated myofibrillar disorganization with Z-band streaming, which may reflect the severity of his clinical and electrographic myotonia. Treatment with mexiletine resulted in resolution of his episodes of laryngospasm and symptoms of myotonia in the extremities.

Discussion

Our case adds to the literature on the potentiating effects of chloride channelopathies on sodium channel myotonia. This is the first reported case of an adult-onset sodium channelopathy manifesting with respiratory failure due to laryngospasm. In addition, we present muscle biopsy findings that have not been described in the recent literature. This case also highlights that a myotonic disorder should be considered in the differential diagnosis for recurrent episodes of mixed hypoxic and hypercarbic respiratory failure.

UCSF